Life and Living in Advanced Age: A Cohort Study in New Zealand -Te Puāwaitanga o Nga Tapuwae Kia Ora Tonu, LiLACS NZ: Study protocol

PubMed Central

2012-01-01

Background The number of people of advanced age (85 years and older) is increasing and health systems may be challenged by increasing health-related needs. Recent overseas evidence suggests relatively high levels of wellbeing in this group, however little is known about people of advanced age, particularly the indigenous Māori, in Aotearoa, New Zealand. This paper outlines the methods of the study Life and Living in Advanced Age: A Cohort Study in New Zealand. The study aimed to establish predictors of successful advanced ageing and understand the relative importance of health, frailty, cultural, social & economic factors to successful ageing for Māori and non-Māori in New Zealand. Methods/design A total population cohort study of those of advanced age. Two cohorts of equal size, Māori aged 80–90 and non-Māori aged 85, oversampling to enable sufficient power, were enrolled. A defined geographic region, living in the Bay of Plenty and Lakes District Health Board areas of New Zealand, defined the sampling frame. Rūnanga (Māori tribal organisations) and Primary Health Organisations were subcontracted to recruit on behalf of the University. Measures - a comprehensive interview schedule was piloted and administered by a trained interviewer using standardised techniques. Socio-demographic and personal history included tribal affiliation for Māori and participation in cultural practices; physical and psychological health status used standardised validated research tools; health behaviours included smoking, alcohol use and nutrition risk; and environmental data included local amenities, type of housing and neighbourhood. Social network structures and social support exchanges are recorded. Measures of physical function; gait speed, leg strength and balance, were completed. Everyday interests and activities, views on ageing and financial interests complete the interview. A physical assessment by a trained nurse included electrocardiograph, blood pressure, hearing and vision, anthropometric measures, respiratory function testing and blood samples. Discussion A longitudinal study of people of advanced age is underway in New Zealand. The health status of a population based sample of older people will be established and predictors of successful ageing determined. PMID:22747503

The Effect of Patient and Surgical Characteristics on Renal Function After Partial Nephrectomy.

PubMed

Winer, Andrew G; Zabor, Emily C; Vacchio, Michael J; Hakimi, A Ari; Russo, Paul; Coleman, Jonathan A; Jaimes, Edgar A

2018-06-01

The purpose of the study was to identify patient and disease characteristics that have an adverse effect on renal function after partial nephrectomy. We conducted a retrospective review of 387 patients who underwent partial nephrectomy for renal tumors between 2006 and 2014. A line plot with a locally weighted scatterplot smoothing was generated to visually assess renal function over time. Univariable and multivariable longitudinal regression analyses incorporated a random intercept and slope to evaluate the association between patient and disease characteristics with renal function after surgery. Median age was 60 years and most patients were male (255 patients [65.9%]) and white (343 patients [88.6%]). In univariable analysis, advanced age at surgery, larger tumor size, male sex, longer ischemia time, history of smoking, and hypertension were significantly associated with lower preoperative estimated glomerular filtration rate (eGFR). In multivariable analysis, independent predictors of reduced renal function after surgery included advanced age, lower preoperative eGFR, and longer ischemia time. Length of time from surgery was strongly associated with improvement in renal function among all patients. Independent predictors of postoperative decline in renal function include advanced age, lower preoperative eGFR, and longer ischemia time. A substantial number of subjects had recovery in renal function over time after surgery, which continued past the 12-month mark. These findings suggest that patients who undergo partial nephrectomy can experience long-term improvement in renal function. This improvement is most pronounced among younger patients with higher preoperative eGFR. Copyright © 2017 Elsevier Inc. All rights reserved.

Impaired muscle efficiency but preserved peripheral hemodynamics and mitochondrial function with advancing age: Evidence from exercise in the young, old, and oldest-old.

PubMed

Layec, Gwenael; Trinity, Joel D; Hart, Corey R; Le Fur, Yann; Zhao, Jia; Reese, Van; Jeong, Eun-Kee; Richardson, Russell S

2018-03-23

Muscle weakness in the elderly has been linked to recurrent falls and morbidity, therefore, elucidating the mechanisms contributing to the loss of muscle function and mobility with advancing age is critical. To this aim, we comprehensively examined skeletal muscle metabolic function and hemodynamics in 11 young (23±2 yrs), 11 old (68±2 yrs), and 10 oldest-old (84±2 yrs) physical activity-matched subjects. Specifically, oxidative stress markers, mitochondrial function and the ATP cost of contraction as well as peripheral hemodynamics were assessed during dynamic plantar flexion exercise at 40% of maximal work rate (WRmax). Both the PCr recovery time constant and the peak rate of mitochondrial ATP synthesis were not significantly different between groups. In contrast, the ATP cost of dynamic contractions (young: 1.5±1.0, old: 3.4±2.1, oldest-old: 6.1±3.6 mM.min-1.W-1) and systemic markers of oxidative stress were signficantly increased with age, with the ATP cost of contraction being negatively correlated with WRmax (r=0.59, P<0.05). End-of-exercise blood flow per Watt rose significantly with increasing age (young: 37±20, old: 82±68, oldest-old: 154±93 ml.min-1.W-1). These findings suggest that the progressive deterioration of muscle contractile efficiency with advancing age may play an important role in the decline in skeletal muscle functional capacity in the elderly.

Visual acuity and contrast sensitivity are two important factors affecting vision-related quality of life in advanced age-related macular degeneration

PubMed Central

Selivanova, Alexandra; Shin, Hyun Joon; Miller, Joan W.; Jackson, Mary Lou

2018-01-01

Purpose Vision loss from age-related macular degeneration (AMD) has a profound effect on vision-related quality of life (VRQoL). The pupose of this study is to identify clinical factors associated with VRQoL using the Rasch- calibrated NEI VFQ-25 scales in bilateral advanced AMD patients. Methods We retrospectively reviewed 47 patients (mean age 83.2 years) with bilateral advanced AMD. Clinical assessment included age, gender, type of AMD, high contrast visual acuity (VA), history of medical conditions, contrast sensitivity (CS), central visual field loss, report of Charles Bonnet Syndrome, current treatment for AMD and Rasch-calibrated NEI VFQ-25 visual function and socioemotional function scales. The NEI VFQ visual function scale includes items of general vision, peripheral vision, distance vision and near vision-related activity while the socioemotional function scale includes items of vision related-social functioning, role difficulties, dependency, and mental health. Multiple regression analysis (structural regression model) was performed using fixed item parameters obtained from the one-parameter item response theory model. Results Multivariate analysis showed that high contrast VA and CS were two factors influencing VRQoL visual function scale (β = -0.25, 95% CI-0.37 to -0.12, p<0.001 and β = 0.35, 95% CI 0.25 to 0.46, p<0.001) and socioemontional functioning scale (β = -0.2, 95% CI -0.37 to -0.03, p = 0.023, and β = 0.3, 95% CI 0.18 to 0.43, p = 0.001). Central visual field loss was not assoicated with either VRQoL visual or socioemontional functioning scale (β = -0.08, 95% CI-0.28 to 0.12,p = 0.44 and β = -0.09, 95% CI -0.03 to 0.16, p = 0.50, respectively). Conclusion In patients with vision impairment secondary to bilateral advanced AMD, high contrast VA and CS are two important factors affecting VRQoL. PMID:29746512

Visual acuity and contrast sensitivity are two important factors affecting vision-related quality of life in advanced age-related macular degeneration.

PubMed

Roh, Miin; Selivanova, Alexandra; Shin, Hyun Joon; Miller, Joan W; Jackson, Mary Lou

2018-01-01

Vision loss from age-related macular degeneration (AMD) has a profound effect on vision-related quality of life (VRQoL). The pupose of this study is to identify clinical factors associated with VRQoL using the Rasch- calibrated NEI VFQ-25 scales in bilateral advanced AMD patients. We retrospectively reviewed 47 patients (mean age 83.2 years) with bilateral advanced AMD. Clinical assessment included age, gender, type of AMD, high contrast visual acuity (VA), history of medical conditions, contrast sensitivity (CS), central visual field loss, report of Charles Bonnet Syndrome, current treatment for AMD and Rasch-calibrated NEI VFQ-25 visual function and socioemotional function scales. The NEI VFQ visual function scale includes items of general vision, peripheral vision, distance vision and near vision-related activity while the socioemotional function scale includes items of vision related-social functioning, role difficulties, dependency, and mental health. Multiple regression analysis (structural regression model) was performed using fixed item parameters obtained from the one-parameter item response theory model. Multivariate analysis showed that high contrast VA and CS were two factors influencing VRQoL visual function scale (β = -0.25, 95% CI-0.37 to -0.12, p<0.001 and β = 0.35, 95% CI 0.25 to 0.46, p<0.001) and socioemontional functioning scale (β = -0.2, 95% CI -0.37 to -0.03, p = 0.023, and β = 0.3, 95% CI 0.18 to 0.43, p = 0.001). Central visual field loss was not assoicated with either VRQoL visual or socioemontional functioning scale (β = -0.08, 95% CI-0.28 to 0.12,p = 0.44 and β = -0.09, 95% CI -0.03 to 0.16, p = 0.50, respectively). In patients with vision impairment secondary to bilateral advanced AMD, high contrast VA and CS are two important factors affecting VRQoL.

Challenged but not threatened: Managing health in advanced age.

PubMed

Wiles, Janine; Miskelly, Philippa; Stewart, Oneroa; Kerse, Ngaire; Rolleston, Anna; Gott, Merryn

2018-06-20

In this paper we reflect on discussions with people of advanced age in Āotearoa New Zealand, and draw on theoretical frameworks of resilience and place in old age, to explore insights about the ways older people maintain quality of life and health. Twenty community-dwelling people of advanced age (85+) were recruited in 2015-16 from a large multidisciplinary longitudinal study of advanced age. These twenty participated in interviews about health in advanced age, impact of illnesses, interactions with clinicians, access to information, support for managing health, and perceptions of primary care, medications, and other forms of assistance. We use a positioning theory framework drawing on thematic and narrative analysis to understand the dynamic ways people in advanced age position themselves and the ways they age well through speech acts and storylines. People in advanced age saw themselves as challenged, rather than threatened, by adversities, and positioned themselves as able to draw on a lifetime of experience and resourcefulness and collaborations with supporters to deal with challenges. Key strategies include downplaying illness and resisting biomedical discourses of complexity, positioning embodied selves as having agency, and creative adaptation in the face of loss. People in advanced age exhibit resilience, maintaining wellbeing, autonomy and good physical and mental quality of life even while living with challenges such as functional decline and multi-morbidities. These findings have significance for supporters of older people, emphasising the need to move away from a narrow focus on problems to working together WITH people in advanced age to offer a more holistic approach that encourages and enhances adaptation and flexibility, rather than rigid and counterproductive coping patterns. Copyright © 2018 Elsevier Ltd. All rights reserved.

ENHANCED RECOVERY METHODS FOR 85KR AGE-DATING GROUNDWATER: ROYAL WATERSHED, MAINE

EPA Science Inventory

Potential widespread use of ⁸⁵Kr, having a constant input function in the northern hemisphere, for groundwater age-dating would advance watershed investigations. The current input function of tritium is not sufficient to estimate young modern recharge waters. While tri...

Progress toward the maintenance and repair of degenerating retinal circuitry.

PubMed

Vugler, Anthony A

2010-01-01

Retinal diseases such as age-related macular degeneration and retinitis pigmentosa remain major causes of severe vision loss in humans. Clinical trials for treatment of retinal degenerations are underway and advancements in our understanding of retinal biology in health/disease have implications for novel therapies. A review of retinal biology is used to inform a discussion of current strategies to maintain/repair neural circuitry in age-related macular degeneration, retinitis pigmentosa, and Type 2 Leber congenital amaurosis. In age-related macular degeneration/retinitis pigmentosa, a progressive loss of rods/cones results in corruption of bipolar cell circuitry, although retinal output neurons/photoreceptive melanopsin cells survive. Visual function can be stabilized/enhanced after treatment in age-related macular degeneration, but in advanced degenerations, reorganization of retinal circuitry may preclude attempts to restore cone function. In Type 2 Leber congenital amaurosis, useful vision can be restored by gene therapy where central cones survive. Remarkable progress has been made in restoring vision to rodents using light-responsive ion channels inserted into bipolar cells/retinal ganglion cells. Advances in genetic, cellular, and prosthetic therapies show varying degrees of promise for treating retinal degenerations. While functional benefits can be obtained after early therapeutic interventions, efforts should be made to minimize circuitry changes as soon as possible after rod/cone loss. Advances in retinal anatomy/physiology and genetic technologies should allow refinement of future reparative strategies.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, M.; Soppet, W.K.; Rink, D.L.

This report provides an update on the evaluation of thermal-aging induced degradation of tensile properties of advanced ferritic-martensitic steels. The report is the first deliverable (level 3) in FY11 (M3A11AN04030103), under the Work Package A-11AN040301, 'Advanced Alloy Testing' performed by Argonne National Laboratory, as part of Advanced Structural Materials Program for the Advanced Reactor Concepts. This work package supports the advanced structural materials development by providing tensile data on aged alloys and a mechanistic model, validated by experiments, with a predictive capability on long-term performance. The scope of work is to evaluate the effect of thermal aging on the tensilemore » properties of advanced alloys such as ferritic-martensitic steels, mod.9Cr-1Mo, NF616, and advanced austenitic stainless steel, HT-UPS. The aging experiments have been conducted over a temperature of 550-750 C for various time periods to simulate the microstructural changes in the alloys as a function of time at temperature. In addition, a mechanistic model based on thermodynamics and kinetics has been used to address the changes in microstructure of the alloys as a function of time and temperature, which is developed in the companion work package at ANL. The focus of this project is advanced alloy testing and understanding the effects of long-term thermal aging on the tensile properties. Advanced materials examined in this project include ferritic-martensitic steels mod.9Cr-1Mo and NF616, and austenitic steel, HT-UPS. The report summarizes the tensile testing results of thermally-aged mod.9Cr-1Mo, NF616 H1 and NF616 H2 ferritic-martensitic steels. NF616 H1 and NF616 H2 experienced different thermal-mechanical treatments before thermal aging experiments. NF616 H1 was normalized and tempered, and NF616 H2 was normalized and tempered and cold-rolled. By examining these two heats, we evaluated the effects of thermal-mechanical treatments on material microstructures and associated mechanical properties during long-term aging at elevated temperatures. Thermal aging experiments at different temperatures and periods of time have been completed: 550 C for up to 5000 h, 600 C for up to 7500 h, and 650 C for more than 10,000 h. Tensile properties were measured on thermally aged specimens and aging effect on tensile behavior was assessed. Effects of thermal aging on deformation and failure mechanisms were investigated by using in-situ straining technique with simultaneous synchrotron XRD measurements.« less

Mitochondria, Cybrids, Aging, and Alzheimer’s Disease

PubMed Central

Swerdlow, Russell H.; Koppel, Scott; Weidling, Ian; Hayley, Clay; Ji, Yan; Wilkins, Heather M.

2018-01-01

Mitochondrial and bioenergetic function change with advancing age and may drive aging phenotypes. Mitochondrial and bioenergetic changes are also documented in various age-related neurodegenerative diseases, including Alzheimer’s disease (AD). In some instances AD mitochondrial and bioenergetic changes are reminiscent of those observed with advancing age, but are greater in magnitude. Mitochondrial and bioenergetic dysfunction could, therefore, link neurodegeneration to brain aging. Interestingly, mitochondrial defects in AD patients are not brain-limited, and mitochondrial function can be linked to classic AD histologic changes including amyloid precursor protein processing to beta amyloid. Also, transferring mitochondria from AD subjects to cell lines depleted of endogenous mitochondrial DNA (mtDNA) creates cytoplasmic hybrid (cybrid) cell lines that recapitulate specific biochemical, molecular, and histologic AD features. Such findings have led to the formulation of a “mitochondrial cascade hypothesis” that places mitochondrial dysfunction at the apex of the AD pathology pyramid. Data pertinent to this premise are reviewed. PMID:28253988

Inhibition of NA+/H+ Exchanger 1 Attenuates Renal Dysfunction Induced by Advanced Glycation End Products in Rats

PubMed Central

Li, Peng; Chen, Geng-Rong; Wang, Fu; Xu, Ping; Liu, Li-Ying; Yin, Ya-Ling; Wang, Shuang-Xi

2016-01-01

It has been recognized that sodium hydrogen exchanger 1 (NHE1) is involved in the development of diabetic nephropathy. The role of NHE1 in kidney dysfunction induced by advanced glycation end products (AGEs) remains unknown. Renal damage was induced by AGEs via tail vein injections in rats. Function and morphology of kidney were determined. Compared to vehicle- or BSA-treated rats, AGEs caused abnormalities of kidney structures and functions in rats, accompanied with higher MDA level and lower GSH content. Gene expressions of NHE1 gene and TGF-β1 in the renal cortex and urine were also increased in AGEs-injected rats. Importantly, all these detrimental effects induced by AGEs were reversed by inhibition of NHE1 or suppression of oxidative stress. These pieces of data demonstrated that AGEs may activate NHE1 to induce renal damage, which is related to TGF-β1. PMID:26697498

Association between advanced glycation end-products and functional performance in Alzheimer's disease and mixed dementia.

PubMed

Drenth, Hans; Zuidema, Sytse U; Krijnen, Wim P; Bautmans, Ivan; van der Schans, Cees; Hobbelen, Hans

2017-09-01

People with Alzheimer's disease (AD) experience, in addition to the progressive loss of cognitive functions, a decline in functional performance such as mobility impairment and disability in activities of daily living (ADL). Functional decline in dementia is mainly linked to the progressive brain pathology. Peripheral biomechanical changes by advanced glycation end-products (AGEs) have been suggested but have yet to be thoroughly studied. A multi-center, longitudinal, one-year follow-up cohort study was conducted in 144 people with early stage AD or mixed Alzheimer's/Vascular dementia. Linear mixed model analyses was used to study associations between AGE-levels (AGE reader) and mobility (Timed Up and Go), and ADL (Groningen Activity Restriction Scale and Barthel index), respectively. A significant association between AGE levels and mobility (β = 3.57, 95%CI: 1.43-5.73) was revealed; however, no significant association between AGE levels and ADL was found. Over a one-year time span, mean AGE levels significantly increased, and mobility and ADL performance decreased. Change in AGE levels was not significantly correlated with change in mobility. This study indicates that high AGE levels could be a contributing factor to impaired mobility but lacks evidence for an association with ADL decline in people with early stage AD or mixed dementia. Future research is necessary on the reduction of functional decline in dementia regarding the effectiveness of interventions such as physical activity programs and dietary advice possibly in combination with pharmacologic strategies targeting AGE accumulation.

Experimental evidence of age-related adaptive changes in human acinar airways

PubMed Central

Quirk, James D.; Sukstanskii, Alexander L.; Woods, Jason C.; Lutey, Barbara A.; Conradi, Mark S.; Gierada, David S.; Yusen, Roger D.; Castro, Mario

2015-01-01

The progressive decline of lung function with aging is associated with changes in lung structure at all levels, from conducting airways to acinar airways (alveolar ducts and sacs). While information on conducting airways is becoming available from computed tomography, in vivo information on the acinar airways is not conventionally available, even though acini occupy 95% of lung volume and serve as major gas exchange units of the lung. The objectives of this study are to measure morphometric parameters of lung acinar airways in living adult humans over a broad range of ages by using an innovative MRI-based technique, in vivo lung morphometry with hyperpolarized 3He gas, and to determine the influence of age-related differences in acinar airway morphometry on lung function. Pulmonary function tests and MRI with hyperpolarized 3He gas were performed on 24 healthy nonsmokers aged 19-71 years. The most significant age-related difference across this population was a 27% loss of alveolar depth, h, leading to a 46% increased acinar airway lumen radius, hence, decreased resistance to acinar air transport. Importantly, the data show a negative correlation between h and the pulmonary function measures forced expiratory volume in 1 s and forced vital capacity. In vivo lung morphometry provides unique information on age-related changes in lung microstructure and their influence on lung function. We hypothesize that the observed reduction of alveolar depth in subjects with advanced aging represents a remodeling process that might be a compensatory mechanism, without which the pulmonary functional decline due to other biological factors with advancing age would be significantly larger. PMID:26542518

[Chronic inflammation and organismal aging].

PubMed

Naito, Atsuhiko T; Komuro, Issei

2013-01-01

Aging is defined as the progressive functional decline of tissue function accompanied by increasing mortality with advancing age. Many researchers proposed various theories of aging, however, precise molecular mechanism of organismal aging remains elusive. The presence of autoantibody and the concentration of various inflammatory cytokines are often correlated to age, even in healthy individuals who do not have autoimmune or infectious diseases. In addition, low grade chronic inflammation has been regarded as a background for many age-related human diseases. These findings suggest that chronic inflammation plays a causative role in organismal aging and that proper regulation of aged immune system may decelerate organismal aging.

Advanced parental ages and low birth weight in autism spectrum disorders--rates and effect on functioning.

PubMed

Ben Itzchak, Esther; Lahat, Eli; Zachor, Ditza A

2011-01-01

(1) To assess the distribution of parental age and birth weight in a large cohort with autism spectrum disorder (ASD) and to compare them to Israeli national data. (2) To examine possible relationships between these risk factors and functioning. The study included 529 participants diagnosed with ASD using standardized tests: the Autism Diagnosis Interview-Revised and the Autism Diagnosis Observation Schedule (ADOS). Medical, developmental and familial histories (gender, age, pregnancy and birth information, parental ages) were obtained. Autism severity was assessed using the new ADOS severity scale and adaptive skill using the Vineland Adaptive Behavior Scales. Advanced parental age was associated with ASD. In the older age range the percentages of mothers (35-44 y) and fathers (30-40 y) were significantly higher in the ASD cohort in comparison to the Israeli newborn data. The ASD cohort had significantly higher percentages of low birth weight (<2500 g) and very low birth weight (VLBW<1500 g) in comparison to the Israeli newborn data. Of these risk factors, only VLBW was associated with lower adaptive functioning. The group with VLBW had lower scores in daily living, socialization and motor skills in comparison to the >1500 g group. Autism severity was not associated with advanced parental age or VLBW. The shift in parental age distribution and birth weight in our ASD cohort suggests that the increase in ASD prevalence in recent years might be associated with novel prenatal insults. An adverse fetal course resulting in VLBW may represent a "second hit" phenomenon, causing a poorer outcome. Copyright © 2011 Elsevier Ltd. All rights reserved.

Skin-autofluorescence, a measure of tissue advanced glycation end-products (AGEs), is related to diastolic function in dialysis patients.

PubMed

Hartog, Jasper W L; Hummel, Yoran M; Voors, Adriaan A; Schalkwijk, Casper G; Miyata, Toshio; Huisman, Roel M; Smit, Andries J; Van Veldhuisen, Dirk J

2008-09-01

Diastolic dysfunction is a frequent cause of heart failure, particularly in dialysis patients. Advanced glycation end-products (AGEs) are increased in dialysis patients and are suggested to play a role in the development of diastolic dysfunction. The aim of our study was to assess whether AGE accumulation in dialysis patients is related to the presence of diastolic dysfunction. Data were analyzed from 43 dialysis patients, age 58 +/- 15 years, of whom 65% were male. Diastolic function was assessed using tissue velocity imaging (TVI) on echocardiography. Tissue AGE accumulation was measured using a validated skin-autofluorescence (skin-AF) reader. Plasma N(epsilon)-(carboxymethyl)lysine (CML) and N(epsilon)-(carboxyethyl)lysine (CEL) were measured by stable-isotope-dilution tandem mass spectrometry. Plasma pentosidine was measured by high-performance liquid chromatography. Skin-AF correlated with mean E' (r = -0.51, P < .001), E/A ratio (r = -0.39, P = .014), and E/E' (r = 0.38, P = .019). Plasma AGEs were not significantly associated with diastolic function. Multivariable linear regression analysis revealed that 54% of the variance of average E' was explained by age (P = .007), dialysis type (P = 0.016), and skin-AF (P = .013). Tissue AGEs measured as skin-AF, but not plasma AGE levels, were related to diastolic function in dialysis patients. Although this may support the concept that tissue AGEs explain part of the increased prevalence of diastolic dysfunction in these patients, the ambiguous relation between plasma and tissue AGEs needs further exploring.

Preserving brain function in aging: The anti-glycative potential of berry fruit

USDA-ARS?s Scientific Manuscript database

Advanced glycation end-products (AGEs) are naturally occurring macromolecules that are formed in vivo by the non-enzymatic modification of proteins, lipids, or nucleic acids by sugar, even in the absence of hyperglycemia. In the diet, AGEs are found in animal products, and additional AGEs are produc...

Advanced glycation end products are elevated in cystic fibrosis-related diabetes and correlate with worse lung function.

PubMed

Hunt, William R; Helfman, Beth R; McCarty, Nael A; Hansen, Jason M

2016-09-01

The onset of cystic fibrosis-related diabetes (CFRD) exacerbates lung function decline and increases mortality. One pathway that may worsen the lung dysfunction associated with CFRD is that of the receptor for advanced glycation end products (RAGE) and its ligands. Human plasma was obtained from age-matched healthy, CF and CFRD patients. Plasma RAGE ligands (i.e. advanced glycation end products, S100A12, and high-mobility group protein B1) and soluble RAGE (sRAGE) levels were measured. CFRD patients had elevated plasma levels of AGEs and S100A12. Soluble RAGE, a RAGE ligand decoy receptor, was not significantly different between groups. Plasma AGE levels and S100A12 levels had significantly negative correlations with FEV1. AGEs are significantly elevated in CFRD and correlate negatively with FEV1. CFRD patients did not have significant increases in the decoy sRAGE, suggesting there may be heightened binding and activation of RAGE in CFRD exacerbating activation of proinflammatory pathways. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Medication and finance management among HIV-infected adults: the impact of age and cognition.

PubMed

Thames, April D; Kim, Michelle S; Becker, Brian W; Foley, Jessica M; Hines, Lindsay J; Singer, Elyse J; Heaton, Robert K; Castellon, Steven A; Hinkin, Charles H

2011-02-01

This study examined the effects of aging and cognitive impairment on medication and finance management in an HIV sample. We observed main effects of age (older < younger) and neuropsychological impairment on functional task performance. Interactions between age and cognition demonstrated that older impaired individuals performed significantly more poorly than all other comparison groups. There were no relationships between laboratory performance and self-reported medication and finance management. The interaction of advancing age and cognitive impairment may confer significant functional limitations for HIV individuals that may be better detected by performance-based measures of functional abilities rather than patient self-report.

Medication and finance management among HIV-infected adults: The impact of age and cognition

PubMed Central

Thames, April D.; Kim, Michelle S.; Becker, Brian W.; Foley, Jessica M.; Hines, Lindsay J.; Singer, Elyse J.; Heaton, Robert K.; Castellon, Steven A.; Hinkin, Charles H.

2013-01-01

This study examined the effects of aging and cognitive impairment on medication and finance management in an HIV sample. We observed main effects of age (older < younger) and neuropsychological impairment on functional task performance. Interactions between age and cognition demonstrated that older impaired individuals performed significantly more poorly than all other comparison groups. There were no relationships between laboratory performance and self-reported medication and finance management. The interaction of advancing age and cognitive impairment may confer significant functional limitations for HIV individuals that may be better detected by performance-based measures of functional abilities rather than patient self-report. PMID:20694873

Impact of genomic damage and ageing on stem cell function

PubMed Central

Behrens, Axel; van Deursen, Jan M.; Rudolph, K. Lenhard; Schumacher, Björn

2014-01-01

Impairment of stem cell function contributes to the progressive deterioration of tissue maintenance and repair with ageing. Evidence is mounting that age-dependent accumulation of DNA damage in both stem cells and cells that comprise the stem cell microenvironment are partly responsible for stem cell dysfunction with ageing. Here, we review the impact of the various types of DNA damage that accumulate with ageing on stem cell functionality, as well as the development of cancer. We discuss DNA-damage-induced cell intrinsic and extrinsic alterations that influence these processes, and review recent advances in understanding systemic adjustments to DNA damage and how they affect stem cells. PMID:24576896

Do Correlates of Pain-Related Stoicism and Cautiousness Differ in Younger and Older People With Advanced Cancer?

PubMed

Mah, Kenneth; Tran, Kim T; Gauthier, Lynn R; Rodin, Gary; Zimmermann, Camilla; Warr, David; Librach, S Lawrence; Moore, Malcolm; Shepherd, Frances A; Gagliese, Lucia

2018-03-01

Age differences are not evident in pain-related stoicism and cautiousness in people with cancer pain. Little is known about the factors associated with these pain-related attitudes or age-related patterns in these associations. The present cross-sectional study investigated the biopsychosocial correlates of the attitudes in younger and older patients with advanced cancer. Pain-related stoicism (fortitude, concealment, superiority) and cautiousness (self-doubt, reluctance) were assessed using the Pain Attitudes Questionnaire-Revised (PAQ-R). Participants, 155 younger (younger than 60 years old) and 114 older (60 years old or older) patients with advanced cancer completed the PAQ-R and measures of sociodemographic and medical characteristics, pain intensity, cognitive-affective pain-related responses, physical functioning, psychological distress and well-being, and psychosocial functioning. Backwards regression analyses identified correlates for each PAQ-R factor separately for younger and older patients. Activity engagement was a frequent correlate, but its relationship with concealment was the only association common to both age groups. Younger and older patients exhibited different avoidance-related constructs suggesting relational challenges in the former group (avoidant attachment) and intrapersonal fear in the latter (cognitive avoidance). Medical correlates also showed age differences: younger patients showed symptom-focused correlates, whereas older patients showed aging-related correlates. Findings support a biopsychosocial framework of cancer-pain adaptation incorporating a lifespan-developmental perspective. To our knowledge, this article is the first to identify biopsychosocial correlates of stoic and cautious attitudes toward cancer pain in younger and older patients with advanced cancer. Findings highlight possible age-related motivations for greater pain-related stoicism or cautiousness and can potentially inform interventions addressing challenges in cancer-pain adaptation in advanced cancer. Copyright © 2017 The American Pain Society. Published by Elsevier Inc. All rights reserved.

Effect of advance seedling size and vigor on survival after clearcutting

Treesearch

David A. Marquis

1982-01-01

In several separate experiments, it was found that survival of advance seedlings after clearcutting in Allegheny hardwood stands is a function of initial seedling size-larger seedlings survive best. Age, number of leaves, and leaf size also were important determinants of survival. In Allegheny hardwood stands, where advance regeneration is typically less than 1 foot in...

Chelation: A Fundamental Mechanism of Action of AGE Inhibitors, AGE Breakers, and Other Inhibitors of Diabetes Complications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagai, Rhoji; Murray, David B.; Metz, Thomas O.

2012-03-01

Advanced glycation or glycoxidation end-products (AGE) increase in tissue proteins with age, and their rate of accumulation is increased in diabetes, nephropathy and inflammatory diseases. AGE inhibitors include a range of compounds that are proposed to act by trapping carbonyl and dicarbonyl intermediates in AGE formation. However, some among the newer generation of AGE inhibitors lack reactive functional groups that would trap reaction intermediates, indicating an alternative mechanism of action. We propose that AGE inhibitors function primarily as chelators, inhibiting metal-catalyzed oxidation reactions. The AGE-inhibitory activity of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers is also consistent with their chelatingmore » activity. Finally, compounds described as AGE breakers, or their hydrolysis products, also have strong chelating activity, suggesting that these compounds also act through their chelating activity. We conclude that chelation is the common, and perhaps the primary, mechanism of action of AGE inhibitors and breakers, and that chronic, mild chelation therapy should prove useful in treatment of diabetes and age-related diseases characterized by oxidative stress, inflammation and increased chemical modification of tissue proteins by advanced glycoxidation and lipoxidation end-products.« less

Age, Gender and Load-Related Influences on Left Ventricular Geometric Remodeling, Systolic Mid-Wall Function, and NT-ProBNP in Asymptomatic Asian Population.

PubMed

Chen, Chi; Sung, Kuo-Tzu; Shih, Shou-Chuan; Liu, Chuan-Chuan; Kuo, Jen-Yuan; Hou, Charles Jia-Yin; Hung, Chung-Lieh; Yeh, Hung-I

2016-01-01

Advanced age is associated with left ventricle (LV) remodeling and impaired cardiac function that may increase the risk of heart failure. Even so, studies regarding age-related cardiac remodeling in a large, asymptomatic Asian population remain limited. We studied 8,410 asymptomatic participants (49.7 ±11.7 y, 38.9% women) in a health evaluation cohort (2004-2012) at a tertiary center in Northern Taiwan. We analyzed age-related alterations for all echocardiography-derived cardiac structures/functions and the associations with circulating N-terminal prohormone of brain natriuretic peptide (NT-proBNP). We also explored sex-related differences in these measures. In our cohort of 8,410 participants, advanced age was associated with greater LV wall thickness, larger LV total mass (+5.08 g/decade), and greater LV mass index (4.41 g/m2/decade), as well as increased serum NT-proBNP level (+18.89 pg/mL/decade). An accompanying reduction of stress-corrected midwall fractional shortening (-0.1%/decade) with aging was apparent in women after multi-variate adjustment (-0.09%/decade, p = 0.001). Furthermore, women demonstrated greater overall increase in LV wall thickness, LV mass index, and NT-proBNP compared to men (p for interaction: <0.001). All blood pressure components, including systolic, diastolic, and pulse pressures were independently associated with greater wall thickness and LV mass index after adjustment for confounders (all p <0.001). The associations between age and cardiac remodeling or mid-wall functions were further confirmed in a subset of study subjects with repeated follow up by GEE model. Significant associations of unfavorable LV remodeling and advanced age in our asymptomatic Asian population were observed, along with sex differences. These data may help explain the incidence of some diverse gender-related cardiovascular diseases, especially heart failure.

Acute macrovascular dysfunction in patients with type 2 diabetes induced by ingestion of advanced glycated β-lactoglobulins.

PubMed

Stirban, Alin; Kotsi, Paraskevi; Franke, Knut; Strijowski, Ulf; Cai, Weijing; Götting, Christian; Tschoepe, Diethelm

2013-05-01

Recent evidence indicates that heat-enhanced food advanced glycation end products (AGEs) adversely affect vascular function. The aim of this study was to examine the acute effects of an oral load of heat-treated, AGE-modified β-lactoglobulins (AGE-BLG) compared with heat-treated, nonglycated BLG (C-BLG) on vascular function in patients with type 2 diabetes mellitus (T2DM). In a double-blind, controlled, randomized, crossover study, 19 patients with T2DM received, on two different occasions, beverages containing either AGE-BLG or C-BLG. We measured macrovascular [brachial ultrasound of flow-mediated dilatation (FMD)] and microvascular (laser-Doppler measurements of reactive hyperemia in the hand) functions at baseline (T0), 90 (T90), and 180 (T180) min. Following the AGE-BLG, FMD decreased at T90 by 80% from baseline and remained decreased by 42% at T180 (P < 0.05 vs. baseline, P < 0.05 vs. C-BLG at T90). By comparison, following C-BLG, FMD decreased by 27% at T90 and 51% at T180 (P < 0.05 vs. baseline at T180). A significant decrease in nitrite (T180) and nitrate (T90 and T180), as well as a significant increase in N(ε)-carboxymethyllisine, accompanied intake of AGE-BLG. There was no change in microvascular function caused by either beverage. In patients with T2DM, acute oral administration of a single AGE-modified protein class significantly though transiently impaired macrovascular function in concert with decreased nitric oxide bioavailability. These AGE-related changes were independent of heat treatment.

Siblings, theory of mind, and executive functioning in children aged 3-6 years: new longitudinal evidence.

PubMed

McAlister, Anna R; Peterson, Candida C

2013-01-01

Longitudinal data were obtained from 157 children aged 3 years 3 months to 5 years 6 months at Time 1. At Time 2 these children had aged an average of 12 months. Theory of mind (ToM) and executive functioning (EF) were measured at both time points. Results suggest that Time 1 ToM scores predict Time 2 EF scores. Detailed examination of sibling influences suggests that benefits-in terms of advanced ToM development-accrue to children with siblings versus without, and to those with a larger number of child-aged siblings. Any advance in either area (ToM or EF) is likely to benefit the other, and early sibling interaction appears to act as a catalyst. © 2012 The Authors. Child Development © 2012 Society for Research in Child Development, Inc.

Advancing paternal age at birth is associated with poorer social functioning earlier and later in life of schizophrenia patients in a founder population.

PubMed

Liebenberg, Rudolf; van Heerden, Brigitte; Ehlers, René; Du Plessis, Anna M E; Roos, J Louw

2016-09-30

Consistent associations have been found between advanced paternal age and an increased risk of psychiatric disorders, such as schizophrenia, in their offspring. This increase appears to be linear as paternal age increases. The present study investigates the relationship between early deviant behaviour in the first 10 years of life of patients as well as longer term functional outcome and paternal age in sporadic Afrikaner founder population cases of schizophrenia. This might improve our understanding of Paternal Age-Related Schizophrenia (PARS). Follow-up psychiatric diagnoses were confirmed by the Diagnostic Interview for Genetic Studies (DIGS). An early deviant childhood behaviour semi-structured questionnaire and the Specific Level of Functioning Assessment (SLOF) were completed. From the logistic regression models fitted, a significant negative relationship was found between paternal age at birth and social dysfunction as early deviant behaviour. Additionally, regression analysis revealed a significant negative relationship between paternal age at birth and the SLOF for interpersonal relationships later in life. Early social dysfunction may represent a phenotypic trait for PARS. Further research is required to understand the relationship between early social dysfunction and deficits in interpersonal relationships later in life. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Advanced Parental Ages and Low Birth Weight in Autism Spectrum Disorders--Rates and Effect on Functioning

ERIC Educational Resources Information Center

Ben Itzchak, Esther; Lahat, Eli; Zachor, Ditza A.

2011-01-01

Objectives: (1) To assess the distribution of parental age and birth weight in a large cohort with autism spectrum disorder (ASD) and to compare them to Israeli national data. (2) To examine possible relationships between these risk factors and functioning. Methods: The study included 529 participants diagnosed with ASD using standardized tests:…

Advanced Glycation End Products and Diabetic Complications

PubMed Central

Singh, Varun Parkash; Bali, Anjana; Singh, Nirmal

2014-01-01

During long standing hyperglycaemic state in diabetes mellitus, glucose forms covalent adducts with the plasma proteins through a non-enzymatic process known as glycation. Protein glycation and formation of advanced glycation end products (AGEs) play an important role in the pathogenesis of diabetic complications like retinopathy, nephropathy, neuropathy, cardiomyopathy along with some other diseases such as rheumatoid arthritis, osteoporosis and aging. Glycation of proteins interferes with their normal functions by disrupting molecular conformation, altering enzymatic activity, and interfering with receptor functioning. AGEs form intra- and extracellular cross linking not only with proteins, but with some other endogenous key molecules including lipids and nucleic acids to contribute in the development of diabetic complications. Recent studies suggest that AGEs interact with plasma membrane localized receptors for AGEs (RAGE) to alter intracellular signaling, gene expression, release of pro-inflammatory molecules and free radicals. The present review discusses the glycation of plasma proteins such as albumin, fibrinogen, globulins and collagen to form different types of AGEs. Furthermore, the role of AGEs in the pathogenesis of diabetic complications including retinopathy, cataract, neuropathy, nephropathy and cardiomyopathy is also discussed. PMID:24634591

Advanced glycation end products and their receptor in age-related, non-communicable chronic inflammatory diseases; Overview of clinical evidence and potential contributions to disease.

PubMed

Reynaert, Niki L; Gopal, Poornima; Rutten, Erica P A; Wouters, Emiel F M; Schalkwijk, Casper G

2016-12-01

Age-related, non-communicable chronic inflammatory diseases represent the major 21st century health problem. Especially in Western countries, the prevalence of non-communicable diseases like chronic obstructive pulmonary disease, cardiovascular disease, type 2 diabetes and osteoporosis are exponentially rising as the population ages. These diseases are determined by common risk factors and share an age-related onset. The affected organs display evidence of accelerated ageing, and are hallmarked by chronic inflammation and oxidative stress. The receptor for advanced glycation end products (RAGE) has been implicated in a number of inflammatory diseases and plays a central role in amplifying inflammatory responses. Advanced glycation end product (AGE) formation and accumulation is accelerated under these conditions. Advanced glycation end products are not only linked to RAGE signaling and inflammation, but to various hallmarks of the ageing process. In addition to these biological functions, circulating levels of the soluble form of RAGE and of advanced glycation end products are candidate biomarkers for many age-related inflammatory diseases. The purpose of this review is to provide an overview of the mechanistic connections between RAGE and advanced glycation end products and the processes of inflammation and ageing. Furthermore, through the presented overview of AGE-RAGE alterations that have been described in clinical studies in chronic obstructive pulmonary disease, cardiovascular disease, type 2 diabetes and osteoporosis, and insight obtained from mechanistic in vitro and animal studies, it can be concluded that these AGE-RAGE disturbances are a common contributing factor to the inflammatory state and pathogenesis of these various conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Buddhist social networks and health in old age: A study in central Thailand.

PubMed

Sasiwongsaroj, Kwanchit; Wada, Taizo; Okumiya, Kiyohito; Imai, Hissei; Ishimoto, Yasuko; Sakamoto, Ryota; Fujisawa, Michiko; Kimura, Yumi; Chen, Wen-ling; Fukutomi, Eriko; Matsubayashi, Kozo

2015-11-01

Religious social networks are well known for their capacity to improve individual health, yet the effects of friendship networks within the Buddhist context remain largely unknown. The present study aimed to compare health status and social support in community-dwelling older adults according to their level of Buddhist social network (BSN) involvement, and to examine the association between BSN involvement and functional health among older adults. A cross-sectional survey was carried out among 427 Buddhist community-dwelling older adults aged ≥60 years in Nakhon Pathom, Thailand. Data were collected from home-based personal interviews using a structured questionnaire. Health status was defined according to the measures of basic and advanced activities of daily living (ADL), the 15-item Geriatric Depression Scale and subjective quality of life. Perceived social support was assessed across the four dimensions of tangible, belonging, emotional and information support. Multiple logistic regression was used for analysis. Older adults with BSN involvement reported better functional, mental and social health status, and perceived greater social support than those without BSN involvement. In addition, BSN involvement was positively associated with independence in basic and advanced ADL. After adjusting for age, sex, education, income, morbidity and depressive symptoms, BSN showed a strong association with advanced ADL and a weak association with basic ADL. The results show that involvement in BSN could contribute positively to functional health, particularly with regard to advanced ADL. Addressing the need for involvement in these networks by older adults might help delay functional decline and save on healthcare costs. © 2014 Japan Geriatrics Society.

Vascular effects of advanced glycation endproducts: Clinical effects and molecular mechanisms☆

PubMed Central

Stirban, Alin; Gawlowski, Thomas; Roden, Michael

2013-01-01

The enhanced generation and accumulation of advanced glycation endproducts (AGEs) have been linked to increased risk for macrovascular and microvascular complications associated with diabetes mellitus. AGEs result from the nonenzymatic reaction of reducing sugars with proteins, lipids, and nucleic acids, potentially altering their function by disrupting molecular conformation, promoting cross-linking, altering enzyme activity, reducing their clearance, and impairing receptor recognition. AGEs may also activate specific receptors, like the receptor for AGEs (RAGE), which is present on the surface of all cells relevant to atherosclerotic processes, triggering oxidative stress, inflammation and apoptosis. Understanding the pathogenic mechanisms of AGEs is paramount to develop strategies against diabetic and cardiovascular complications. PMID:24634815

Thalamic structures and associated cognitive functions: Relations with age and aging.

PubMed

Fama, Rosemary; Sullivan, Edith V

2015-07-01

The thalamus, with its cortical, subcortical, and cerebellar connections, is a critical node in networks supporting cognitive functions known to decline in normal aging, including component processes of memory and executive functions of attention and information processing. The macrostructure, microstructure, and neural connectivity of the thalamus changes across the adult lifespan. Structural and functional magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) have demonstrated, regional thalamic volume shrinkage and microstructural degradation, with anterior regions generally more compromised than posterior regions. The integrity of selective thalamic nuclei and projections decline with advancing age, particularly those in thalamofrontal, thalamoparietal, and thalamolimbic networks. This review presents studies that assess the relations between age and aging and the structure, function, and connectivity of the thalamus and associated neural networks and focuses on their relations with processes of attention, speed of information processing, and working and episodic memory. Copyright © 2015 Elsevier Ltd. All rights reserved.

Exercise physiology and its role in disease prevention and in rehabilitation.

PubMed

Astrand, P O

1987-05-01

It is an impressive fact that many musicians can perform perfectly at an advanced age. Arthur Rubenstein played very demanding compositions of Chopin at the age of 88 and Andre Segovia at the age of 91 is still giving concerts on the classical guitar. Apparently, through practice very demanding neuromuscular activities can be maintained at advanced ages. Yet hours of daily "training" are behind these achievements. This review discusses some of the general aspects of training and their effects on function and health. As an overall goal it is more important to add life to years rather than add years to life.

Safety profile of platinum-based chemotherapy in the treatment of advanced non-small cell lung cancer in elderly patients.

PubMed

Rossi, Antonio; Maione, Paolo; Gridelli, Cesare

2005-11-01

Non-small cell lung cancer (NSCLC) may be considered typical of advanced age. More than 50% of NSCLC patients are diagnosed at > 65 years of age and approximately one-third of all patients are > 70 years of age. Elderly patients tolerate chemotherapy poorly compared with their younger counterpart because of the progressive reduction of organ function and comorbidities related to age. For this reason, these patients are often not considered eligible for aggressive platinum-based chemotherapy, the standard medical treatment for advanced NSCLC. In clinical practice, single-agent chemotherapy should remain the standard treatment. Feasibility of platinum-based chemotherapy remains an open issue and has to be proven prospectively. Moreover, a multidimensional geriatric assessment for individualised treatment choice in NSCLC elderly patients is mandatory. This review focuses on the currently-available evidences for the treatment of elderly patients affected by advanced NSCLC with regards to the role and safety of platinum-based chemotherapy.

Advanced glycation end products and their receptor contribute to ovarian ageing.

PubMed

Stensen, Mette Haug; Tanbo, Tom; Storeng, Ritsa; Fedorcsak, Peter

2014-01-01

Do advanced glycation end products (AGE) and the receptor for advanced glycation end products (RAGE) affect the cells of the human ovarian follicle? AGE accumulate on the surface of ovarian granulosa-lutein (GL) cells and monocytes by binding to RAGE and other receptors with possible functional effects on these cells. AGE and RAGE are expressed in granulosa and theca cells, as well as in luteinized cells derived from the ovary. In this prospective cohort study, human follicle fluid-derived cells were isolated from aspirates of ovarian follicles of women who underwent assisted reproduction treatment. Immunofluorescence microscopy and multi-colour flow cytometry were used to determine the presence of AGE and RAGE on the surface of follicular fluid-derived cells and to characterize downstream effects of RAGE activation. GL cells and ovarian monocytes were found to contain AGE and RAGE and to bind AGE-bovine serum albumin (BSA) in correlation with the patients' chronological age. AGE-BSA and BSA failed to induce significantly the cleavage of caspase-3, phosphorylation of nuclear factor-κB or the binding of annexin V (the latter was marginally increased). AGE-fibronectin was found to induce detachment of cultured GL cells in vitro. The impact of AGE and RAGE in the ovary, shown here in cells in culture, remains to be affirmed in clinical settings. The ligands of RAGE and their effects in the ovary remain uncertain but this study implies that AGEs in the form of structural long-lived extracellular matrix proteins, rather than soluble AGEs, may play a role in the decline of ovarian function during ageing. The project was funded by the Norwegian Resource Centre for Women's Health, Oslo University Hospital. The authors have no conflicts of interests.

Below the Radar: Advanced Glycation End Products that Detour “around the side”

PubMed Central

2005-01-01

Advanced glycation is the irreversible attachment of reducing sugars onto the free amino groups of proteins. Its physiological roles are thought to include the identification of senescent proteins and hence there is a time dependent accumulation of advanced glycation end products (AGEs). AGE labelled proteins are catabolised by cells into low molecular weight peptides and amino acids and excreted primarily via the kidneys. This process appears to be tightly controlled by AGE clearance receptor complexes containing AGE-R1, AGE-R2 and AGE-R3 and scavenger receptors such as CD36, SR-AII and SR-BI. Conditions such as diabetes, however, which have a metabolic overload of reducing sugars, rapidly accelerate AGE formation. In addition, advanced glycation is facilitated by oxidative stress and renal disease even in the absence of increases in reducing sugar concentrations. As part of our western diet, we also ingest AGEs of which approximately 50–80% are absorbed, catabolised and excreted over a period of two days. As AGE levels rise during diabetes, interruption of normal function occurs via three distinct mechanisms, namely AGE induced cross-linking of extracellular matrices, stiffening elastic fibres, disturbing cellular adhesion and preventing turnover. The second is by intracellular formation of AGEs, which causes generalised cellular dysfunction. The third is via the chronic activation of specific receptors such as RAGE, the receptor for advanced glycation end products, which produces excesses in inflammatory molecule production. Due to the range of dysfunction produced by the accumulation of AGEs in diabetes, there is a growing need for early recognition and intervention in this process. PMID:16648883

Therapeutic potential of systemic brain rejuvenation strategies for neurodegenerative disease

PubMed Central

Horowitz, Alana M.; Villeda, Saul A.

2017-01-01

Neurodegenerative diseases are a devastating group of conditions that cause progressive loss of neuronal integrity, affecting cognitive and motor functioning in an ever-increasing number of older individuals. Attempts to slow neurodegenerative disease advancement have met with little success in the clinic; however, a new therapeutic approach may stem from classic interventions, such as caloric restriction, exercise, and parabiosis. For decades, researchers have reported that these systemic-level manipulations can promote major functional changes that extend organismal lifespan and healthspan. Only recently, however, have the functional effects of these interventions on the brain begun to be appreciated at a molecular and cellular level. The potential to counteract the effects of aging in the brain, in effect rejuvenating the aged brain, could offer broad therapeutic potential to combat dementia-related neurodegenerative disease in the elderly. In particular, results from heterochronic parabiosis and young plasma administration studies indicate that pro-aging and rejuvenating factors exist in the circulation that can independently promote or reverse age-related phenotypes. The recent demonstration that human umbilical cord blood similarly functions to rejuvenate the aged brain further advances this work to clinical translation. In this review, we focus on these blood-based rejuvenation strategies and their capacity to delay age-related molecular and functional decline in the aging brain. We discuss new findings that extend the beneficial effects of young blood to neurodegenerative disease models. Lastly, we explore the translational potential of blood-based interventions, highlighting current clinical trials aimed at addressing therapeutic applications for the treatment of dementia-related neurodegenerative disease in humans. PMID:28815019

Lumbar spinal mobility changes among adults with advancing age

PubMed Central

Saidu, Ismaila Adamu; Maduagwu, Stanley Monday; Abbas, Abdullahi Digil; Adetunji, Omotayo O.; Jajere, Abdurahman Mohammed

2011-01-01

Background: Limitations in spinal mobility can interfere with the attainment of important functional skills and activities of daily living and restrictions in spinal mobility are usually the earliest and reliable indicator of diseases. Objective: The aim of this study was to determine the differences of lumbar spinal mobility among healthy adults with advancing age. Materials and Methods: The modified Schober's method was used to measure anterior flexion. The guideline of the American Academy of Orthopaedic Surgeons was adapted to measure lateral flexion and extension. Results: The results of this study indicate that spinal mobility decreases with advancing age. The most significant (P < 0.05) differences occurred between the two youngest and the two oldest age categories. Conclusion: Using these data, we developed normative values of spinal mobility for each sex and age group. This study helps the clinicians to understand and correlate the restrictions of lumbar spinal mobility due to age and differentiate the limitations due to disease. PMID:22408334

Current Heavy Alcohol Consumption is Associated with Greater Cognitive Impairment in Older Adults

PubMed Central

Woods, Adam J.; Porges, Eric C.; Bryant, Vaughn E.; Seider, Talia; Gongvatana, Assawin; Kahler, Christopher W.; de la Monte, Suzanne; Monti, Peter M.; Cohen, Ronald A.

2016-01-01

Background The acute consumption of excessive quantities of alcohol causes well-recognized neurophysiological and cognitive alterations. As people reach advanced age, they are more prone to cognitive decline. To date, the interaction of current heavy alcohol (ETOH) consumption and aging remain unclear. The current paper tested the hypothesis that negative consequences of current heavy alcohol consumption on neurocognitive function are worse with advanced age. Further, we evaluated the relations between lifetime history of alcohol dependence and neurocognitive function Methods Sixty-six participants underwent a comprehensive neurocognitive battery. Current heavy ETOH drinkers were classified using NIAAA criteria (ETOH Heavy, n = 21) based on the Timeline follow-back and a structured clinical interview and compared to non-drinkers, and moderate drinkers (ETOH Low, n = 45). Fifty-three-point-three percent of the total population had a lifetime history of alcohol dependence. Neurocognitive data were grouped and analyzed relative to global and domain scores assessing: global cognitive function, attention/executive function, learning, memory, motor function, verbal function, and speed of processing. Results Heavy current ETOH consumption in older adults was associated with poorer global cognitive function, learning, memory, and motor function (p’s<.05). Furthermore, lifetime history of alcohol dependence was associated with poorer function in the same neurocognitive domains, in addition to the attention/executive domain, irrespective of age (p’s<.05). Conclusions These data suggest that while heavy current alcohol consumption is associated with significant impairment in a number of neurocognitive domains, history of alcohol dependence, even in the absence of heavy current alcohol use, is associated with lasting negative consequences for neurocognitive function. PMID:27658235

Telomere biology in aging and cancer: early history and perspectives.

PubMed

Hayashi, Makoto T

2018-01-20

The ends of eukaryotic linear chromosomes are protected from undesired enzymatic activities by a nucleoprotein complex called the telomere. Expanding evidence indicates that telomeres have central functions in human aging and tumorigenesis. While it is undoubtedly important to follow current advances in telomere biology, it is also fruitful to be well informed in seminal historical studies for a comprehensive understanding of telomere biology, and for the anticipation of future directions. With this in mind, I here summarize the early history of telomere biology and current advances in the field, mostly focusing on mammalian studies relevant to aging and cancer.

The in vitro effects of advanced glycation end products on basophil functions.

PubMed

Han, Kaiyu; Suzukawa, Maho; Yamaguchi, Masao; Sugimoto, Naoya; Nakase, Yuko; Toda, Takako; Nagase, Hiroyuki; Ohta, Ken

2011-01-01

Basophils are thought to play pivotal roles in the pathogenesis of allergic reactions, but their roles in inflammation associated with systemic abnormalities such as metabolic disorders remain largely unknown. Advanced glycation end products (AGEs) are potentially important substances produced in high-glucose disease conditions. In this in vitro study, we investigated whether the biological functions of human basophils can be influenced by AGEs. We analyzed the effects of AGEs on various functions and markers of human basophils, including CD11b expression, apoptosis, degranulation, and cytokine production. Flow cytometric analysis indicated that the level of the receptor for AGEs (RAGE) on the surface of freshly isolated basophils was very low but was clearly upregulated by IL-3. Apoptosis of basophils was induced by high concentrations of glycated albumin. Although glycated albumin failed to affect the level of surface CD11b expression or to trigger degranulation or production of IL-4 and IL-13 in basophils, it dose-dependently induced IL-6 and IL-8 secretion. AGEs seem to act on human basophils; they suppress the cells' longevity but elicit secretion of inflammatory cytokines. Through these biological changes, basophils might play some roles in inflammatory conditions associated with metabolic disorders presenting elevated levels of AGEs. Copyright © 2011 S. Karger AG, Basel.

Management of locally advanced and metastatic colon cancer in elderly patients.

PubMed

Kurniali, Peter C; Hrinczenko, Borys; Al-Janadi, Anas

2014-02-28

Colon cancer is the second leading cause of cancer mortality in the United States with a median age at diagnosis of 69 years. Sixty percent are diagnosed over the age of 65 years and 36% are 75 years or older. At diagnosis, approximately 58% of patients will have locally advanced and metastatic disease, for which systemic chemotherapy has been shown to improve survival. Treatment of cancer in elderly patients is more challenging due to multiple factors, including disabling co-morbidities as well as a decline in organ function. Cancer treatment of elderly patients is often associated with more toxicities that may lead to frequent hospitalizations. In locally advanced disease, fewer older patients receive adjuvant chemotherapy despite survival benefit and similar toxicity when compared to their younger counterparts. A survival benefit is also observed in the palliative chemotherapy setting for elderly patients with metastatic disease. When treating elderly patients with colon cancer, one has to consider drug pharmacokinetics and pharmacodynamics. Since chronological age is a poor marker of a patient's functional status, several methods of functional assessment including performance status and activities of daily living (ADL) or instrumental ADL, or even a comprehensive geriatric assessment, may be used. There is no ideal chemotherapy regimen that fits all elderly patients and so a regimen needs to be tailored for each individual. Important considerations when treating elderly patients include convenience and tolerability. This review will discuss approaches to the management of elderly patients with locally advanced and metastatic colon cancer.

Potential involvement of dietary advanced glycation end products in impairment of skeletal muscle growth and muscle contractile function in mice.

PubMed

Egawa, Tatsuro; Tsuda, Satoshi; Goto, Ayumi; Ohno, Yoshitaka; Yokoyama, Shingo; Goto, Katsumasa; Hayashi, Tatsuya

2017-01-01

Diets enriched with advanced glycation end products (AGE) have recently been related to muscle dysfunction processes. However, it remains unclear whether long-term exposure to an AGE-enriched diet impacts physiological characteristics of skeletal muscles. Therefore, we explored the differences in skeletal muscle mass, contractile function and molecular responses between mice receiving a diet high in AGE (H-AGE) and low in AGE (L-AGE) for 16 weeks. There were no significant differences between L-AGE and H-AGE mice with regard to body weight, food intake or epididymal fat pad weight. However, extensor digitorum longus (EDL) and plantaris (PLA) muscle weights in H-AGE mice were lower compared with L-AGE mice. Higher levels of N ε -(carboxymethyl)-l-lysine, a marker for AGE, in EDL muscles of H-AGE mice were observed compared with L-AGE mice. H-AGE mice showed lower muscle strength and endurance in vivo and lower muscle force production of PLA muscle in vitro. mRNA expression levels of myogenic factors including myogenic factor 5 and myogenic differentiation in EDL muscle were lower in H-AGE mice compared with L-AGE mice. The phosphorylation status of 70-kDa ribosomal protein S6 kinase Thr389, an indicator of protein synthesis signalling, was lower in EDL muscle of H-AGE mice than that of L-AGE mice. These findings suggest that long-term exposure to an AGE-enriched diet impairs skeletal muscle growth and muscle contractile function, and that these muscle dysfunctions may be attributed to the inhibition of myogenic potential and protein synthesis.

Skeletal maturation in children with cerebral palsy and its relationship with motor functioning.

PubMed

van Eck, Mirjam; Dallmeijer, Annet J; Voorman, Jeanine M; Becher, Jules G

2008-07-01

The objective of this study was to describe skeletal maturation in relation to chronological age in children with cerebral palsy (CP) aged 9 to 16 years, and to analyze the relationship between skeletal maturation and motor functioning. The skeletal age of 100 children with CP (37 females, 63 males; age 9, 11, or 13 y; 73 ambulant, 27 non-ambulant) was determined over a period of 3 years based on X-rays of the hand (Greulich and Pyle technique). Motor functioning was measured with the Gross Motor Function Measure-66. The skeletal age of females with CP was significantly higher than their chronological age, but this did not apply to males. Longitudinal analysis showed no difference in the course of skeletal age in relation to chronological age over a 3-year period for sex or for level of ambulation. No association was found between changes in skeletal age and changes in gross motor function over the 3-year period. Skeletal age during (pre-)puberty in females with CP is advanced in relation to chronological age. No evidence was found that children with CP are at risk for deterioration in gross motor function as a result of skeletal maturation during puberty.

Interactive Tools for Measuring Visual Scanning Performance and Reaction Time

PubMed Central

Seeanner, Julia; Hennessy, Sarah; Manganelli, Joseph; Crisler, Matthew; Rosopa, Patrick; Jenkins, Casey; Anderson, Michael; Drouin, Nathalie; Belle, Leah; Truesdail, Constance; Tanner, Stephanie

2017-01-01

Occupational therapists are constantly searching for engaging, high-technology interactive tasks that provide immediate feedback to evaluate and train clients with visual scanning deficits. This study examined the relationship between two tools: the VISION COACH™ interactive light board and the Functional Object Detection© (FOD) Advanced driving simulator scenario. Fifty-four healthy drivers, ages 21–66 yr, were divided into three age groups. Participants performed braking response and visual target (E) detection tasks of the FOD Advanced driving scenario, followed by two sets of three trials using the VISION COACH Full Field 60 task. Results showed no significant effect of age on FOD Advanced performance but a significant effect of age on VISION COACH performance. Correlations showed that participants’ performance on both braking and E detection tasks were significantly positively correlated with performance on the VISION COACH (.37 < r < .40, p < .01). These tools provide new options for therapists. PMID:28218598

Integration of Immunity with Physical and Cognitive Function in Definitions of Successful Aging

PubMed Central

Griffin, Patricia; Michel, Joshua J.; Huysman, Kristy; Logar, Alison J.; Vallejo, Abbe N.

2012-01-01

Studies comparing chronologically “young” versus “old” humans document age-related decline of classical immunological functions. However, older adults aged ≥65 years have very heterogeneous health phenotypes. A significant number of them are functionally independent and are surviving well into their 8th–11th decade life, observations indicating that aging or old age is not synonymous with immune incompetence. While there are dramatic age-related changes in the immune system, not all of these changes may be considered detrimental. Here, we review evidences for novel immunologic processes that become elaborated with advancing age that complement preserved classical immune functions and promote immune homeostasis later in life. We propose that elaboration such of late life immunologic properties is indicative of beneficial immune remodeling that is an integral component of successful aging, an emerging physiologic construct associated with similar age-related physiologic adaptations underlying maintenance of physical and cognitive function. We suggest that a systems approach integrating immune, physical, and cognitive functions, rather than a strict immunodeficiency-minded approach, will be key towards innovations in clinical interventions to better promote protective immunity and functional independence among the elderly. PMID:22500270

Aging and the Immune Response to the Haemophilus influenzae Type b Capsular Polysaccharide: Retention of the Dominant Idiotype and Antibody Function in the Elderly

PubMed Central

Lucas, Alexander H.; Reason, Donald C.

1998-01-01

Anti-Haemophilus influenzae b polysaccharide (Hib PS) antibodies elicited in elderly subjects following conjugate vaccination expressed a light-chain variable-region (VL)-associated idiotype and had functional activities similar to those previously observed in children and younger adults. These findings indicate that advanced age is not accompanied by shifts in the major VL component of the Hib PS-specific repertoire or by diminution of the protective function of antibodies. PMID:9529108

Sleep and circadian rhythms

NASA Technical Reports Server (NTRS)

Monk, Timothy H.

1991-01-01

Three interacting processes are involved in the preservation of circadian rhythms: (1) endogenous rhythm generation mechanisms, (2) entrainment mechanisms to keep these rhythms 'on track', and (3) exogenous masking processes stemming from changes in environment and bahavior. These processes, particularly the latter two, can be dramatically affected in individuals of advanced age and in space travelers, with a consequent disruption in sleep and daytime functioning. This paper presents results of a phase-shift experiment investigating the age-related effects of the exogeneous component of circadian rhythms in various physiological and psychological functions by comparing these functions in middle aged and old subjects. Dramatic differences were found between the two age groups in measures of sleep, mood, activation, and performance efficiency.

Does advancing male age influence the expression levels and localisation patterns of phospholipase C zeta (PLCζ) in human sperm?

PubMed Central

Yeste, Marc; Jones, Celine; Amdani, Siti Nornadhirah; Yelumalai, Suseela; Mounce, Ginny; da Silva, Sarah J. Martins; Child, Tim; Coward, Kevin

2016-01-01

Socio-economic factors have led to an increasing trend for couples to delay parenthood. However, advancing age exerts detrimental effects upon gametes which can have serious consequences upon embryo viability. While such effects are well documented for the oocyte, relatively little is known with regard to the sperm. One fundamental role of sperm is to activate the oocyte at fertilisation, a process initiated by phospholipase C zeta (PLCζ), a sperm-specific protein. While PLCζ deficiency can lead to oocyte activation deficiency and infertility, it is currently unknown whether the expression or function of PLCζ is compromised by advancing male age. Here, we evaluate sperm motility and the proportion of sperm expressing PLCζ in 71 males (22–54 years; 44 fertile controls and 27 infertile patients), along with total levels and localisation patterns of PLCζ within the sperm head. Three different statistical approaches were deployed with male age considered both as a categorical and a continuous factor. While progressive motility was negatively correlated with male age, all three statistical models concurred that no PLCζ–related parameter was associated with male age, suggesting that advancing male age is unlikely to cause problems in terms of the sperm’s fundamental ability to activate an oocyte. PMID:27270687

Age-Related Differences in Memory and Executive Functions in Healthy "APOE"[epsilon]4 Carriers: The Contribution of Individual Differences in Prefrontal Volumes and Systolic Blood Pressure

ERIC Educational Resources Information Center

Bender, Andrew R.; Raz, Naftali

2012-01-01

Advanced age and vascular risk are associated with declines in the volumes of multiple brain regions, especially the prefrontal cortex, and the hippocampus. Older adults, even unencumbered by declining health, perform less well than their younger counterparts in multiple cognitive domains, such as episodic memory, executive functions, and speed of…

Volunteering in the Community: Potential Benefits for Cognitive Aging.

PubMed

Guiney, Hayley; Machado, Liana

2018-03-02

This review aims to advance understanding of the potential benefits of volunteering in the community for older adults' cognitive functioning by taking an in-depth look at the relevant evidence to date. This review describes the main pathways through which volunteering could plausibly benefit cognitive functioning and critically examines research that has specifically investigated links between volunteering and cognition. Fifteen articles that assessed in adults aged ≥ 55 years the relationship between volunteering (predictor) and cognitive functioning (outcome) were identified via literature database searches. On balance, evidence from the small number of relevant studies to date supports the idea that volunteering can protect against cognitive aging with respect to global functioning and at least some specific cognitive domains. Studies that used robust designs and assessed domain-specific cognitive functioning produced the largest effect sizes. To help advance the field, this review puts forward recommendations for future research, with an emphasis on the need for robust study designs and specific investigations into the nature and extent of the cognitive benefits of volunteering. Through that work, researchers can determine how a simple and accessible activity like volunteering can best be used to help reduce the burden of age-related cognitive decline. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A Pilot of a Gerontological Advanced Practice Nurse Preventive Intervention

ERIC Educational Resources Information Center

Hahn, Joan Earle; Aronow, Harriet Udin

2005-01-01

Background: Persons with an intellectual and developmental disability frequently face barriers in accessing preventive services in community-based health care systems. As they age into middle years, they are at increased risk for functional decline. This paper presents a description of an advanced practice nurse (APN) intervention used in a pilot…

Successful Aging: Advancing the Science of Physical Independence in Older Adults

PubMed Central

Anton, Stephen D.; Woods, Adam J.; Ashizawa, Tetso; Barb, Diana; Buford, Thomas W.; Carter, Christy S.; Clark, David J.; Cohen, Ronald A.; Corbett, Duane B.; Cruz-Almeida, Yenisel; Dotson, Vonetta; Ebner, Natalie; Efron, Philip A.; Fillingim, Roger B.; Foster, Thomas C.; Gundermann, David M.; Joseph, Anna-Maria; Karabetian, Christy; Leeuwenburgh, Christiaan; Manini, Todd M.; Marsiske, Michael; Mankowski, Robert T.; Mutchie, Heather L.; Perri, Michael G.; Ranka, Sanjay; Rashidi, Parisa; Sandesara, Bhanuprasad; Scarpace, Philip J.; Sibille, Kimberly T.; Solberg, Laurence M.; Someya, Shinichi; Uphold, Connie; Wohlgemuth, Stephanie; Wu, Samuel Shangwu; Pahor, Marco

2015-01-01

The concept of ‘Successful Aging’ has long intrigued the scientific community. Despite this long-standing interest, a consensus definition has proven to be a difficult task, due to the inherent challenge involved in defining such a complex, multi-dimensional phenomenon. The lack of a clear set of defining characteristics for the construct of successful aging has made comparison of findings across studies difficult and has limited advances in aging research. The domain in which consensus on markers of successful aging is furthest developed is the domain of physical functioning. For example, walking speed appears to be an excellent surrogate marker of overall health and predicts the maintenance of physical independence, a cornerstone of successful aging. The purpose of the present article is to provide an overview and discussion of specific health conditions, behavioral factors, and biological mechanisms that mark declining mobility and physical function and promising interventions to counter these effects. With life expectancy continuing to increase in the United States and developed countries throughout the world, there is an increasing public health focus on the maintenance of physical independence among all older adults. PMID:26462882

Advanced glycation end-products as markers of aging and longevity in the long-lived Ansell's mole-rat (Fukomys anselli).

PubMed

Dammann, Philip; Sell, David R; Begall, Sabine; Strauch, Christopher; Monnier, Vincent M

2012-06-01

Mole-rat of the genus Fukomys are mammals whose life span is strongly influenced by reproductive status with breeders far outliving nonbreeders. This raises the important question of whether increased longevity of the breeders is reflected in atypical expression of biochemical markers of aging. Here, we measured markers of glycation and advanced glycation end-products formed in insoluble skin collagen of Ansell's mole-rat Fukomys anselli as a function of age and breeding status. Glucosepane, pentosidine, and total advanced glycation end-product content significantly increased with age after correction for breeder status and sex. Unexpectedly, total advanced glycation end-products, glucosepane, and carboxymethyl-lysine (CML) were significantly higher in breeders versus nonbreeders suggesting that breeders have evolved powerful defenses against combined oxidant and carbonyl stress compared with nonbreeders. Most interestingly, when compared with other mammals, pentosidine formation rate was lower in mole-rat compared with other short-lived rodents confirming previous observations of an inverse relationship between longevity and pentosidine formation rates in skin collagen.

Advanced Glycation End-Products as Markers of Aging and Longevity in the Long-Lived Ansell’s Mole-Rat (Fukomys anselli)

PubMed Central

Dammann, Philip; Begall, Sabine; Strauch, Christopher; Monnier, Vincent M.

2012-01-01

Mole-rat of the genus Fukomys are mammals whose life span is strongly influenced by reproductive status with breeders far outliving nonbreeders. This raises the important question of whether increased longevity of the breeders is reflected in atypical expression of biochemical markers of aging. Here, we measured markers of glycation and advanced glycation end-products formed in insoluble skin collagen of Ansell’s mole-rat Fukomys anselli as a function of age and breeding status. Glucosepane, pentosidine, and total advanced glycation end-product content significantly increased with age after correction for breeder status and sex. Unexpectedly, total advanced glycation end-products, glucosepane, and carboxymethyl-lysine (CML) were significantly higher in breeders versus nonbreeders suggesting that breeders have evolved powerful defenses against combined oxidant and carbonyl stress compared with nonbreeders. Most interestingly, when compared with other mammals, pentosidine formation rate was lower in mole-rat compared with other short-lived rodents confirming previous observations of an inverse relationship between longevity and pentosidine formation rates in skin collagen. PMID:22156473

Maturity-Associated Variation in Functional Characteristics Of Elite Youth Tennis Players.

PubMed

Myburgh, Gillian K; Cumming, Sean P; Silva, Manuel Coelho E; Cooke, Karl; Malina, Robert M

2016-11-01

To evaluate relationships among skeletal maturity, body size, and functional capacities of elite junior tennis players. Participants were 88 elite British Junior tennis players (44 male; 44 female), 8-16 years of age (12.4 } 1.9 years). Skeletal age estimated maturty. Anthropometry, grip strength, countermovement jump, squat jump, forehand agility, backhand agility, Yo-Yo, 5-m, 10-m and 20-m sprints were measured. Comparative analysis for each sex was performed, relating advanced maturers (Male: 15; Female: 29) to a combination of on-time and late maturers (Male: 29; Female: 31). ANCOVAs were used to determine absolute differences between male and female players and between the 2 maturity subgroups, with chronological age as the covariate. Advanced maturity afforded male players advantages in absolute measures of grip strength, speed, upper and lower body power but not in acceleration, agility or aerobic endurance. Male players were significantly taller than females in the U13-U16 age group. Advanced maturity in female players afforded advantages in absolute measures of grip strength, agility and overhead power, but not in backhand agility, aerobic endurance or squat jump power. It is important that talent identification protocols consider the maturity of youth athletes to more satisfactorily address athletic potential rather than transient physical capabilities.

Regulation of skeletal muscle blood flow during exercise in ageing humans

PubMed Central

Hearon, Christopher M.

2015-01-01

Abstract The regulation of skeletal muscle blood flow and oxygen delivery to contracting skeletal muscle is complex and involves the mechanical effects of muscle contraction; local metabolic, red blood cell and endothelium‐derived substances; and the sympathetic nervous system (SNS). With advancing age in humans, skeletal muscle blood flow is typically reduced during dynamic exercise and this is due to a lower vascular conductance, which could ultimately contribute to age‐associated reductions in aerobic exercise capacity, a primary predictor of mortality in both healthy and diseased ageing populations. Recent findings have highlighted the contribution of endothelium‐derived substances to blood flow control in contracting muscle of older adults. With advancing age, impaired nitric oxide availability due to scavenging by reactive oxygen species, in conjunction with elevated vasoconstrictor signalling via endothelin‐1, reduces the local vasodilatory response to muscle contraction. Additionally, ageing impairs the ability of contracting skeletal muscle to blunt sympathetic vasoconstriction (i.e. ‘functional sympatholysis’), which is critical for the proper regulation of tissue blood flow distribution and oxygen delivery, and could further reduce skeletal muscle perfusion during high intensity and/or large muscle mass exercise in older adults. We propose that initiation of endothelium‐dependent hyperpolarization is the underlying signalling event necessary to properly modulate sympathetic vasoconstriction in contracting muscle, and that age‐associated impairments in red blood cell adenosine triphosphate release and stimulation of endothelium‐dependent vasodilatation may explain impairments in both local vasodilatation and functional sympatholysis with advancing age in humans. PMID:26332887

Knee Instability and Basic and Advanced Function Decline in Knee Osteoarthritis.

PubMed

Sharma, Leena; Chmiel, Joan S; Almagor, Orit; Moisio, Kirsten; Chang, Alison H; Belisle, Laura; Zhang, Yunhui; Hayes, Karen W

2015-08-01

Manifestations of instability in knee osteoarthritis (OA) include low overall knee confidence, low confidence that the knees will not buckle, buckling, and excessive motion during gait. Confidence and buckling may particularly influence activity choices, contributing to events leading to disability. Buckling is more likely to affect advanced than basic functional tasks. In this prospective longitudinal study, we tested the hypothesis that overall knee confidence, buckling confidence, buckling, and frontal plane motion during gait are associated with advanced 2-year function outcomes in persons with knee OA. Persons with knee OA were queried about overall knee confidence (higher score = worse confidence), buckling confidence, and knee buckling, and underwent quantitative gait analysis to quantify varus-valgus excursion and angular velocity. Physical function was assessed using the Late-Life Function and Disability Instrument Basic and Advanced Lower Extremity Domain scores. Logistic regression was used to evaluate the relationship between baseline instability measures and baseline-to-2-year function outcome, adjusting for potential confounders. The sample was comprised of 212 persons (mean age 64.6 years, 76.9% women). Buckling was significantly associated with poor advanced function outcome (adjusted odds ratio [OR] 2.08, 95% confidence interval [95% CI] 1.03-4.20) but not basic function outcome. Overall knee confidence was significantly associated with advanced outcome (adjusted OR 1.65, 95% CI 1.01-2.70), while associations between buckling confidence and both outcomes approached significance. Neither varus-valgus excursion nor angular velocity during gait was associated with either outcome. Knee buckling and low knee confidence were each associated with poor 2-year advanced function outcomes. Current treatment does not address these modifiable factors; interventions to address them may improve outcome in knee OA. © 2015, American College of Rheumatology.

Advance care planning for older people in Australia presenting to the emergency department from the community or residential aged care facilities.

PubMed

Street, Maryann; Ottmann, Goetz; Johnstone, Megan-Jane; Considine, Julie; Livingston, Patricia M

2015-09-01

The purpose of this retrospective, cross-sectional study was to determine the prevalence of advance care planning (ACP) among older people presenting to an Emergency Department (ED) from the community or a residential aged care facility. The study sample comprised 300 older people (aged 65+ years) presenting to three Victorian EDs in 2011. A total of 150 patients transferred from residential aged care to ED were randomly selected and then matched to 150 people who lived in the community and attended the ED by age, gender, reason for ED attendance and triage category on arrival. Overall prevalence of ACP was 13.3% (n = 40/300); over one-quarter (26.6%, n = 40/150) of those presenting to the ED from residential aged care had a documented Advance Care Plan, compared to none (0%, n = 0/150) of the people from the community. There were no significant differences in the median ED length of stay, number of investigations and interventions undertaken in ED, time seen by a doctor or rate of hospital admission for those with an Advance Care Plan compared to those without. Those with a comorbidity of cerebrovascular disease or dementia and those assessed with impaired brain function were more likely to have a documented Advance Care Plan on arrival at ED. Length of hospital stay was shorter for those with an Advance Care Plan [median (IQR) = 3 days (2-6) vs. 6 days (2-10), P = 0.027] and readmission lower (0% vs. 13.7%). In conclusion, older people from the community transferred to ED were unlikely to have a documented Advance Care Plan. Those from residential aged care who were cognitively impaired more frequently had an Advance Care Plan. In the ED, decisions of care did not appear to be influenced by the presence or absence of Advance Care Plans, but length of hospital admission was shorter for those with an Advance Care Plan. © 2014 John Wiley & Sons Ltd.

Old Maids: Aging and Its Impact on Microglia Function

PubMed Central

Koellhoffer, Edward C.; McCullough, Louise D.; Ritzel, Rodney M.

2017-01-01

Microglia are highly active and vigilant housekeepers of the central nervous system that function to promote neuronal growth and activity. With advanced age, however, dysregulated inflammatory signaling and defects in phagocytosis impede their ability to perform the most essential of homeostatic functions, including immune surveillance and debris clearance. Microglial activation is one of the hallmarks of the aging brain and coincides with age-related neurodegeneration and cognitive decline. Age-associated microglial dysfunction leads to cellular senescence and can profoundly alter the response to sterile injuries and immune diseases, often resulting in maladaptive responses, chronic inflammation, and worsened outcomes after injury. Our knowledge of microglia aging and the factors that regulate age-related microglial dysfunction remain limited, as the majority of pre-clinical studies are performed in young animals, and human brain samples are difficult to obtain quickly post-mortem or in large numbers. This review outlines the impact of normal aging on microglial function, highlights the potential mechanisms underlying age-related changes in microglia, and discusses how aging can shape the recovery process following injury. PMID:28379162

Associations of advanced glycation end-products with cognitive functions in individuals with and without type 2 diabetes: the maastricht study.

PubMed

Spauwen, P J J; van Eupen, M G A; Köhler, S; Stehouwer, C D A; Verhey, F R J; van der Kallen, C J H; Sep, S J S; Koster, A; Schaper, N C; Dagnelie, P C; Schalkwijk, C G; Schram, M T; van Boxtel, M P J

2015-03-01

Advanced glycation end-products (AGEs) are thought to be involved in the pathogenesis of Alzheimer's disease. AGEs are products resulting from nonenzymatic chemical reactions between reduced sugars and proteins, which accumulate during natural aging, and their accumulation is accelerated in hyperglycemic conditions such as type 2 diabetes mellitus. The objective of the study was to examine associations between AGEs and cognitive functions. This study was performed as part of the Maastricht Study, a population-based cohort study in which, by design, 215 participants (28.1%) had type 2 diabetes mellitus. We examined associations of skin autofluorescence (SAF) (n = 764), an overall estimate of skin AGEs, and specific plasma protein-bound AGEs (n = 781) with performance on tests for global cognitive functioning, information processing speed, verbal memory (immediate and delayed word recall), and response inhibition. After adjustment for demographics, diabetes, smoking, alcohol, waist circumference, total cholesterol/high-density lipoprotein cholesterol ratio, triglycerides, and lipid-lowering medication use, higher SAF was significantly associated with worse delayed word recall (regression coefficient, b = -0.44; P = .04), and response inhibition (b = 0.03; P = .04). After further adjustment for systolic blood pressure, cardiovascular disease, estimated glomerular filtration rate, and depression, associations were attenuated (delayed word recall, b = -0.38, P = .07; response inhibition, b = 0.02, P = .07). Higher pentosidine levels were associated with worse global cognitive functioning (b = -0.61; P = .04) after full adjustment, but other plasma AGEs were not. Associations did not differ between individuals with and without diabetes. We found inverse associations of SAF (a noninvasive marker for tissue AGEs) with cognitive performance, which were attenuated after adjustment for vascular risk factors and depression.

Sleep, Cognition, and Normal Aging: Integrating a Half-Century of Multidisciplinary Research

PubMed Central

Scullin, Michael K.; Bliwise, Donald L.

2014-01-01

Sleep is implicated in cognitive functioning in young adults. With increasing age there are substantial changes to sleep quantity and quality including changes to slow wave sleep, spindle density, and sleep continuity/fragmentation. A provocative question for the field of cognitive aging is whether such changes in sleep physiology affect cognition (e.g., memory consolidation). We review nearly a half-century of research studies across 7 diverse correlational and experimental literature domains, which historically have had little crosstalk. Broadly speaking, sleep and cognitive functions are often related in advancing age, though the prevalence of null effects (including correlations in the unexpected, negative direction) in healthy older adults indicates that age may be an effect modifier of these associations. We interpret the literature as suggesting that maintaining good sleep quality, at least in young adulthood and middle age, promotes better cognitive functioning and serves to protect against age-related cognitive declines. PMID:25620997

Effects of advanced aging on the neural correlates of successful recognition memory

PubMed Central

Wang, Tracy H.; Kruggel, Frithjof; Rugg, Michael D.

2009-01-01

Functional neuroimaging studies have reported that the neural correlates of retrieval success (old>new effects) are larger and more widespread in older than in young adults. In the present study we investigated whether this pattern of age-related ‘over-recruitment’ continues into advanced age. Using functional magnetic resonance imaging (fMRI), retrieval-related activity from two groups (N = 18 per group) of older adults aged 84–96 yrs (‘old-old’) and 64–77 yrs (‘young-old’) was contrasted. Subjects studied a series of pictures, half of which were presented once, and half twice. At test, subjects indicated whether each presented picture was old or new. Recognition performance of the old-old subjects for twice-studied items was equivalent to that of the young-old subjects for once-studied items. Old>new effects common to the two groups were identified in several cortical regions, including medial and lateral parietal and prefrontal cortex. There were no regions where these effects were of greater magnitude in the old-old group, and thus no evidence of over-recruitment in this group relative to the young-old individuals. In one region of medial parietal cortex, effects were greater (and only significant) in the young-old group. The failure to find evidence of over-recruitment in the old-old subjects relative to the young-old group, despite their markedly poorer cognitive performance, suggests that age-related over-recruitment effects plateau in advanced age. The findings for the medial parietal cortex underscore the sensitivity of this cortical region to increasing age. PMID:19428399

The role of executive functions and theory of mind in children's prosocial lie-telling.

PubMed

Williams, Shanna; Moore, Kelsey; Crossman, Angela M; Talwar, Victoria

2016-01-01

Children's prosocial lying was examined in relation to executive functioning skills and theory of mind development. Prosocial lying was observed using a disappointing gift paradigm. Of the 79 children (ages 6-12 years) who completed the disappointing gift paradigm, 47 (59.5%) told a prosocial lie to a research assistant about liking their prize. In addition, of those children who told prosocial lies, 25 (53.2%) maintained semantic leakage control during follow-up questioning, thereby demonstrating advanced lie-telling skills. When executive functioning was examined, children who told prosocial lies were found to have significantly higher performance on measures of working memory and inhibitory control. In addition, children who lied and maintained semantic leakage control also displayed more advanced theory of mind understanding. Although children's age was not a predictor of lie-telling behavior (i.e., truthful vs. lie-teller), age was a significant predictor of semantic leakage control, with older children being more likely to maintain their lies during follow-up questioning. Copyright © 2015 Elsevier Inc. All rights reserved.

Maternal Age at Childbirth and Social Development in Infancy

ERIC Educational Resources Information Center

Koyama, Tomonori; Kamio, Yoko; Inada, Naoko; Inokuchi, Eiko

2011-01-01

Difficulties in social communication are not necessarily observed only in individuals with autism spectrum disorders (ASD), and there are many subclinical cases in the general populations. Although advanced parental age at childbirth has often been considered a possible risk factor of ASD, it might contribute to poor social functioning in…

Serum levels of advanced glycation end-products (AGEs) and the decoy soluble receptor for AGEs (sRAGE) can identify non-alcoholic fatty liver disease in age-, sex- and BMI-matched normo-glycemic adults.

PubMed

Palma-Duran, Susana A; Kontogianni, Meropi D; Vlassopoulos, Antonis; Zhao, Shudong; Margariti, Aikaterini; Georgoulis, Michael; Papatheodoridis, George; Combet, Emilie

2018-06-01

Non-alcoholic fatty liver disease (NAFLD) is a serious health problem affecting ~25% of the global population. While NAFLD pathogenesis is still unclear, multiple NAFLD parameters, including reduced insulin sensitivity, impaired glucose metabolism and increased oxidative stress are hypothesised to foster the formation of advanced glycation end-products (AGEs). Given the link of AGEs with end organ damage, there is scope to examine the role of the AGE/RAGE axis activation in liver injury and NAFLD. Age, sex and body mass index matched normo-glycemic NAFLD adults (n = 58) and healthy controls (n = 58) were enrolled in the study. AGEs were analysed by liquid chromatography-mass spectrometry (CML, CEL), fluorescence (pentosidine, AGE fluorescence), colorimetry (fructosamine) and ELISA (sRAGE). Their association with liver function, inflammation, fibrosis and stage of NAFLD was examined. Early and advanced glycation end-products, except N ε -carboxymethyl-L-lysine (CML), were 10-30% higher, sRAGE levels 1.7-fold lower, and glycation/sRAGE ratios 4-fold higher in the NAFLD cases compared to controls. While AGEs presented weak to moderate correlations with indices of liver function and damage (AST/ALT, HOMA-IR, TNF-α and TGF-β1), including sRAGE to characterize the AGEs/sRAGE axis strengthened the associations observed. High glycation/sRAGE ratios were associated with 1.3 to 14-fold likelihood of lower AST/ALT ratios. The sum of AGEs/sRAGE ratios accurately distinguished between healthy controls and NAFLD patients (area under the curve of 0.85). Elevated AGEs/sRAGE (>7.8 mmol/pmol) was associated with a 12-fold likelihood of the presence of NAFLD. These findings strengthen the involvement of AGEs-RAGE axis in liver injury and the pathogenesis of NAFLD. Copyright © 2018 Elsevier Inc. All rights reserved.

Advanced Age Dissociates Dual Functions of the Perirhinal Cortex

PubMed Central

Burke, Sara N.; Maurer, Andrew P.; Nematollahi, Saman; Uprety, Ajay; Wallace, Jenelle L.

2014-01-01

The perirhinal cortex (PRC) is proposed to both represent high-order sensory information and maintain those representations across delays. These cognitive processes are required for recognition memory, which declines during normal aging. Whether or not advanced age affects the ability of PRC principal cells to support these dual roles, however, is not known. The current experiment recorded PRC neurons as young and aged rats traversed a track. When objects were placed on the track, a subset of the neurons became active at discrete locations adjacent to objects. Importantly, the aged rats had a lower proportion of neurons that were activated by objects. Once PRC activity patterns in the presence of objects were established, however, both age groups maintained these representations across delays up to 2 h. These data support the hypothesis that age-associated deficits in stimulus recognition arise from impairments in high-order stimulus representation rather than difficulty in sustaining stable activity patterns over time. PMID:24403147

Advanced age dissociates dual functions of the perirhinal cortex.

PubMed

Burke, Sara N; Maurer, Andrew P; Nematollahi, Saman; Uprety, Ajay; Wallace, Jenelle L; Barnes, Carol A

2014-01-08

The perirhinal cortex (PRC) is proposed to both represent high-order sensory information and maintain those representations across delays. These cognitive processes are required for recognition memory, which declines during normal aging. Whether or not advanced age affects the ability of PRC principal cells to support these dual roles, however, is not known. The current experiment recorded PRC neurons as young and aged rats traversed a track. When objects were placed on the track, a subset of the neurons became active at discrete locations adjacent to objects. Importantly, the aged rats had a lower proportion of neurons that were activated by objects. Once PRC activity patterns in the presence of objects were established, however, both age groups maintained these representations across delays up to 2 h. These data support the hypothesis that age-associated deficits in stimulus recognition arise from impairments in high-order stimulus representation rather than difficulty in sustaining stable activity patterns over time.

Edward F. Adolph Distinguished Lecture: The remarkable anti-aging effects of aerobic exercise on systemic arteries

PubMed Central

2014-01-01

Cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality in modern societies, and advancing age is the major risk factor for CVD. Arterial dysfunction, characterized by large elastic artery stiffening and endothelial dysfunction, is the key event leading to age-associated CVD. Our work shows that regular aerobic exercise inhibits large elastic artery stiffening with aging (optimizes arterial compliance) and preserves endothelial function. Importantly, among previously sedentary late middle-aged and older adults, aerobic exercise improves arterial stiffness and enhances endothelial function in most groups and, therefore, also can be considered a treatment for age-associated arterial dysfunction. The mechanisms by which regular aerobic exercise destiffens large elastic arteries are incompletely understood, but existing evidence suggests that reductions in oxidative stress associated with decreases in both adventitial collagen (fibrosis) and advanced glycation end-products (structural protein cross-linking molecules), play a key role. Aerobic exercise preserves endothelial function with aging by maintaining nitric oxide bioavailability via suppression of excessive superoxide-associated oxidative stress, and by inhibiting the development of chronic low-grade vascular inflammation. Recent work from our laboratory supports the novel hypothesis that aerobic exercise may exert these beneficial effects by directly inducing protection to aging arteries against multiple adverse factors to which they are chronically exposed. Regular aerobic exercise should be viewed as a “first line” strategy for prevention and treatment of arterial aging and a vital component of a contemporary public health approach for reducing the projected increase in population CVD burden. PMID:24855137

Edward F. Adolph Distinguished Lecture: The remarkable anti-aging effects of aerobic exercise on systemic arteries.

PubMed

Seals, Douglas R

2014-09-01

Cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality in modern societies, and advancing age is the major risk factor for CVD. Arterial dysfunction, characterized by large elastic artery stiffening and endothelial dysfunction, is the key event leading to age-associated CVD. Our work shows that regular aerobic exercise inhibits large elastic artery stiffening with aging (optimizes arterial compliance) and preserves endothelial function. Importantly, among previously sedentary late middle-aged and older adults, aerobic exercise improves arterial stiffness and enhances endothelial function in most groups and, therefore, also can be considered a treatment for age-associated arterial dysfunction. The mechanisms by which regular aerobic exercise destiffens large elastic arteries are incompletely understood, but existing evidence suggests that reductions in oxidative stress associated with decreases in both adventitial collagen (fibrosis) and advanced glycation end-products (structural protein cross-linking molecules), play a key role. Aerobic exercise preserves endothelial function with aging by maintaining nitric oxide bioavailability via suppression of excessive superoxide-associated oxidative stress, and by inhibiting the development of chronic low-grade vascular inflammation. Recent work from our laboratory supports the novel hypothesis that aerobic exercise may exert these beneficial effects by directly inducing protection to aging arteries against multiple adverse factors to which they are chronically exposed. Regular aerobic exercise should be viewed as a "first line" strategy for prevention and treatment of arterial aging and a vital component of a contemporary public health approach for reducing the projected increase in population CVD burden. Copyright © 2014 the American Physiological Society.

Reference Values of Impulse Oscillometric Lung Function Indices in Adults of Advanced Age

PubMed Central

Schulz, Holger; Flexeder, Claudia; Behr, Jürgen; Heier, Margit; Holle, Rolf; Huber, Rudolf M.; Jörres, Rudolf A.; Nowak, Dennis; Peters, Annette; Wichmann, H.-Erich; Heinrich, Joachim; Karrasch, Stefan

2013-01-01

Background Impulse oscillometry (IOS) is a non-demanding lung function test. Its diagnostic use may be particularly useful in patients of advanced age with physical or mental limitations unable to perform spirometry. Only few reference equations are available for Caucasians, none of them covering the old age. Here, we provide reference equations up to advanced age and compare them with currently available equations. Methods IOS was performed in a population-based sample of 1990 subjects, aged 45–91 years, from KORA cohorts (Augsburg, Germany). From those, 397 never-smoking, lung healthy subjects with normal spirometry were identified and sex-specific quantile regression models with age, height and body weight as predictors for respiratory system impedance, resistance, reactance, and other parameters of IOS applied. Results Women (n = 243) showed higher resistance values than men (n = 154), while reactance at low frequencies (up to 20 Hz) was lower (p<0.05). A significant age dependency was observed for the difference between resistance values at 5 Hz and 20 Hz (R5–R20), the integrated area of low-frequency reactance (AX), and resonant frequency (Fres) in both sexes whereas reactance at 5 Hz (X5) was age dependent only in females. In the healthy subjects (n = 397), mean differences between observed values and predictions for resistance (5 Hz and 20 Hz) and reactance (5 Hz) ranged between −1% and 5% when using the present model. In contrast, differences based on the currently applied equations (Vogel & Smidt 1994) ranged between −34% and 76%. Regarding our equations the indices were beyond the limits of normal in 8.1% to 18.6% of the entire KORA cohort (n = 1990), and in 0.7% to 9.4% with the currently applied equations. Conclusions Our study provides up-to-date reference equations for IOS in Caucasians aged 45 to 85 years. We suggest the use of the present equations particularly in advanced age in order to detect airway dysfunction. PMID:23691036

50 Years of Cognitive Aging Theory.

PubMed

Anderson, Nicole D; Craik, Fergus I M

2017-01-01

The objectives of this Introduction to the Journal of Gerontology: Psychological Sciences special issue on "50 Years of Cognitive Aging Theory" are to provide a brief overview of cognitive aging research prior to 1965 and to highlight significant developments in cognitive aging theory over the last 50 years. Historical and recent theories of cognitive aging were reviewed, with a particular focus on those not directly covered by the articles included in this special issue. Prior to 1965, cognitive aging research was predominantly descriptive, identifying what aspects of intellectual functioning are affected in older compared with younger adults. Since the mid-1960s, there has been an increasing interest in how and why specific components of cognitive domains are differentially affected in aging and a growing focus on cognitive aging neuroscience. Significant advances have taken place in our theoretical understanding of how and why certain components of cognitive functioning are or are not affected by aging. We also know much more now than we did 50 years ago about the underlying neural mechanisms of these changes. The next 50 years undoubtedly will bring new theories, as well as new tools (e.g., neuroimaging advances, neuromodulation, and technology), that will further our understanding of cognitive aging. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Aging of the immune system – focus on inflammation and vaccination

PubMed Central

Pinti, Marcello; Appay, Victor; Campisi, Judith; Frasca, Daniela; Fülöp, Tamas; Sauce, Delphine; Larbi, Anis; Weinberger, Birgit; Cossarizza, Andrea

2016-01-01

Major advances in preventing, delaying or curing individual pathologies are responsible for an increasingly long life span in the developed parts of our planet, and indeed reaching 8–9 decades of life is nowadays extremely frequent. However, medical and sanitary advances have not prevented or delayed the underlying cause of the disparate pathologies occurring in the elderly: aging itself. The identification of the basis of the aging processes that drives the multiple pathologies and loss of function typical of older individuals is a major challenge in current aging research. Among the possible causes, an impairment of the immune system plays a major role, and indeed numerous studies have described immunological changes which occur with age. Far from the intention of being exhaustive, this review will focus on recent advances and views on the role that modifications of cell signalling and remodelling of the immune response play during human aging and longevity, paying particular attention to phenomena which are linked to the so called inflammaging process, such as dysregulation of innate immunity, altered T-cell or B-cell maturation and differentiation, as well as to the implications of immune aging for vaccination strategies in the elderly. PMID:27595500

Effects of high glucose and advanced glycation end products on the expressions of sclerostin and RANKL as well as apoptosis in osteocyte-like MLO-Y4-A2 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tanaka, Ken-ichiro, E-mail: ken1nai@med.shimane-u.ac.jp; Yamaguchi, Toru, E-mail: yamaguch@med.shimane-u.ac.jp; Kanazawa, Ippei, E-mail: ippei.k@med.shimane-u.ac.jp

In diabetes mellitus (DM), high glucose (HG) and advanced glycation end products (AGEs) are involved in bone quality deterioration. Osteocytes produce sclerostin and receptor activator of nuclear factor-kB ligand (RANKL) and regulate osteoblast and osteoclast function. However, whether HG or AGEs directly affect osteocytes and regulate sclerostin and RANKL production is unknown. Here, we examined the effects of HG, AGE2, and AGE3 on the expression of sclerostin and RANKL and on apoptosis in osteocyte-like MLO-Y4-A2 cells. Treatment of the cells with 22 mM glucose, 100 μg/mL either AGE2 or AGE3 significantly increased the expression of sclerostin protein and mRNA; however, both AGEs,more » but not glucose, significantly decreased the expression of RANKL protein and mRNA. Moreover, treatment of the cells with HG, AGE2, or AGE3 for 72 h induced significant apoptosis. These detrimental effects of HG, AGE2, and AGE3 on sclerostin and RANKL expressions and on apoptosis were antagonized by pretreatment of the cells with 10{sup −8} M human parathyroid hormone (PTH)-(1–34). Thus, HG and AGEs likely suppress bone formation by increasing sclerostin expression in osteocytes, whereas AGEs suppress bone resorption by decreasing RANKL expression. Together, these processes may cause low bone turnover in DM. In addition, HG and AGEs may cause cortical bone deterioration by inducing osteocyte apoptosis. PTH may effectively treat these pathological processes and improve osteocyte function. - Highlights: • AGEs are involved in bone quality deterioration in diabetes mellitus (DM). • AGEs increased sclerostin as well as apoptosis, and decreased RANKL in osteocytes. • The effects of AGEs on osteocyte function were antagonized by human PTH-(1–34). • AGEs may cause low bone turnover and cortical porosity in DM. • PTH may be effective in bone quality deterioration by improving osteocyte function.« less

Interactive Tools for Measuring Visual Scanning Performance and Reaction Time.

PubMed

Brooks, Johnell; Seeanner, Julia; Hennessy, Sarah; Manganelli, Joseph; Crisler, Matthew; Rosopa, Patrick; Jenkins, Casey; Anderson, Michael; Drouin, Nathalie; Belle, Leah; Truesdail, Constance; Tanner, Stephanie

Occupational therapists are constantly searching for engaging, high-technology interactive tasks that provide immediate feedback to evaluate and train clients with visual scanning deficits. This study examined the relationship between two tools: the VISION COACH™ interactive light board and the Functional Object Detection © (FOD) Advanced driving simulator scenario. Fifty-four healthy drivers, ages 21-66 yr, were divided into three age groups. Participants performed braking response and visual target (E) detection tasks of the FOD Advanced driving scenario, followed by two sets of three trials using the VISION COACH Full Field 60 task. Results showed no significant effect of age on FOD Advanced performance but a significant effect of age on VISION COACH performance. Correlations showed that participants' performance on both braking and E detection tasks were significantly positively correlated with performance on the VISION COACH (.37 < r < .40, p < .01). These tools provide new options for therapists. Copyright © 2017 by the American Occupational Therapy Association, Inc.

Investigation of the Relationship between Anterior Knee Pain and Chondromalacia Patellae and Patellofemoral Malalignment.

PubMed

Aysin, Idil Kurut; Askin, Ayhan; Mete, Berna Dirim; Guvendi, Ece; Aysin, Murat; Kocyigit, Hikmet

2018-02-01

The study aimed to investigate whether there is any association of anterior knee pain and knee function with chondromalacia stage and patellofemoral alignment in patients with anterior knee pain for over a month and with chondromalacia patellae (CMP) detected by magnetic resonance imaging (MRI). We reviewed the medical records of 38 patients who underwent a knee MRI examination and were diagnosed with chondromalacia based on the MRI. Knee MRI images were evaluated by a radiologist for chondromalacia staging. Patients were divided into two groups as early stage (stage 1-2) and advanced stage (stage 3-4) chondromalacia. Patients' demographical data (age, sex, and occupation), clinical features, physical examination findings and patellofemoral pain severity scale, kujala patellofemoral scoring system, and functional index questionnaire scores were obtained from their medical records. Trochlear sulcus angle, sulcus depth, lateral patellofemoral angle, patellar translation, and Insall-Salvati index were measured using the MRI images. The mean patient age was higher in the advanced stage CMP group compared to the early stage CMP group (p=0.038). There was no statistically significant difference regarding other demographical data (p>0.05). MRI measurement parameters did not show difference between the groups (p>0.05). Patients in the advanced stage CMP group had higher patellofemoral pain severity score, lower kujala patellofemoral score, and lower functional index questionnaire score compared to the early stage CMP group. The differences were statistically significant (p=0.008, p=0.012, and p=0.026, respectively). As chondromalacia stage advances, the symptom severity worsens and knee functions decline; however, MRI measurements do not show difference between early and advanced stage CMP patients.

Investigation of the Relationship between Anterior Knee Pain and Chondromalacia Patellae and Patellofemoral Malalignment

PubMed Central

Aysin, Idil Kurut; Askin, Ayhan; Mete, Berna Dirim; Guvendi, Ece; Aysin, Murat; Kocyigit, Hikmet

2018-01-01

Objective: The study aimed to investigate whether there is any association of anterior knee pain and knee function with chondromalacia stage and patellofemoral alignment in patients with anterior knee pain for over a month and with chondromalacia patellae (CMP) detected by magnetic resonance imaging (MRI). Materials and Methods: We reviewed the medical records of 38 patients who underwent a knee MRI examination and were diagnosed with chondromalacia based on the MRI. Knee MRI images were evaluated by a radiologist for chondromalacia staging. Patients were divided into two groups as early stage (stage 1–2) and advanced stage (stage 3–4) chondromalacia. Patients’ demographical data (age, sex, and occupation), clinical features, physical examination findings and patellofemoral pain severity scale, kujala patellofemoral scoring system, and functional index questionnaire scores were obtained from their medical records. Trochlear sulcus angle, sulcus depth, lateral patellofemoral angle, patellar translation, and Insall–Salvati index were measured using the MRI images. Results: The mean patient age was higher in the advanced stage CMP group compared to the early stage CMP group (p=0.038). There was no statistically significant difference regarding other demographical data (p>0.05). MRI measurement parameters did not show difference between the groups (p>0.05). Patients in the advanced stage CMP group had higher patellofemoral pain severity score, lower kujala patellofemoral score, and lower functional index questionnaire score compared to the early stage CMP group. The differences were statistically significant (p=0.008, p=0.012, and p=0.026, respectively). Conclusion: As chondromalacia stage advances, the symptom severity worsens and knee functions decline; however, MRI measurements do not show difference between early and advanced stage CMP patients. PMID:29531488

Genetic association study of Age-Related Macular Degeneration in the Spanish population

PubMed Central

Brión, María; Sanchez-Salorio, Manuel; Cortón, Marta; de la Fuente, Maria; Pazos, Belen; Othman, Mohammad; Swaroop, Anand; Abecasis, Goncalo; Sobrino, Beatriz; Carracedo, Angel

2017-01-01

Purpose To investigate new genetic risk factors and replicate reported associations with advanced age related macular degeneration (AMD) in a prospective case - control study developed with a Spanish cohort. Methods Three hundred and fifty-three unrelated patients with advanced AMD (225 with atrophic AMD, 57 with neovascular AMD, and 71 with mixed AMD) and 282 age-matched controls were included. Functional and tagging SNPs in 55 candidate genes were genotyped using the SNPlex™ genotyping system. Single SNP and haplotype association analysis were performed to determine possible genetic associations; interaction effects between SNPs were also investigated. Results In agreement with previous reports, ARMS2 and CFH genes were strongly associated with AMD in the studied Spanish population. Moreover, both loci influenced risk independently giving support to different pathways implicated in AMD pathogenesis. No evidence for association of advanced AMD with other previous reported susceptibility genes, such as CST3, CX3CR1, FBLN5, HMCN1, PON1, SOD2, TLR4, VEGF and VLDLR, was detected. However, two additional genes appear to be candidate markers for the development of advanced AMD. A variant located at the 3´UTR of the FGF2 gene (rs6820411) was highly associated with atrophic AMD, and the functional SNP rs3112831 at ABCA4 showed a marginal association with the disease. Conclusion We performed a large gene association study in advanced AMD in a Spanish population. Our findings show that CFH and ARMS2 genes seem to be the principal risk loci contributing independently to AMD in our cohort. We report new significant associations that could also influence the development of advanced AMD. These findings should be confirmed in further studies with larger cohorts. PMID:21106043

An automated compound screening for anti-aging effects on the function of C. elegans sensory neurons.

PubMed

Bazopoulou, Daphne; Chaudhury, Amrita R; Pantazis, Alexandros; Chronis, Nikos

2017-08-24

Discovery of molecular targets or compounds that alter neuronal function can lead to therapeutic advances that ameliorate age-related neurodegenerative pathologies. Currently, there is a lack of in vivo screening technologies for the discovery of compounds that affect the age-dependent neuronal physiology. Here, we present a high-throughput, microfluidic-based assay for automated manipulation and on-chip monitoring and analysis of stimulus-evoked calcium responses of intact C. elegans at various life stages. First, we successfully applied our technology to quantify the effects of aging and age-related genetic and chemical factors in the calcium transients of the ASH sensory neuron. We then performed a large-scale screen of a library of 107 FDA-approved compounds to identify hits that prevented the age-dependent functional deterioration of ASH. The robust performance of our assay makes it a valuable tool for future high-throughput applications based on in vivo functional imaging.

Theory of mind through the ages: older and middle-aged adults exhibit more errors than do younger adults on a continuous false belief task.

PubMed

Bernstein, Daniel M; Thornton, Wendy Loken; Sommerville, Jessica A

2011-10-01

Theory of mind (ToM), or the ability to understand mental states, is a fundamental aspect of social cognition. Previous research has documented marked advances in ToM in preschoolers, and declines in ToM in older-aged adults. In the present study, younger (n=37), middle-aged (n=20), and older (n=37) adults completed a continuous false belief task measuring ToM. Middle-aged and older adults exhibited more false belief bias than did younger adults, irrespective of language ability, executive function, processing speed, and memory. The authors conclude that ToM declines from younger to older adulthood, independent of age-related changes to domain-general cognitive functioning.

[Melatonin secretion in women of advanced reproductive age].

PubMed

Ermolenko, K S; Rapoport, S I; Solov'eva, A V

2013-01-01

The patient's age is a key factor determining success of in vitro fertilization. The ovarian reserve and oocyte quality are known to decrease with age. Much attention has been given recently to the role of epiphysis and its hormone, melatonin, in synchronization of daily and seasonal biorhythms in anti-stress protection and neuroregulation of reproductive processes. The aim of our work was to study melatonin levels in infertile women of reproductive age. We also measured sex hormones, anti-Mullerian hormone, FSH, and LH in blood and melatonin sulfate in urine at 8 points (RIA). Women of advanced reproductive age showed markedly reduced melatonin secretion due to functional disorders in the hypothalamic-pituitary-gonadal axis. Results of the study suggest the necessity of prescription of exogenous melatonin to the patients included in assisted reproduction programs for the improvement of their efficacy.

Physiological Aging: Links Among Adipose Tissue Dysfunction, Diabetes, and Frailty

PubMed Central

Stout, Michael B.; Justice, Jamie N.; Nicklas, Barbara J.; Kirkland, James L.

2016-01-01

Advancing age is associated with progressive declines in physiological function that lead to overt chronic disease, frailty, and eventual mortality. Importantly, age-related physiological changes occur in cellularity, insulin-responsiveness, secretory profiles, and inflammatory status of adipose tissue, leading to adipose tissue dysfunction. Although the mechanisms underlying adipose tissue dysfunction are multifactorial, the consequences result in secretion of proinflammatory cytokines and chemokines, immune cell infiltration, an accumulation of senescent cells, and an increase in senescence-associated secretory phenotype (SASP). These processes synergistically promote chronic sterile inflammation, insulin resistance, and lipid redistribution away from subcutaneous adipose tissue. Without intervention, these effects contribute to age-related systemic metabolic dysfunction, physical limitations, and frailty. Thus adipose tissue dysfunction may be a fundamental contributor to the elevated risk of chronic disease, disability, and adverse health outcomes with advancing age. PMID:27927801

Vulnerable Parkin Loss-of-Function Drosophila Dopaminergic Neurons Have Advanced Mitochondrial Aging, Mitochondrial Network Loss and Transiently Reduced Autophagosome Recruitment.

PubMed

Cackovic, Juliana; Gutierrez-Luke, Susana; Call, Gerald B; Juba, Amber; O'Brien, Stephanie; Jun, Charles H; Buhlman, Lori M

2018-01-01

Selective degeneration of substantia nigra dopaminergic (DA) neurons is a hallmark pathology of familial Parkinson's disease (PD). While the mechanism of degeneration is elusive, abnormalities in mitochondrial function and turnover are strongly implicated. An Autosomal Recessive-Juvenile Parkinsonism (AR-JP) Drosophila melanogaster model exhibits DA neurodegeneration as well as aberrant mitochondrial dynamics and function. Disruptions in mitophagy have been observed in parkin loss-of-function models, and changes in mitochondrial respiration have been reported in patient fibroblasts. Whether loss of parkin causes selective DA neurodegeneration in vivo as a result of lost or decreased mitophagy is unknown. This study employs the use of fluorescent constructs expressed in Drosophila DA neurons that are functionally homologous to those of the mammalian substantia nigra. We provide evidence that degenerating DA neurons in parkin loss-of-function mutant flies have advanced mitochondrial aging, and that mitochondrial networks are fragmented and contain swollen organelles. We also found that mitophagy initiation is decreased in park ( Drosophila parkin/PARK2 ortholog) homozygous mutants, but autophagosome formation is unaffected, and mitochondrial network volumes are decreased. As the fly ages, autophagosome recruitment becomes similar to control, while mitochondria continue to show signs of damage, and climbing deficits persist. Interestingly, aberrant mitochondrial morphology, aging and mitophagy initiation were not observed in DA neurons that do not degenerate. Our results suggest that parkin is important for mitochondrial homeostasis in vulnerable Drosophila DA neurons, and that loss of parkin-mediated mitophagy may play a role in degeneration of relevant DA neurons or motor deficits in this model.

Effects of low- and high-advanced glycation endproduct meals on macro- and microvascular endothelial function and oxidative stress in patients with type 2 diabetes mellitus.

PubMed

Negrean, Monica; Stirban, Alin; Stratmann, Bernd; Gawlowski, Thomas; Horstmann, Tina; Götting, Christian; Kleesiek, Knut; Mueller-Roesel, Michaela; Koschinsky, Theodor; Uribarri, Jaime; Vlassara, Helen; Tschoepe, Diethelm

2007-05-01

An advanced glycation endproducts (AGEs)-rich diet induces significant increases in inflammatory and endothelial dysfunction markers in type 2 diabetes mellitus (T2DM). The aim was to investigate the acute effects of dietary AGEs on vascular function in T2DM patients. Twenty inpatients with T2DM [x (+/-SEM) age: 55.4 +/- 2.2 y; glycated hemoglobin: 8.8 +/- 0.5%] were investigated. In a randomized crossover design, the effects of a low-AGE (LAGE) and high-AGE (HAGE) meal on macrovascular [by flow-mediated dilatation (FMD)] and microvascular (by Laser-Doppler flowmetry) function, serum markers of endothelial dysfunction (E-selectin, intracellular adhesion molecule 1, and vascular cell adhesion molecule 1), oxidative stress, and serum AGE were assessed. The meals had identical ingredients but different AGE amounts (15.100 compared with 2.750 kU AGE for the HAGE and LAGE meals, respectively), which were obtained by varying the cooking temperature and time. The measurements were performed at baseline and 2, 4, and 6 h after each meal. After the HAGE meal, FMD decreased by 36.2%, from 5.77 +/- 0.65% (baseline) to 3.93 +/- 0.48 (2 h), 3.70 +/- 0.42 (4 h), and 4.42 +/- 0.54% (6 h) (P<0.01 for all compared with baseline). After the LAGE meal, FMD decreased by 20.9%, from 6.04 +/- 0.68% (baseline) to 4.75 +/- 0.48% (2 h), 4.69 +/- 0.51% (4 h), and 5.62 +/- 0.63% (6 h), respectively (P<0.01 for all compared with baseline; P<0.001 for all compared with the HAGE meal). This impairment of macrovascular function after the HAGE meal was paralleled by an impairment of microvascular function (-67.2%) and increased concentrations of serum AGE and markers of endothelial dysfunction and oxidative stress. In patients with T2DM, a HAGE meal induces a more pronounced acute impairment of vascular function than does an otherwise identical LAGE meal. Therefore, chemical modifications of food by means of cooking play a major role in influencing the extent of postprandial vascular dysfunction.

Autism risk associated with parental age and with increasing difference in age between the parents.

PubMed

Sandin, S; Schendel, D; Magnusson, P; Hultman, C; Surén, P; Susser, E; Grønborg, T; Gissler, M; Gunnes, N; Gross, R; Henning, M; Bresnahan, M; Sourander, A; Hornig, M; Carter, K; Francis, R; Parner, E; Leonard, H; Rosanoff, M; Stoltenberg, C; Reichenberg, A

2016-05-01

Advancing paternal and maternal age have both been associated with risk for autism spectrum disorders (ASD). However, the shape of the association remains unclear, and results on the joint associations is lacking. This study tests if advancing paternal and maternal ages are independently associated with ASD risk and estimates the functional form of the associations. In a population-based cohort study from five countries (Denmark, Israel, Norway, Sweden and Western Australia) comprising 5 766 794 children born 1985-2004 and followed up to the end of 2004-2009, the relative risk (RR) of ASD was estimated by using logistic regression and splines. Our analyses included 30 902 cases of ASD. Advancing paternal and maternal age were each associated with increased RR of ASD after adjusting for confounding and the other parent's age (mothers 40-49 years vs 20-29 years, RR=1.15 (95% confidence interval (CI): 1.06-1.24), P-value<0.001; fathers⩾50 years vs 20-29 years, RR=1.66 (95% CI: 1.49-1.85), P-value<0.001). Younger maternal age was also associated with increased risk for ASD (mothers <20 years vs 20-29 years, RR=1.18 (95% CI: 1.08-1.29), P-value<0.001). There was a joint effect of maternal and paternal age with increasing risk of ASD for couples with increasing differences in parental ages. We did not find any support for a modifying effect by the sex of the offspring. In conclusion, as shown in multiple geographic regions, increases in ASD was not only limited to advancing paternal or maternal age alone but also to differences parental age including younger or older similarly aged parents as well as disparately aged parents.

20 CFR 416.963 - Your age as a vocational factor.

Code of Federal Regulations, 2012 CFR

2012-04-01

... your residual functional capacity, education, and work experience. We will not consider your ability to... person's ability to adjust to other work, we consider advancing age to be an increasingly limiting factor... this section. If you are unemployed but you still have the ability to adjust to other work, we will...

20 CFR 404.1563 - Your age as a vocational factor.

Code of Federal Regulations, 2012 CFR

2012-04-01

... your residual functional capacity, education, and work experience. We will not consider your ability to... person's ability to adjust to other work, we consider advancing age to be an increasingly limiting factor... this section. If you are unemployed but you still have the ability to adjust to other work, we will...

Longitudinal Analysis of Calorie Restriction on Rat Taste Bud Morphology and Expression of Sweet Taste Modulators

PubMed Central

Cai, Huan; Daimon, Caitlin M.; Cong, Wei-na; Wang, Rui; Chirdon, Patrick; de Cabo, Rafael; Sévigny, Jean; Maudsley, Stuart; Martin, Bronwen

2014-01-01

Calorie restriction (CR) is a lifestyle intervention employed to reduce body weight and improve metabolic functions primarily via reduction of ingested carbohydrates and fats. Taste perception is highly related to functional metabolic status and body adiposity. We have previously shown that sweet taste perception diminishes with age; however, relatively little is known about the effects of various lengths of CR upon taste cell morphology and function. We investigated the effects of CR on taste bud morphology and expression of sweet taste–related modulators in 5-, 17-, and 30-month-old rats. In ad libitum (AL) and CR rats, we consistently found the following parameters altered significantly with advancing age: reduction of taste bud size and taste cell numbers per taste bud and reduced expression of sonic hedgehog, type 1 taste receptor 3 (T1r3), α-gustducin, and glucagon-like peptide-1 (GLP-1). In the oldest rats, CR affected a significant reduction of tongue T1r3, GLP-1, and α-gustducin expression compared with age-matched AL rats. Leptin receptor immunopositive cells were elevated in 17- and 30-month-old CR rats compared with age-matched AL rats. These alterations of sweet taste–related modulators, specifically during advanced aging, suggest that sweet taste perception may be altered in response to different lengths of CR. PMID:24077597

Longitudinal analysis of calorie restriction on rat taste bud morphology and expression of sweet taste modulators.

PubMed

Cai, Huan; Daimon, Caitlin M; Cong, Wei-Na; Wang, Rui; Chirdon, Patrick; de Cabo, Rafael; Sévigny, Jean; Maudsley, Stuart; Martin, Bronwen

2014-05-01

Calorie restriction (CR) is a lifestyle intervention employed to reduce body weight and improve metabolic functions primarily via reduction of ingested carbohydrates and fats. Taste perception is highly related to functional metabolic status and body adiposity. We have previously shown that sweet taste perception diminishes with age; however, relatively little is known about the effects of various lengths of CR upon taste cell morphology and function. We investigated the effects of CR on taste bud morphology and expression of sweet taste-related modulators in 5-, 17-, and 30-month-old rats. In ad libitum (AL) and CR rats, we consistently found the following parameters altered significantly with advancing age: reduction of taste bud size and taste cell numbers per taste bud and reduced expression of sonic hedgehog, type 1 taste receptor 3 (T1r3), α-gustducin, and glucagon-like peptide-1 (GLP-1). In the oldest rats, CR affected a significant reduction of tongue T1r3, GLP-1, and α-gustducin expression compared with age-matched AL rats. Leptin receptor immunopositive cells were elevated in 17- and 30-month-old CR rats compared with age-matched AL rats. These alterations of sweet taste-related modulators, specifically during advanced aging, suggest that sweet taste perception may be altered in response to different lengths of CR.

Cardiomyocyte mitochondrial respiration is reduced by receptor for advanced glycation end-product signaling in a ceramide-dependent manner.

PubMed

Nelson, Michael B; Swensen, Adam C; Winden, Duane R; Bodine, Jared S; Bikman, Benjamin T; Reynolds, Paul R

2015-07-01

Cigarette smoke exposure is associated with an increased risk of cardiovascular complications. The role of advanced glycation end products (AGEs) is already well established in numerous comorbidities, including cardiomyopathy. Given the role of AGEs and their receptor, RAGE, in activating inflammatory pathways, we sought to determine whether ceramides could be a mediator of RAGE-induced altered heart mitochondrial function. Using an in vitro model, we treated H9C2 cardiomyocytes with the AGE carboxy-methyllysine before mitochondrial respiration assessment. We discovered that mitochondrial respiration was significantly impaired in AGE-treated cells, but not when cotreated with myriocin, an inhibitor of de novo ceramide biosynthesis. Moreover, we exposed wild-type and RAGE knockout mice to secondhand cigarette smoke and found reduced mitochondrial respiration in the left ventricular myocardium from wild-type mice, but RAGE knockout mice were protected from this effect. Finally, conditional overexpression of RAGE in the lungs of transgenic mice elicited a robust increase in left ventricular ceramides in the absence of smoke exposure. Taken together, these findings suggest a RAGE-ceramide axis as an important contributor to AGE-mediated disrupted cardiomyocyte mitochondrial function. Copyright © 2015 the American Physiological Society.

Depressed perivascular sensory innervation of mouse mesenteric arteries with advanced age.

PubMed

Boerman, Erika M; Segal, Steven S

2016-04-15

The dilatory role for sensory innervation of mesenteric arteries (MAs) is impaired in Old (∼24 months) versus Young (∼4 months) mice. We investigated the nature of this impairment in isolated pressurized MAs. With perivascular sensory nerve stimulation, dilatation and inhibition of sympathetic vasoconstriction observed in Young MAs were lost in Old MAs along with impaired dilatation to calcitonin gene-related peptide (CGRP). Inhibiting NO and prostaglandin synthesis increased CGRP EC50 in Young and Old MAs. Endothelial denudation attenuated dilatation to CGRP in Old MAs yet enhanced dilatation to CGRP in Young MAs while abolishing all dilatations to ACh. In Old MAs, sensory nerve density was reduced and RAMP1 (CGRP receptor component) associated with nuclear regions of endothelial cells in a manner not seen in Young MAs or in smooth muscle cells of either age. With advanced age, loss of dilatory signalling mediated through perivascular sensory nerves may compromise perfusion of visceral organs. Vascular dysfunction and sympathetic nerve activity increase with advancing age. In the gut, blood flow is governed by perivascular sensory and sympathetic nerves but little is known of how their functional role is affected by advanced age. We tested the hypothesis that functional sensory innervation of mesenteric arteries (MAs) is impaired for Old (24 months) versus Young (4 months) C57BL/6 male mice. In cannulated pressurized MAs preconstricted 50% with noradrenaline and treated with guanethidine (to inhibit sympathetic neurotransmission), perivascular nerve stimulation (PNS) evoked dilatation in Young but not Old MAs while dilatations to ACh were not different between age groups. In Young MAs, capsaicin (to inhibit sensory neurotransmission) blocked dilatation and increased constriction during PNS. With no difference in efficacy, the EC50 of CGRP as a vasodilator was ∼6-fold greater in Old versus Young MAs. Inhibiting nitric oxide (l-NAME) and prostaglandin (indomethacin) synthesis increased CGRP EC50 in both age groups. Endothelial denudation reduced the efficacy of dilatation to CGRP by ∼30% in Old MAs yet increased this efficacy ∼15% in Young MAs while all dilatations to ACh were abolished. Immunolabelling revealed reduced density of sensory (CGRP) but not sympathetic (tyrosine hydroxylase) innervation for Old versus Young MAs. Whereas the distribution of CGRP receptor proteins was similar in SMCs, RAMP1 associated with nuclear regions of endothelial cells of Old but not Young MAs. With advanced age, the loss of sensory nerve function and diminished effectiveness of CGRP as a vasodilator is multifaceted and may adversely affect splanchnic perfusion. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Idiopathic Short Stature due to Novel Heterozygous Mutation of the Aggrecan Gene

PubMed Central

Quintos, Jose Bernardo; Guo, Michael H.; Dauber, Andrew

2015-01-01

Background Recently, whole exome sequencing identified heterozygous defects in the Aggrecan gene (ACAN) in three families with short stature and advanced bone age. Objective We report a novel frameshift mutation in ACAN in a family with dominantly inherited short stature, advanced bone age, and premature growth cessation. This is the first case of targeted sequencing of ACAN in this phenotype and confirms that ACAN sequencing is warranted in patients with this rare constellation of findings. Results We present a 5 1/2 year old male with a family history of short stature in 3 generations. The maternal grandfather stands 144.5 cm (Ht SDS -4.7), mother 147.7 cm (Ht SDS -2.6), and index case 99.2 cm (Ht SDS -2.7). Our prepubertal patient has significant bone age advancement (bone age 8 years at chronologic age 5 1/2 years) resulting in a poor predicted adult height of 142 cm (Ht SDS -5.1). DNA sequencing identified a novel heterozygous variant in ACAN, which encodes aggrecan, a proteoglycan in the extracellular matrix of growth plate and other cartilaginous tissues. The mutation (p.Gly1797Glyfs*52) results in premature truncation and presumed loss of protein function. Conclusion Mutations in aggrecan gene should be included in the differential diagnosis of the child with idiopathic short stature or familial short stature and bone age advancement. PMID:25741789

The potential of virtual reality and gaming to assist successful aging with disability.

PubMed

Lange, B S; Requejo, P; Flynn, S M; Rizzo, A A; Valero-Cuevas, F J; Baker, L; Winstein, C

2010-05-01

Using the advances in computing power, software and hardware technologies, virtual reality (VR), and gaming applications have the potential to address clinical challenges for a range of disabilities. VR-based games can potentially provide the ability to assess and augment cognitive and motor rehabilitation under a range of stimulus conditions that are not easily controllable and quantifiable in the real world. This article discusses an approach for maximizing function and participation for those aging with and into a disability by combining task-specific training with advances in VR and gaming technologies to enable positive behavioral modifications for independence in the home and community. There is potential for the use of VR and game applications for rehabilitating, maintaining, and enhancing those processes that are affected by aging with and into disability, particularly the need to attain a balance in the interplay between sensorimotor function and cognitive demands and to reap the benefits of task-specific training and regular physical activity and exercise.

Paternal Age Alters Social Development in Offspring.

PubMed

Janecka, Magdalena; Haworth, Claire M A; Ronald, Angelica; Krapohl, Eva; Happé, Francesca; Mill, Jonathan; Schalkwyk, Leonard C; Fernandes, Cathy; Reichenberg, Abraham; Rijsdijk, Frühling

2017-05-01

Advanced paternal age (APA) at conception has been linked with autism and schizophrenia in offspring, neurodevelopmental disorders that affect social functioning. The current study explored the effects of paternal age on social development in the general population. We used multilevel growth modeling to investigate APA effects on socioemotional development from early childhood until adolescence, as measured by the Strengths and Difficulties Questionnaire (SDQ) in the Twins Early Development Study (TEDS) sample. We also investigated genetic and environmental underpinnings of the paternal age effects on development, using the Additive genetics, Common environment, unique Environment (ACE) and gene-environment (GxE) models. In the general population, both very young and advanced paternal ages were associated with altered trajectory of social development (intercept: p = .01; slope: p = .03). No other behavioral domain was affected by either young or advanced age at fatherhood, suggesting specificity of paternal age effects. Increased importance of genetic factors in social development was recorded in the offspring of older but not very young fathers, suggesting distinct underpinnings of the paternal age effects at these two extremes. Our findings highlight that the APA-related deficits that lead to autism and schizophrenia are likely continuously distributed in the population. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Exercise, cognitive function, and aging

PubMed Central

2015-01-01

Increasing the lifespan of a population is often a marker of a country's success. With the percentage of the population over 65 yr of age expanding, managing the health and independence of this population is an ongoing concern. Advancing age is associated with a decrease in cognitive function that ultimately affects quality of life. Understanding potential adverse effects of aging on brain blood flow and cognition may help to determine effective strategies to mitigate these effects on the population. Exercise may be one strategy to prevent or delay cognitive decline. This review describes how aging is associated with cardiovascular disease risks, vascular dysfunction, and increasing Alzheimer's disease pathology. It will also discuss the possible effects of aging on cerebral vascular physiology, cerebral perfusion, and brain atrophy rates. Clinically, these changes will present as reduced cognitive function, neurodegeneration, and the onset of dementia. Regular exercise has been shown to improve cognitive function, and we hypothesize that this occurs through beneficial adaptations in vascular physiology and improved neurovascular coupling. This review highlights the potential interactions and ideas of how the age-associated variables may affect cognition and may be moderated by regular exercise. PMID:26031719

Advanced Theory of Mind in patients at early stage of Parkinson's disease.

PubMed

Yu, Rwei-Ling; Wu, Ruey-Meei; Chiu, Ming-Jang; Tai, Chun-Hwei; Lin, Chin-Hsien; Hua, Mau-Sun

2012-01-01

Advanced Theory of Mind (ToM) refers to the sophisticated ability to infer other people's thoughts, intentions, or emotions in social situations. With appropriate advanced ToM, one can behave well in social interactions and can understand the intention of others' behavior. Prefrontal cortex plays a vital role in this ability, as shown in functional brain imaging and lesion studies. Considering the primary neuropathology of Parkinson's disease (PD) involving the frontal lobe system, patients with PD are expected to exhibit deficits in advanced ToM. However, few studies on this issue have been explored, and whether advanced ToM is independent of executive functions remains uncertain. Thirty-nine early non-demented PD patients and 40 normal control subjects were included. Both groups were matched in age, level of education, and verbal intelligence quotient. Each participant received advanced ToM, executive functions, and verbal intelligence quotient tests. We discovered that the performance of the PD patients on the Cartoon ToM task was significantly poorer than that of their normal counterparts. Correlation analysis revealed that performance scores of advanced ToM in PD patients were significantly associated with their executive functions scores; however, this is not the case for normal controls. We conclude that dysfunction of advanced ToM develops in early PD patients, who require more cognitive abilities than their normal counterparts to generate advanced ToM. Our findings might be helpful in developing educational and medical care programs for PD patients in the future. Copyright © 2011 Elsevier Ltd. All rights reserved.

Functional Neuroimaging of Speech Perception during a Pivotal Period in Language Acquisition

ERIC Educational Resources Information Center

Redcay, Elizabeth; Haist, Frank; Courchesne, Eric

2008-01-01

A pivotal period in the development of language occurs in the second year of life, when language comprehension undergoes rapid acceleration. However, the brain bases of these advances remain speculative as there is currently no functional magnetic resonance imaging (fMRI) data from healthy, typically developing toddlers at this age. We…

Treatment of Chronic Hepatitis C in the Aged - Does It Impact Life Expectancy? A Decision Analysis.

PubMed

Maor, Yaakov; Malnick, Stephen D H; Melzer, Ehud; Leshno, Moshe

2016-01-01

Recent studies have demonstrated that the efficacy of interferon-free direct-acting antiviral agents (DAAs) in patients over 70 is similar to that of younger age groups. Evidence continues to mount that life expectancy (LE) increases with successful treatment of hepatitis C (HCV) patients with advanced fibrosis. The evidence in older people is more limited. Our aim was to estimate the life year (LY) and quality-adjusted life year (QALY) gained by treatment of naïve patients with HCV as a function of patient's age and fibrosis stage. We constructed a Markov model of HCV progression toward advanced liver disease. The primary outcome was LY and QALY saved. The model and the sustained virological response of HCV infected subjects treated with a fixed-dose combination of the NS5B polymerase inhibitor Sofosbuvir and the NS5A replication complex inhibitor Ledipasvir were based on the published literature and expert opinion. Generally, both the number of LY gained and QALY gained gradually decreased with advancing age but the rate of decline was slower with more advanced fibrosis stage. For patients with fibrosis stage F1, F2 and F3, LY gained dropped below six months if treated by the age of 55, 65 or 70 years, respectively, while for a patient with fibrosis stage F4, the gain was one LY if treated by the age of 75. The QALY gained for treated over untreated elderly were reasonably high even for those treated at early fibrosis stage. There is a significant life expectancy benefit to HCV treatment in patients up to age 75 with advanced-stage fibrosis.

Treatment of Chronic Hepatitis C in the Aged – Does It Impact Life Expectancy? A Decision Analysis

PubMed Central

Maor, Yaakov; Malnick, Stephen D. H.; Melzer, Ehud; Leshno, Moshe

2016-01-01

Background and Aims Recent studies have demonstrated that the efficacy of interferon-free direct-acting antiviral agents (DAAs) in patients over 70 is similar to that of younger age groups. Evidence continues to mount that life expectancy (LE) increases with successful treatment of hepatitis C (HCV) patients with advanced fibrosis. The evidence in older people is more limited. Our aim was to estimate the life year (LY) and quality-adjusted life year (QALY) gained by treatment of naïve patients with HCV as a function of patient's age and fibrosis stage. Methods We constructed a Markov model of HCV progression toward advanced liver disease. The primary outcome was LY and QALY saved. The model and the sustained virological response of HCV infected subjects treated with a fixed-dose combination of the NS5B polymerase inhibitor Sofosbuvir and the NS5A replication complex inhibitor Ledipasvir were based on the published literature and expert opinion. Results Generally, both the number of LY gained and QALY gained gradually decreased with advancing age but the rate of decline was slower with more advanced fibrosis stage. For patients with fibrosis stage F1, F2 and F3, LY gained dropped below six months if treated by the age of 55, 65 or 70 years, respectively, while for a patient with fibrosis stage F4, the gain was one LY if treated by the age of 75. The QALY gained for treated over untreated elderly were reasonably high even for those treated at early fibrosis stage. Conclusions There is a significant life expectancy benefit to HCV treatment in patients up to age 75 with advanced-stage fibrosis. PMID:27410963

Physiological Aging: Links Among Adipose Tissue Dysfunction, Diabetes, and Frailty.

PubMed

Stout, Michael B; Justice, Jamie N; Nicklas, Barbara J; Kirkland, James L

2017-01-01

Advancing age is associated with progressive declines in physiological function that lead to overt chronic disease, frailty, and eventual mortality. Importantly, age-related physiological changes occur in cellularity, insulin-responsiveness, secretory profiles, and inflammatory status of adipose tissue, leading to adipose tissue dysfunction. Although the mechanisms underlying adipose tissue dysfunction are multifactorial, the consequences result in secretion of proinflammatory cytokines and chemokines, immune cell infiltration, an accumulation of senescent cells, and an increase in senescence-associated secretory phenotype (SASP). These processes synergistically promote chronic sterile inflammation, insulin resistance, and lipid redistribution away from subcutaneous adipose tissue. Without intervention, these effects contribute to age-related systemic metabolic dysfunction, physical limitations, and frailty. Thus adipose tissue dysfunction may be a fundamental contributor to the elevated risk of chronic disease, disability, and adverse health outcomes with advancing age. ©2017 Int. Union Physiol. Sci./Am. Physiol. Soc.

Increased functional connectivity with puberty in the mentalising network involved in social emotion processing

PubMed Central

Klapwijk, Eduard T.; Goddings, Anne-Lise; Heyes, Stephanie Burnett; Bird, Geoffrey; Viner, Russell M.; Blakemore, Sarah-Jayne

2015-01-01

There is increasing evidence that puberty plays an important role in the structural and functional brain development seen in adolescence, but little is known of the pubertal influence on changes in functional connectivity. We explored how pubertal indicators (salivary concentrations of testosterone, oestradiol and DHEA; pubertal stage; menarcheal status) relate to functional connectivity between components of a mentalising network identified to be engaged in social emotion processing by our prior work, using psychophysiological interaction (PPI) analysis. Female adolescents aged 11 to 13 years were scanned whilst silently reading scenarios designed to evoke either social emotions (guilt and embarrassment) or basic emotions (disgust and fear), of which only social compared to basic emotions require the representation of another person’s mental states. Pubertal stage and menarcheal status were used to assign participants to pre/early or mid/late puberty groups. We found increased functional connectivity between the dorsomedial prefrontal cortex (DMPFC) and the right posterior superior temporal sulcus (pSTS) and right temporo-parietal junction (TPJ) during social relative to basic emotion processing. Moreover, increasing oestradiol concentrations were associated with increased functional connectivity between the DMPFC and the right TPJ during social relative to basic emotion processing, independent of age. Our analysis of the PPI data by phenotypic pubertal status showed that more advanced puberty stage was associated with enhanced functional connectivity between the DMPFC and the left anterior temporal cortex (ATC) during social relative to basic emotion processing, also independent of age. Our results suggest increased functional maturation of the social brain network with the advancement of puberty in girls. PMID:23998674

Stimulatory effects of advanced glycation endproducts (AGEs) on fibronectin matrix assembly.

PubMed

Pastino, Alexandra K; Greco, Todd M; Mathias, Rommel A; Cristea, Ileana M; Schwarzbauer, Jean E

2017-05-01

Advanced glycation endproducts (AGEs) are a heterogeneous group of compounds that form via non-enzymatic glycation of proteins throughout our lifespan and at a higher rate in certain chronic diseases such as diabetes. AGEs contribute to the progression of fibrosis, in part by stimulating cellular pathways that affect gene expression. Long-lived ECM proteins are targets for non-enzymatic glycation but the question of whether the AGE-modified ECM leads to excess ECM accumulation and fibrosis remains unanswered. In this study, cellular changes due to AGE accretion in the ECM were investigated. Non-enzymatic glycation of proteins in a decellularized fibroblast ECM was achieved by incubating the ECM in a solution of methylglyoxal (MGO). Mass spectrometry of fibronectin (FN) isolated from the glycated matrix identified twenty-eight previously unidentified MGO-derived AGE modification sites including functional sites such as the RGD integrin-binding sequence. Mesangial cells grown on the glycated, decellularized matrix assembled increased amounts of FN matrix. Soluble AGE-modified bovine serum albumin (BSA) also stimulated FN matrix assembly and this effect was reduced by function-blocking antibodies against the receptor for AGE (RAGE). These results indicate that cells respond to AGEs by increasing matrix assembly and that RAGE is involved in this response. This raises the possibility that the accumulation of ECM during the progression of fibrosis may be enhanced by cell interactions with AGEs on a glycated ECM. Copyright © 2016 Elsevier B.V. All rights reserved.

Transoral laser microsurgery for locally advanced (T3-T4a) supraglottic squamous cell carcinoma: Sixteen years of experience.

PubMed

Vilaseca, Isabel; Blanch, José Luis; Berenguer, Joan; Grau, Juan José; Verger, Eugenia; Muxí, África; Bernal-Sprekelsen, Manuel

2016-07-01

Controversy exists regarding treatment of advanced laryngeal cancer. The purpose of this study was to evaluate the oncologic and functional outcomes of T3 to T4a supraglottic squamous carcinomas treated with transoral laser microsurgery (TLM). We conducted a retrospective analysis from an SPSS database. Primary outcomes were: locoregional control, overall survival (OS), disease-specific survival (DSS), laryngectomy-free survival, and function-preservation rates. Secondary objectives were: rate of tracheostomies and gastrostomies according to age. Risk factors for local control and larynx preservation were also evaluated. One hundred fifty-four consecutive patients were chosen for this study. Median follow-up was 40.7 + /- 32.8 months. Five and 10-year OS, DSS, and laryngectomy-free survival were 55.6% and 47%, 67.6% and 58.6%, and 75.2% and 59.5%, respectively. Paraglottic involvement was an independent factor for larynx preservation. Six patients (3.9%) needed a definitive tracheostomy, a gastrostomy, or both. The gastrostomy rate was higher in the group of patients above 65 years of age (p = .03). Five-year laryngectomy-free survival with preserved function was 74.5%. TLM constitutes a true alternative for organ preservation in locally advanced supraglottic carcinomas with good oncologic and functional outcomes. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1050-1057, 2016. © 2016 Wiley Periodicals, Inc.

Chronic inflammation potentiates kidney aging.

PubMed

Mei, Changlin; Zheng, Feng

2009-11-01

Chronic inflammation, characterized by increased serum levels of tumor necrosis factor-alpha, interleukin-6, C-reactive protein, and plasminogen activator inhibitor-1, and the presence of inflammatory-related diseases, are seen commonly in aging. Both the dysregulation of immune cells and phenotypic changes in parenchymal cells may contribute to chronic inflammation in aging. Moreover, senescent cells are an important source of inflammatory factors. Oxidative stress, via activation of p38 and c-Jun N-terminal kinase and induction of cell senescence, is likely to play a critical role in inflammation. Endoplasmic reticulum stress also may be present in aging and be involved in inflammation. Advanced glycation end products also are important contributors to inflammation in aging. Because the kidney is a major site for the excretion, and perhaps the degradation, of advanced glycation end products and small inflammatory molecules, reduced renal function in aging may promote oxidative stress and inflammation. Chronic inflammation in turn may potentiate the initiation and progression of lesions in the aging kidney.

[Cognitive capacity in advanced age: initial results of the Berlin Aging Study].

PubMed

Lindenberger, U; Baltes, P B

1995-01-01

This study reports data on intellectual functioning in old and very old age from the Berlin Aging Study (N = 516; age range = 70-103 years; mean age = 85 years). A psychometric battery of 14 tests was used to assess five cognitive abilities: reasoning, memory, and perceptual speed from the broad fluid-mechanical as well as knowledge and fluency from the broad crystallized-pragmatic domains. Cognitive abilities had a negative linear relationship with age, with more pronounced age-based reductions in fluid-mechanical than crystallized-pragmatic abilities. At the same time, ability intercorrelations formed a highly positive manifold, and did not follow the fluid-crystallized distinction. Interindividual variability was of about equal magnitude across the entire age range studied. There was, however, no evidence for substantial sex differences. As to origins of individual differences, indicators of sensory and sensorimotor functioning were more powerful predictors of intellectual functioning than cultural-biographical variables, and the two sets of predictors were, consistent with theoretical expectations, differentially related to measures of fluid-mechanical (perceptual speed) and crystallized pragmatic (knowledge) functioning. Results, in general indicative of sizeable and general losses with age, are consistent with the view that aging-induced biological influences are a prominent source of individual differences in intellectual functioning in old and very old age. Longitudinal follow-ups are underway to examine the role of cohort effects, selective mortality, and interindividual differences in change trajectories.

Characterizing cognitive aging in humans with links to animal models

PubMed Central

Alexander, Gene E.; Ryan, Lee; Bowers, Dawn; Foster, Thomas C.; Bizon, Jennifer L.; Geldmacher, David S.; Glisky, Elizabeth L.

2012-01-01

With the population of older adults expected to grow rapidly over the next two decades, it has become increasingly important to advance research efforts to elucidate the mechanisms associated with cognitive aging, with the ultimate goal of developing effective interventions and prevention therapies. Although there has been a vast research literature on the use of cognitive tests to evaluate the effects of aging and age-related neurodegenerative disease, the need for a set of standardized measures to characterize the cognitive profiles specific to healthy aging has been widely recognized. Here we present a review of selected methods and approaches that have been applied in human research studies to evaluate the effects of aging on cognition, including executive function, memory, processing speed, language, and visuospatial function. The effects of healthy aging on each of these cognitive domains are discussed with examples from cognitive/experimental and clinical/neuropsychological approaches. Further, we consider those measures that have clear conceptual and methodological links to tasks currently in use for non-human animal studies of aging, as well as those that have the potential for translation to animal aging research. Having a complementary set of measures to assess the cognitive profiles of healthy aging across species provides a unique opportunity to enhance research efforts for cross-sectional, longitudinal, and intervention studies of cognitive aging. Taking a cross-species, translational approach will help to advance cognitive aging research, leading to a greater understanding of associated neurobiological mechanisms with the potential for developing effective interventions and prevention therapies for age-related cognitive decline. PMID:22988439

Spermidine Suppresses Age-Associated Memory Impairment by Preventing Adverse Increase of Presynaptic Active Zone Size and Release

PubMed Central

Gupta, Varun K.; Pech, Ulrike; Fulterer, Andreas; Ender, Anatoli; Mauermann, Stephan F.; Andlauer, Till F. M.; Beuschel, Christine; Thriene, Kerstin; Quentin, Christine; Schwärzel, Martin; Mielke, Thorsten; Madeo, Frank; Dengjel, Joern; Fiala, André; Sigrist, Stephan J.

2016-01-01

Memories are assumed to be formed by sets of synapses changing their structural or functional performance. The efficacy of forming new memories declines with advancing age, but the synaptic changes underlying age-induced memory impairment remain poorly understood. Recently, we found spermidine feeding to specifically suppress age-dependent impairments in forming olfactory memories, providing a mean to search for synaptic changes involved in age-dependent memory impairment. Here, we show that a specific synaptic compartment, the presynaptic active zone (AZ), increases the size of its ultrastructural elaboration and releases significantly more synaptic vesicles with advancing age. These age-induced AZ changes, however, were fully suppressed by spermidine feeding. A genetically enforced enlargement of AZ scaffolds (four gene-copies of BRP) impaired memory formation in young animals. Thus, in the Drosophila nervous system, aging AZs seem to steer towards the upper limit of their operational range, limiting synaptic plasticity and contributing to impairment of memory formation. Spermidine feeding suppresses age-dependent memory impairment by counteracting these age-dependent changes directly at the synapse. PMID:27684064

[Hand transplantation and implantation of nerve chips. New developments within hand surgery].

PubMed

Dahlin, L; Fridén, J; Hagberg, L; Lundborg, G

1999-10-06

Injuries and diseases of the hand naturally have an enormous impact on hand function and on quality of life, both occupational and social. The majority of hand-injury patients are under 30 years of age. Hand surgery, an established specialty in Sweden since 1969, is of great importance in terms of clinical developments, education and research. In the coming decade, scientific and clinical advances are to be expected in several fields such as nerve injuries including brachial plexus lesion, microsurgery, flexor tendon injuries and tendon transfer. Bioimplant research and new advances at the biotechnological interface will yield new options in nerve reconstruction, microchip implants in the nervous system, and the restoration of muscle-tendon function following injury. Artificial limbs with advanced motor and sensory functions will be important future aids in the rehabilitation of amputees. Transplantation of human hands is another promising reconstructive procedure which may open up new perspectives in the coming millennium.

[Hand transplantation and implantation of nerve chips. New developments within hand surgery].

PubMed

Dahlin, L; Fridén, J; Hagberg, L; Lundborg, G

2000-03-20

Injuries and diseases of the hand naturally have an enormous impact on hand function and on quality of life, both occupational and social. The majority of hand-injury patients are under 30 years of age. Hand surgery, an established specialty in Sweden since 1969, is of great importance in terms of clinical developments, education and research. In the coming decade, scientific and clinical advances are to be expected in several fields such as nerve injuries including brachial plexus lesion, microsurgery, flexor tendon injuries and tendon transfer. Bioimplant research and new advances at the biotechnological interface will yield new options in nerve reconstruction, microchip implants in the nervous system, and the restoration of muscle-tendon function following injury. Artificial limbs with advanced motor and sensory functions will be important future aids in the rehabilitation of amputees. Transplantation of human hands is another promising reconstructive procedure which may open iup new perspectives in the coming millennium.

Methylglyoxal-derived advanced glycation end products contribute to negative cardiac remodeling and dysfunction post-myocardial infarction.

PubMed

Blackburn, Nick J R; Vulesevic, Branka; McNeill, Brian; Cimenci, Cagla Eren; Ahmadi, Ali; Gonzalez-Gomez, Mayte; Ostojic, Aleksandra; Zhong, Zhiyuan; Brownlee, Michael; Beisswenger, Paul J; Milne, Ross W; Suuronen, Erik J

2017-09-01

Advanced glycation end-products (AGEs) have been associated with poorer outcomes after myocardial infarction (MI), and linked with heart failure. Methylglyoxal (MG) is considered the most important AGE precursor, but its role in MI is unknown. In this study, we investigated the involvement of MG-derived AGEs (MG-AGEs) in MI using transgenic mice that over-express the MG-metabolizing enzyme glyoxalase-1 (GLO1). MI was induced in GLO1 mice and wild-type (WT) littermates. At 6 h post-MI, mass spectrometry revealed that MG-H1 (a principal MG-AGE) was increased in the hearts of WT mice, and immunohistochemistry demonstrated that this persisted for 4 weeks. GLO1 over-expression reduced MG-AGE levels at 6 h and 4 weeks, and GLO1 mice exhibited superior cardiac function at 4 weeks post-MI compared to WT mice. Immunohistochemistry revealed greater vascular density and reduced cardiomyocyte apoptosis in GLO1 vs. WT mice. The recruitment of c-kit + cells and their incorporation into the vasculature (c-kit + CD31 + cells) was higher in the infarcted myocardium of GLO1 mice. MG-AGEs appeared to accumulate in type I collagen surrounding arterioles, prompting investigation in vitro. In culture, the interaction of angiogenic bone marrow cells with MG-modified collagen resulted in reduced cell adhesion, increased susceptibility to apoptosis, fewer progenitor cells, and reduced angiogenic potential. This study reveals that MG-AGEs are produced post-MI and identifies a causative role for their accumulation in the cellular changes, adverse remodeling and functional loss of the heart after MI. MG may represent a novel target for preventing damage and improving function of the infarcted heart.

Relationship between Advanced Glycation End Products and Steroidogenesis in PCOS.

PubMed

Garg, Deepika; Merhi, Zaher

2016-10-21

Women with PCOS have elevated levels of the harmful Advanced Glycation End Products (AGEs), which are highly reactive molecules formed after glycation of lipids and proteins. Additionally, AGEs accumulate in the ovaries of women with PCOS potentially contributing to the well-documented abnormal steroidogenesis and folliculogenesis. A systematic review of articles and abstracts available in PubMed was conducted and presented in a systemic manner. This article reports changes in steroidogenic enzyme activity in granulosa and theca cells in PCOS and PCOS-models. It also described the changes in AGEs and their receptors in the ovaries of women with PCOS and presents the underlying mechanism(s) whereby AGEs could be responsible for the PCOS-related changes in granulosa and theca cell function thus adversely impacting steroidogenesis and follicular development. AGEs are associated with hyperandrogenism in PCOS possibly by altering the activity of various enzymes such as cholesterol side-chain cleavage enzyme cytochrome P450, steroidogenic acute regulatory protein, 17α-hydroxylase, and 3β-hydroxysteroid dehydrogenase. AGEs also affect luteinizing hormone receptor and anti-Mullerian hormone receptor expression as well as their signaling pathways in granulosa cells. A better understanding of how AGEs alter granulosa and theca cell function is likely to contribute meaningfully to a conceptual framework whereby new interventions to prevent and/or treat ovarian dysfunction in PCOS can ultimately be developed.

Neuropsychological functions and rCBF SPECT in Parkinson's disease patients considered candidates for deep brain stimulation.

PubMed

Paschali, Anna; Messinis, Lambros; Lyros, Epameinondas; Constantoyannis, Costas; Kefalopoulou, Zinovia; Lakiotis, Velissarios; Papathanasopoulos, Panagiotis; Vassilakos, Paulos

2009-11-01

In the present study, we examined relationships between neuropsychological functions and brain single photon emission computed tomography (SPECT) regional cerebral blood flow (rCBF) observed at presurgical evaluation for deep brain stimulation (DBS) of the subthalamic nucleus (STN) in advanced Parkinson's disease (PD) patients. Twenty advanced non-demented PD patients, candidates for DBS surgery, underwent perfusion brain SPECT study and neuropsychological assessment prior to surgery (range: 30-50 days). Patients were further assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr (H&Y) scale. During all assessments patients were "on" standard medication. NeuroGam software, which permits voxel by voxel analysis, was used to compare the brain perfusion of PD patients with a normal database adjusted for sex and age. Neuropsychological scores were compared to age, education and sex-adjusted normative databases. Our results indicated that the distribution of rCBF showed significant differences when compared to an age- and sex-adjusted normative database. We found impaired blood flow in 17 (85%) of our patients in the left prefrontal lobe, in 14 (70%) in the right prefrontal lobe and in 11 (55%) in the left frontal and right parietal lobes. Neuropsychological testing revealed that 18 (90%) of our patients had significant impairments in measures of executive functions (set-shifting) and 15 (75%) in response inhibition. Furthermore, we found significant correlations between measures of visual attention, executive functions and the right frontal lobe region. The presence of widespread blood flow reduction was observed mainly in the frontal lobes of dementia-free patients with advanced PD. Furthermore, performance on specific cognitive measures was highly related to perfusion brain SPECT findings.

Adipose stem cells’ antagonism in glycosylation of D-galactose-induced skin aging of nude mice and its skin recovery function

PubMed Central

Wang, Haiying; Wei, Shuyue; Xue, Xinxin; You, Yuntian; Ma, Qiang

2016-01-01

This study aims to discuss adipose stem cells’ (ASCs) antagonism in glycosylation of D-galactose-induced skin aging of nude mice and its skin recovery function; the study also aims to explore a new mechanism of anti-aging to provide clinical anti-aging therapy with new thoughts and methods. We selected 40 healthy specific pathogen-free (SPF) nude mice and divided them randomly into four groups which were: blank control group; D-galactose + phosphate buffer saline (PBS) group; D-galactose + ASCs treatment group; and D-galactose + aminoguanidine (AG) group. Results showed that the superoxide dismutase (SOD) level of mice in the D-galactose-induced model group (87.15 ± 4.95 U/g) decreased significantly compared with that of control group (146.21 ± 4.76 U/g), while malonaldehyde (MDA) level of mice in D-galactose induced model group (11.12 ± 2.08 nmol/mg) increased significantly compared with that of control group (5.46 ± 2.05 nmol/mg) (P <0.05); thus D-galactose induced sub-acutely aging mice models were duplicated successfully. Results also indicated that transplantation of ASCs could reverse expression of aging-related biomarkers such as MDA, SOD, and advanced glycosylation end products (AGEs); hematoxylin and eosin (HE) staining showed that thickness of the dermis layer as well as the collagen content of mice in the D-galactose-induced model group increased significantly after ASC transplantation compared with that of control group. In addition, immunohistochemical assay showed that expression quantity of CD31 and vascular endothelial growth factor (VEGF) of mice in the D-galactose-induced model group increased significantly after ASC transplantation compared with that of control group. In conclusion, ASCs can trace cell distribution successfully through bioluminescence, and they survive for a short time in the skin after transplantation, which provides a basis for the application of ASC transplantation in clinical practices. Moreover, ASCs can control glycosylation level of D-galactose-induced skin aging of nude mice, reverse expression of aging-related biomarkers as well as restrain formation of advanced glycation end products, which are similar to the effects of AG inhibitors of advanced glycation end products. Thus, ASCs can prevent glycosylation-induced skin aging as well as recover functions of skin. PMID:26916459

Adipose stem cells' antagonism in glycosylation of D-galactose-induced skin aging of nude mice and its skin recovery function.

PubMed

Wang, Haiying; Wei, Shuyue; Xue, Xinxin; You, Yuntian; Ma, Qiang

2016-09-01

This study aims to discuss adipose stem cells' (ASCs) antagonism in glycosylation of D-galactose-induced skin aging of nude mice and its skin recovery function; the study also aims to explore a new mechanism of anti-aging to provide clinical anti-aging therapy with new thoughts and methods. We selected 40 healthy specific pathogen-free (SPF) nude mice and divided them randomly into four groups which were: blank control group; D-galactose + phosphate buffer saline (PBS) group; D-galactose + ASCs treatment group; and D-galactose + aminoguanidine (AG) group. Results showed that the superoxide dismutase (SOD) level of mice in the D-galactose-induced model group (87.15 ± 4.95 U/g) decreased significantly compared with that of control group (146.21 ± 4.76 U/g), while malonaldehyde (MDA) level of mice in D-galactose induced model group (11.12 ± 2.08 nmol/mg) increased significantly compared with that of control group (5.46 ± 2.05 nmol/mg) (P <0.05); thus D-galactose induced sub-acutely aging mice models were duplicated successfully. Results also indicated that transplantation of ASCs could reverse expression of aging-related biomarkers such as MDA, SOD, and advanced glycosylation end products (AGEs); hematoxylin and eosin (HE) staining showed that thickness of the dermis layer as well as the collagen content of mice in the D-galactose-induced model group increased significantly after ASC transplantation compared with that of control group. In addition, immunohistochemical assay showed that expression quantity of CD31 and vascular endothelial growth factor (VEGF) of mice in the D-galactose-induced model group increased significantly after ASC transplantation compared with that of control group. In conclusion, ASCs can trace cell distribution successfully through bioluminescence, and they survive for a short time in the skin after transplantation, which provides a basis for the application of ASC transplantation in clinical practices. Moreover, ASCs can control glycosylation level of D-galactose-induced skin aging of nude mice, reverse expression of aging-related biomarkers as well as restrain formation of advanced glycation end products, which are similar to the effects of AG inhibitors of advanced glycation end products. Thus, ASCs can prevent glycosylation-induced skin aging as well as recover functions of skin. © The Author(s) 2016.

AGEs Decreased SIRT3 Expression and SIRT3 Activation Protected AGEs-Induced EPCs' Dysfunction and Strengthened Anti-oxidant Capacity.

PubMed

Chang, Mingze; Zhang, Bei; Tian, Ye; Hu, Ming; Zhang, Gejuan; Di, Zhengli; Wang, Xinlai; Liu, Zhiqin; Gu, Naibin; Liu, Yong

2017-04-01

Advanced glycation end products (AGEs) have been confirmed to induce dysfunction in endothelial progenitor cells (EPCs) and play key roles in pathogenesis of diabetes-related vascular complications. The major function of sirtuin 3 (SIRT3) is to orchestrate oxidative metabolism and control reactive oxygen species (ROS) homeostasis, which are more closely related to EPCs' dysfunction. Our study therefore was designed to explore the role of SIRT3 on AGEs-induced EPCs dysfunction of. EPCs isolated from healthy adults were stimulated with AGEs and the expression of SIRT3 was assessed. Then, EPCs transfected with ad-SIRT3 or siRNA-SIRT3 were cultured with or without AGEs. EPCs function, including proliferation, migration; expression of manganese superoxide dismutase (MnSOD), ROS production, and interleukin-8 (IL-8); and vascular endothelial growth factor (VEGF) production were measured. In some experiments, EPCs were pre-cultured with anti-receptor for advanced glycation end products (RAGE) antibody or anti-neutralizing antibody, and then proliferation, migration, expression of MnSOD, ROS production, and IL-8 and VEGF production were measured. Our results showed that SIRT3 expressed in EPCs and AGEs decreased SIRT3 expression. SIRT3 knockdown with siRNA-SIRT3 promoted dysfunction in EPCs whereas SIRT3 activation with ad-SIRT3 strengthened anti-oxidant capacity and protected AGE-impaired dysfunction. Moreover, RAGE may involve in AGEs-decreased SIRT3 expression in EPCs. These data suggested an important role of SIRT3 in regulating EPCs bioactivity.

Regulation of Stem Cell Aging by Metabolism and Epigenetics.

PubMed

Ren, Ruotong; Ocampo, Alejandro; Liu, Guang-Hui; Izpisua Belmonte, Juan Carlos

2017-09-05

Stem cell aging and exhaustion are considered important drivers of organismal aging. Age-associated declines in stem cell function are characterized by metabolic and epigenetic changes. Understanding the mechanisms underlying these changes will likely reveal novel therapeutic targets for ameliorating age-associated phenotypes and for prolonging human healthspan. Recent studies have shown that metabolism plays an important role in regulating epigenetic modifications and that this regulation dramatically affects the aging process. This review focuses on current knowledge regarding the mechanisms of stem cell aging, and the links between cellular metabolism and epigenetic regulation. In addition, we discuss how these interactions sense and respond to environmental stress in order to maintain stem cell homeostasis, and how environmental stimuli regulate stem cell function. Additionally, we highlight recent advances in the development of therapeutic strategies to rejuvenate dysfunctional aged stem cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Cross-sectional and longitudinal relationship between neuroticism and cognitive ability in advanced old age: the moderating role of severe sensory impairment.

PubMed

Wettstein, Markus; Kuźma, Elżbieta; Wahl, Hans-Werner; Heyl, Vera

2016-09-01

Gaining a comprehensive picture of the network of constructs in which cognitive functioning is embedded is crucial across the full lifespan. With respect to personality, previous findings support a relationship between neuroticism and cognitive abilities. However, findings regarding old age are inconsistent. In particular, little is known about potentially moderating variables which might explain some of the inconsistency. Our aim was to examine the moderating effect of severe sensory impairment on cross-sectional and longitudinal associations between neuroticism and cognitive functioning. The study sample consisted of 121 visually impaired (VI), 116 hearing impaired (HI), and 150 sensory unimpaired older adults (UI). Mean age was 82.50 years (SD = 4.71 years). Neuroticism was assessed by the NEO Five Factor Inventory, and multiple established tests were used for the assessment of cognitive performance (e.g., subtests of the revised Wechsler Adult Intelligence Scale). Bivariate correlations and multi-group structural equation models indicated stronger relationships between cognitive abilities and neuroticism in both sensory impaired groups (VI and HI) compared to UI older individuals. This relationship was attenuated but still significant in both sensory impaired groups when controlling for age, education and health (number of chronic conditions). In cross-lagged panel models, higher baseline neuroticism was significantly associated with lower cognitive performance four years later in VI and HI individuals. Our results suggest that sensory impairment moderates both cross-sectional and longitudinal associations between neuroticism and cognitive function in advanced old age.

Using FLIM in the study of permeability barrier function of aged and young skin

NASA Astrophysics Data System (ADS)

Xu, P.; Choi, E. H.; Man, M. Q.; Crumrine, D.; Mauro, T.; Elias, P.

2006-02-01

Aged skin commonly is afflicted by inflammatory skin diseases or xerosis/eczema that can be triggered or exacerbated by impaired epidermal permeability barrier homeostasis. It has been previously described a permeability barrier defect in humans of advanced age (> 75 years), which in a murine analog >18 mos, could be attributed to reduced lipid synthesis synthesis. However, the functional abnormality in moderately aged mice is due not to decreased lipid synthesis, but rather to a specific defect in stratum corneum (SC) acidification causing impaired lipid processing processing. Endogenous Na +/H + antiporter (NHE1) level was found declined in moderately aged mouse epidermis. This acidification defect leads to perturbed permeability barrier homeostasis through more than one pathways, we addressed suboptimal activation of the essential, lipid-processing enzyme, β-glucocerebrosidase (BGC) is linked to elevated SC pH. Finally, the importance of the epidermis acidity is shown by the normalization of barrier function after exogenous acidification of moderately aged skin.

School-Aged Children Born Preterm: Review of Functioning across Multiple Domains and Guidelines for Assessment

ERIC Educational Resources Information Center

Dempsey, Allison G.; Keller-Margulis, Milena; Mire, Sarah; Abrahamson, Catherine; Dutt, Sonia; Llorens, Ashlie; Payan, Anita

2015-01-01

Children born preterm are at risk for developmental deficits across multiple functional domains. As the rate of survival for preterm infants increases due to medical advancements, a greater understanding is needed for how to meet the needs of this growing population in schools. Because approximately 50-70% of children born preterm require…

Development and Application of Advanced Ophthalmic Imaging Technology to Enhance Military Ocular Health Capabilities

DTIC Science & Technology

2009-04-01

active military personnel and veterans, are affected by three major blinding diseases of the retina and optic nerve: diabetic retinopathy , age-related...disease is detected early. New advanced detection methods are available, but are only interpretable by very experienced specialists. The goal of this...consist of several steps [1-3]: feature detection ; transform model estimation; optimization function design; and optimization strategies. We do not

Real-Time fMRI in Neuroscience Research and Its Use in Studying the Aging Brain

PubMed Central

Rana, Mohit; Varan, Andrew Q.; Davoudi, Anis; Cohen, Ronald A.; Sitaram, Ranganatha; Ebner, Natalie C.

2016-01-01

Cognitive decline is a major concern in the aging population. It is normative to experience some deterioration in cognitive abilities with advanced age such as related to memory performance, attention distraction to interference, task switching, and processing speed. However, intact cognitive functioning in old age is important for leading an independent day-to-day life. Thus, studying ways to counteract or delay the onset of cognitive decline in aging is crucial. The literature offers various explanations for the decline in cognitive performance in aging; among those are age-related gray and white matter atrophy, synaptic degeneration, blood flow reduction, neurochemical alterations, and change in connectivity patterns with advanced age. An emerging literature on neurofeedback and Brain Computer Interface (BCI) reports exciting results supporting the benefits of volitional modulation of brain activity on cognition and behavior. Neurofeedback studies based on real-time functional magnetic resonance imaging (rtfMRI) have shown behavioral changes in schizophrenia and behavioral benefits in nicotine addiction. This article integrates research on cognitive and brain aging with evidence of brain and behavioral modification due to rtfMRI neurofeedback. We offer a state-of-the-art description of the rtfMRI technique with an eye towards its application in aging. We present preliminary results of a feasibility study exploring the possibility of using rtfMRI to train older adults to volitionally control brain activity. Based on these first findings, we discuss possible implementations of rtfMRI neurofeedback as a novel technique to study and alleviate cognitive decline in healthy and pathological aging. PMID:27803662

The effects of advanced glycation end products (AGEs) on dermal wound healing and scar formation: a systematic review

PubMed Central

Van Putte, Lennert; De Schrijver, Sofie; Moortgat, Peter

2016-01-01

Introduction: With ageing, the skin gradually loses its youthful appearance and functions like wound healing and scar formation. The pathophysiological theory of Advanced Glycation End products (AGEs) has gained traction during the last decade. This review aims to document the influence of AGEs on the mechanical and physiologic properties of the skin, how they affect dermal wound healing and scar formation in high-AGE populations like elderly patients and diabetics, and potential therapeutic strategies. Methods: This systematic literature study involved a structured search in Pubmed and Web of Science with qualitative analysis of 14 articles after a three-staged selection process with the use of in- and exclusion criteria. Results: Overall, AGEs cause shortened, thinned, and disorganized collagen fibrils, consequently reducing elasticity and skin/scar thickness with increased contraction and delayed wound closure. Documented therapeutic strategies include dietary AGE restriction, sRAGE decoy receptors, aminoguanidine, RAGE-blocking antibodies, targeted therapy, thymosin β4, anti-oxidant agents and gold nanoparticles, ethyl pyruvate, Gal-3 manipulation and metformin. Discussion: With lack of evidence concerning scars, no definitive conclusions can yet be made about the role of AGEs on possible appearance or function of scar tissue. However, all results suggest that scars tend to be more rigid and contractile with persistent redness and reduced tendency towards hypertrophy as AGEs accumulate. Conclusion: Abundant evidence supports the pathologic role of AGEs in ageing and dermal wound healing and the effectiveness of possible therapeutic agents. More research is required to conclude its role in scar formation and scar therapy.

Learning a Foreign Language: A New Path to Enhancement of Cognitive Functions.

PubMed

Shoghi Javan, Sara; Ghonsooly, Behzad

2018-02-01

The complicated cognitive processes involved in natural (primary) bilingualism lead to significant cognitive development. Executive functions as a fundamental component of human cognition are deemed to be affected by language learning. To date, a large number of studies have investigated how natural (primary) bilingualism influences executive functions; however, the way acquired (secondary) bilingualism manipulates executive functions is poorly understood. To fill this gap, controlling for age, gender, IQ, and socio-economic status, the researchers compared 60 advanced learners of English as a foreign language (EFL) to 60 beginners on measures of executive functions involving Stroop, Wisconsin Card Sorting Task (WCST) and Wechsler's digit span tasks. The results suggested that mastering English as a foreign language causes considerable enhancement in two components of executive functions, namely cognitive flexibility and working memory. However, no significant difference was observed in inhibitory control between the advanced EFL learners and beginners.

Skin aging: molecular pathology, dermal remodelling and the imaging revolution.

PubMed

Newton, V L; Mcconnell, J C; Hibbert, S A; Graham, H K; Watson, R E

2015-12-01

Skin is a multifunctional organ but, alongside every other organ system, is subject to both intrinsic (chronological) and extrinsic (environmental) aging, resulting in a loss of functional capacity. Cutaneous aging manifests as an observable change in the external appearance of the skin, the major accelerator of the aging process being our interactions with our environment, such as chronic exposure to solar irradiation (UV, IR or visible wavelengths of light). The aim of this contribution, therefore, was to provide a review of the pathological mechanisms which may play roles in the development of extrinsic, mainly photo-, aging and to review how these molecular changes impact on the structure of the organ as a whole, resulting in loss of function. Finally, we will describe the advances which are occurring in imaging techniques which may allow further characterisation of aged skin.

Socioeconomic correlates of quality of life for non-Māori in advanced age: Te Puāwaitanga o Nga Tapuwae Kia ora Tonu. Life and Living in Advanced Age: a Cohort Study in New Zealand (LiLACS NZ).

PubMed

Kerse, Ngaire; Teh, Ruth; Moyes, Simon A; Dyall, Lorna; Wiles, Janine L; Kēpa, Mere; Wham, Carol; Hayman, Karen; Connolly, Martin; Wilkinson, Tim; Wright St Clair, Valerie; Keeling, Sally; Broad, Joanna; Jatrana, Santosh; Lumley, Thomas

2016-09-09

To establish socioeconomic and cultural profiles and correlates of quality of life (QoL) in non-Māori of advanced age. A cross sectional analysis of the baseline data of a cohort study of 516 non-Māori aged 85 years living in the Bay of Plenty and Rotorua areas of New Zealand. Socioeconomic and cultural characteristics were established by face-to-face interviews in 2010. Health-related QoL (HRQoL) was assessed with the SF-12. Of the 516 non-Māori participants enrolled in the study, 89% identified as New Zealand European, 10% other European, 1% were of Pacific, Asian or Middle Eastern ethnicity; 20% were born overseas and half of these identified as 'New Zealand European.' More men were married (59%) and more women lived alone (63%). While 89% owned their own home, 30% received only the New Zealand Superannuation as income and 22% reported that they had 'just enough to get along on'. More than 85% reported that they had sufficient practical and emotional support; 11% and 6% reported unmet need for practical and emotional support respectively. Multivariate analyses showed that those with unmet needs for practical and emotional support had lower mental HR QoL (p<0.005). Reporting that family were important to wellbeing was associated with higher mental HR QoL (p=0.038). Those that did not need practical help (p=0.047) and those that reported feeling comfortable with their money situation (0.0191) had higher physical HRQoL. High functional status was strongly associated with both high mental and high physical HR QoL (p<0.001). Among our sample of non-Māori people of advanced age, those with unmet support needs reported low HRQoL. Functional status was most strongly associated with mental and physical HRQoL.

Loss of Function of P2X7 Receptor Scavenger Activity in Aging Mice: A Novel Model for Investigating the Early Pathogenesis of Age-Related Macular Degeneration.

PubMed

Vessey, Kirstan A; Gu, Ben J; Jobling, Andrew I; Phipps, Joanna A; Greferath, Ursula; Tran, Mai X; Dixon, Michael A; Baird, Paul N; Guymer, Robyn H; Wiley, James S; Fletcher, Erica L

2017-08-01

Age-related macular degeneration (AMD) is a leading cause of irreversible, severe vision loss in Western countries. Recently, we identified a novel pathway involving P2X7 receptor scavenger function expressed on ocular immune cells as a risk factor for advanced AMD. In this study, we investigate the effect of loss of P2X7 receptor function on retinal structure and function during aging. P2X7-null and wild-type C57bl6J mice were investigated at 4, 12, and 18 months of age for macrophage phagocytosis activity, ocular histological changes, and retinal function. Phagocytosis activity of blood-borne macrophages decreased with age at 18 months in the wild-type mouse. Lack of P2X7 receptor function reduced phagocytosis at all ages compared to wild-type mice. At 12 months of age, P2X7-null mice had thickening of Bruchs membrane and retinal pigment epithelium dysfunction. By 18 months of age, P2X7-null mice displayed phenotypic characteristics consistent with early AMD, including Bruchs membrane thickening, retinal pigment epithelium cell loss, retinal functional deficits, and signs of subretinal inflammation. Our present study shows that loss of function of the P2X7 receptor in mice induces retinal changes representing characteristics of early AMD, providing a valuable model for investigating the role of scavenger receptor function and the immune system in the development of this age-related disease. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

A peripheral blood transcriptome biomarker test to diagnose functional recovery potential in advanced heart failure.

PubMed

Deng, Mario C

2018-05-08

Heart failure (HF) is a complex clinical syndrome that causes systemic hypoperfusion and failure to meet the body's metabolic demands. In an attempt to compensate, chronic upregulation of the sympathetic nervous system and renin-angiotensin-aldosterone leads to further myocardial injury, HF progression and reduced O 2 delivery. This triggers progressive organ dysfunction, immune system activation and profound metabolic derangements, creating a milieu similar to other chronic systemic diseases and presenting as advanced HF with severely limited prognosis. We hypothesize that 1-year survival in advanced HF is linked to functional recovery potential (FRP), a novel clinical composite parameter that includes HF severity, secondary organ dysfunction, co-morbidities, frailty, disabilities as well as chronological age and that can be diagnosed by a molecular biomarker.

Control of Maillard Reactions in Foods: Strategies and Chemical Mechanisms.

PubMed

Lund, Marianne N; Ray, Colin A

2017-06-14

Maillard reactions lead to changes in food color, organoleptic properties, protein functionality, and protein digestibility. Numerous different strategies for controlling Maillard reactions in foods have been attempted during the past decades. In this paper, recent advances in strategies for controlling the Maillard reaction and subsequent downstream reaction products in food systems are critically reviewed. The underlying mechanisms at play are presented, strengths and weaknesses of each strategy are discussed, and reasonable reaction mechanisms are proposed to reinforce the evaluations. The review includes strategies involving addition of functional ingredients, such as plant polyphenols and vitamins, as well as enzymes. The resulting trapping or modification of Maillard targets, reactive intermediates, and advanced glycation endproducts (AGEs) are presented with their potential unwanted side effects. Finally, recent advances in processing for control of Maillard reactions are discussed.

Advanced Glycation End Products: A Molecular Target for Vascular Complications in Diabetes.

PubMed

Yamagishi, Sho-Ichi; Nakamura, Nobutaka; Suematsu, Mika; Kaseda, Kuniyoshi; Matsui, Takanori

2015-10-27

A nonenzymatic reaction between reducing sugars and amino groups of proteins, lipids and nucleic acids contributes to the aging of macromolecules and subsequently alters their structural integrity and function. This process has been known to progress at an accelerated rate under hyperglycemic and/or oxidative stress conditions. Over a course of days to weeks, early glycation products undergo further reactions such as rearrangements and dehydration to become irreversibly cross-linked, fluorescent and senescent macroprotein derivatives termed advanced glycation end products (AGEs). There is a growing body of evidence indicating that interaction of AGEs with their receptor (RAGE) elicits oxidative stress generation and as a result evokes proliferative, inflammatory, thrombotic and fibrotic reactions in a variety of cells. This evidence supports AGEs' involvement in diabetes- and aging-associated disorders such as diabetic vascular complications, cancer, Alzheimer's disease and osteoporosis. Therefore, inhibition of AGE formation could be a novel molecular target for organ protection in diabetes. This report summarizes the pathophysiological role of AGEs in vascular complications in diabetes and discusses the potential clinical utility of measurement of serum levels of AGEs for evaluating organ damage in diabetes.

Physical Therapy for Neurological Conditions in Geriatric Populations.

PubMed

Carmeli, Eli

2017-01-01

With more of the world's population surviving longer, individuals often face age-related neurology disorders and decline of function that can affect lifestyle and well-being. Despite neurophysiological changes affecting the brain function and structure, the aged brain, in some degree, can learn and relearn due to neuroplasticity. Recent advances in rehabilitation techniques have produced better functional outcomes in age-related neurological conditions. Physical therapy (PT) of the elderly individual focuses in particular on sensory-motor impairments, postural control coordination, and prevention of sarcopenia. Geriatric PT has a significant influence on quality of life, independent living, and life expectancy. However, in many developed and developing countries, the profession of PT is underfunded and understaffed. This article provides a brief overview on (a) age-related disease of central nervous system and (b) the principles, approaches, and doctrines of motor skill learning and point out the most common treatment models that PTs use for neurological patients.

Physical Therapy for Neurological Conditions in Geriatric Populations

PubMed Central

Carmeli, Eli

2017-01-01

With more of the world’s population surviving longer, individuals often face age-related neurology disorders and decline of function that can affect lifestyle and well-being. Despite neurophysiological changes affecting the brain function and structure, the aged brain, in some degree, can learn and relearn due to neuroplasticity. Recent advances in rehabilitation techniques have produced better functional outcomes in age-related neurological conditions. Physical therapy (PT) of the elderly individual focuses in particular on sensory–motor impairments, postural control coordination, and prevention of sarcopenia. Geriatric PT has a significant influence on quality of life, independent living, and life expectancy. However, in many developed and developing countries, the profession of PT is underfunded and understaffed. This article provides a brief overview on (a) age-related disease of central nervous system and (b) the principles, approaches, and doctrines of motor skill learning and point out the most common treatment models that PTs use for neurological patients. PMID:29270402

Age-dependent changes at the blood-brain barrier. A Comparative structural and functional study in young adult and middle aged rats.

PubMed

Bors, Luca; Tóth, Kinga; Tóth, Estilla Zsófia; Bajza, Ágnes; Csorba, Attila; Szigeti, Krisztián; Máthé, Domokos; Perlaki, Gábor; Orsi, Gergely; Tóth, Gábor K; Erdő, Franciska

2018-05-01

Decreased beta-amyloid clearance in Alzheimer's disease and increased blood-brain barrier permeability in aged subjects have been reported in several articles. However, morphological and functional characterization of blood-brain barrier and its membrane transporter activity have not been described in physiological aging yet. The aim of our study was to explore the structural changes in the brain microvessels and possible functional alterations of P-glycoprotein at the blood-brain barrier with aging. Our approach included MR imaging for anatomical orientation in middle aged rats, electronmicroscopy and immunohistochemistry to analyse the alterations at cellular level, dual or triple-probe microdialysis and SPECT to test P-glycoprotein functionality in young and middle aged rats. Our results indicate that the thickness of basal lamina increases, the number of tight junctions decreases and the size of astrocyte endfeet extends with advanced age. On the basis of microdialysis and SPECT results the P-gp function is reduced in old rats. With our multiparametric approach a complex regulation can be suggested which includes elements leading to increased permeability of blood-brain barrier by enhanced paracellular and transcellular transport, and factors working against it. To verify the role of P-gp pumps in brain aging further studies are warranted. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Surgical management of patients with a history of early Le Fort III advancement after they have attained skeletal maturity.

PubMed

Caterson, E J; Shetye, Pradip R; Grayson, Barry H; McCarthy, Joseph G

2013-10-01

The classic Le Fort III procedure was recommended in syndromic craniosynostotic children to reduce exorbitism, improve airway function, and decrease dysmorphism. This study reports on a cohort of syndromic craniosynostosis patients who have undergone early primary subcranial (classic Tessier) Le Fort III advancement and who have been followed longitudinally through skeletal maturity and beyond. In this study, the Le Fort III advancements all occurred between the ages of 3 to 5 years, with a mean age of 4.6 years. Subsequently, these early Le Fort III patients were followed throughout development with longitudinal dental, medical, radiographic, and photographic evaluations conducted through skeletal maturity and beyond. For study inclusion, the patients had to have preoperative medical photographs and cephalometric studies at 6 months and 1, 5, and 10 years postoperatively after the primary Le Fort III advancement as well as cephalometric documentation 6 months and 1 year after the secondary midface advancement after skeletal maturity. After early or primary Le Fort III advancement, there was no evidence of relapse and only minimal anterior or horizontal postoperative growth of the midface. However, there was also a return of occlusal disharmony from "anticipated" mandibular growth, approaching a maximum at skeletal maturity. The dysmorphic concave facial profile and malocclusion, and airway and ocular considerations, provided the impetus for secondary midface surgery after skeletal maturity was attained. The data demonstrate that early Le Fort III advancement performed before the age of mixed dentition does not obviate the need for a secondary advancement after skeletal maturity is reached. Therapeutic, IV.

Atorvastatin prevents advanced glycation end products (AGEs)-induced cardiac fibrosis via activating peroxisome proliferator-activated receptor gamma (PPAR-γ).

PubMed

Chen, Miao; Li, Hongwei; Wang, Guoxing; Shen, Xuhua; Zhao, Shumei; Su, Wen

2016-04-01

Previous studies have shown that the activation of advanced glycation end products (AGEs) contributed to the cardiac fibrosis in diabetic patients. Although it had been reported that statins have beneficial effects on cardiac fibrosis in hypertension and myocardial ischemia models, their effects on AGEs models have not been studied. We aimed to investigate the effects of atorvastatin (Ator) on the AGEs-induced cardiac fibrosis both in vitro and vivo. Male Sprague-Dawley rats were randomly divided into four groups: Control, AGEs, Ator or AGEs+Ator. The cardiac function was evaluated with the echocardiography at the second and the third month. Fibrosis area, α-SMA and RAGE expression in cardiac tissue were measured. For in vitro study, rat cardiac fibroblasts were treated with PD98059 (ERK inhibitor), Ator or Ator+GW9662 (PPAR-γ antagonist), and then were stimulated with AGEs. Fibroblasts proliferation, ERK1/2, phosphorylated ERK1/2, α-SMA, and RAGE expression were studied. Compared with the control group, in vivo treatment with Ator significantly retarded the AGEs-induced diastolic function and attenuated cardiac fibrosis, α-SMA, and RAGE over expression induced by AGEs. Consistently, Ator prominently downregulated RAGE and α-SMA, while inhibited phosphorylation of ERK1/2 and fibroblast proliferation induced by AGEs in vitro. The GW9662 neutralized these effects of Ator on cardiac fibroblasts stimulated by AGEs. In this study, we demonstrated that AGEs-induced fibroblast proliferation and differentiation were dependent on AGEs-RAGE-ERK1/2 pathway and that atorvastatin could block this pathway via activating PPAR-γ. Copyright © 2016 Elsevier Inc. All rights reserved.

[Recent advances in anti-aging study of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucopyranoside--a main component of Polygonum multiflorum].

PubMed

Li, Yi-Han; Wang, Yue-Fei; Zhu, Yan

2016-01-01

Aging is an inevitable process of life caused by a combination of organs and tissues events which manifests as loss of structure and function. It is accompanied with organ hypofunction, decline in defense against stress and energy metabolism, and lots of age-related diseases. Therefore, it is critical to understand the mechanism of aging, as well as to discover new drugs to slow aging. Polygonum multiflorum has long been recognized in traditional Chinese medicine as anti-aging medicine. Interestingly, its extract has been shown to prolong lifespan in drosophila and elegans. Tetrahydroxystilbene glucoside (TSG), the main ingredient of P. multiflorum, shares a strong structural similarity with resveratrol, a well-known anti-aging natural product. This review summarized up-to-date literature reports and our laboratory findings on the mechanism of TSG anti-aging efficiency and function against age-related disease. It could provide reference for searching for anti-aging tradition Chinese medicine. Copyright© by the Chinese Pharmaceutical Association.

Subgroup effects of occupational therapy-based intervention for people with advanced cancer.

PubMed

Sampedro Pilegaard, Marc; Oestergaard, Lisa Gregersen; la Cour, Karen; Thit Johnsen, Anna; Brandt, Åse

2018-03-23

Many people with advanced cancer have decreased ability to perform activities of daily living (ADL). We recently performed a randomized, controlled trial (RCT) assessing the efficacy of an occupational therapy-based program, the 'Cancer Home-Life Intervention' in people with advanced cancer (N = 242) and found no overall effects on ADL ability. However, heterogeneity of treatment effect may disguise subgroup differences. To investigate whether subgroups of people with advanced cancer gain positive effects from the 'Cancer Home-Life Intervention' on ADL ability. An exploratory subgroup analysis including 191 participants from a RCT. The outcome was ADL motor ability measured by the Assessment of Motor and Process Skills (AMPS). Subgroups were defined by age, gender, years of education, type of primary tumor, functional level, and activity problems. The 'Cancer Home-Life Intervention' had no statistically significant effect in the six subgroups. Modifying effects of age (0.30 [95% CI: -0.05 to 0.64]) and gender (0.23 [95% CI: -0.11 to 0.57]) were not found. There were no subgroup effects of the 'Cancer Home-Life Intervention'on ADL motor ability. Some indications suggest greater effects for those aged below 69 years; however, this result should be interpreted with caution.

Modeling Longitudinal Changes in Older Adults’ Memory for Spoken Discourse: Findings from the ACTIVE Cohort

PubMed Central

Payne, Brennan R.; Gross, Alden L.; Parisi, Jeanine M.; Sisco, Shannon M.; Stine-Morrow, Elizabeth A. L.; Marsiske, Michael; Rebok, George W.

2014-01-01

Episodic memory shows substantial declines with advancing age, but research on longitudinal trajectories of spoken discourse memory (SDM) in older adulthood is limited. Using parallel process latent growth curve models, we examined 10 years of longitudinal data from the no-contact control group (N = 698) of the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) randomized controlled trial in order to test (a) the degree to which SDM declines with advancing age, (b) predictors of these age-related declines, and (c) the within-person relationship between longitudinal changes in SDM and longitudinal changes in fluid reasoning and verbal ability over 10 years, independent of age. Individuals who were younger, White, had more years of formal education, were male, and had better global cognitive function and episodic memory performance at baseline demonstrated greater levels of SDM on average. However, only age at baseline uniquely predicted longitudinal changes in SDM, such that declines accelerated with greater age. Independent of age, within-person decline in reasoning ability over the 10-year study period was substantially correlated with decline in SDM (r = .87). An analogous association with SDM did not hold for verbal ability. The findings suggest that longitudinal declines in fluid cognition are associated with reduced spoken language comprehension. Unlike findings from memory for written prose, preserved verbal ability may not protect against developmental declines in memory for speech. PMID:24304364

Ageing and the immune system: focus on macrophages.

PubMed

Linehan, E; Fitzgerald, D C

2015-03-01

A fully functioning immune system is essential in order to maintain good health. However, the immune system deteriorates with advancing age, and this contributes to increased susceptibility to infection, autoimmunity, and cancer in the older population. Progress has been made in identifying age-related defects in the adaptive immune system. In contrast, relatively little research has been carried out on the impact of ageing on the innate immune response. This area requires further research as the innate immune system plays a crucial role in protection against infection and represents a first line of defence. Macrophages are central effector cells of the innate immune system and have many diverse functions. As a result, age-related impairments in macrophage function are likely to have important consequences for the health of the older population. It has been reported that ageing in macrophages impacts on many processes including toll-like receptor signalling, polarisation, phagocytosis, and wound repair. A detailed understanding of the impact of ageing on macrophages is required in order to develop therapeutics that will boost immune responses in the older population.

Active Aging in Very Old Age and the Relevance of Psychological Aspects.

PubMed

Paúl, Constança; Teixeira, Laetitia; Ribeiro, Oscar

2017-01-01

Active aging encompasses a socially and individually designed mix of different domains that range from personal and familial, to social and professional. In being a key policy concept often focused on the young-old individuals, efforts in studying its dimensions in advanced ages have seldom been made. Nevertheless, there is a recognized need to promote adequate responses to the growing number of individuals reaching advanced ages and to recognize their specific dependability on health-related aspects, services attendance, social interactions, or on psychological characteristics for what it means to "age actively." This study provides a secondary analysis of data and follows the preceding work on the operationalization of the World Health Organization's (WHO) active aging model by means of an assessment protocol to measure which variables, within the model's determinants, contribute the most for an active aging process (1). Authors used the achieved model (composed by six factors: health, psychological component, cognitive performance, social relationships, biological component, and personality) and performed multi-group analysis of structural invariance to examine hypothetical differences between age groups (<75 years vs. ≥75 years) and to contrast obtained findings with the originally achieved model for the total sample (1,322 individuals aged 55 +). The structural covariances for the two age groups were statistically different. The comparison of components between age groups revealed a major relevance of the psychological component for the older age group. These findings reinforce the importance of psychological functioning in active aging in oldest old, and the need for further research on specific psychological features underlying the subjective meaning of active aging in more advanced ages.

[Perspectives of psychological aging research].

PubMed

Wahl, H-W; Diegelmann, M

2015-12-01

Psychological aging research (PAF) focuses on age-related changes and behavioral stability (e.g. structure of social relations), performance and competences (e.g. cognitive functioning) as well as experiences (e.g. well-being) in advanced age. Knowledge is based in particular on currently available longitudinal studies, which historically for the first time allow very long observational periods (nearly across the complete life span). Additionally, innovative statistical analytical methods co-developed in the PAF nowadays allow a better understanding of the dynamics of change than ever before. This results in a new picture of psychological aging that confirms the multifaceted strengths of human aging but also reveals new risks of the current "prolonged aging".

Age and mortality after injury: is the association linear?

PubMed

Friese, R S; Wynne, J; Joseph, B; Hashmi, A; Diven, C; Pandit, V; O'Keeffe, T; Zangbar, B; Kulvatunyou, N; Rhee, P

2014-10-01

Multiple studies have demonstrated a linear association between advancing age and mortality after injury. An inflection point, or an age at which outcomes begin to differ, has not been previously described. We hypothesized that the relationship between age and mortality after injury is non-linear and an inflection point exists. We performed a retrospective cohort analysis at our urban level I center from 2007 through 2009. All patients aged 65 years and older with the admission diagnosis of injury were included. Non-parametric logistic regression was used to identify the functional form between mortality and age. Multivariate logistic regression was utilized to explore the association between age and mortality. Age 65 years was used as the reference. Significance was defined as p < 0.05. A total of 1,107 patients were included in the analysis. One-third required intensive care unit (ICU) admission and 48 % had traumatic brain injury. 229 patients (20.6 %) were 84 years of age or older. The overall mortality was 7.2 %. Our model indicates that mortality is a quadratic function of age. After controlling for confounders, age is associated with mortality with a regression coefficient of 1.08 for the linear term (p = 0.02) and a regression coefficient of -0.006 for the quadratic term (p = 0.03). The model identified 84.4 years of age as the inflection point at which mortality rates begin to decline. The risk of death after injury varies linearly with age until 84 years. After 84 years of age, the mortality rates decline. These findings may reflect the varying severity of comorbidities and differences in baseline functional status in elderly trauma patients. Specifically, a proportion of our injured patient population less than 84 years old may be more frail, contributing to increased mortality after trauma, whereas a larger proportion of our injured patients over 84 years old, by virtue of reaching this advanced age, may, in fact, be less frail, contributing to less risk of death.

Epicatechin breaks preformed glycated serum albumin and reverses the retinal accumulation of advanced glycation end products.

PubMed

Kim, Junghyun; Kim, Chan-Sik; Moon, Min Kyong; Kim, Jin Sook

2015-02-05

The accumulation of advanced glycation end products (AGEs) is associated with many of the complications of diabetes mellitus, including diabetic retinopathy. AGE-breakers, such as N-phenacylthiazolium and alagebrium, have been proposed as therapeutic agents for reversing the increase in protein crosslinking in diabetes. (-)-Epicatechin is a major dietary flavonoid with a wide range of health-promoting biological activities. The aim of this study was to determine the potential effect of (-)-epicatechin in reducing the burden of AGEs in vitro and in vivo and to evaluate whether the reduced AGE burden could translate into improvement in retinal vascular function in exogenously AGE-injected rats. Glycated human serum albumin was purified from patients with diabetes. The breakdown of the already formed AGEs was studied by treating glycated human serum albumin with (-)-epicatechin. To study the effect of (-)-epicatechin on retinal vascular function, exogenously AGE-injected rats were treated with (-)-epicatechin (50 and 100 mg/kg i.p.) for two weeks. Apoptosis of retinal vascular cells was quantified using TUNEL staining. The AGE load in the retinas was determined via immunohistochemical staining and western blot analysis. (-)-Epicatechin was able to break preformed glycated human serum albumin in vitro as well as reduce AGE accumulation in retinas in vivo in a dose dependent manner. In exogenously AGE-injected rats, treatment with (-)-epicatechin was evidenced by an improved retinal vascular apoptosis. AGE burden in retinas was also reduced upon treatment. This study suggests that (-)-epicatechin could represent a valuable drug for the treatment of diabetic retinopathy by reducing the AGE burden. Copyright © 2014 Elsevier B.V. All rights reserved.

Ratio of serum levels of AGEs to soluble form of RAGE is a predictor of endothelial function.

PubMed

Kajikawa, Masato; Nakashima, Ayumu; Fujimura, Noritaka; Maruhashi, Tatsuya; Iwamoto, Yumiko; Iwamoto, Akimichi; Matsumoto, Takeshi; Oda, Nozomu; Hidaka, Takayuki; Kihara, Yasuki; Chayama, Kazuaki; Goto, Chikara; Aibara, Yoshiki; Noma, Kensuke; Takeuchi, Masayoshi; Matsui, Takanori; Yamagishi, Sho-Ichi; Higashi, Yukihito

2015-01-01

Advanced glycation end products (AGEs) and their specific receptor, the receptor for AGEs (RAGE), play an important role in atherosclerosis. Recently, a soluble form of RAGE (sRAGE) has been identified in human serum. However, the role of sRAGE in cardiovascular disease is still controversial. There is no information on the association between simultaneous measurements of AGEs and sRAGE and vascular function. In this study, we evaluated the associations between serum levels of AGEs and sRAGE, ratio of AGEs to sRAGE, and vascular function. We measured serum levels of AGEs and sRAGE and assessed vascular function by measurement of flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation in 110 subjects who underwent health examinations. Multivariate regression analyses were performed to identify factors associated with vascular function. Univariate regression analysis revealed that FMD correlated with age, BMI, systolic blood pressure, diastolic blood pressure, heart rate, triglycerides, HDL cholesterol, glucose, smoking pack-years, nitroglycerine-induced vasodilation, serum levels of AGEs and sRAGE, and ratio of AGEs to sRAGE. Multivariate analysis revealed that the ratio of AGEs to sRAGE remained an independent predictor of FMD, while serum level of AGEs alone or sRAGE alone was not associated with FMD. These findings suggest that sRAGE may have a counterregulatory mechanism that is activated to counteract the vasotoxic effect of the AGE-RAGE axis. The ratio of AGEs to sRAGE may be a new chemical biomarker of endothelial function. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Aging, metabolism and stem cells: Spotlight on muscle stem cells.

PubMed

García-Prat, Laura; Muñoz-Cánoves, Pura

2017-04-15

All tissues and organs undergo a progressive regenerative decline as they age. This decline has been mainly attributed to loss of stem cell number and/or function, and both stem cell-intrinsic changes and alterations in local niches and/or systemic environment over time are known to contribute to the stem cell aging phenotype. Advancing in the molecular understanding of the deterioration of stem cell cells with aging is key for targeting the specific causes of tissue regenerative dysfunction at advanced stages of life. Here, we revise exciting recent findings on why stem cells age and the consequences on tissue regeneration, with a special focus on regeneration of skeletal muscle. We also highlight newly identified common molecular pathways affecting diverse types of aging stem cells, such as altered proteostasis, metabolism, or senescence entry, and discuss the questions raised by these findings. Finally, we comment on emerging stem cell rejuvenation strategies, principally emanating from studies on muscle stem cells, which will surely burst tissue regeneration research for future benefit of the increasing human aging population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Docosahexaenoic Acid and Cognition throughout the Lifespan

PubMed Central

Weiser, Michael J.; Butt, Christopher M.; Mohajeri, M. Hasan

2016-01-01

Docosahexaenoic acid (DHA) is the predominant omega-3 (n-3) polyunsaturated fatty acid (PUFA) found in the brain and can affect neurological function by modulating signal transduction pathways, neurotransmission, neurogenesis, myelination, membrane receptor function, synaptic plasticity, neuroinflammation, membrane integrity and membrane organization. DHA is rapidly accumulated in the brain during gestation and early infancy, and the availability of DHA via transfer from maternal stores impacts the degree of DHA incorporation into neural tissues. The consumption of DHA leads to many positive physiological and behavioral effects, including those on cognition. Advanced cognitive function is uniquely human, and the optimal development and aging of cognitive abilities has profound impacts on quality of life, productivity, and advancement of society in general. However, the modern diet typically lacks appreciable amounts of DHA. Therefore, in modern populations, maintaining optimal levels of DHA in the brain throughout the lifespan likely requires obtaining preformed DHA via dietary or supplemental sources. In this review, we examine the role of DHA in optimal cognition during development, adulthood, and aging with a focus on human evidence and putative mechanisms of action. PMID:26901223

Advanced glycation end-products: Mechanics of aged collagen from molecule to tissue.

PubMed

Gautieri, Alfonso; Passini, Fabian S; Silván, Unai; Guizar-Sicairos, Manuel; Carimati, Giulia; Volpi, Piero; Moretti, Matteo; Schoenhuber, Herbert; Redaelli, Alberto; Berli, Martin; Snedeker, Jess G

2017-05-01

Concurrent with a progressive loss of regenerative capacity, connective tissue aging is characterized by a progressive accumulation of Advanced Glycation End-products (AGEs). Besides being part of the typical aging process, type II diabetics are particularly affected by AGE accumulation due to abnormally high levels of systemic glucose that increases the glycation rate of long-lived proteins such as collagen. Although AGEs are associated with a wide range of clinical disorders, the mechanisms by which AGEs contribute to connective tissue disease in aging and diabetes are still poorly understood. The present study harnesses advanced multiscale imaging techniques to characterize a widely employed in vitro model of ribose induced collagen aging and further benchmarks these data against experiments on native human tissues from donors of different age. These efforts yield unprecedented insight into the mechanical changes in collagen tissues across hierarchical scales from molecular, to fiber, to tissue-levels. We observed a linear increase in molecular spacing (from 1.45nm to 1.5nm) and a decrease in the D-period length (from 67.5nm to 67.1nm) in aged tissues, both using the ribose model of in vitro glycation and in native human probes. Multiscale mechanical analysis of in vitro glycated tendons strongly suggests that AGEs reduce tissue viscoelasticity by severely limiting fiber-fiber and fibril-fibril sliding. This study lays an important foundation for interpreting the functional and biological effects of AGEs in collagen connective tissues, by exploiting experimental models of AGEs crosslinking and benchmarking them for the first time against endogenous AGEs in native tissue. Copyright © 2016 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

PROCESS OF PHYSICAL DISABILITY AMONG OLDER ADULTS―CONTRIBUTION OF FRAILTY IN THE SUPER-AGED SOCIETY

PubMed Central

KUZUYA, MASAFUMI

2012-01-01

ABSTRACT One of the critical issues that Japan, well known for the world’s highest proportion of older adults, a super-aged society, is currently confronting is how to prevent physical disability in old age. This issue is particularly important not only from a medical perspective such as functional prognoses but also from a socio-economic angle in view of reducing the rapid rise in the cost of medical and long-term care insurance services. Functional decline in old age results not only from acute diseases but also from frailty. Such a common and important syndrome that is increasingly prevalent with advancing age can be the cause. The present article intends to review what is known about frailty, including its definition, epidemiology, and pathophysiology, and to examine potential areas of future research. PMID:22515109

Plasma Proteins Modified by Advanced Glycation End Products (AGEs) Reveal Site-specific Susceptibilities to Glycemic Control in Patients with Type 2 Diabetes.

PubMed

Greifenhagen, Uta; Frolov, Andrej; Blüher, Matthias; Hoffmann, Ralf

2016-04-29

Protein glycation refers to the reversible reaction between aldoses (or ketoses) and amino groups yielding relatively stable Amadori (or Heyns) products. Consecutive oxidative cleavage reactions of these products or the reaction of amino groups with other reactive substances (e.g. α-dicarbonyls) yield advanced glycation end products (AGEs) that can alter the structures and functions of proteins. AGEs have been identified in all organisms, and their contents appear to rise with some diseases, such as diabetes and obesity. Here, we report a pilot study using highly sensitive and specific proteomics approach to identify and quantify AGE modification sites in plasma proteins by reversed phase HPLC mass spectrometry in tryptic plasma digests. In total, 19 AGE modification sites corresponding to 11 proteins were identified in patients with type 2 diabetes mellitus under poor glycemic control. The modification degrees of 15 modification sites did not differ among cohorts of normoglycemic lean or obese and type 2 diabetes mellitus patients under good and poor glycemic control. The contents of two amide-AGEs in human serum albumin and apolipoprotein A-II were significantly higher in patients with poor glycemic control, although the plasma levels of both proteins were similar among all plasma samples. These two modification sites might be useful to predict long term, AGE-related complications in diabetic patients, such as impaired vision, increased arterial stiffness, or decreased kidney function. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Development of a cognitive function test using virtual reality technology: examination in healthy participants.

PubMed

Sakai, Hiromi; Nagano, Akinori; Seki, Keiko; Okahashi, Sayaka; Kojima, Maki; Luo, Zhiwei

2018-07-01

We developed a virtual reality test to assess the cognitive function of Japanese people in near-daily-life environment, namely, a virtual shopping test (VST). In this test, participants were asked to execute shopping tasks using touch panel operations in a "virtual shopping mall." We examined differences in VST performances among healthy participants of different ages and correlations between VST and screening tests, such as the Mini-Mental State Examination (MMSE) and Everyday Memory Checklist (EMC). We included 285 healthy participants between 20 and 86 years of age in seven age groups. Therefore, each VST index tended to decrease with advancing age; differences among age groups were significant. Most VST indices had a significantly negative correlation with MMSE and significantly positive correlation with EMC. VST may be useful for assessing general cognitive decline; effects of age must be considered for proper interpretation of the VST scores.

Social Relationships and Inflammatory Markers in the MIDUS Cohort.

PubMed

Elliot, Ari J; Heffner, Kathi L; Mooney, Christopher J; Moynihan, Jan A; Chapman, Benjamin P

2017-03-01

To better understand age and gender differences in associations of social relationships with chronic inflammation. Using a sample of middle-aged and older adults ( N = 963) from the Midlife Development in the United States (MIDUS) biomarker project, we examined interactions of age and gender with structural and functional social network measures in predicting interleukin-6 (IL-6) and C-reactive protein (CRP). Significant interactions involving age and gender showed that social support was associated with lower IL-6 in older women, whereas perceived positive relationships and social integration were related to lower IL-6 in both men and women of advanced age. Functional measures were associated with higher CRP in both men and women after adjustment for health conditions and behaviors, with some further variation by age. Greater social support may be related to lower IL-6 in older women. Further research is needed to understand observed associations of social support with higher CRP.

Glycation of H1 Histone by 3-Deoxyglucosone: Effects on Protein Structure and Generation of Different Advanced Glycation End Products

PubMed Central

Ashraf, Jalaluddin Mohammad; Rabbani, Gulam; Ahmad, Saheem; Hasan, Qambar; Khan, Rizwan Hasan; Alam, Khursheed; Choi, Inho

2015-01-01

Advanced glycation end products (AGEs) culminate from the non-enzymatic reaction between a free carbonyl group of a reducing sugar and free amino group of proteins. 3-deoxyglucosone (3-DG) is one of the dicarbonyl species that rapidly forms several protein-AGE complexes that are believed to be involved in the pathogenesis of several diseases, particularly diabetic complications. In this study, the generation of AGEs (Nε-carboxymethyl lysine and pentosidine) by 3-DG in H1 histone protein was characterized by evaluating extent of side chain modification (lysine and arginine) and formation of Amadori products as well as carbonyl contents using several physicochemical techniques. Results strongly suggested that 3-DG is a potent glycating agent that forms various intermediates and AGEs during glycation reactions and affects the secondary structure of the H1 protein. Structural changes and AGE formation may influence the function of H1 histone and compromise chromatin structures in cases of secondary diabetic complications. PMID:26121680

Developmental precursors of young school-age children's hostile attribution bias.

PubMed

Choe, Daniel Ewon; Lane, Jonathan D; Grabell, Adam S; Olson, Sheryl L

2013-12-01

This prospective longitudinal study provides evidence of preschool-age precursors of hostile attribution bias in young school-age children, a topic that has received little empirical attention. We examined multiple risk domains, including laboratory and observational assessments of children's social-cognition, general cognitive functioning, effortful control, and peer aggression. Preschoolers (N = 231) with a more advanced theory-of-mind, better emotion understanding, and higher IQ made fewer hostile attributions of intent in the early school years. Further exploration of these significant predictors revealed that only certain components of these capacities (i.e., nonstereotypical emotion understanding, false-belief explanation, and verbal IQ) were robust predictors of a hostile attribution bias in young school-age children and were especially strong predictors among children with more advanced effortful control. These relations were prospective in nature-the effects of preschool variables persisted after accounting for similar variables at school age. We conclude by discussing the implications of our findings for future research and prevention. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Unexpected Crosslinking and Diglycation as Advanced Glycation End-Products from Glyoxal

NASA Astrophysics Data System (ADS)

Lopez-Clavijo, Andrea F.; Duque-Daza, Carlos A.; Soulby, Andrew; Canelon, Isolda Romero; Barrow, Mark; O'Connor, Peter B.

2014-12-01

Glyoxal-derived advanced glycation end-products (AGEs) are formed in physiological systems affecting protein/peptide function and structure. These AGEs are generated during aging and chronic diseases such as diabetes and are considered arginine glycating agents. Thus, the study of glyoxal-derived AGEs in lysine residues and amino acid competition is addressed here using acetylated and non-acetylated undecapeptides, with one arginine and one lysine residue available for glycation. Tandem mass spectrometry results from a Fourier transform ion cyclotron resonance mass spectrometer showed glycated species at both the arginine and lysine residues. One species with the mass addition of 116.01096 Da is formed at the arginine residue. A possible structure is proposed to explain this finding (Nδ-[2-(dihydroxymethyl)-2H,3aH,4H,6aH-[1, 3]dioxolo[5,6-d]imidazolin-5-yl]-L-ornithine-derived AGE). The second species corresponded to intramolecular crosslink involving the lysine residue and its presence is checked with ion-mobility mass spectrometry.

Cognitive reserve and emotional stimuli in older individuals: level of education moderates the age-related positivity effect.

PubMed

Bruno, Davide; Brown, Adam D; Kapucu, Aycan; Marmar, Charles R; Pomara, Nunzio

2014-01-01

BACKGROUND/STUDY CONTEXT: A frequently observed age-related effect is a preference in older individuals for positive stimuli. The cognitive control model proposes that this positivity effect may be mediated by executive functions. We propose that cognitive reserve, operationally defined as years of education, which tempers cognitive decline and has been linked to executive functions, should also influence the age-related positivity effect, especially as age advances. An emotional free recall test was administered to a group of 84 cognitively intact individuals aged 60 to 88, who varied in years of education. As part of a larger test battery, data were obtained on measures of executive functioning and depression. Multiple regression and moderation analyses were performed, controlling for general cognitive function, severity of depressive symptoms, and executive function. In our data, years of education appeared to moderate the effect of age on the positivity effect; age was negatively associated with recall of positive words in participants with fewer years of education, whereas a nonsignificant positive correlation was observed between age and positivity in participants with more education. Cognitive reserve appears to play a role in explaining individual differences in the positivity effect in healthy older individuals. Future studies should investigate whether cognitive reserve is also implicated in the ability to process a wide range of emotional stimuli and whether greater reserve is reflected in improved emotional regulation.

Differential effects of Cdh23(753A) on auditory and vestibular functional aging in C57BL/6J mice.

PubMed

Mock, Bruce E; Vijayakumar, Sarath; Pierce, Jessica; Jones, Timothy A; Jones, Sherri M

2016-07-01

The C57BL/6J (B6) mouse strain carries a cadherin 23 mutation (Cdh23(753A), also known as Ahl), which affects inner ear structures and results in age-related hearing loss. The B6.CAST strain harbors the wild type Cdh23 gene, and hence, the influence of Ahl is absent. The purpose of the present study was to characterize the effect of age and gender on gravity receptor function in B6 and B6.CAST strains and to compare functional aging between auditory and vestibular modalities. Auditory sensitivity declined at significantly faster rates than gravity receptor sensitivity for both strains. Indeed, vestibular functional aging was minimal for both strains. The comparatively smaller loss of macular versus cochlear sensitivity in both the B6 and B6.CAST strains suggests that the contribution of Ahl to the aging of the vestibular system is minimal, and thus very different than its influence on aging of the auditory system. Alternatively, there exist unidentified genes or gene modifiers that serve to slow the degeneration of gravity receptor structures and maintain gravity receptor sensitivity into advanced age. Copyright © 2016 Elsevier Inc. All rights reserved.

Interactions between social/ behavioral factors and ADRB2 genotypes may be associated with health at advanced ages in China.

PubMed

Zeng, Yi; Cheng, Lingguo; Zhao, Ling; Tan, Qihua; Feng, Qiushi; Chen, Huashuai; Shen, Ke; Li, Jianxin; Zhang, Fengyu; Cao, Huiqing; Gregory, Simon G; Yang, Ze; Gu, Jun; Tao, Wei; Tian, Xiao-Li; Hauser, Elizabeth R

2013-09-09

Existing literature indicates that ADRB2 gene is associated with health and longevity, but none of previous studies investigated associations of carrying the ADRB2 minor alleles and interactions between ADRB2 genotypes and social/behavioral factors(GxE) with health outcomes at advanced ages. This study intends to fill in this research gap. We conducted an exploratory analysis, using longitudinal survey phenotype/genotype data from 877 oldest-old aged 90+. To estimate association of GxE interactions with health outcome, adjusted for the potential correlation between genotypes and social/behavioral factors and various other potentially confounding factors, we develop and test an innovative three-step procedure which combines logistic regression and structural equation methods. Interaction between regular exercise and carrying rs1042718 minor allele is significantly and positively associated with good cognitive function; interaction between regular exercise and carrying rs1042718 or rs1042719 minor allele is significantly and positively associated with self-reported good health; and interaction between social-leisure activities and carrying rs1042719 minor allele is significantly and positively associated with self-reported good health. Carrying rs1042718 or rs1042719 minor alleles is significantly and negatively associated with negative emotion, but the ADRB2 SNPs are not significantly associated with cognitive function and self-reported health. Our structural equation analysis found that, adjusted for the confounding effects of correlation of the ADRB2 SNPs with negative emotion, interaction between negative emotion and carrying rs1042718 or rs1042719 minor allele is significantly and negatively associated with cognitive function. The positive association of regular exercise and social-leisure activities with cognitive function and self-reported health, and negative association of negative emotion with cognitive function, were much stronger among carriers of rs1042718 or rs1042719 alleles, compared to the non-carriers. The results indicate significant positive associations of interactions between social/behavioral factors and the ADRB2 genotypes with health outcomes of cognitive function and self-reported health, and negative associations of carrying rs1042718 or rs1042719 minor alleles with negative emotion, at advanced ages in China. Our findings are exploratory rather than causal conclusions. This study implies that near-future health promotion programs considering individuals' genetic profiles, with appropriate protection of privacy/confidentiality, would yield increased benefits and reduced costs to the programs and their participants.

A Younger Dryas re-advance of local glaciers in north Greenland

NASA Astrophysics Data System (ADS)

Larsen, Nicolaj K.; Funder, Svend; Linge, Henriette; Möller, Per; Schomacker, Anders; Fabel, Derek; Xu, Sheng; Kjær, Kurt H.

2016-09-01

The Younger Dryas (YD) is a well-constrained cold event from 12,900 to 11,700 years ago but it remains unclear how the cooling and subsequent abrupt warming recorded in ice cores was translated into ice margin fluctuations in Greenland. Here we present 10Be surface exposure ages from three moraines in front of local glaciers on a 50 km stretch along the north coast of Greenland, facing the Arctic Ocean. Ten ages range from 11.6 ± 0.5 to 27.2 ± 0.9 ka with a mean age of 12.5 ± 0.7 ka after exclusion of two outliers. We consider this to be a minimum age for the abandonment of the moraines. The ages of the moraines are furthermore constrained using Optically Stimulated Luminescence (OSL) dating of epishelf sediments, which were deposited prior to the ice advance that formed the moraines, yielding a maximum age of 12.4 ± 0.6 ka, and bracketing the formation and subsequent abandonment of the moraines to within the interval 11.8-13.0 ka ago. This is the first time a synchronous YD glacier advance and subsequent retreat has been recorded for several independent glaciers in Greenland. In most other areas, there is no evidence for re-advance and glaciers were retreating during YD. We explain the different behaviour of the glaciers in northernmost Greenland as a function of their remoteness from the Atlantic Meridional Overturning Circulation (AMOC), which in other areas has been held responsible for modifying the YD drop in temperatures.

Dysregulation of the Bmi-1/p16Ink4a pathway provokes an aging-associated decline of submandibular gland function

PubMed Central

Yamakoshi, Kimi; Katano, Satoshi; Iida, Mayu; Kimura, Hiromi; Okuma, Atsushi; Ikemoto-Uezumi, Madoka; Ohtani, Naoko; Hara, Eiji; Maruyama, Mitsuo

2015-01-01

Bmi-1 prevents stem cell aging, at least partly, by blocking expression of the cyclin-dependent kinase inhibitor p16Ink4a. Therefore, dysregulation of the Bmi-1/p16Ink4a pathway is considered key to the loss of tissue homeostasis and development of associated degenerative diseases during aging. However, because Bmi-1 knockout (KO) mice die within 20 weeks after birth, it is difficult to determine exactly where and when dysregulation of the Bmi-1/p16Ink4a pathway occurs during aging in vivo. Using real-time in vivo imaging of p16Ink4a expression in Bmi-1-KO mice, we uncovered a novel function of the Bmi-1/p16Ink4a pathway in controlling homeostasis of the submandibular glands (SMGs), which secrete saliva into the oral cavity. This pathway is dysregulated during aging in vivo, leading to induction of p16Ink4a expression and subsequent declined SMG function. These findings will advance our understanding of the molecular mechanisms underlying the aging-related decline of SMG function and associated salivary gland hypofunction, which is particularly problematic among the elderly. PMID:25832744

Recent advances in the cell biology of aging.

PubMed

Hayflick, L

1980-01-01

Cultured normal human and animal cells are predestined to undergo irreversible functional decrements that mimic age changes in the whole organism. When normal human embryonic fibroblasts are cultured in vitro, 50 +/- 10 population doublings occur. This maximum potential is diminished in cells derived from older donors and appears to be inversely proportional to their age. The 50 population doubling limit can account for all cells produced during a lifetime. The limitation on doubling potential of cultured normal cells is also expressed in vivo when serial transplants are made. There may be a direct correlation between the mean maximum life spans of several species and the population doubling potential of their cultured cells. A plethora of functional decrements occurs in cultured normal cells as they approach their maximum division capability. Many of these decrements are similar to those occurring in intact animals as they age. We have concluded that these functional decrements expressed in vitro, rather than cessation of cell division, are the essential contributors to age changes in intact animals. Thus, the study of events leading to functional losses in cultured normal cells may provide useful insights into the biology of aging.

Ablation of toll-like receptor 4 attenuates aging-induced myocardial remodeling and contractile dysfunction through NCoRI-HDAC1-mediated regulation of autophagy.

PubMed

Wang, Shuyi; Ge, Wei; Harns, Carrie; Meng, Xianzhong; Zhang, Yingmei; Ren, Jun

2018-04-13

Aging is usually accompanied with overt structural and functional changes as well as suppressed autophagy in the heart although the precise regulatory mechanisms are somewhat unknown. Here we evaluated the role of the innate proinflammatory mediator toll-like receptor 4 (TLR4) in cardiac aging and the underlying mechanism with a focus on autophagy. Cardiac geometry and function were monitored in young or old wild-type (WT) and TLR4 knockout (TLR4 -/- ) mice using echocardiography, IonOptix® edge-detection and fura-2 techniques. Levels of autophagy and mitophagy, nuclear receptor corepressor 1 (NCoR1) and histone deacetylase I (HDAC1) were examined using western blot. Transmission electronic microscopy (TEM) was employed to monitor myocardial ultrastructure. Our results revealed that TLR4 ablation alleviated advanced aging (24 months)-induced changes in myocardial remodeling (increased heart weight, chamber size, cardiomyocyte cross-sectional area), contractile function and intracellular Ca 2+ handling as well as autophagy and mitophagy [Beclin-1, Atg5, LC3B, PTEN-induced putative kinase 1 (PINK1), Parkin and p62]. Aging downregulated levels of NCoR1 and HDAC1 as well as their interaction, the effects were significantly attenuated or negated by TLR4 ablation. Advanced aging disturbed myocardial ultrastructure as evidenced by loss of myofilament alignment and swollen mitochondria, which was obliterated by TLR4 ablation. Moreover, aging suppressed autophagy (GFP-LC3B puncta) in neonatal mouse cardiomyocytes, the effect of which was negated by the TLR4 inhibitor CLI-095. Inhibition of HDCA1 using apicidin cancelled off CLI095-induced beneficial response of GFP-LC3B puncta against aging. Our data collectively indicate a role for TLR4-mediated autophagy in cardiac remodeling and contractile dysfunction in aging through a HDAC1-NCoR1-dependent mechanism. Copyright © 2018 Elsevier Ltd. All rights reserved.

Aging with HIV-1 Infection: Motor Functions, Cognition, and Attention--A Comparison with Parkinson's Disease.

PubMed

DeVaughn, S; Müller-Oehring, E M; Markey, B; Brontë-Stewart, H M; Schulte, T

2015-12-01

Recent advances in highly active anti-retroviral therapy (HAART) in their various combinations have dramatically increased the life expectancies of HIV-infected persons. People diagnosed with HIV are living beyond the age of 50 but are experiencing the cumulative effects of HIV infection and aging on brain function. In HIV-infected aging individuals, the potential synergy between immunosenescence and HIV viral loads increases susceptibility to HIV-related brain injury and functional brain network degradation similar to that seen in Parkinson's disease (PD), the second most common neurodegenerative disorder in the aging population. Although there are clear diagnostic differences in the primary pathology of both diseases, i.e., death of dopamine-generating cells in the substantia nigra in PD and neuroinflammation in HIV, neurotoxicity to dopaminergic terminals in the basal ganglia (BG) has been implied in the pathogenesis of HIV and neuroinflammation in the pathogenesis of PD. Similar to PD, HIV infection affects structures of the BG, which are part of interconnected circuits including mesocorticolimbic pathways linking brainstem nuclei to BG and cortices subserving attention, cognitive control, and motor functions. The present review discusses the combined effects of aging and neuroinflammation in HIV individuals on cognition and motor function in comparison with age-related neurodegenerative processes in PD. Despite the many challenges, some HIV patients manage to age successfully, most likely by redistribution of neural network resources to enhance function, as occurs in healthy elderly; such compensation could be curtailed by emerging PD.

Age- and Sex-Related Influences on Left Ventricular Mechanics in Elderly Individuals Free of Prevalent Heart Failure: The ARIC Study (Atherosclerosis Risk in Communities).

PubMed

Hung, Chung-Lieh; Gonçalves, Alexandra; Shah, Amil M; Cheng, Susan; Kitzman, Dalane; Solomon, Scott D

2017-01-01

Advanced age is related to left ventricular (LV) remodeling. We sought to investigate the relationships between aging, elevated hemodynamic load, cardiac mechanics, and LV remodeling in an elderly community-based population. We studied 1105 subjects (76±5 years, 61% women) without prevalent heart failure, who attended the visit 5 of the ARIC study (Atherosclerosis Risk in Communities). LV global longitudinal strain, global circumferential strain, and torsion indices were analyzed using 3-dimensional echocardiography. Advanced age was associated with greater LV concentricity, lower myocardial diastolic relaxation, reduced global longitudinal strain (adjusted estimate, 0.39±0.19% (SE)/decade; P=0.038), borderline greater global circumferential strain (adjusted estimate, -0.59±0.36% (SE)/decade; P=0.08), and higher torsion indices (adjusted estimate for torsion, 0.33±0.04° (SE)/decade; P<0.001). In addition, greater concentricity was associated with decreased global longitudinal strain and greater torsion in multivariable models (all P<0.001). Women showed smaller LV cavity size, greater concentricity, lower myocardial relaxation velocity E', though demonstrated greater global longitudinal strain, global circumferential strain, and torsion than men (all P<0.05). Overall, subjects with hypertension and increasing age were more likely to have higher torsion, though the association between advanced age and greater torsion was more pronounced in women than in men (both interaction P<0.05). In an asymptomatic, senescent community-dwelling population, we observed a distinct, sex-specific pattern of cardiac remodeling. Although we observed worse diastolic and longitudinal function with advanced age or elevated load in both sexes, a significant increase of torsion was more pronounced in women. © 2017 American Heart Association, Inc.

Risk factors for competing noncancer mortality after definitive treatment for advanced-stage head and neck cancer.

PubMed

Kim, Yong Han; Roh, Jong-Lyel; Kim, Sung-Bae; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon

2018-05-27

Patients with head and neck cancer (HNC) can die of index tumor progression and second tumor or noncancer causes. Here, we investigated the risk factors for competing noncancer mortality (NCM) in a prospective cohort of patients with advanced-stage HNC. A prospective observational study was conducted with 604 patients who underwent definitive treatment for advanced-stage HNC between 2010 and 2015. Main outcomes were NCM and cancer mortality (CM) defined as death from noncancer causes and HNC or second cancers, respectively. Cumulative incidence and cause-specific hazard functions were used to analyze the risk factors of NCM and CM. Age, smoking, Charlson comorbidity index (CCI), performance status, body mass index, rural residence, education and hemoglobin level at diagnosis, and chemotherapy were significantly associated with NCM (all P<0.05). Multivariate analyses showed that age, CCI, and hemoglobin were independent factors of NCM. Age (≥65 years), CCI (≥2), and hemoglobin (<11 g/dL) were related to 4.5-, 3.2-, and 2.7-fold increased adjusted risk of NCM, respectively. Old age, comorbidity, and hemoglobin at diagnosis were independent predictors of NCM. The risk factors could be used to predict noncancer death after definitive treatment for advanced-stage HNC. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Changes in glomerular parietal epithelial cells in mouse kidneys with advanced age

PubMed Central

Roeder, Sebastian S.; Stefanska, Ania; Eng, Diana G.; Kaverina, Natalya; Sunseri, Maria W.; McNicholas, Bairbre A.; Rabinovitch, Peter; Engel, Felix B.; Daniel, Christoph; Amann, Kerstin; Lichtnekert, Julia; Pippin, Jeffrey W.

2015-01-01

Kidney aging is accompanied by characteristic changes in the glomerulus, but little is known about the effect of aging on glomerular parietal epithelial cells (PECs), nor if the characteristic glomerular changes in humans and rats also occur in very old mice. Accordingly, a descriptive analysis was undertaken in 27-mo-old C57B6 mice, considered advanced age. PEC density was significantly lower in older mice compared with young mice (aged 3 mo), and the decrease was more pronounced in juxtamedullary glomeruli compared with outer cortical glomeruli. In addition to segmental and global glomerulosclerosis in older mice, staining for matrix proteins collagen type IV and heparan sulfate proteoglycan were markedly increased in Bowman's capsules of older mouse glomeruli, consistent with increased extracellular matrix production by PECs. De novo staining for CD44, a marker of activated and profibrotic PECs, was significantly increased in aged glomeruli. CD44 staining was more pronounced in the juxtamedullary region and colocalized with phosphorylated ERK. Additionally, a subset of aged PECs de novo expressed the epithelial-to-mesenchymal transition markers α-smooth muscle and vimentin, with no changes in epithelial-to-mesenchymal transition markers E-cadherin and β-catenin. The mural cell markers neural/glial antigen 2, PDGF receptor-β, and CD146 as well as Notch 3 were also substantially increased in aged PECs. These data show that mice can be used to better understand the aging kidney and that PECs undergo substantial changes, especially in juxtamedullary glomeruli, that may participate in the overall decline in glomerular structure and function with advancing age. PMID:26017974

Follow-up of extreme neonatal hyperbilirubinaemia in 5- to 10-year-old children: a Danish population-based study.

PubMed

Vandborg, Pernille Kure; Hansen, Bo Moelholm; Greisen, Gorm; Mathiasen, Rene; Kasper, Frederikke; Ebbesen, Finn

2015-04-01

To investigate whether infants with neonatal hyperbilirubinaemia but without intermediate or advanced bilirubin encephalopathy develop long-term sequelae, with impairment of motor development, executive function, or hearing. This nested double-cohort study included 167 exposed children (107 males, 60 females) born in Denmark 2000 to 2005 at gestational age ≥35 weeks with a total serum bilirubin ≥450 μmol/L (26.3mg/dL) and 163 age-, sex-, and gestational age-matched unexposed children (103 males, 60 females). The children were examined at a mean age of 7.7 years (SD 1.7y) using the Movement Assessment Battery for Children-Second Edition (MABC-2), pure tone audiometry, and the Behavioural Regulation Inventory of Executive Function (BRIEF) questionnaire. The follow-up rate was 70% of the eligible infants in the exposed group and 45% in the unexposed group. Mean difference was -0.2 (95% confidence interval [CI] -1.1 to 0.8) in adjusted standard score for MABC-2 and 0.3 (95% CI -2.9 to 3.5) in adjusted BRIEF executive composite standard score. No children had significant hearing impairment or a diagnosis of cerebral palsy, attention-deficit-hyperactive disorder, or autism spectrum disorder recorded in national registries. No evidence was found of an increased risk of deficits in motor development, executive function, or hearing in children with extreme hyperbilirubinaemia who did not have intermediate or advanced bilirubin encephalopathy. © 2014 Mac Keith Press.

Recent and past musical activity predicts cognitive aging variability: direct comparison with general lifestyle activities.

PubMed

Hanna-Pladdy, Brenda; Gajewski, Byron

2012-01-01

Studies evaluating the impact of modifiable lifestyle factors on cognition offer potential insights into sources of cognitive aging variability. Recently, we reported an association between extent of musical instrumental practice throughout the life span (greater than 10 years) on preserved cognitive functioning in advanced age. These findings raise the question of whether there are training-induced brain changes in musicians that can transfer to non-musical cognitive abilities to allow for compensation of age-related cognitive declines. However, because of the relationship between engagement in general lifestyle activities and preserved cognition, it remains unclear whether these findings are specifically driven by musical training or the types of individuals likely to engage in greater activities in general. The current study controlled for general activity level in evaluating cognition between musicians and nomusicians. Also, the timing of engagement (age of acquisition, past versus recent) was assessed in predictive models of successful cognitive aging. Seventy age and education matched older musicians (>10 years) and non-musicians (ages 59-80) were evaluated on neuropsychological tests and general lifestyle activities. Musicians scored higher on tests of phonemic fluency, verbal working memory, verbal immediate recall, visuospatial judgment, and motor dexterity, but did not differ in other general leisure activities. Partition analyses were conducted on significant cognitive measures to determine aspects of musical training predictive of enhanced cognition. The first partition analysis revealed education best predicted visuospatial functions in musicians, followed by recent musical engagement which offset low education. In the second partition analysis, early age of musical acquisition (<9 years) predicted enhanced verbal working memory in musicians, while analyses for other measures were not predictive. Recent and past musical activity, but not general lifestyle activities, predicted variability across both verbal and visuospatial domains in aging. These findings are suggestive of different use-dependent adaptation periods depending on cognitive domain. Furthermore, they imply that early age of musical acquisition, sustained and maintained during advanced age, may enhance cognitive functions and buffer age and education influences.

Vascular Ageing and Exercise: Focus on Cellular Reparative Processes.

PubMed

Ross, Mark D; Malone, Eva; Florida-James, Geraint

2016-01-01

Ageing is associated with an increased risk of developing noncommunicable diseases (NCDs), such as diabetes and cardiovascular disease (CVD). The increased risk can be attributable to increased prolonged exposure to oxidative stress. Often, CVD is preceded by endothelial dysfunction, which carries with it a proatherothrombotic phenotype. Endothelial senescence and reduced production and release of nitric oxide (NO) are associated with "vascular ageing" and are often accompanied by a reduced ability for the body to repair vascular damage, termed "reendothelialization." Exercise has been repeatedly shown to confer protection against CVD and diabetes risk and incidence. Regular exercise promotes endothelial function and can prevent endothelial senescence, often through a reduction in oxidative stress. Recently, endothelial precursors, endothelial progenitor cells (EPC), have been shown to repair damaged endothelium, and reduced circulating number and/or function of these cells is associated with ageing. Exercise can modulate both number and function of these cells to promote endothelial homeostasis. In this review we look at the effects of advancing age on the endothelium and these endothelial precursors and how exercise appears to offset this "vascular ageing" process.

Self-reported optometric practise patterns in age-related macular degeneration.

PubMed

Ly, Angelica; Nivison-Smith, Lisa; Zangerl, Barbara; Assaad, Nagi; Kalloniatis, Michael

2017-11-01

The use of advanced imaging in clinical practice is emerging and the use of this technology by optometrists in assessing patients with age-related macular degeneration is of interest. Therefore, this study explored contemporary, self-reported patterns of practice regarding age-related macular degeneration diagnosis and management using a cross-sectional survey of optometrists in Australia and New Zealand. Practising optometrists were surveyed on four key areas, namely, demographics, clinical skills and experience, assessment and management of age-related macular degeneration. Questions pertaining to self-rated competency, knowledge and attitudes used a five-point Likert scale. Completed responses were received from 127 and 87 practising optometrists in Australia and New Zealand, respectively. Advanced imaging showed greater variation in service delivery than traditional techniques (such as slitlamp funduscopy) and trended toward optical coherence tomography, which was routinely performed in age-related macular degeneration by 49 per cent of respondents. Optical coherence tomography was also associated with higher self-rated competency, knowledge and perceived relevance to practice than other modalities. Most respondents (93 per cent) indicated that they regularly applied patient symptoms, case history, visual function results and signs from traditional testing, when queried about their management of patients with age-related macular degeneration. Over half (63 per cent) also considered advanced imaging, while 31 per cent additionally considered all of these as well as the disease stage and clinical guidelines. Contrary to the evidence base, 68 and 34 per cent rated nutritional supplements as highly relevant or relevant in early age-related macular degeneration and normal aging changes, respectively. These results highlight the emergence of multimodal and advanced imaging (especially optical coherence tomography) in the assessment of age-related macular degeneration by optometrists. Clinically significant variations in self-rated test competency and the understanding regarding nutritional supplements for different stages of age-related macular degeneration suggest that further work to up-skill optometrists may be required. © 2017 Optometry Australia.

The Moderating Effect of Chronological Age on the Relation Between Neuroticism and Physical Functioning: Cross-Sectional Evidence From Two French Samples.

PubMed

Canada, Brice; Stephan, Yannick; Jaconelli, Alban; Duberstein, Paul R

2016-01-01

Prior studies of age-restricted samples have demonstrated that, in older adulthood, neuroticism is negatively associated with difficulties performing specific daily activities. No studies of neuroticism and physical functioning have been conducted on life-span samples. This study tested the hypothesis that the relationship between neuroticism and physical functioning is stronger in older people compared with younger and middle-aged adults. Data were obtained from 2 independent French samples (n = 1,132 and 1,661 for Samples 1 and 2, respectively) ranging in age from 18 to 97. In addition to reporting sociodemographics, participants completed the Big Five Inventory, the physical functioning scale of the 36-Item Short Form Health Survey, and measures of disease burden. In both samples, regression analysis indicated that neuroticism is more negatively associated with physical functioning with advancing age, controlling for gender, marital status, disease burden, and educational attainment. In life-span samples of more than 2,700 adults, neuroticism was more strongly associated with worse physical functioning among older people compared with younger and middle-aged adults. Longitudinal research is needed to confirm this finding and to identify potential mediators. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Sociodemographic Characteristics and Health Profile of the Elderly Seeking Health Care in Kampala, Uganda

PubMed Central

Söderberg, Martin; Midlöv, Patrik; Ajambo, Aidah; Nakasujja, Noeline

2018-01-01

Aging entails health challenges globally, but pertinent data from low-income countries like Uganda remains scarce. A cross-sectional study was carried out at Mulago National Referral Hospital in Kampala, among 134 patients (38% men and 62% women) aged ≥60 years. Data was collected on sociodemographic characteristics, medical disorders, cognitive function, hearing handicap, and functional status, that is, Basic Activities of Daily Living (BADL) and Instrumental Activities of Daily Living (IADL). The participants had high independency in BADL (89%) and IADL (75%). The most common medical conditions were bone/joint pain (35%), hypertension (24%), and visual problems (20%). More women (54%) than men (37%) reported bone and joint pain. The majority (80%) of the participants did not report any hearing handicap, and half (54%) did not have any cognitive impairment. Dependency in IADL was associated with advanced age, being female, and being financially dependent, and the risk of having a hearing handicap was higher among those above the median age (68 years). In adjusted models, the effects remained similar although statistical significance was only achieved for advanced age versus dependency in IADL (RR: 2.38, 95% CI: 1.12–5.08) and hearing handicap (RR: 2.67, 95% CI: 1.17–6.12). Thus, socioeconomic status and gender are relevant aspects when attempting to understand the health profile of the elderly in Kampala, Uganda. PMID:29861722

Sociodemographic Characteristics and Health Profile of the Elderly Seeking Health Care in Kampala, Uganda.

PubMed

Nawagi, Faith; Söderberg, Martin; Berggren, Vanja; Midlöv, Patrik; Ajambo, Aidah; Nakasujja, Noeline

2018-01-01

Aging entails health challenges globally, but pertinent data from low-income countries like Uganda remains scarce. A cross-sectional study was carried out at Mulago National Referral Hospital in Kampala, among 134 patients (38% men and 62% women) aged ≥60 years. Data was collected on sociodemographic characteristics, medical disorders, cognitive function, hearing handicap, and functional status, that is, Basic Activities of Daily Living (BADL) and Instrumental Activities of Daily Living (IADL). The participants had high independency in BADL (89%) and IADL (75%). The most common medical conditions were bone/joint pain (35%), hypertension (24%), and visual problems (20%). More women (54%) than men (37%) reported bone and joint pain. The majority (80%) of the participants did not report any hearing handicap, and half (54%) did not have any cognitive impairment. Dependency in IADL was associated with advanced age, being female, and being financially dependent, and the risk of having a hearing handicap was higher among those above the median age (68 years). In adjusted models, the effects remained similar although statistical significance was only achieved for advanced age versus dependency in IADL (RR: 2.38, 95% CI: 1.12-5.08) and hearing handicap (RR: 2.67, 95% CI: 1.17-6.12). Thus, socioeconomic status and gender are relevant aspects when attempting to understand the health profile of the elderly in Kampala, Uganda.

ASRC Aerospace Corporation Selects Dynamically Reconfigurable Anadigm(Registered Trademark) FPAA For Advanced Data Acquisition System

NASA Technical Reports Server (NTRS)

Mata, Carlos T.

2003-01-01

Anadigm(registered trademark) today announced that ASRC Aerospace Corporation has designed Anadigm's dynamically reconfigurable Field Programmable Analog Array (FPAA) technology into an advanced data acquisition system developed under contract for NASA. ASRC Aerospace designed in the Anadigm(registered trademark) FPAA to provide complex analog signal conditioning in its intelligent, self-calibrating, and self-healing advanced data acquisition system (ADAS). The ADAS has potential applications in industrial, manufacturing, and aerospace markets. This system offers highly reliable operation while reducing the need for user interaction. Anadigm(registered trademark)'s dynamically reconfigurable FPAAs can be reconfigured in-system by the designer or on the fly by a microprocessor. A single device can thus be programmed to implement multiple analog functions and/or to adapt on-the-fly to maintain precision operation despite system degradation and aging. In the case of the ASRC advanced data acquisition system, the FPAA helps ensure that the system will continue to operating at 100% functionality despite changes in the environment, component degradation, and/or component failures.

'Tagging' along memories in aging: Synaptic tagging and capture mechanisms in the aged hippocampus.

PubMed

Shivarama Shetty, Mahesh; Sajikumar, Sreedharan

2017-05-01

Aging is accompanied by a general decline in the physiological functions of the body with the deteriorating organ systems. Brain is no exception to this and deficits in cognitive functions are quite common in advanced aging. Though a variety of age-related alterations are observed in the structure and function throughout the brain, certain regions show selective vulnerability. Medial temporal lobe, especially the hippocampus, is one such preferentially vulnerable region and is a crucial structure involved in the learning and long-term memory functions. Hippocampal synaptic plasticity, such as long-term potentiation (LTP) and depression (LTD), are candidate cellular correlates of learning and memory and alterations in these properties have been well documented in aging. A related phenomenon called synaptic tagging and capture (STC) has been proposed as a mechanism for cellular memory consolidation and to account for temporal association of memories. Mounting evidences from behavioral settings suggest that STC could be a physiological phenomenon. In this article, we review the recent data concerning STC and provide a framework for how alterations in STC-related mechanisms could contribute to the age-associated memory impairments. The enormity of impairment in learning and memory functions demands an understanding of age-associated memory deficits at the fundamental level given its impact in the everyday tasks, thereby in the quality of life. Such an understanding is also crucial for designing interventions and preventive measures for successful brain aging. Copyright © 2017 National University of Singapore. Published by Elsevier B.V. All rights reserved.

Advanced glycation end products and the progressive course of renal disease.

PubMed

Heidland, A; Sebekova, K; Schinzel, R

2001-10-01

In experimental and human diabetic nephropathy (DN), it has been shown that advanced glycation end products (AGEs), in particular, carboxymethyl-lysine and pentosidine, accumulate with malondialdehyde in glomerular lesions in relation to disease severity and in the presence of an upregulated receptor for AGE (RAGE) in podocytes. Toxic effects of AGEs result from structural and functional alterations in plasma and extracellular matrix (ECM) proteins, in particular, from cross-linking of proteins and interaction of AGEs with their receptors and/or binding proteins. In mesangial and endothelial cells, the AGE-RAGE interaction caused enhanced formation of oxygen radicals with subsequent activation of nuclear factor-kappaB and release of pro-inflammatory cytokines (interleukin-6, tumor necrosis factor-alpha), growth factors (transforming growth factor-beta1 [TGF-beta1], insulin-like growth factor-1), and adhesion molecules (vascular cell adhesion molecule-1, intercellular adhesion molecule-1). In tubular cells, incubation with AGE albumin was followed by stimulation of the mitogen-activating protein (MAP) kinase pathway and its downstream target, the activating protien-1 (AP-1) complex, TGF-beta1 overexpression, enhanced protein kinase C activity, decreased cell proliferation, and impaired protein degradation rate, in part caused by decreased cathepsin activities. The pathogenic relevance of AGEs was further verified by in vivo experiments in euglycemic rats and mice by the parenteral administration of AGE albumin, leading in the glomeruli to TGF-beta1 overproduction, enhanced gene expression of ECM proteins, and morphological lesions similar to those of DN. Evidence for the pathogenic relevance of AGEs in DN also comes from experimental studies in which the formation and/or action of AGEs was modulated by aminoguanidine, OPB-9195, pyridoxamine, soluble RAGEs, serine protease trypsin, and antioxidants, resulting in improved cell and/or renal function.

Disordered APP metabolism and neurovasculature in trauma and aging: Combined risks for chronic neurodegenerative disorders.

PubMed

Ikonomovic, Milos D; Mi, Zhiping; Abrahamson, Eric E

2017-03-01

Traumatic brain injury (TBI), advanced age, and cerebral vascular disease are factors conferring increased risk for late onset Alzheimer's disease (AD). These conditions are also related pathologically through multiple interacting mechanisms. The hallmark pathology of AD consists of pathological aggregates of amyloid-β (Aβ) peptides and tau proteins. These molecules are also involved in neuropathology of several other chronic neurodegenerative diseases, and are under intense investigation in the aftermath of TBI as potential contributors to the risk for developing AD and chronic traumatic encephalopathy (CTE). The pathology of TBI is complex and dependent on injury severity, age-at-injury, and length of time between injury and neuropathological evaluation. In addition, the mechanisms influencing pathology and recovery after TBI likely involve genetic/epigenetic factors as well as additional disorders or comorbid states related to age and central and peripheral vascular health. In this regard, dysfunction of the aging neurovascular system could be an important link between TBI and chronic neurodegenerative diseases, either as a precipitating event or related to accumulation of AD-like pathology which is amplified in the context of aging. Thus with advanced age and vascular dysfunction, TBI can trigger self-propagating cycles of neuronal injury, pathological protein aggregation, and synaptic loss resulting in chronic neurodegenerative disease. In this review we discuss evidence supporting TBI and aging as dual, interacting risk factors for AD, and the role of Aβ and cerebral vascular dysfunction in this relationship. Evidence is discussed that Aβ is involved in cyto- and synapto-toxicity after severe TBI, and that its chronic effects are potentiated by aging and impaired cerebral vascular function. From a therapeutic perspective, we emphasize that in the fields of TBI- and aging-related neurodegeneration protective strategies should include preservation of neurovascular function. Published by Elsevier B.V.

Executive functioning in healthy elderly Chinese people.

PubMed

Lin, Han; Chan, Raymond C K; Zheng, Liuning; Yang, Tianxiao; Wang, Ya

2007-05-01

This study aimed to explore the executive function of healthy elderly Chinese people. A sample of 58 healthy Chinese aged 60 and over was recruited from Guangzhou in China. They were divided into two age groups, a younger age group (aged 60-70) and an older age group (aged over 70). Executive function was measured by a battery of seven tests which were assumed to capture specific components of executive function. The tests were initiation (Hayling Sentence Completion Test (HSC)), sustained attention (Monotone Counting Test), switching and flexibility (word fluency and modified Wisconsin Card Sorting Test (WCST)), disinhibition (Modified Six Element Task (SET), Stroop Test, and HSC), attention allocation and planning (SET and modified version of WCST), and updating (Chinese Letter-Number Span). When independent neurocognitive tests were analyzed, there were significant age differences in the WCST (perseverative errors and category completed, p=0.025, 0.023) and the SET (raw score, p=0.050). The older age group tended to do worse in the total profile score of the SET and correct responses of the HSC Part A. However, when these tests were grouped into specific executive function components, a significant difference was found between the two groups in attention allocation and planning (p=0.007) and total component score (p=0.026). Regression analyses also indicated that age accounted for only very little variance of executive function in this narrow band of the elderly, whereas educational level accounted for a large part of the variance in initiation (R(2)=0.252, p<0.001), switching and flexibility (R(2)=0.211, p<0.001), and updating (R(2)=0.236, p<0.001) components of executive function. Our findings suggest that a significant decline in general executive functioning with advancing age was only evident in some putative tests in this sample. In addition, executive functions were selectively affected by older age, with attention location and planning and initiation being the components that were most affected.

Endothelial ischemia-reperfusion injury in humans: association with age and habitual exercise.

PubMed

Devan, Allison E; Umpierre, Daniel; Harrison, Michelle L; Lin, Hsin-Fu; Tarumi, Takashi; Renzi, Christopher P; Dhindsa, Mandeep; Hunter, Stacy D; Tanaka, Hirofumi

2011-03-01

Advancing age is a major risk factor for coronary artery disease. Endothelial dysfunction accompanied by increased oxidative stress and inflammation with aging may predispose older arteries to greater ischemia-reperfusion (I/R) injury. Because coronary artery ischemia cannot be induced safely, the effects of age and habitual endurance exercise on endothelial I/R injury have not been determined in humans. Using the brachial artery as a surrogate model of the coronary arteries, endothelial function, assessed by brachial artery flow-mediated dilation (FMD), was measured before and after 20 min of continuous forearm occlusion in young sedentary (n = 10, 24 ± 2 yr) and middle-aged (n = 9, 48 ± 2 yr) sedentary adults to gain insight into the effects of primary aging on endothelial I/R injury. Young (n = 9, 25 ± 1 yr) and middle-aged endurance-trained (n = 9, 50 ± 2 yr) adults were also studied to determine whether habitual exercise provides protection from I/R injury. Fifteen minutes after ischemic injury, FMD decreased significantly by 37% in young sedentary, 35% in young endurance-trained, 68% in middle-aged sedentary, and 50% in middle-aged endurance-trained subjects. FMD returned to baseline levels within 30 min in young sedentary and endurance-trained subjects but remained depressed in middle-aged sedentary and endurance-trained subjects. Circulating markers of antioxidant capacity and inflammation were not related to FMD. In conclusion, advancing age is associated with a greater magnitude and delayed recovery from endothelial I/R injury in humans. Habitual endurance exercise may provide partial protection to the endothelium against this form of I/R injury with advancing age.

In vivo and in vitro evidence that intrinsic upper- and lower-limb skeletal muscle function is unaffected by ageing and disuse in oldest-old humans.

PubMed

Venturelli, M; Saggin, P; Muti, E; Naro, F; Cancellara, L; Toniolo, L; Tarperi, C; Calabria, E; Richardson, R S; Reggiani, C; Schena, F

2015-09-01

To parse out the impact of advanced ageing and disuse on skeletal muscle function, we utilized both in vivo and in vitro techniques to comprehensively assess upper- and lower-limb muscle contractile properties in 8 young (YG; 25 ± 6 years) and 8 oldest-old mobile (OM; 87 ± 5 years) and 8 immobile (OI; 88 ± 4 years) women. In vivo, maximal voluntary contraction (MVC), electrically evoked resting twitch force (RT), and physiological cross-sectional area (PCSA) of the quadriceps and elbow flexors were assessed. Muscle biopsies of the vastus lateralis and biceps brachii facilitated the in vitro assessment of single fibre-specific tension (Po). In vivo, compared to the young, both the OM and OI exhibited a more pronounced loss of MVC in the lower limb [OM (-60%) and OI (-75%)] than the upper limb (OM = -51%; OI = -47%). Taking into account the reduction in muscle PCSA (OM = -10%; OI = -18%), only evident in the lower limb, by calculating voluntary muscle-specific force, the lower limb of the OI (-40%) was more compromised than the OM (-13%). However, in vivo, RT in both upper and lower limbs (approx. 9.8 N m cm(-2) ) and Po (approx. 123 mN mm(-2) ), assessed in vitro, implies preserved intrinsic contractile function in all muscles of the oldest-old and were well correlated (r = 0.81). These findings suggest that in the oldest-old, neither advanced ageing nor disuse, per se, impacts intrinsic skeletal muscle function, as assessed in vitro. However, in vivo, muscle function is attenuated by age and exacerbated by disuse, implicating factors other than skeletal muscle, such as neuromuscular control, in this diminution of function. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Extracellular matrix glycation and receptor for advanced glycation end-products activation: a missing piece in the puzzle of the association between diabetes and cancer.

PubMed

Rojas, Armando; Añazco, Carolina; González, Ileana; Araya, Paulina

2018-04-05

A growing body of epidemiologic evidence suggests that people with diabetes are at a significantly higher risk of many forms of cancer. However, the molecular mechanisms underlying this association are not fully understood. Cancer cells are surrounded by a complex milieu, also known as tumor microenvironment, which contributes to the development and metastasis of tumors. Of note, one of the major components of this niche is the extracellular matrix (ECM), which becomes highly disorganized during neoplastic progression, thereby stimulating cancer cell transformation, growth and spread. One of the consequences of chronic hyperglycemia, the most frequently observed sign of diabetes and the etiological source of diabetes complications, is the irreversible glycation and oxidation of proteins and lipids leading to the formation of the advanced glycation end-products (AGEs). These compounds may covalently crosslink and biochemically modify structure and functions of many proteins, and AGEs accumulation is particularly high in long-living proteins with low biological turnover, features that are shared by most, if not all, ECM proteins. AGEs-modified proteins are recognized by AGE-binding proteins, and thus glycated ECM components have the potential to trigger Receptor for advanced glycation end-products-dependent mechanisms. The biological consequence of receptor for advanced glycation end-products activation mechanisms seems to be connected, in different ways, to drive some hallmarks of cancer onset and tumor growth. The present review intends to highlight the potential impact of ECM glycation on tumor progression by triggering receptor for advanced glycation end-products-mediated mechanisms.

Expression Patterns of Odorant Receptors and Response Properties of Olfactory Sensory Neurons in Aged Mice

PubMed Central

Lee, Anderson C.; Tian, Huikai; Grosmaitre, Xavier

2009-01-01

The sense of smell deteriorates in normal aging, but the underling mechanisms are still elusive. Here we investigated age-related alterations in expression patterns of odorant receptor (OR) genes and functional properties of olfactory sensory neurons (OSNs)—2 critical factors that define the odor detection threshold in the olfactory epithelium. Using in situ hybridization for 9 representative OR genes, we compared the cell densities of each OR in coronal nose sections at different ages (3–27 months). The cell density for different ORs peaked at different time points and a decline was observed for 6 of 9 ORs at advanced ages. Using patch clamp recordings, we then examined the odorant responses of individual OSNs coexpressing a defined OR (MOR23) and green fluorescent protein. The MOR23 neurons recorded from aged animals maintained a similar sensitivity and dynamic range in response to the cognate odorant (lyral) as those from younger mice. The results indicate that although the cell densities of OSNs expressing certain types of ORs decline at advanced ages, individual OSNs can retain their sensitivity. The implications of these findings in age-related olfactory deterioration are discussed. PMID:19759360

Expression patterns of odorant receptors and response properties of olfactory sensory neurons in aged mice.

PubMed

Lee, Anderson C; Tian, Huikai; Grosmaitre, Xavier; Ma, Minghong

2009-10-01

The sense of smell deteriorates in normal aging, but the underling mechanisms are still elusive. Here we investigated age-related alterations in expression patterns of odorant receptor (OR) genes and functional properties of olfactory sensory neurons (OSNs)-2 critical factors that define the odor detection threshold in the olfactory epithelium. Using in situ hybridization for 9 representative OR genes, we compared the cell densities of each OR in coronal nose sections at different ages (3-27 months). The cell density for different ORs peaked at different time points and a decline was observed for 6 of 9 ORs at advanced ages. Using patch clamp recordings, we then examined the odorant responses of individual OSNs coexpressing a defined OR (MOR23) and green fluorescent protein. The MOR23 neurons recorded from aged animals maintained a similar sensitivity and dynamic range in response to the cognate odorant (lyral) as those from younger mice. The results indicate that although the cell densities of OSNs expressing certain types of ORs decline at advanced ages, individual OSNs can retain their sensitivity. The implications of these findings in age-related olfactory deterioration are discussed.

Arterial stiffness and decline of renal function in a primary care population.

PubMed

van Varik, Bernard J; Vossen, Liv M; Rennenberg, Roger J; Stoffers, Henri E; Kessels, Alfons G; de Leeuw, Peter W; Kroon, Abraham A

2017-01-01

Arterial stiffness is an important pathophysiological factor linking cardiovascular disease and kidney disease. Controversy exists as to whether arterial stiffness causes renal function decline, or kidney dysfunction leads to stiffening or whether the association is mutual. We aimed to investigate the longitudinal association between arterial stiffness and annual rate of renal function decline. We prospectively investigated in a primary care population whether carotid-femoral pulse wave velocity (PWV) was associated with estimated glomerular filtration rate (eGFR) and annual decline in eGFR in participants aged ⩾40 years without overt kidney disease. Baseline data on PWV and eGFR were available for 587 participants; follow-up measurements with a mean duration of 5.6 years were available for 222 patients. PWV, female gender and mean arterial pressure were independently associated with eGFR at baseline, although age confounded this association. More importantly, baseline PWV, age and eGFR were independent predictors of renal function decline. Stratification for age showed that the effect of PWV on rate of eGFR decline was amplified with advancing age. On the other hand, baseline eGFR did not determine annual change in PWV, suggesting a unidirectional association between arterial stiffness and eGFR. Arterial stiffness amplifies age-related renal function decline, suggesting that arterial stiffness plays a causal role in the development of renal damage, at least at later stages of age-related renal function decline, possibly through impaired renal autoregulation and increased arterial blood pressure pulsatility.

Aging in HIV-Infected Subjects: A New Scenario and a New View.

PubMed

Negredo, Eugenia; Back, David; Blanco, José-Ramón; Blanco, Julià; Erlandson, Kristine M; Garolera, Maite; Guaraldi, Giovanni; Mallon, Patrick; Moltó, José; Serra, José Antonio; Clotet, Bonaventura

2017-01-01

The prevalence of HIV-infected people aged 50 years or older is increasing rapidly; the proportion will increase from 28% to 73% in 2030. In addition, HIV-infected individuals may be more vulnerable to age-related condition. There is growing evidence that the prevalence of comorbidities and other age-related conditions (geriatric syndromes, functional or neurocognitive/mental problems, polypharmacy, and social difficulties) is higher in the HIV-infected population than in their uninfected counterparts. However, despite the potential impact of this situation on health care, little information exists about the optimal clinical management of older HIV-infected people. Here we examine the age-related conditions in older HIV-infected persons and address clinical management according to author expertise and published literature. Our aim is to advance the debate about the most appropriate management of this population, including less well-studied aspects, such as frequency of screening for psychological/mental and social and functional capabilities.

Sarcopenia and age-related changes in body composition and functional capacity.

PubMed

Evans, W J; Campbell, W W

1993-02-01

Advancing adult age is associated with profound changes in body composition. One of the most prominent of these changes is sarcopenia, defined as the age-related loss in skeletal muscle mass, which results in decreased strength and aerobic capacity and thus functional capacity. Sarcopenia is also closely linked to age-related losses in bone mineral, basal metabolic rate and increased body fat content. Through physical exercise and training, especially resistance training, it may be possible to prevent sarcopenia and the remarkable array of associated abnormalities, such as type II diabetes, coronary artery disease, hypertension, osteoporosis and obesity. Using an exercise program of sufficient frequency, intensity and duration, it is quite possible to increase muscle strength and endurance at any age. There is no pharmacological intervention that holds a greater promise of improving health and promoting independence in the elderly than does exercise.

Recent advances in calorie restriction research on aging.

PubMed

Chung, K W; Kim, D H; Park, M H; Choi, Y J; Kim, N D; Lee, J; Yu, B P; Chung, H Y

2013-10-01

The extension of both median and maximum lifespan and the suppression of age-related diseases in laboratory animals by reduced food intake, i.e., calorie restriction (CR) are regarded as hallmarks of CR's anti-aging action. The diverse efficacy of CR to counteract aging effects and its experimental reproducibility has made it the gold standard of many aging intervention studies of recent years. Although CR originally was used as a tool to perturb the aging process of laboratory animals as to uncover clues of underlying mechanisms of aging processes, current CR research interests have shifted to the retardation of aging-related functional decline and the prevention of age-related diseases. Advances in CR research on non-human primates and recent endeavors using human subjects offer a promising outlook for CR's beneficial effects in healthy human aging. In this review, several major issues related to CR's anti-aging mechanisms are discussed by highlighting the importance of modulating deleterious chronic inflammation at molecular levels and the impact of epigenetic chromatin and histone modifications by CR at the ultimate control sites of gene expression. The recent research on rapamycin as a CR mimetic is summarized and a brief description of intermittent feeding patterns is reviewed in comparison to the CR effect. Copyright © 2012 Elsevier Inc. All rights reserved.

Age and amyloid-related alterations in default network habituation to stimulus repetition

PubMed Central

Vannini, Patrizia; Hedden, Trey; Becker, John A.; Sullivan, Caroline; Putcha, Deepti; Rentz, Dorene; Johnson, Keith A.; Sperling, Reisa. A.

2011-01-01

The neural networks supporting encoding of new information are thought to decline with age, although mnemonic techniques such as repetition may enhance performance in older individuals. Accumulation of amyloid-β, one hallmark pathology of Alzheimer’s disease (AD), may contribute to functional alterations in memory networks measured with functional magnetic resonance imaging (fMRI) prior to onset of cognitive impairment. We investigated the effects of age and amyloid burden on fMRI activity in the default network and hippocampus during repetitive encoding. Older individuals, particularly those with high amyloid burden, demonstrated decreased task-induced deactivation in the posteromedial cortices during initial stimulus presentation and failed to modulate fMRI activity in response to repeated trials, whereas young subjects demonstrated a stepwise decrease in deactivation with repetition. The hippocampus demonstrated similar patterns across the groups, showing task-induced activity that decreased in response to repetition. These findings demonstrate that age and amyloid have dissociable functional effects on specific nodes within a distributed memory network, and suggest that functional brain changes may begin far in advance of symptomatic AD. PMID:21334099

Exercise counteracts declining hippocampal function in aging and Alzheimer's disease.

PubMed

Intlekofer, Karlie A; Cotman, Carl W

2013-09-01

Alzheimer's disease (AD) afflicts more than 5.4 million Americans and ranks as the most common type of dementia (Thies and Bleiler, 2011), yet effective pharmacological treatments have not been identified. Substantial evidence indicates that physical activity enhances learning and memory for people of all ages, including individuals that suffer from cognitive impairment. The mechanisms that underlie these benefits have been explored using animal models, including transgenic models of AD. Accumulating research shows that physical activity reinstates hippocampal function by enhancing the expression of brain-derived neurotrophic factor (BDNF) and other growth factors that promote neurogenesis, angiogenesis, and synaptic plasticity. In addition, several studies have found that physical activity counteracts age- and AD-associated declines in mitochondrial and immune system function. A growing body of evidence also suggests that exercise interventions hold the potential to reduce the pathological features associated with AD. Taken together, animal and human studies indicate that exercise provides a powerful stimulus that can countervail the molecular changes that underlie the progressive loss of hippocampal function in advanced age and AD. 2012 Published by Elsevier Inc

Influence of aging on human sound localization

PubMed Central

Dobreva, Marina S.; O'Neill, William E.

2011-01-01

Errors in sound localization, associated with age-related changes in peripheral and central auditory function, can pose threats to self and others in a commonly encountered environment such as a busy traffic intersection. This study aimed to quantify the accuracy and precision (repeatability) of free-field human sound localization as a function of advancing age. Head-fixed young, middle-aged, and elderly listeners localized band-passed targets using visually guided manual laser pointing in a darkened room. Targets were presented in the frontal field by a robotically controlled loudspeaker assembly hidden behind a screen. Broadband targets (0.1–20 kHz) activated all auditory spatial channels, whereas low-pass and high-pass targets selectively isolated interaural time and intensity difference cues (ITDs and IIDs) for azimuth and high-frequency spectral cues for elevation. In addition, to assess the upper frequency limit of ITD utilization across age groups more thoroughly, narrowband targets were presented at 250-Hz intervals from 250 Hz up to ∼2 kHz. Young subjects generally showed horizontal overestimation (overshoot) and vertical underestimation (undershoot) of auditory target location, and this effect varied with frequency band. Accuracy and/or precision worsened in older individuals for broadband, high-pass, and low-pass targets, reflective of peripheral but also central auditory aging. In addition, compared with young adults, middle-aged, and elderly listeners showed pronounced horizontal localization deficiencies (imprecision) for narrowband targets within 1,250–1,575 Hz, congruent with age-related central decline in auditory temporal processing. Findings underscore the distinct neural processing of the auditory spatial cues in sound localization and their selective deterioration with advancing age. PMID:21368004

Age-related functional brain changes in young children.

PubMed

Long, Xiangyu; Benischek, Alina; Dewey, Deborah; Lebel, Catherine

2017-07-15

Brain function and structure change significantly during the toddler and preschool years. However, most studies focus on older or younger children, so the specific nature of these changes is unclear. In the present study, we analyzed 77 functional magnetic resonance imaging datasets from 44 children aged 2-6 years. We extracted measures of both local (amplitude of low frequency fluctuation and regional homogeneity) and global (eigenvector centrality mapping) activity and connectivity, and examined their relationships with age using robust linear correlation analysis and strict control for head motion. Brain areas within the default mode network and the frontoparietal network, such as the middle frontal gyrus, the inferior parietal lobule and the posterior cingulate cortex, showed increases in local and global functional features with age. Several brain areas such as the superior parietal lobule and superior temporal gyrus presented opposite development trajectories of local and global functional features, suggesting a shifting connectivity framework in early childhood. This development of functional connectivity in early childhood likely underlies major advances in cognitive abilities, including language and development of theory of mind. These findings provide important insight into the development patterns of brain function during the preschool years, and lay the foundation for future studies of altered brain development in young children with brain disorders or injury. Copyright © 2017 Elsevier Inc. All rights reserved.

AMS+ALS: Kinetic and Product Studies of the Heterogeneous Oxidation of Organic Aerosol at the Advanced Light Source

NASA Astrophysics Data System (ADS)

Kroll, J. H.; Wilson, K. R.; Kessler, S. H.; Browne, E. C.; Nah, T.; Smith, J.; Worsnop, D. R.

2014-12-01

The atmospheric oxidation of condensed-phase organic species can have a major influence on the composition, properties, and impacts of organic aerosol (OA); however the rates and products of such "aging" reactions are poorly constrained. Here we describe a series of laboratory experiments aimed at better understanding one class of aging reactions, the heterogeneous oxidation of OA by gas-phase oxidants. Central to these experiments is the availability of vacuum ultraviolet (VUV) light at the Chemical Dynamics Beamline of the Advanced Light Source at LBNL, which enables the implementation of VUV photoionization aerosol mass spectrometry. This technique allows for the real-time, speciated measurement of OA composition, yielding molecular information that is highly complementary to ensemble data from electron-impact ionization. OA composition is measured with both ionization schemes as a function of oxidant exposure within a flow reactor, providing detailed information on the kinetics and products of heterogeneous oxidation over multiple generations of oxidation. Specific topics investigated include the branching between functionalization and fragmentation of OA components, the formation of secondary organic aerosol from photolytically-generated radical species, and the heterogeneous aging of soot-associated organic species.

Short Stature, Accelerated Bone Maturation, and Early Growth Cessation Due to Heterozygous Aggrecan Mutations

PubMed Central

Nilsson, Ola; Guo, Michael H.; Dunbar, Nancy; Popovic, Jadranka; Flynn, Daniel; Jacobsen, Christina; Lui, Julian C.; Hirschhorn, Joel N.; Baron, Jeffrey

2014-01-01

Context: Many children with idiopathic short stature have a delayed bone age. Idiopathic short stature with advanced bone age is far less common. Objective: The aim was to identify underlying genetic causes of short stature with advanced bone age. Setting and Design: We used whole-exome sequencing to study three families with autosomal-dominant short stature, advanced bone age, and premature growth cessation. Results: Affected individuals presented with short stature [adult heights −2.3 to −4.2 standard deviation scores (SDS)] with histories of early growth cessation or childhood short stature (height SDS −1.9 to −3.5 SDS), advancement of bone age, and normal endocrine evaluations. Whole-exome sequencing identified novel heterozygous variants in ACAN, which encodes aggrecan, a proteoglycan in the extracellular matrix of growth plate and other cartilaginous tissues. The variants were present in all affected, but in no unaffected, family members. In Family 1, a novel frameshift mutation in exon 3 (c.272delA) was identified, which is predicted to cause early truncation of the aggrecan protein. In Family 2, a base-pair substitution was found in a highly conserved location within a splice donor site (c.2026+1G>A), which is also likely to alter the amino acid sequence of a large portion of the protein. In Family 3, a missense variant (c.7064T>C) in exon 14 affects a highly conserved residue (L2355P) and is strongly predicted to perturb protein function. Conclusions: Our study demonstrates that heterozygous mutations in ACAN can cause a mild skeletal dysplasia, which presents clinically as short stature with advanced bone age. The accelerating effect on skeletal maturation has not previously been noted in the few prior reports of human ACAN mutations. Our findings thus expand the spectrum of ACAN defects and provide a new molecular genetic etiology for the unusual child who presents with short stature and accelerated skeletal maturation. PMID:24762113

The specific localization of advanced glycation end-products (AGEs) in rat pancreatic islets.

PubMed

Morioka, Yuta; Teshigawara, Kiyoshi; Tomono, Yasuko; Wang, Dengli; Izushi, Yasuhisa; Wake, Hidenori; Liu, Keyue; Takahashi, Hideo Kohka; Mori, Shuji; Nishibori, Masahiro

2017-08-01

Advanced glycation end-products (AGEs) are produced by non-enzymatic glycation between protein and reducing sugar such as glucose. Although glyceraldehyde-derived AGEs (Glycer-AGEs), one of the AGEs subspecies, have been reported to be involved in the pathogenesis of various age-relating diseases such as diabetes mellitus or arteriosclerosis, little is known about the pathological and physiological mechanism of AGEs in vivo. In present study, we produced 4 kinds of polyclonal antibodies against AGEs subspecies and investigated the localization of AGEs-modified proteins in rat peripheral tissues, making use of these antibodies. We found that Glycer-AGEs and methylglyoxal-derived AGEs (MGO-AGEs) were present in pancreatic islets of healthy rats, distinguished clearly into the pancreatic α and β cells, respectively. Although streptozotocin-induced diabetic rats suffered from remarkable impairment of pancreatic islets, the localization and deposit levels of the Glycer- and MGO-AGEs were not altered in the remaining α and β cells. Remarkably, the MGO-AGEs in pancreatic β cells were localized into the insulin-secretory granules. These results suggest that the cell-specific localization of AGEs-modified proteins are presence generally in healthy peripheral tissues, involved in physiological intracellular roles, such as a post-translational modulator contributing to the secretory and/or maturational functions of insulin. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Attachment to place in advanced age: A study of the LiLACS NZ cohort.

PubMed

Wiles, Janine L; Rolleston, Anna; Pillai, Avinesh; Broad, Joanna; Teh, Ruth; Gott, Merryn; Kerse, Ngaire

2017-07-01

An extensive body of research theorises that attachment to place is positively associated with health, particularly for older people. Building on this, we measure how indicators of attachment to place are associated with health for in people of advanced age in New Zealand. We use data from a cohort study (LiLACS NZ), which includes an indigenous Māori cohort aged 80-90 years and a non-Māori cohort aged 85 years from a mixed urban/rural region in New Zealand. Each cohort undertook a comprehensive interview and health assessment (n = 267 Māori and n = 404 non-Māori). Using multivariate regression analyses, we explore participants' feelings for and connectedness with their home, community and neighbourhood; nature and the outdoors; expectations about and enthusiasm for residential mobility; and how all these are associated with measures of health (e.g., SF-12 physical and mental health related quality of life) and functional status (e.g., NEADL). We demonstrate that people in advanced age hold strong feelings of attachment to place. We also establish some positive associations between attachment to place and health in advanced age, and show how these differ for the indigenous and non-indigenous cohorts. For older Māori there were strong associations between various health measures and the importance of nature and the outdoors, and connectedness to neighbourhood and community. For older non-Māori, there were strong associations between health and liking home and neighbourhood, and feeling connected to their community and neighbourhood. Place attachment, and particularly its relationship to health, operates in different ways for different groups. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chronobiology of the neuroimmunoendocrine system and aging.

PubMed

Mate, Ianire; Madrid, Juan Antonio; De la Fuente, Mónica

2014-01-01

The health maintenance depends on the preservation of the homeostatic systems, such as nervous, endocrine and immune system, and a proper communication between them. In this regard, the circadian system, which promotes a better physiological system functions and thus well being, could be considered part of that homeostatic complex, since the neuroimmunoendocrine system possesses circadian patterns in most variables, as well as circannual or seasonal variations. With aging, an impairment of the homeostatic systems occurs and an alteration of circadian system regulation has been demonstrated. In the immune system, several function parameters, which are good markers of health and of the rate of aging, change not only with age (immunosenescence) but also throughout the day and year. Indeed, with advancing age there is a modification of immune cell circadian function especially in lymphocytes. Moreover, immune functions at early afternoon correspond to more aged values than at morning, especially in mature subjects (60-79 years of age). In addition, these mature men and women showed a significant impaired immune cell function, which is especially remarkable in the winter. It is noteworthy the role of immunomodulatory hormones, such as melatonin, in the regulation of biological rhythms and their involvement in the aging process. Furthermore, the evidence of a neuroimmune regulation of the circadian system and its disturbance with aging, highlights the importance of proinflammatory cytokines in this complex cross-talk. The biological rhythms disruption with age and some diseases (jet lag, cancer and seasonal affective disorder), could contribute increasing the immune system impairment and consequently the loss of health.

Impairment of IGF-I Expression and Anabolic Signaling Following Ischemia/Reperfusion in Skeletal Muscle of Old Mice

DTIC Science & Technology

2011-04-01

has a role in the impaired recovery of skeletal muscle with age. Keywords Tourniquet; sarcopenia ; muscle regeneration; mTOR; FoxO Correspondence...Prescribed by ANSI Std Z39-18 INTRODUCTION Sarcopenia is the progressive decline in skeletal muscle mass and function with advanced aging (See Adamo...clinically-relevant problem. Considering the large proportion of orthopedic surgeries performed on elderly individuals, the extent of damage and subsequent

Dietary Advanced Glycation End Products and Cardiometabolic Risk.

PubMed

Luévano-Contreras, Claudia; Gómez-Ojeda, Armando; Macías-Cervantes, Maciste Habacuc; Garay-Sevilla, Ma Eugenia

2017-08-01

This report analyzes emerging evidence about the role of dietary advanced glycation end products (AGEs) as a cardiometabolic risk factor. Two important aspects are discussed: First, the modulation of AGE load by dietary AGEs; second, if the evidence of clinical and observational studies is enough to make dietary recommendations towards lowering AGE intake. Clinical studies in subjects with diabetes mellitus have shown that high intake of dietary AGEs increases inflammation markers, oxidative stress, and could impair endothelial function. In subjects at risk for cardiometabolic diseases (with overweight, obesity, or prediabetes), dietary AGE restriction decreases some inflammatory molecules and improves insulin sensitivity. However, studies in healthy subjects are limited, and not all of the studies have shown a decrease in circulating AGEs. Therefore, it is still unclear if dietary AGEs represent a health concern for people potentially at risk for cardiometabolic diseases. The evidence shows that dietary AGEs are bioavailable and absorbed, and the rate of excretion depends on dietary intake. The metabolic fate of most dietary AGEs remains unknown. Regardless, most studies have shown that by diminishing AGE intake, circulating levels will also decrease. Thus, dietary AGEs can modulate the AGE load at least in patients with DM, overweight, or obesity. Studies with specific clinical outcomes and large-scale observational studies are needed for a better risk assessment of dietary AGEs and to establish dietary recommendations accordingly.

Vascular ageing and interventions: lessons and learnings

PubMed Central

Williams, Bryan

2016-01-01

This review discusses the relationship between elevated blood pressure, hypertension, arterial stiffness and hence vascular ageing. This is a complex process and the majority of treatments target the consequences of this, rather than the pathophysiology of ageing itself. This is because preventing vascular ageing from occurring is complex and would require very early intervention and lifelong treatment. The process of arteriosclerosis is known to result from reversible and irreversible functional components, and, together, these are responsible for the increased systolic and decreased diastolic blood pressure seen with advancing age. Indeed, hypertension develops as it becomes more difficult for the heart to drive blood flow around the body, as a result of poor ventricular coupling and increased arterial stiffness. Elevated blood pressure is therefore a clinical manifestation of ageing that continues to increase with advancing years, and is also linked with an increased risk of cardiac, cerebrovascular and chronic kidney disease. These manifestations arise due to changing haemodynamics associated with ageing, and therefore treatments that reduce the development of these conditions or delay their progression have the potential to improve patient outcomes. This may be possible with existing therapies as well as new treatments currently under investigation. PMID:27102114

A preclinical cognitive test battery to parallel the National Institute of Health Toolbox in humans: bridging the translational gap.

PubMed

Snigdha, Shikha; Milgram, Norton W; Willis, Sherry L; Albert, Marylin; Weintraub, S; Fortin, Norbert J; Cotman, Carl W

2013-07-01

A major goal of animal research is to identify interventions that can promote successful aging and delay or reverse age-related cognitive decline in humans. Recent advances in standardizing cognitive assessment tools for humans have the potential to bring preclinical work closer to human research in aging and Alzheimer's disease. The National Institute of Health (NIH) has led an initiative to develop a comprehensive Toolbox for Neurologic Behavioral Function (NIH Toolbox) to evaluate cognitive, motor, sensory and emotional function for use in epidemiologic and clinical studies spanning 3 to 85 years of age. This paper aims to analyze the strengths and limitations of animal behavioral tests that can be used to parallel those in the NIH Toolbox. We conclude that there are several paradigms available to define a preclinical battery that parallels the NIH Toolbox. We also suggest areas in which new tests may benefit the development of a comprehensive preclinical test battery for assessment of cognitive function in animal models of aging and Alzheimer's disease. Copyright © 2013 Elsevier Inc. All rights reserved.

A preclinical cognitive test battery to parallel the National Institute of Health Toolbox in humans: bridging the translational gap

PubMed Central

Snigdha, Shikha; Milgram, Norton W.; Willis, Sherry L.; Albert, Marylin; Weintraub, S.; Fortin, Norbert J.; Cotman, Carl W.

2013-01-01

A major goal of animal research is to identify interventions that can promote successful aging and delay or reverse age-related cognitive decline in humans. Recent advances in standardizing cognitive assessment tools for humans have the potential to bring preclinical work closer to human research in aging and Alzheimer’s disease. The National Institute of Health (NIH) has led an initiative to develop a comprehensive Toolbox for Neurologic Behavioral Function (NIH Toolbox) to evaluate cognitive, motor, sensory and emotional function for use in epidemiologic and clinical studies spanning 3 to 85 years of age. This paper aims to analyze the strengths and limitations of animal behavioral tests that can be used to parallel those in the NIH Toolbox. We conclude that there are several paradigms available to define a preclinical battery that parallels the NIH Toolbox. We also suggest areas in which new tests may benefit the development of a comprehensive preclinical test battery for assessment of cognitive function in animal models of aging and Alzheimer’s disease. PMID:23434040

Strength of Structural and Functional Frontostriatal Connectivity Predicts Self-Control in the Healthy Elderly

PubMed Central

Hänggi, Jürgen; Lohrey, Corinna; Drobetz, Reinhard; Baetschmann, Hansruedi; Forstmeier, Simon; Maercker, Andreas; Jäncke, Lutz

2016-01-01

Self-regulation refers to the successful use of executive functions and initiation of top-down processes to control one's thoughts, behavior, and emotions, and it is crucial to perform self-control. Self-control is needed to overcome impulses and can be assessed by delay of gratification (DoG) and delay discounting (DD) paradigms. In children/adolescents, good DoG/DD ability depends on the maturity of frontostriatal connectivity, and its decline in strength with advancing age might adversely affect self-control because prefrontal brain regions are more prone to normal age-related atrophy than other regions. Here, we aimed at highlighting the relationship between frontostriatal connectivity strength and DoG performance in advanced age. We recruited 40 healthy elderly individuals (mean age 74.0 ± 7.7 years) and assessed the DoG ability using the German version of the DoG test for adults in addition to the delay discounting (DD) paradigm. Based on diffusion-weighted and resting-state functional magnetic resonance imaging data, respectively, the structural and functional whole-brain connectome were reconstructed based on 90 different brain regions of interest in addition to a 12-node frontostriatal DoG-specific network and the resulting connectivity matrices were subjected to network-based statistics. The 90-nodes whole-brain connectome analyses revealed subnetworks significantly associated with DoG and DD with a preponderance of frontostriatal nodes involved suggesting a high specificity of the findings. Structural and functional connectivity strengths between the putamen, caudate nucleus, and nucleus accumbens on the one hand and orbitofrontal, dorsal, and ventral lateral prefrontal cortices on the other hand showed strong positive correlations with DoG and negative correlations with DD corrected for age, sex, intracranial volume, and head motion parameters. These associations cannot be explained by differences in impulsivity and executive functioning. This pattern of correlations between structural or functional frontostriatal connectivity strength and self-control suggests that, in addition to the importance of the frontostriatal nodes itself, the structural and functional properties of different connections within the frontostriatal network are crucial for self-controlled behaviors in the healthy elderly. Because high DoG/low DD is a significant predictor of willpower and wellbeing in the elderly population, interventions aiming at strengthening frontostriatal connectivity to strengthen self-controlled behavior are needed in the future. PMID:28105013

When stem cells grow old: phenotypes and mechanisms of stem cell aging.

PubMed

Schultz, Michael B; Sinclair, David A

2016-01-01

All multicellular organisms undergo a decline in tissue and organ function as they age. An attractive theory is that a loss in stem cell number and/or activity over time causes this decline. In accordance with this theory, aging phenotypes have been described for stem cells of multiple tissues, including those of the hematopoietic system, intestine, muscle, brain, skin and germline. Here, we discuss recent advances in our understanding of why adult stem cells age and how this aging impacts diseases and lifespan. With this increased understanding, it is feasible to design and test interventions that delay stem cell aging and improve both health and lifespan. © 2016. Published by The Company of Biologists Ltd.

When stem cells grow old: phenotypes and mechanisms of stem cell aging

PubMed Central

Schultz, Michael B.; Sinclair, David A.

2016-01-01

All multicellular organisms undergo a decline in tissue and organ function as they age. An attractive theory is that a loss in stem cell number and/or activity over time causes this decline. In accordance with this theory, aging phenotypes have been described for stem cells of multiple tissues, including those of the hematopoietic system, intestine, muscle, brain, skin and germline. Here, we discuss recent advances in our understanding of why adult stem cells age and how this aging impacts diseases and lifespan. With this increased understanding, it is feasible to design and test interventions that delay stem cell aging and improve both health and lifespan. PMID:26732838

How can we utilize livers from advanced aged donors for liver transplantation for hepatitis C?

PubMed

Uemura, Tadahiro; Nikkel, Lucas E; Hollenbeak, Christopher S; Ramprasad, Varun; Schaefer, Eric; Kadry, Zakiyah

2012-06-01

Advanced age donors have inferior outcomes of liver transplantation for Hepatitis C (HCV). Aged donors grafts may be transplanted into young or low model for end stage liver disease (MELD) patients in order to offset the effect of donor age. However, it is not well understood how to utilize liver grafts from advanced aged donors for HCV patients. Using the UNOS database, we retrospectively studied 7508 HCV patients who underwent primary liver transplantation. Risk factors for graft failure and graft survival using advanced aged grafts (donor age ≥ 60 years) were analyzed by Cox hazards models, donor risk index (DRI) and organ patient index (OPI). Recipient's age did not affect on graft survival regardless of donor age. Advanced aged grafts had significant inferior survival compared to younger aged grafts regardless of MELD score (P < 0.0001). Risk factors of HCV patients receiving advanced aged grafts included donation after cardiac death (DCD, HR: 1.69) and recent hospitalization (HR: 1.43). Advanced aged grafts showed significant difference in graft survival of HCV patients with stratification of DRI and OPI. In conclusion, there was no offsetting effect by use of advanced aged grafts into younger or low MELD patients. Advanced aged grafts, especially DCD, should be judiciously used for HCV patients with low MELD score. © 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.

Expansions of NK-like αβT cells with chronologic aging: Novel lymphocyte effectors that compensate for functional deficits of conventional NK cells and T cells

PubMed Central

Vallejo, Abbe N.; Mueller, Robert G.; Hamel, David L.; Way, Amanda; Dvergsten, Jeffrey A.; Griffin, Patricia; Newman, Anne B.

2010-01-01

As the repertoire of αβT cell receptors (TCR) contracts with advancing age, there is an associated age-dependent accumulation of oligoclonal T cells expressing of a variety of receptors (NKR), normally expressed on natural killer (NK) cells. Evidences for differential regulation of expression of particular NKRs between T cells and NK cells suggest that NKR expression on T cells is physiologically programmed rather than a random event of the aging process. Experimental studies show NKRs on aged αβT cells may function either as independent receptors, and/or as costimulatory receptors to the TCR. Considering the reported deficits of conventional αβTCR-driven activation and also functional deficits of classical NK cells, NKR+ αβT cells likely represent novel immune effectors that are capable of combining innate and adaptive functions. Inasmuch as immunity is a determinant of individual fitness, the type and density of NKRs could be important contributing factors to the wide heterogeneity of health characteristics of older adults, ranging from institutionalized frail elders who are unable to mount immune responses to functionally independent community-dwelling elders who exhibit protective immunity. Understanding the biology of NKR+ αβT cells could lead to new avenues for age-specific intervention to improve protective immunity. PMID:20932941

Executive function in middle childhood and the relationship with theory of mind.

PubMed

Wilson, Jennifer; Andrews, Glenda; Hogan, Christy; Wang, Si; Shum, David H K

2018-01-01

A group of 126 typically developing children (aged 5-12 years) completed three cool executive function tasks (spatial working memory, stop signal, intra-extra dimensional shift), two hot executive function tasks (gambling, delay of gratification), one advanced theory of mind task (strange stories with high versus low affective tone), and a vocabulary test. Older children performed better than younger children, consistent with the protracted development of hot and cool executive functions and theory of mind. Multiple regression analyses showed that hot and cool executive functions were correlated but they predicted theory of mind in different ways.

Staying young at heart: autophagy and adaptation to cardiac aging.

PubMed

Leon, Leonardo J; Gustafsson, Åsa B

2016-06-01

Aging is a predominant risk factor for developing cardiovascular disease. Therefore, the cellular processes that contribute to aging are attractive targets for therapeutic interventions that can delay or prevent the development of age-related diseases. Our understanding of the underlying mechanisms that contribute to the decline in cell and tissue functions with age has greatly advanced over the past decade. Classical hallmarks of aging cells include increased levels of reactive oxygen species, DNA damage, accumulation of dysfunctional organelles, oxidized proteins and lipids. These all contribute to a progressive decline in the normal physiological function of the cell and to the onset of age-related conditions. A major cause of the aging process is progressive loss of cellular quality control. Autophagy is an important quality control pathway and is necessary to maintain cardiac homeostasis and to adapt to stress. A reduction in autophagy has been observed in a number of aging models and there is compelling evidence that enhanced autophagy delays aging and extends life span. Enhancing autophagy counteracts age-associated accumulation of protein aggregates and damaged organelles in cells. In this review, we discuss the functional role of autophagy in maintaining homeostasis in the heart, and how a decline is associated with accelerated cardiac aging. We also evaluate therapeutic approaches being researched in an effort to maintain a healthy young heart. Copyright © 2015 Elsevier Ltd. All rights reserved.

Therapeutic potential of nanoceria in regenerative medicine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Das, Soumen; Chigurupati, Srinivasulu; Dowding, Janet

Tissue engineering and regenerative medicine aim to achieve functional restoration of tissue or cells damaged through disease, aging or trauma. Advancement of tissue engineering requires innovation in the field of 3D scaffolding, and functionalization with bioactive molecules. Nanotechnology offers advanced materials with patterned nano-morphologies for cell growth and different molecular substrates which can support cell survival and functions. Cerium oxide nanoparticles (nanoceria) can control intracellular as well as extracellular reactive oxygen and nitrogen species. Recent findings suggest that nanoceria can enhance long-term cell survival, enable cell migration and proliferation, and promote stem cell differentiation. Moreover, the self-regenerative property of nanoceriamore » permits a small dose to remain catalytically active for extended time. This review summarizes the possibilities and applications of nanoceria in the field of tissue engineering and regenerative medicine.« less

Therapeutic Potential and Recent Advances of Curcumin in the Treatment of Aging-Associated Diseases.

PubMed

Sundar Dhilip Kumar, Sathish; Houreld, Nicolette Nadene; Abrahamse, Heidi

2018-04-05

Curcumin, a low molecular weight, lipophilic, major yellow natural polyphenolic, and the most well-known plant-derived compound, is extracted from the rhizomes of the turmeric ( Curcuma longa ) plant. Curcumin has been demonstrated as an effective therapeutic agent in traditional medicine for the treatment and prevention of different diseases. It has also shown a wide range of biological and pharmacological effects in drug delivery, and has actively been used for the treatment of aging-associated diseases, including cardiovascular diseases, atherosclerosis, neurodegenerative diseases, cancer, rheumatoid arthritis, ocular diseases, osteoporosis, diabetes, hypertension, chronic kidney diseases, chronic inflammation and infection. The functional application and therapeutic potential of curcumin in the treatment of aging-associated diseases is well documented in the literature. This review article focuses mainly on the potential role of plant-derived natural compounds such as curcumin, their mechanism of action and recent advances in the treatment of aging-associated diseases. Moreover, the review briefly recaps on the recent progress made in the preparation of nanocurcumins and their therapeutic potential in clinical research for the treatment of aging-associated diseases.

Nutritional Cognitive Neuroscience: Innovations for Healthy Brain Aging.

PubMed

Zamroziewicz, Marta K; Barbey, Aron K

2016-01-01

Nutritional cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand nutrition's impact on cognition and brain health across the life span. Research in this burgeoning field demonstrates that many aspects of nutrition-from entire diets to specific nutrients-affect brain structure and function, and therefore have profound implications for understanding the nature of healthy brain aging. The aim of this Focused Review is to examine recent advances in nutritional cognitive neuroscience, with an emphasis on methods that enable discovery of nutrient biomarkers that predict healthy brain aging. We propose an integrative framework that calls for the synthesis of research in nutritional epidemiology and cognitive neuroscience, incorporating: (i) methods for the precise characterization of nutritional health based on the analysis of nutrient biomarker patterns (NBPs), along with (ii) modern indices of brain health derived from high-resolution magnetic resonance imaging (MRI). By integrating cutting-edge techniques from nutritional epidemiology and cognitive neuroscience, nutritional cognitive neuroscience will continue to advance our understanding of the beneficial effects of nutrition on the aging brain and establish effective nutritional interventions to promote healthy brain aging.

GxE Interactions between FOXO Genotypes and Tea Drinking Are Significantly Associated with Cognitive Disability at Advanced Ages in China

PubMed Central

Zeng, Yi; Chen, Huashuai; Ni, Ting; Ruan, Rongping; Feng, Lei; Nie, Chao; Cheng, Lingguo; Li, Yang; Tao, Wei; Gu, Jun; Land, Kenneth C.; Yashin, Anatoli; Tan, Qihua; Yang, Ze; Bolund, Lars; Yang, Huanming; Hauser, Elizabeth; Willcox, D. Craig; Willcox, Bradley J.; Tian, Xiao-Li; Vaupel, James W.

2015-01-01

Logistic regression analysis based on data from 822 Han Chinese oldest old aged 92+ demonstrated that interactions between carrying FOXO1A-266 or FOXO3-310 or FOXO3-292 and tea drinking at around age 60 or at present time were significantly associated with lower risk of cognitive disability at advanced ages. Associations between tea drinking and reduced cognitive disability were much stronger among carriers of the genotypes of FOXO1A-266 or FOXO3-310 or FOXO3-292 compared with noncarriers, and it was reconfirmed by analysis of three-way interactions across FOXO genotypes, tea drinking at around age 60, and at present time. Based on prior findings from animal and human cell models, we postulate that intake of tea compounds may activate FOXO gene expression, which in turn may positively affect cognitive function in the oldest old population. Our empirical findings imply that the health benefits of particular nutritional interventions, including tea drinking, may, in part, depend upon individual genetic profiles. PMID:24895270

Nutritional Cognitive Neuroscience: Innovations for Healthy Brain Aging

PubMed Central

Zamroziewicz, Marta K.; Barbey, Aron K.

2016-01-01

Nutritional cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand nutrition's impact on cognition and brain health across the life span. Research in this burgeoning field demonstrates that many aspects of nutrition—from entire diets to specific nutrients—affect brain structure and function, and therefore have profound implications for understanding the nature of healthy brain aging. The aim of this Focused Review is to examine recent advances in nutritional cognitive neuroscience, with an emphasis on methods that enable discovery of nutrient biomarkers that predict healthy brain aging. We propose an integrative framework that calls for the synthesis of research in nutritional epidemiology and cognitive neuroscience, incorporating: (i) methods for the precise characterization of nutritional health based on the analysis of nutrient biomarker patterns (NBPs), along with (ii) modern indices of brain health derived from high-resolution magnetic resonance imaging (MRI). By integrating cutting-edge techniques from nutritional epidemiology and cognitive neuroscience, nutritional cognitive neuroscience will continue to advance our understanding of the beneficial effects of nutrition on the aging brain and establish effective nutritional interventions to promote healthy brain aging. PMID:27375409

Crosslink Density and Molecular Weight Effects on the Viscoelastic Response of a Glassy High-Performance Polyimide

NASA Technical Reports Server (NTRS)

Nicholson, Lee M.; Whitley, Karen S.; Gates, Thomas S.

2001-01-01

Durability and long-term performance are among the primary concerns for the use of advanced polymer matrix composites (PMCs) in modern aerospace structural applications. For a PMC subJected to long-term exposure at elevated temperatures. the viscoelastic nature of the polymer matrix will contribute to macroscopic changes in composite stiffness, strength and fatigue life. Over time. changes in the polymer due to physical aging will have profound effects on tile viscoelastic compliance of the material, hence affecting its long-term durability. Thus, the ability to predict material performance using intrinsic properties, such as crosslink density and molecular weight, would greatly enhance the efficiency of design and development of PMCs. The objective of this paper is to discuss and present the results of an experimental study that considers the effects of crosslink density, molecular weight and temperature on the viscoelastic behavior including physical aging of an advanced polymer. Five distinct variations in crosslink density were used to evaluate the differences in mechanical performance of an advanced polyimide. The physical aging behavior was isolated by conducting sequenced, short-term isothermal creep compliance tests in tension. These tests were performed over a range of sub-glass transition temperatures. The material constants, material master curves and physical aging-related parameters were evaluated as a function of temperature crosslink density and molecular weight using time-temperature and time-aging time superposition techniques.

Aging of the T cell compartment in mice and humans: from no naïve expectations to foggy memories

PubMed Central

Nikolich-Žugich, Janko

2014-01-01

Until the mid-20th century, infectious diseases were the major cause of morbidity and mortality in humans. Massive vaccination campaigns, antibiotics, antivirals and advanced public health measures drastically reduced sickness and death of infections in children and younger adults. Older adults (>65yr of age), however, remain vulnerable to infections, and to date infectious diseases remain amongst the top 5–10 causes of death in this population. The aging of the immune system, often referred to as immune senescence, is the key phenomenon underlying this vulnerability. This review centers on age-related changes in T cells, which are dramatically and reproducibly altered with aging. I will discuss changes in T cell production, maintenance, function and response to latent persistent infection, particularly against the cytomegalovirus (CMV), that exerts profound influence on the aging T cell pool, concluding with a brief list of measures to improve immune function in older adults. PMID:25193936

Aging and vascular endothelial function in humans

PubMed Central

SEALS, Douglas R.; JABLONSKI, Kristen L.; DONATO, Anthony J.

2012-01-01

Advancing age is the major risk factor for the development of CVD (cardiovascular diseases). This is attributable, in part, to the development of vascular endothelial dysfunction, as indicated by reduced peripheral artery EDD (endothelium-dependent dilation) in response to chemical [typically ACh (acetylcholine)] or mechanical (intravascular shear) stimuli. Reduced bioavailability of the endothelium-synthesized dilating molecule NO (nitric oxide) as a result of oxidative stress is the key mechanism mediating reduced EDD with aging. Vascular oxidative stress increases with age as a consequence of greater production of reactive oxygen species (e.g. superoxide) without a compensatory increase in antioxidant defences. Sources of increased superoxide production include up-regulation of the oxidant enzyme NADPH oxidase, uncoupling of the normally NO-producing enzyme, eNOS (endothelial NO synthase) (due to reduced availability of the cofactor tetrahydrobiopterin) and increased mitochondrial synthesis during oxidative phosphorylation. Increased bioactivity of the potent endothelial-derived constricting factor ET-1 (endothelin-1), reduced endothelial production of/responsiveness to dilatory prostaglandins, the development of vascular inflammation, formation of AGEs (advanced glycation end-products), an increased rate of endothelial apoptosis and reduced expression of oestrogen receptor α (in postmenopausal females) also probably contribute to impaired EDD with aging. Several lifestyle and biological factors modulate vascular endothelial function with aging, including regular aerobic exercise, dietary factors (e.g. processed compared with non-processed foods), body weight/fatness, vitamin D status, menopause/oestrogen deficiency and a number of conventional and non-conventional risk factors for CVD. Given the number of older adults now and in the future, more information is needed on effective strategies for the prevention and treatment of vascular endothelial aging. PMID:21244363

Skin autofluorescence is associated with renal function and cardiovascular diseases in pre-dialysis chronic kidney disease patients.

PubMed

Tanaka, Kenichi; Tani, Yoshihiro; Asai, Jun; Nemoto, Fumihiko; Kusano, Yuki; Suzuki, Hodaka; Hayashi, Yoshimitsu; Asahi, Koichi; Katoh, Tetsuo; Miyata, Toshio; Watanabe, Tsuyoshi

2011-01-01

Tissue accumulation of advanced glycation end-products (AGE) is thought to be a contributing factor to the progression of cardiovascular disease (CVD). Skin autofluorescence, a non-invasive measure of AGE accumulation using autofluorescence of the skin under ultraviolet light, has shown associations with CVD in haemodialysis patients. The present study aimed to evaluate relationships of skin autofluorescence to renal function as well as CVD in pre-dialysis patients with chronic kidney disease (CKD). Subjects in this cross-sectional analysis comprised 304 pre-dialysis CKD patients [median age, 62.0 years; median estimated glomerular filtration rate (eGFR), 54.3 mL/min/1.73 m(2); diabetes, n = 81 (26.6%)]. AGE accumulation in skin was assessed by skin autofluorescence using an autofluorescence reader. Relationships between skin autofluorescence, eGFR, CVD history and other parameters were evaluated. Skin autofluorescence correlated negatively with eGFR (r = -0.42, P < 0.01) and increased as CKD stage advanced. Multiple regression analysis revealed significant correlations of skin autofluorescence with age, presence of diabetes, eGFR and CVD history in CKD patients (R(2) = 30%). Age, male gender, smoking history, skin autofluorescence and eGFR were significantly correlated with CVD history, and multiple logistic regression analysis identified age [odds ratio (OR), 1.09; 95% confidence interval (CI), 1.03-1.15; P < 0.01], history of smoking (OR, 6.50; 95%CI, 1.94-21.83; P < 0.01) and skin autofluorescence (OR, 3.74; 95%CI, 1.54-9.24; P < 0.01) as independent factors. Tissue AGE accumulation measured as skin autofluorescence increased as GFR decreased and was related to CVD history in CKD patients. Non-invasive autofluorescence readers may provide potential markers for clinical risk assessment in pre-dialysis CKD patients.

Functional consequences of neurite orientation dispersion and density in humans across the adult lifespan.

PubMed

Nazeri, Arash; Chakravarty, M Mallar; Rotenberg, David J; Rajji, Tarek K; Rathi, Yogesh; Michailovich, Oleg V; Voineskos, Aristotle N

2015-01-28

As humans age, a characteristic pattern of widespread neocortical dendritic disruption coupled with compensatory effects in hippocampus and other subcortical structures is shown in postmortem investigations. It is now possible to address age-related effects on gray matter (GM) neuritic organization and density in humans using multishell diffusion-weighted MRI and the neurite-orientation dispersion and density imaging (NODDI) model. In 45 healthy individuals across the adult lifespan (21-84 years), we used a multishell diffusion imaging and the NODDI model to assess the intraneurite volume fraction and neurite orientation-dispersion index (ODI) in GM tissues. We also determined the functional correlates of variations in GM microstructure by obtaining resting-state fMRI and behavioral data. We found a significant age-related deficit in neocortical ODI (most prominently in frontoparietal regions), whereas increased ODI was observed in hippocampus and cerebellum with advancing age. Neocortical ODI outperformed cortical thickness and white matter fractional anisotropy for the prediction of chronological age in the same individuals. Higher GM ODI sampled from resting-state networks with known age-related susceptibility (default mode and visual association networks) was associated with increased functional connectivity of these networks, whereas the task-positive networks tended to show no association or even decreased connectivity. Frontal pole ODI mediated the negative relationship of age with executive function, whereas hippocampal ODI mediated the positive relationship of age with executive function. Our in vivo findings align very closely with the postmortem data and provide evidence for vulnerability and compensatory neural mechanisms of aging in GM microstructure that have functional and cognitive impact in vivo. Copyright © 2015 the authors 0270-6474/15/351753-10$15.00/0.

Role of oxidants/inflammation in declining renal function in chronic kidney disease and normal aging.

PubMed

Vlassara, Helen; Torreggiani, Massimo; Post, James B; Zheng, Feng; Uribarri, Jaime; Striker, Gary E

2009-12-01

Oxidant stress (OS) and inflammation increase in normal aging and in chronic kidney disease (CKD), as observed in human and animal studies. In cross-sectional studies of the US population, these changes are associated with a decrease in renal function, which is exhibited by a significant proportion of the population. However, since many normal adults have intact renal function, and longitudinal studies show that some persons maintain normal renal function with age, the link between OS, inflammation, and renal decline is not clear. In aging mice, greater oxidant intake is associated with increased age-related CKD and mortality, which suggests that interventions that reduce OS and inflammation may be beneficial for older individuals. Both OS and inflammation can be readily lowered in normal subjects and patients with CKD stage 3-4 by a simple dietary modification that lowers intake and results in reduced serum and tissue levels of advanced glycation end products. Diabetic patients, including those with microalbuminuria, have a decreased ability to metabolize and excrete oxidants prior to observable changes in serum creatinine. Thus, OS and inflammation may occur in the diabetic kidney at an early time. We review the evidence that oxidants in the diet directly lead to increased serum levels of OS and inflammatory mediators in normal aging and in CKD. We also discuss a simple dietary intervention that helps reduce OS and inflammation, an important and achievable therapeutic goal for patients with CKD and aging individuals with reduced renal function.

Dopaminergic Functioning and Preschoolers' Theory of Mind

ERIC Educational Resources Information Center

Lackner, Christine L.; Bowman, Lindsay C.; Sabbagh, Mark A.

2010-01-01

Representational theory of mind (RTM) development follows a universal developmental timetable whereby major advances in reasoning about mental representations occur between the ages of 3 and 5 years old. This progression appears to be only absent in the case of specific neurodevelopmental impairments, such as autism. Taken together, this suggests…

A New Interactive Method to Distance English Learning in Conceptual Age

ERIC Educational Resources Information Center

Xu, Wei

2013-01-01

Latest advance in information technology and innovative teaching confronts DEL (distance English learning) with new challenges and problems. According to the DEL analysis, the paper firstly presents cloud service's functions to the support service, which serves to distribute and store quality learning resources. Meanwhile, practice-focused…

Genetic and environmental models of circadian disruption link SRC-2 function to hepatic pathology

USDA-ARS?s Scientific Manuscript database

Circadian rhythmicity is a fundamental process that synchronizes behavioral cues with metabolic homeostasis. Disruption of daily cycles due to jet lag or shift work results in severe physiological consequences including advanced aging, metabolic syndrome, and even cancer. Our understanding of the mo...

Gene expression changes in male accessory glands during ageing are accompanied by reproductive decline in Drosophila melanogaster.

PubMed

Koppik, Mareike; Fricke, Claudia

2017-12-01

Senescence is accompanied by loss of reproductive functions. Here, we studied reproductive ageing in Drosophila melanogaster males and asked whether the expected decline in male reproductive success is due to diminished functionality of the male accessory gland (AG). The male AG produces the majority of seminal fluid proteins (SFPs) transferred to the female at mating. SFPs induce female postmating changes and are key to male reproductive success. We measured age-dependent gene expression changes for five representative SFP genes in males from four different age groups ranging from 1 to 6 weeks after eclosion. Simultaneously, we also measured male reproductive success in postmating traits mediated by transfer of these five SFPs. We found a decreased in male SFP gene expression with advancing age and an accompanying decline in male postmating success. Hence, male reproductive senescence is associated with a decline in functionality of the male AG. While overall individual SFP genes decreased in expression, our results point towards the idea that the composition of an ejaculate might change with male age as the rate of change was variable for those five genes. © 2017 John Wiley & Sons Ltd.

Age and Vascular Burden Determinants of Cortical Hemodynamics Underlying Verbal Fluency.

PubMed

Heinzel, Sebastian; Metzger, Florian G; Ehlis, Ann-Christine; Korell, Robert; Alboji, Ahmed; Haeussinger, Florian B; Wurster, Isabel; Brockmann, Kathrin; Suenkel, Ulrike; Eschweiler, Gerhard W; Maetzler, Walter; Berg, Daniela; Fallgatter, Andreas J

2015-01-01

Aging processes and several vascular burden factors have been shown to increase the risk of dementia including Alzheimer's disease. While pathological alterations in dementia precede diagnosis by many years, reorganization of brain processing might temporarily delay cognitive decline. We hypothesized that in healthy elderly individuals both age-related neural and vascular factors known to be related to the development of dementia impact functional cortical hemodynamics during increased cognitive demands. Vascular burden factors and cortical functional hemodynamics during verbal fluency were assessed in 1052 non-demented elderly individuals (51 to 83 years; cross-sectional data of the longitudinal TREND study) using functional near-infrared spectroscopy (fNIRS). The prediction of functional hemodynamic responses by age in multiple regressions and the impact of single and cumulative vascular burden factors including hypertension, diabetes, obesity, smoking and atherosclerosis were investigated. Replicating and extending previous findings we could show that increasing age predicted functional hemodynamics to be increased in right prefrontal and bilateral parietal cortex, and decreased in bilateral inferior frontal junction during phonological fluency. Cumulative vascular burden factors, with hypertension in particular, decreased left inferior frontal junction hemodynamic responses during phonological fluency. However, age and vascular burden factors showed no statistical interaction on functional hemodynamics. Based on these findings, one might hypothesize that increased fronto-parietal processing may represent age-related compensatory reorganization during increased cognitive demands. Vascular burden factors, such as hypertension, may contribute to regional cerebral hypoperfusion. These neural and vascular hemodynamic determinants should be investigated longitudinally and combined with other markers to advance the prediction of future cognitive decline and dementia.

Predicting Age Using Neuroimaging: Innovative Brain Ageing Biomarkers.

PubMed

Cole, James H; Franke, Katja

2017-12-01

The brain changes as we age and these changes are associated with functional deterioration and neurodegenerative disease. It is vital that we better understand individual differences in the brain ageing process; hence, techniques for making individualised predictions of brain ageing have been developed. We present evidence supporting the use of neuroimaging-based 'brain age' as a biomarker of an individual's brain health. Increasingly, research is showing how brain disease or poor physical health negatively impacts brain age. Importantly, recent evidence shows that having an 'older'-appearing brain relates to advanced physiological and cognitive ageing and the risk of mortality. We discuss controversies surrounding brain age and highlight emerging trends such as the use of multimodality neuroimaging and the employment of 'deep learning' methods. Copyright © 2017 Elsevier Ltd. All rights reserved.

Satisfaction with life during pregnancy and early motherhood in first-time mothers of advanced age: a population-based longitudinal study.

PubMed

Aasheim, Vigdis; Waldenström, Ulla; Rasmussen, Svein; Espehaug, Birgitte; Schytt, Erica

2014-02-25

The trend to delay motherhood to the age of 30 and beyond is established in most high-income countries but relatively little is known about potential effects on maternal emotional well-being. This study investigates satisfaction with life during pregnancy and the first three years of motherhood in women expecting their first baby at an advanced and very advanced age. The study was based on the National Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health. Data on 18 565 nulliparous women recruited in the second trimester 1999-2008 were used. Four questionnaires were completed: at around gestational weeks 17 and 30, and at six months and three years after the birth. Medical data were retrieved from the national Medical Birth Register. Advanced age was defined as 32-37 years, very advanced age as ≥38 years and the reference group as 25-31 years. The distribution of satisfaction with life from age 25 to ≥40 years was investigated, and the mean satisfaction with life at the four time points was estimated. Logistic regression analyses based on generalised estimation equations were used to investigate associations between advanced and very advanced age and satisfaction with life when controlling for socio-demographic factors. Satisfaction with life decreased from around age 28 to age 40 and beyond, when measured in gestational weeks 17 and 30, and at six months and three years after the birth. When comparing women of advanced and very advanced age with the reference group, satisfaction with life was slightly reduced in the two older age groups and most of all in women of very advanced age. Women of very advanced age had the lowest scores at all time points and this was most pronounced at three years after the birth. First-time mothers of advanced and very advanced age reported a slightly lower degree of satisfaction with life compared with the reference group of younger women, and the age-related effect was greatest when the child was three years of age.

Age, overtime, and employee health, safety and productivity outcomes: a case study.

PubMed

Allen, Harris; Woock, Christopher; Barrington, Linda; Bunn, William

2008-08-01

To expand a study of the impact of overtime on employee health, safety, and productivity outcomes, previously reported in this journal, with tests comparing older versus younger workers on these relationships. Secondary analyses of a longitudinal panel (n = 2746) representing workers at US sites for a heavy manufacturer during 2001 to 2002. Structural equation techniques were used to assess two hypotheses in the context of multiple group models positing the prediction of a broad set of employee outcomes using a three-step causal sequence. One set of models compared overtime impact for three age groups (<45, 45 to 49, 50+) at the aggregate level. Two others compared overtime impact for the three age groups by compensation type (hourly vs salaried). Advancing age was linked to greater rates of adverse consequences as a function of overtime (hypothesis #1), but these increases were largely confined to hourly employees working extended overtime (averaging 60+ hours per week) and occurred on only four of the nine study outcomes. With respect to moderate overtime (48.01 to 59.99 hours) and to variables reflecting the possible impact of past overtime (eg, prior disability episodes), increases in age among hourly employees did not lead to stronger associations between overtime and adverse outcomes on most tests and in fact in many cases were linked to decrements in these associations (hypothesis #2). Salaried employees recorded no greater linkages between overtime and adverse outcomes with advancing age across all tests involving hypothesized overtime effects or "possibly a function of overtime" effects. The results support the proposition that, when employees work overtime, adverse outcomes--and indirect costs--do not increase with advancing age in any kind of wholesale fashion. Where rates of adverse outcomes do increase, they are confined to certain subgroups of employees doing certain types of work and occur on certain dimensions at certain levels of longer work hours. It is argued that carefully calibrated approaches vis-à-vis older workers are needed to maximize employer capacity to address the unique challenges posed by this increasingly important portion of the workforce.

Obesity associated advanced glycation end products within the human uterine cavity adversely impact endometrial function and embryo implantation competence.

PubMed

Antoniotti, Gabriella S; Coughlan, Melinda; Salamonsen, Lois A; Evans, Jemma

2018-04-01

Do obese levels of advanced glycation end products (AGEs) within the uterine cavity detrimentally alter tissue function in embryo implantation and placental development? Obese levels of AGEs activate inflammatory signaling (p65 NFκB) within endometrial epithelial cells and alter their function, cause endoplasmic reticulum (ER) stress in endometrial stromal cells and impair decidualization, compromise implantation of blastocyst mimics and inhibit trophoblast invasion. Obese women experience a higher incidence of infertility, recurrent miscarriage and pregnancy complications compared with lean women. Oocyte donation cycles suggest a detrimental uterine environment plays a role in these outcomes. Uterine lavage and tissues from lean (BMI 19.5-24.9, n = 17) and obese (BMI > 30, n = 16) women examined. Cell culture experiments utilizing human endometrial epithelial, trophectoderm and trophoblast cell lines and primary human stromal cells used to examine the functional impact of obese levels of AGEs. Levels of AGEs examined within uterine lavage assessed by ELISA to determine differences between lean and obese women. Expression and localization of AGEs, receptor for AGEs (RAGE) and NFκB within endometrial tissues obtained from lean and obese women determined by immunohistochemistry. Endometrial epithelial cells (ECC-1), primary human stromal cells and trophoblast cells (HTR8-SVneo) treated with lean (2000 nmol/mol lysine) or obese (8000 nmol/mol lysine) uterine levels of AGEs and p65 NFκB (western immunoblot), real-time adhesion, proliferation migration and invasion (xCelligence real-time cell function analysis), decidualization (cell morphology and prolactin release), ER stress (western immunoblot for p-PERK) determined. Co-cultures of endometrial epithelial cells and blastocyst mimics (trophectoderm spheroids) similarly treated with lean or obese uterine levels of AGEs to determine their impact on embryo implantation. AGEs were significantly elevated (P = 0.004) within the obese (6503.59 μmol/mol lysine) versus lean (2165.88 μmol/mol lysine) uterine cavity (uterine lavage) with increased immunostaining for AGEs, RAGE and NFkB within obese endometrial tissues during the proliferative phase of the menstrual cycle. Obese uterine levels of AGEs inhibited adhesion and proliferation of endometrial epithelial (ECC-1) cells compared to treatment with lean uterine levels of AGEs. Obese uterine AGE levels impacted primary human endometrial stromal cell decidualization and activated ER stress within these cells. Obese uterine levels of AGEs also inhibited trophectodermal spheroid adhesion to hormonally primed endometrial epithelial cells and trophoblast cell line HTR8/SV-neo invasion. N/A. Mechanistic studies are performed in vitro and may not completely recapitulate cell function in vivo. These data corroborate clinical data suggesting the presence of an altered uterine environment in obese women and demonstrate that elevated uterine levels of AGEs within these women may detrimentally impact endometrial function, embryo implantation and placental development. Uterine AGE assessment in infertility work up may prove useful in determining underlying causes of infertility. AGEs can be targeted pharmacologically and such treatments may prove effective in improving reproductive complications experience by obese women. Supported by NHMRC Fellowship (#1002028 to L.A.S.), and the Victorian Government's Operational Infrastructure Support Program. MTC is supported by a JDRF Australia Clinical Research Network Career Development Award. The authors have declared that no conflict of interest exists.

Phytochemicals Against Advanced Glycation End Products (AGEs) and the Receptor System.

PubMed

Yamagishi, Sho-Ichi; Matsui, Takanori; Ishibashi, Yuji; Isami, Fumiyuki; Abe, Yumi; Sakaguchi, Tatsuya; Higashimoto, Yuichiro

2017-01-01

Reducing sugars can react non-enzymatically with amino groups of proteins and lipids to form irreversibly cross-linked macroprotein derivatives called as advanced glycation end products (AGEs). Cross-linking modification of extracellular matrix proteins by AGEs deteriorate their tertiary structural integrity and function, contributing to aging-related organ damage and diabetes-associated complications, such as cardiovascular disease (CVD). Moreover, engagement of receptor for AGEs, RAGE with the ligands evoke oxidative stress generation and inflammatory, thrombotic and fibrotic reactions in various kinds of tissues, further exacerbating the deleterious effects of AGEs on multiple organ systems. So the AGE-RAGE axis is a novel therapeutic target for numerous devastating disorders. Several observational studies have shown the association of dietary consumption of fruits and vegetables with the reduced risk of CVD in a general population. Although beneficial effects of fruits and vegetables against CVD could mainly be ascribed to its anti-oxidative properties, blockade of the AGERAGE axis by phytochemicals may also contribute to cardiovascular event protection. Therefore, in this review, we focus on 4 phytochemicals (quercetin, sulforaphane, iridoids, and curcumin) and summarize their effects on AGE formation as well as RAGE-mediated signaling pathway in various cell types and organs, including endothelial cells, vessels, and heart. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Change blindness, aging, and cognition

PubMed Central

Rizzo, Matthew; Sparks, JonDavid; McEvoy, Sean; Viamonte, Sarah; Kellison, Ida; Vecera, Shaun P.

2011-01-01

Change blindness (CB), the inability to detect changes in visual scenes, may increase with age and early Alzheimer’s disease (AD). To test this hypothesis, participants were asked to localize changes in natural scenes. Dependent measures were response time (RT), hit rate, false positives (FP), and true sensitivity (d′). Increased age correlated with increased sensitivity and RT; AD predicted even slower RT. Accuracy and RT were negatively correlated. Differences in FP were nonsignificant. CB correlated with impaired attention, working memory, and executive function. Advanced age and AD were associated with increased CB, perhaps due to declining memory and attention. CB could affect real-world tasks, like automobile driving. PMID:19051127

Change blindness, aging, and cognition.

PubMed

Rizzo, Matthew; Sparks, Jondavid; McEvoy, Sean; Viamonte, Sarah; Kellison, Ida; Vecera, Shaun P

2009-02-01

Change blindness (CB), the inability to detect changes in visual scenes, may increase with age and early Alzheimer's disease (AD). To test this hypothesis, participants were asked to localize changes in natural scenes. Dependent measures were response time (RT), hit rate, false positives (FP), and true sensitivity (d'). Increased age correlated with increased sensitivity and RT; AD predicted even slower RT. Accuracy and RT were negatively correlated. Differences in FP were nonsignificant. CB correlated with impaired attention, working memory, and executive function. Advanced age and AD were associated with increased CB, perhaps due to declining memory and attention. CB could affect real-world tasks, like automobile driving.

Rejuvenating Strategies for Stem Cell-based Therapies in Aging

PubMed Central

Neves, Joana; Sousa-Victor, Pedro; Jasper, Heinrich

2017-01-01

SUMMARY Recent advances in our understanding of tissue regeneration and the development of efficient approaches to induce and differentiate pluripotent stem cells for cell replacement therapies promise exciting avenues for treating degenerative age-related diseases. However, clinical studies and insights from model organisms have identified major roadblocks that normal aging processes impose on tissue regeneration. These new insights suggest that specific targeting of environmental niche components, including growth factors, ECM and immune cells, and intrinsic stem cell properties that are affected by aging will be critical for development of new strategies to improve stem cell function and optimize tissue repair processes. PMID:28157498

Manipulation of Behavioral Decline in Caenorhabditis elegans with the Rag GTPase raga-1

PubMed Central

Schreiber, Matthew A.; Pierce-Shimomura, Jonathan T.; Chan, Stefan; Parry, Dianne; McIntire, Steven L.

2010-01-01

Normal aging leads to an inexorable decline in motor performance, contributing to medical morbidity and decreased quality of life. While much has been discovered about genetic determinants of lifespan, less is known about modifiers of age-related behavioral decline and whether new gene targets may be found which extend vigorous activity, with or without extending lifespan. Using Caenorhabditis elegans, we have developed a model of declining neuromuscular function and conducted a screen for increased behavioral activity in aged animals. In this model, behavioral function suffers from profound reductions in locomotory frequency, but coordination is strikingly preserved until very old age. By screening for enhancers of locomotion at advanced ages we identified the ras-related Rag GTPase raga-1 as a novel modifier of behavioral aging. raga-1 loss of function mutants showed vigorous swimming late in life. Genetic manipulations revealed that a gain of function raga-1 curtailed behavioral vitality and shortened lifespan, while a dominant negative raga-1 lengthened lifespan. Dietary restriction results indicated that a raga-1 mutant is relatively protected from the life-shortening effects of highly concentrated food, while RNAi experiments suggested that raga-1 acts in the highly conserved target of rapamycin (TOR) pathway in C. elegans. Rag GTPases were recently shown to mediate nutrient-dependent activation of TOR. This is the first demonstration of their dramatic effects on behavior and aging. This work indicates that novel modulators of behavioral function can be identified in screens, with implications for future study of the clinical amelioration of age-related decline. PMID:20523893

Long-term functional recovery and health-related quality of life of elderly out-of-hospital cardiac arrest survivors.

PubMed

Andrew, Emily; Mercier, Eric; Nehme, Ziad; Bernard, Stephen; Smith, Karen

2018-05-01

Understanding the prognosis of elderly out-of-hospital cardiac arrest (OHCA) patients is vital to informing resuscitation and advanced care planning decisions. However, short-term outcomes such as survival to hospital discharge do not account for post-arrest quality of life. We describe the 12-month functional recovery and health-related quality of life (HR-QOL) of elderly OHCA survivors, including those arresting in aged care facilities. We conducted a retrospective analysis of Victorian Ambulance Cardiac Arrest Registry data for all OHCA survivors to hospital discharge aged ≥65 years between 1 January 2010 and 30 June 2016. The influence of age on functional recovery and independent living was assessed using multivariable logistic regression. During the study period, 20,103 elderly OHCAs were attended, 9016 (44.9%) of whom received a resuscitation attempt. In total, 876 (9.7%) patients survived to hospital discharge and 777 were alive 12 months post-arrest. Of these, 651 participated in 12-month follow-up (response rate 83.8%). Most (60.6%) resided at home without additional care and 66.6% reported a good functional recovery, however both measures decreased with increasing age (p < 0.001). Mental HR-QOL increased with increasing age and was significantly better than the age- and sex-matched Australian population. Each 10-year increase in age was associated with a 40.8% (95%CI 25.6-53.0%) reduction in the odds of good functional recovery, and a 65.8% (95%CI 55.8-73.5%) reduction in the odds of living independently. Of the 2575 OHCAs in an aged care facility, 2.2% survived to hospital discharge, however no patient reported a good 12-month functional recovery. Most elderly OHCA survivors resided independently with good functionality 12 months post-arrest. However, increasing age was associated with less favourable outcomes. New strategies are needed with regard to resuscitation in aged care facilities. Copyright © 2018 Elsevier B.V. All rights reserved.

Detection of advanced glycation end products (AGEs) on human skin by in vivo confocal Raman spectroscopy

NASA Astrophysics Data System (ADS)

Martin, A. A.; Pereira, L.; Ali, S. M.; Pizzol, C. D.; Tellez, C. A.; Favero, P. P.; Santos, L.; da Silva, V. V.; Praes, C. E. O.

2016-03-01

The aging process involves the reduction in the production of the major components of skin tissue. During intrinsic aging and photoaging processes, in dermis of human skin, fibroblasts become senescent and have decreased activity, which produce low levels of collagen. Moreover, there is accumulation of advanced glycation end products (AGEs). AGEs have incidence in the progression of age-related diseases, principally in diabetes mellitus and in Alzheimer's diseases. AGEs causes intracellular damage and/or apoptosis leading to an increase of the free radicals, generating a crosslink with skin proteins and oxidative stress. The aim of this study is to detect AGEs markers on human skin by in vivo Confocal Raman spectroscopy. Spectra were obtained by using a Rivers Diagnostic System, 785 nm laser excitation and a CCD detector from the skin surface down to 120 μm depth. We analyzed the confocal Raman spectra of the skin dermis of 30 women volunteers divided into 3 groups: 10 volunteers with diabetes mellitus type II, 65-80 years old (DEW); 10 young healthy women, 20-33 years old (HYW); and 10 elderly healthy women, 65-80 years old (HEW). Pentosidine and glucosepane were the principally identified AGEs in the hydroxyproline and proline Raman spectral region (1000-800 cm-1), in the 1.260-1.320 cm-1 region assignable to alpha-helical amide III modes, and in the Amide I region. Pentosidine and glucosepane calculated vibrational spectra were performed through Density Functional Theory using the B3LYP functional with 3-21G basis set. Difference between the Raman spectra of diabetic elderly women and healthy young women, and between healthy elderly women and healthy young women were also obtained with the purpose of identifying AGEs Raman bands markers. AGEs peaks and collagen changes have been identified and used to quantify the glycation process in human skin.

Improved motor and cognitive performance with sodium nitrite supplementation is related to small metabolite signatures: a pilot trial in middle-aged and older adults

PubMed Central

DeVan, Allison E.; Cruickshank-Quinn, Charmion; Reisdorph, Nichole; Bassett, Candace J.; Evans, Trent D.; Brooks, Forrest A.; Bryan, Nathan S.; Chonchol, Michel B.; Giordano, Tony; McQueen, Matthew B.; Seals, Douglas R.

2015-01-01

Advancing age is associated with reductions in nitric oxide bioavailability and changes in metabolic activity, which are implicated in declines in motor and cognitive function. In preclinical models, sodium nitrite supplementation (SN) increases plasma nitrite and improves motor function, whereas other nitric oxide-boosting agents improve cognitive function. This pilot study was designed to translate these findings to middle-aged and older (MA/O) humans to provide proof-of-concept support for larger trials. SN (10 weeks, 80 or 160 mg/day capsules, TheraVasc, Inc.) acutely and chronically increased plasma nitrite and improved performance on measures of motor and cognitive outcomes (all p<0.05 or better) in healthy MA/O adults (62 ± 7 years). Untargeted metabolomics analysis revealed that SN significantly altered 33 (160 mg/day) to 45 (80 mg/day) different metabolites, 13 of which were related to changes in functional outcomes; baseline concentrations of 99 different metabolites predicted functional improvements with SN. This pilot study provides the first evidence that SN improves aspects of motor and cognitive function in healthy MA/O adults, and that these improvements are associated with, and predicted by, the plasma metabolome. Our findings provide the necessary support for larger clinical trials on this promising pharmacological strategy for preserving physiological function with aging. PMID:26626856

Chemical Reactivity Theory Study of Advanced Glycation Endproduct Inhibitors.

PubMed

Frau, Juan; Glossman-Mitnik, Daniel

2017-02-02

Several compounds with the known ability to perform as inhibitors of advanced glycation endproducts (AGE) have been studied with Density Functional Theory (DFT) through the use of anumberofdensityfunctionalswhoseaccuracyhasbeentestedacrossabroadspectrumofdatabases in Chemistry and Physics. The chemical reactivity descriptors for these systems have been calculated through Conceptual DFT in an attempt to relate their intrinsic chemical reactivity with the ability to inhibit the action of glycating carbonyl compounds on amino acids and proteins. This knowledge could be useful in the design and development of new drugs which can be potential medicines for diabetes and Alzheimer's disease.

[Aging of the respiratory system: anatomical changes and physiological consequences].

PubMed

Ketata, W; Rekik, W K; Ayadi, H; Kammoun, S

2012-10-01

The respiratory system undergoes progressive involution with age, resulting in anatomical and functional changes that are exerted on all levels. The rib cage stiffens and respiratory muscles weaken. Distal bronchioles have reduced diameter and tend to be collapsed. Mobilized lung volumes decrease with age while residual volume increases. Gas exchanges are modified with a linear decrease of PaO(2) up to the age of 70 years and a decreased diffusing capacity of carbon monoxide. Ventilatory responses to hypercapnia, hypoxia and exercise decrease in the elderly. Knowledge of changes in the respiratory system related to advancing age is a medical issue of great importance in order to distinguish the effects of aging from those of diseases. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Nutrition in the Very Old

PubMed Central

Granic, Antoneta; Mendonça, Nuno; Hill, Tom R.; Jagger, Carol; Stevenson, Emma J.; Mathers, John C.; Sayer, Avan A.

2018-01-01

The population of older adults aged 85 years and over (the very old) is growing rapidly in many societies because of increases in life expectancy and reduced mortality at older ages. In 2016, 27.3 million very old adults were living in the European Union, and in the UK, 2.4% of the population (1.6 million) were aged 85 and over. Very old age is associated with increased risks of malnutrition, multimorbidity, and disability. Diet (nutrition) is a modifiable risk factor for multiple age-related conditions, including sarcopenia and functional decline. Dietary characteristics and nutrient intakes of the very old have been investigated in several European studies of ageing to better understand their nutritional requirements, which may differ from those in the young-old. However, there is a major gap in regard to evidence for the role of dietary patterns, protein, vitamin D and other nutrients for the maintenance of physical and cognitive functioning in later life. The Newcastle 85+ Study, UK and the Life and Living in Advanced Age, New Zealand are unique studies involving single birth cohorts which aim to assess health trajectories in very old adults and their biological, social and environmental influences, including nutrition. In this review, we have updated the latest findings in nutritional epidemiology with results from these studies, concentrating on the diet–physical functioning relationship. PMID:29495468

The Fruit Fly Drosophila melanogaster as a Model for Aging Research.

PubMed

Brandt, Annely; Vilcinskas, Andreas

2013-01-01

: Average human life expectancy is increasing and so is the impact on society of aging and age-related diseases. Here we highlight recent advances in the diverse and multidisciplinary field of aging research, focusing on the fruit fly Drosophila melanogaster, an excellent model system in which to dissect the genetic and molecular basis of the aging processes. The conservation of human disease genes in D. melanogaster allows the functional analysis of orthologues implicated in human aging and age-related diseases. D. melanogaster models have been developed for a variety of age-related processes and disorders, including stem cell decline, Alzheimer's disease, and cardiovascular deterioration. Understanding the detailed molecular events involved in normal aging and age-related diseases could facilitate the development of strategies and treatments that reduce their impact, thus improving human health and increasing longevity.

Fatigue, emotional functioning, and executive dysfunction in pediatric multiple sclerosis.

PubMed

Holland, Alice Ann; Graves, Donna; Greenberg, Benjamin M; Harder, Lana L

2014-01-01

Fatigue, depression, anxiety, and executive dysfunction are associated with multiple sclerosis (MS) in adults. Existing research suggests similar problems in pediatric MS, but relationships between these variables have not been investigated. This study investigates the associations between executive functioning and fatigue, emotional functioning, age of onset, and disease duration in pediatric MS. Twenty-six MS or Clinically Isolated Syndrome (CIS) patients, ages 7 to 18, were evaluated through a multidisciplinary demyelinating diseases clinic. Participants completed neuropsychological screening including Verbal Fluency, Digit Span, and Trail-Making Test. Parents completed rating forms of behavioral, emotional, and executive functioning. Patients and parents completed questionnaires related to the patient's quality of life and fatigue. Pearson's correlation coefficients were calculated to investigate relationships between fatigue, emotional functioning, and executive functioning, as well as to examine correlations between parent and child reports of fatigue. Rates of parent-reported anxiety, depression, fatigue, and executive dysfunction varied widely. Means were below average on the Trail-Making Test and average on Verbal Fluency and Digit Span, though scores varied widely. Various fatigue and emotional functioning indices-but not age of onset or disease duration-significantly correlated with various performance-based measures of executive functioning. Results indicate pediatric MS is associated with some degree of fatigue, emotional difficulties, and executive dysfunction, the latter of which is associated with the two former. Notably, age of onset and disease duration did not significantly correlate with executive functioning. Results advance understanding of psychological and clinical variables related to neurocognitive outcomes in pediatric MS.

Arterial ageing: from endothelial dysfunction to vascular calcification.

PubMed

Tesauro, M; Mauriello, A; Rovella, V; Annicchiarico-Petruzzelli, M; Cardillo, C; Melino, G; Di Daniele, N

2017-05-01

Complex structural and functional changes occur in the arterial system with advancing age. The aged artery is characterized by changes in microRNA expression patterns, autophagy, smooth muscle cell migration and proliferation, and arterial calcification with progressively increased mechanical vessel rigidity and stiffness. With age the vascular smooth muscle cells modify their phenotype from contractile to 'synthetic' determining the development of intimal thickening as early as the second decade of life as an adaptive response to forces acting on the arterial wall. The increased permeability observed in intimal thickening could represent the substrate on which low-level atherosclerotic stimuli can promote the development of advanced atherosclerotic lesions. In elderly patients the atherosclerotic plaques tend to be larger with increased vascular stenosis. In these plaques there is a progressive accumulation of both lipids and collagen and a decrease of inflammation. Similarly the plaques from elderly patients show more calcification as compared with those from younger patients. The coronary artery calcium score is a well-established marker of adverse cardiovascular outcomes. The presence of diffuse calcification in a severely stenotic segment probably induces changes in mechanical properties and shear stress of the arterial wall favouring the rupture of a vulnerable lesion in a less stenotic adjacent segment. Oxidative stress and inflammation appear to be the two primary pathological mechanisms of ageing-related endothelial dysfunction even in the absence of clinical disease. Arterial ageing is no longer considered an inexorable process. Only a better understanding of the link between ageing and vascular dysfunction can lead to significant advances in both preventative and therapeutic treatments with the aim that in the future vascular ageing may be halted or even reversed. © 2017 The Association for the Publication of the Journal of Internal Medicine.

Mechanisms and consequences of oxidative stress in lung disease: therapeutic implications for an aging populace.

PubMed

Hecker, Louise

2018-04-01

The rapid expansion of the elderly population has led to the recent epidemic of age-related diseases, including increased incidence and mortality of chronic and acute lung diseases. Numerous studies have implicated aging and oxidative stress in the pathogenesis of various pulmonary diseases; however, despite recent advances in these fields, the specific contributions of aging and oxidative stress remain elusive. This review will discuss the consequences of aging on lung morphology and physiology, and how redox imbalance with aging contributes to lung disease susceptibility. Here, we focus on three lung diseases for which aging is a significant risk factor: acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). Preclinical and clinical development for redox- and senescence-altering therapeutic strategies are discussed, as well as scientific advancements that may direct current and future therapeutic development. A deeper understanding of how aging impacts normal lung function, redox balance, and injury-repair processes will inspire the development of new therapies to prevent and/or reverse age-associated pulmonary diseases, and ultimately increase health span and longevity. This review is intended to encourage basic, clinical, and translational research that will bridge knowledge gaps at the intersection of aging, oxidative stress, and lung disease to fuel the development of more effective therapeutic strategies for lung diseases that disproportionately afflict the elderly.

Long-Term Moderate Exercise Rescues Age-Related Decline in Hippocampal Neuronal Complexity and Memory.

PubMed

Tsai, Sheng-Feng; Ku, Nai-Wen; Wang, Tzu-Feng; Yang, Yan-Hsiang; Shih, Yao-Hsiang; Wu, Shih-Ying; Lee, Chu-Wan; Yu, Megan; Yang, Ting-Ting; Kuo, Yu-Min

2018-05-07

Aging impairs hippocampal neuroplasticity and hippocampus-related learning and memory. In contrast, exercise training is known to improve hippocampal neuronal function. However, whether exercise is capable of restoring memory function in old animals is less clear. Here, we investigated the effects of exercise on the hippocampal neuroplasticity and memory functions during aging. Young (3 months), middle-aged (9-12 months), and old (18 months) mice underwent moderate-intensity treadmill running training for 6 weeks, and their hippocampus-related learning and memory, and the plasticity of their CA1 neurons was evaluated. The memory performance (Morris water maze and novel object recognition tests), and dendritic complexity (branch and length) and spine density of their hippocampal CA1 neurons decreased as their age increased. The induction and maintenance of high-frequency stimulation-induced long-term potentiation in the CA1 area and the expressions of neuroplasticity-related proteins were not affected by age. Treadmill running increased CA1 neuron long-term potentiation and dendritic complexity in all three age groups, and it restored the learning and memory ability in middle-aged and old mice. Furthermore, treadmill running upregulated the hippocampal expressions of brain-derived neurotrophic factor and monocarboxylate transporter-4 in middle-aged mice, glutamine synthetase in old mice, and full-length TrkB in middle-aged and old mice. The hippocampus-related memory function declines from middle age, but long-term moderate-intensity running effectively increased hippocampal neuroplasticity and memory in mice of different ages, even when the memory impairment had progressed to an advanced stage. Thus, long-term, moderate intensity exercise training might be a way of delaying and treating aging-related memory decline. © 2018 S. Karger AG, Basel.

Recovery and Recrystallization of Cold Rolled Al-3.3 Mg-1.22 Mn Alloy Sheet; Precipitation Hardening as a Function of Aging Temperature; Effect of Rate of Quenching on Age-hardening

NASA Astrophysics Data System (ADS)

Khalique, Abdul; Khan, Mohammad Riaz

1997-07-01

The present scientific and technological advancement in space travel has given an added impetus to the development and production of light metal high strength alloys, capable of enduring rapid changes in temperature and other environmental conditions. Al-3.3 Mg-1.22 Mn (weight %) cold rolled alloy sheet of 2 mm thickness was selected for the study. This alloy falls in the category of non-heat treatable, corrosive resistant alloys. The change in mechanical behaviour when age-softened in N2 gas atomsphere was studied. In addition, mechanical properties of samples when artificially aged in the temperature range of 150°C-250°C for 3 hours each, after solution treatment at 450°C for 12 h followed by quenching to room temperature were investigated. It is revealed that improvement, though limited, in tensile strength, surface hardness and ductility during aging is a function of cooling rate during quenching.

Protein function prediction--the power of multiplicity.

PubMed

Rentzsch, Robert; Orengo, Christine A

2009-04-01

Advances in experimental and computational methods have quietly ushered in a new era in protein function annotation. This 'age of multiplicity' is marked by the notion that only the use of multiple tools, multiple evidence and considering the multiple aspects of function can give us the broad picture that 21st century biology will need to link and alter micro- and macroscopic phenotypes. It might also help us to undo past mistakes by removing errors from our databases and prevent us from producing more. On the downside, multiplicity is often confusing. We therefore systematically review methods and resources for automated protein function prediction, looking at individual (biochemical) and contextual (network) functions, respectively.

Resilient protein co-expression network in male orbitofrontal cortex layer 2/3 during human aging.

PubMed

Pabba, Mohan; Scifo, Enzo; Kapadia, Fenika; Nikolova, Yuliya S; Ma, Tianzhou; Mechawar, Naguib; Tseng, George C; Sibille, Etienne

2017-10-01

The orbitofrontal cortex (OFC) is vulnerable to normal and pathologic aging. Currently, layer resolution large-scale proteomic studies describing "normal" age-related alterations at OFC are not available. Here, we performed a large-scale exploratory high-throughput mass spectrometry-based protein analysis on OFC layer 2/3 from 15 "young" (15-43 years) and 18 "old" (62-88 years) human male subjects. We detected 4193 proteins and identified 127 differentially expressed (DE) proteins (p-value ≤0.05; effect size >20%), including 65 up- and 62 downregulated proteins (e.g., GFAP, CALB1). Using a previously described categorization of biological aging based on somatic tissues, that is, peripheral "hallmarks of aging," and considering overlap in protein function, we show the highest representation of altered cell-cell communication (54%), deregulated nutrient sensing (39%), and loss of proteostasis (35%) in the set of OFC layer 2/3 DE proteins. DE proteins also showed a significant association with several neurologic disorders; for example, Alzheimer's disease and schizophrenia. Notably, despite age-related changes in individual protein levels, protein co-expression modules were remarkably conserved across age groups, suggesting robust functional homeostasis. Collectively, these results provide biological insight into aging and associated homeostatic mechanisms that maintain normal brain function with advancing age. Copyright © 2017 Elsevier Inc. All rights reserved.

Volumetric changes in the aging rat brain and its impact on cognitive and locomotor functions.

PubMed

Hamezah, Hamizah Shahirah; Durani, Lina Wati; Ibrahim, Nor Faeizah; Yanagisawa, Daijiro; Kato, Tomoko; Shiino, Akihiko; Tanaka, Sachiko; Damanhuri, Hanafi Ahmad; Ngah, Wan Zurinah Wan; Tooyama, Ikuo

2017-12-01

Impairments in cognitive and locomotor functions usually occur with advanced age, as do changes in brain volume. This study was conducted to assess changes in brain volume, cognitive and locomotor functions, and oxidative stress levels in middle- to late-aged rats. Forty-four male Sprague-Dawley rats were divided into four groups: 14, 18, 23, and 27months of age. 1 H magnetic resonance imaging (MRI) was performed using a 7.0-Tesla MR scanner system. The volumes of the lateral ventricles, medial prefrontal cortex (mPFC), hippocampus, striatum, cerebellum, and whole brain were measured. Open field, object recognition, and Morris water maze tests were conducted to assess cognitive and locomotor functions. Blood was taken for measurements of malondialdehyde (MDA), protein carbonyl content, and antioxidant enzyme activity. The lateral ventricle volumes were larger, whereas the mPFC, hippocampus, and striatum volumes were smaller in 27-month-old rats than in 14-month-old rats. In behavioral tasks, the 27-month-old rats showed less exploratory activity and poorer spatial learning and memory than did the 14-month-old rats. Biochemical measurements likewise showed increased MDA and lower glutathione peroxidase (GPx) activity in the 27-month-old rats. In conclusion, age-related increases in oxidative stress, impairment in cognitive and locomotor functions, and changes in brain volume were observed, with the most marked impairments observed in later age. Copyright © 2017. Published by Elsevier Inc.

Large-Scale Behavior-Change Initiative for Infant and Young Child Feeding Advanced Language and Motor Development in a Cluster-Randomized Program Evaluation in Bangladesh.

PubMed

Frongillo, Edward A; Nguyen, Phuong H; Saha, Kuntal K; Sanghvi, Tina; Afsana, Kaosar; Haque, Raisul; Baker, Jean; Ruel, Marie T; Rawat, Rahul; Menon, Purnima

2017-02-01

Promoting adequate nutrition through interventions to improve infant and young child feeding (IYCF) has the potential to contribute to child development. We examined whether an intensive intervention package that was aimed at improving IYCF at scale through the Alive & Thrive initiative in Bangladesh also advanced language and gross motor development, and whether advancements in language and gross motor development were explained through improved complementary feeding. A cluster-randomized design compared 2 intervention packages: intensive interpersonal counseling on IYCF, mass media campaign, and community mobilization (intensive) compared with usual nutrition counseling and mass media campaign (nonintensive). Twenty subdistricts were randomly assigned to receive either the intensive or the nonintensive intervention. Household surveys were conducted at baseline (2010) and at endline (2014) in the same communities (n = ∼4000 children aged 0-47.9 mo for each round). Child development was measured by asking mothers if their child had reached each of multiple milestones, with some observed. Linear regression accounting for clustering was used to derive difference-in-differences (DID) impact estimates, and path analysis was used to examine developmental advancement through indicators of improved IYCF and other factors. The DID in language development between intensive and nonintensive groups was 1.05 milestones (P = 0.001) among children aged 6-23.9 mo and 0.76 milestones (P = 0.038) among children aged 24-47.9 mo. For gross motor development, the DID was 0.85 milestones (P = 0.035) among children aged 6-23.9 mo. The differences observed corresponded to age- and sex-adjusted effect sizes of 0.35 for language and 0.23 for gross motor development. Developmental advancement at 6-23.9 mo was partially explained through improved minimum dietary diversity and the consumption of iron-rich food. Intensive IYCF intervention differentially advanced language and gross motor development, which was partially explained through improved complementary feeding. Measuring a diverse set of child outcomes, including functional outcomes such as child development, is important when evaluating integrated nutrition programs. This trial was registered at clinicaltrials.gov as NCT01678716. © 2017 American Society for Nutrition.

Effects of Sex and Education on Cognitive Change Over a 27-Year Period in Older Adults: The Rancho Bernardo Study.

PubMed

Reas, Emilie T; Laughlin, Gail A; Bergstrom, Jaclyn; Kritz-Silverstein, Donna; Barrett-Connor, Elizabeth; McEvoy, Linda K

2017-08-01

This study investigated how cognitive function changes with age and whether rates of decline vary by sex or education in a large, homogenous longitudinal cohort characterized by high participation rates, long duration of follow-up, and minimal loss to follow-up. Between 1988 and 2016, 2,225 community-dwelling participants of the Rancho Bernardo Study, aged 31 to 99 years at their initial cognitive assessment, completed neuropsychological testing approximately every 4 years, over a maximum 27-year follow-up. Linear mixed effects regression models defined sex-specific cognitive trajectories, adjusting for education and retest effects. Significant decline across all cognitive domains began around age 65 years and accelerated after age 80 years. Patterns of decline were generally similar between sexes, although men declined more rapidly than women on the global function test. Higher education was associated with slower decline on the tests of executive and global functions. After excluding 517 participants with evidence of cognitive impairment, accelerating decline with age remained for all tests, and women declined more rapidly than men on the executive function test. Accelerating decline with advancing age occurs across multiple cognitive domains in community-dwelling older adults, with few differences in rates of decline between men and women. Higher education may provide some protection against executive and global function decline with age. These findings better characterize normal cognitive aging, a critical prerequisite for identifying individuals at risk for cognitive impairment, and lay the groundwork for future studies of health and behavioral factors that affect age-related decline in this cohort. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Functionally Diverse NK-Like T Cells Are Effectors and Predictors of Successful Aging

PubMed Central

Michel, Joshua J.; Griffin, Patricia; Vallejo, Abbe N.

2016-01-01

The fundamental challenge of aging and long-term survivorship is maintenance of functional independence and compression of morbidity despite a life history of disease. Inasmuch as immunity is a determinant of individual health and fitness, unraveling novel mechanisms of immune homeostasis in late life is of paramount interest. Comparative studies of young and old persons have documented age-related atrophy of the thymus, the contraction of diversity of the T cell receptor (TCR) repertoire, and the intrinsic inefficiency of classical TCR signaling in aged T cells. However, the elderly have highly heterogeneous health phenotypes. Studies of defined populations of persons aged 75 and older have led to the recognition of successful aging, a distinct physiologic construct characterized by high physical and cognitive functioning without measurable disability. Significantly, successful agers have a unique T cell repertoire; namely, the dominance of highly oligoclonal αβT cells expressing a diverse array of receptors normally expressed by NK cells. Despite their properties of cell senescence, these unusual NK-like T cells are functionally active effectors that do not require engagement of their clonotypic TCR. Thus, NK-like T cells represent a beneficial remodeling of the immune repertoire with advancing age, consistent with the concept of immune plasticity. Significantly, certain subsets are predictors of physical/cognitive performance among older adults. Further understanding of the roles of these NK-like T cells to host defense, and how they integrate with other physiologic domains of function are new frontiers for investigation in Aging Biology. Such pursuits will require a research paradigm shift from the usual young-versus-old comparison to the analysis of defined elderly populations. These endeavors may also pave way to age-appropriate, group-targeted immune interventions for the growing elderly population. PMID:27933066

Functionally Diverse NK-Like T Cells Are Effectors and Predictors of Successful Aging.

PubMed

Michel, Joshua J; Griffin, Patricia; Vallejo, Abbe N

2016-01-01

The fundamental challenge of aging and long-term survivorship is maintenance of functional independence and compression of morbidity despite a life history of disease. Inasmuch as immunity is a determinant of individual health and fitness, unraveling novel mechanisms of immune homeostasis in late life is of paramount interest. Comparative studies of young and old persons have documented age-related atrophy of the thymus, the contraction of diversity of the T cell receptor (TCR) repertoire, and the intrinsic inefficiency of classical TCR signaling in aged T cells. However, the elderly have highly heterogeneous health phenotypes. Studies of defined populations of persons aged 75 and older have led to the recognition of successful aging, a distinct physiologic construct characterized by high physical and cognitive functioning without measurable disability. Significantly, successful agers have a unique T cell repertoire; namely, the dominance of highly oligoclonal αβT cells expressing a diverse array of receptors normally expressed by NK cells. Despite their properties of cell senescence, these unusual NK-like T cells are functionally active effectors that do not require engagement of their clonotypic TCR. Thus, NK-like T cells represent a beneficial remodeling of the immune repertoire with advancing age, consistent with the concept of immune plasticity. Significantly, certain subsets are predictors of physical/cognitive performance among older adults. Further understanding of the roles of these NK-like T cells to host defense, and how they integrate with other physiologic domains of function are new frontiers for investigation in Aging Biology. Such pursuits will require a research paradigm shift from the usual young-versus-old comparison to the analysis of defined elderly populations. These endeavors may also pave way to age-appropriate, group-targeted immune interventions for the growing elderly population.

The Age-ility Project (Phase 1): Structural and functional imaging and electrophysiological data repository.

PubMed

Karayanidis, Frini; Keuken, Max C; Wong, Aaron; Rennie, Jaime L; de Hollander, Gilles; Cooper, Patrick S; Ross Fulham, W; Lenroot, Rhoshel; Parsons, Mark; Phillips, Natalie; Michie, Patricia T; Forstmann, Birte U

2016-01-01

Our understanding of the complex interplay between structural and functional organisation of brain networks is being advanced by the development of novel multi-modal analyses approaches. The Age-ility Project (Phase 1) data repository offers open access to structural MRI, diffusion MRI, and resting-state fMRI scans, as well as resting-state EEG recorded from the same community participants (n=131, 15-35 y, 66 male). Raw imaging and electrophysiological data as well as essential demographics are made available via the NITRC website. All data have been reviewed for artifacts using a rigorous quality control protocol and detailed case notes are provided. Copyright © 2015. Published by Elsevier Inc.

[Effects of planning and executive functions on young children's script change strategy: A developmental perspective].

PubMed

Yanaoka, Kaichi

2016-02-01

This research examined the effects of planning and executive functions on young children's (ages 3-to 5-years) strategies in changing scripts. Young children (N = 77) performed a script task (doll task), three executive function tasks (DCCS, red/blue task, and nine box task), a planning task, and a receptive vocabulary task. In the doll task, young children first enacted a "changing clothes" script, and then faced a situation in which some elements of the script were inappropriate. They needed to enact a script by compensating inappropriate items for the other-script items or by changing to the other script in advance. The results showed that shifting, a factor of executive function, had a positive influence on whether young children could compensate inappropriate items. In addition, planning was also an important factor that helped children to change to the other script in advance. These findings suggest that shifting and planning play different roles in using the two strategies appropriately when young children enact scripts in unexpected situations.

Advancing Creative Visual Thinking with Constructive Function-Based Modelling

ERIC Educational Resources Information Center

Pasko, Alexander; Adzhiev, Valery; Malikova, Evgeniya; Pilyugin, Victor

2013-01-01

Modern education technologies are destined to reflect the realities of a modern digital age. The juxtaposition of real and synthetic (computer-generated) worlds as well as a greater emphasis on visual dimension are especially important characteristics that have to be taken into account in learning and teaching. We describe the ways in which an…

Above-Level Test Item Functioning across Examinee Age Groups

ERIC Educational Resources Information Center

Warne, Russell T.; Doty, Kristine J.; Malbica, Anne Marie; Angeles, Victor R.; Innes, Scott; Hall, Jared; Masterson-Nixon, Kelli

2016-01-01

"Above-level testing" (also called "above-grade testing," "out-of-level testing," and "off-level testing") is the practice of administering to a child a test that is designed for an examinee population that is older or in a more advanced grade. Above-level testing is frequently used to help educators design…

Intraindividual Variability in Executive Function Performance in Healthy Adults: Cross-Sectional Analysis of the NAB Executive Functions Module.

PubMed

Buczylowska, Dorota; Petermann, Franz

2018-01-01

The current study was aimed at investigating across-tasks intraindividual variability, also termed dispersion, in EF performance. The German adaptation of the Neuropsychological Assessment Battery (NAB) was used as a measure of EFs. Data of 444 participants aged 18-99 from six NAB Executive Functions Module subtests (i.e., Planning, Mazes, Letter Fluency, Judgment, Categories, and Word Generation) along with the NAB Total Index score as a measure of overall cognitive ability were analyzed. Maximum discrepancy (MD) was applied as a measure of dispersion. MD values ranged from 0.47 to 5.20 indicating substantial across-tasks dispersion in EF performance. Furthermore, dispersion moderately decreased with advancing age. Taking overall cognitive ability into account revealed that dispersion might be lower at older ages; especially, when associated with low overall ability levels. The dedifferentiation hypothesis offers a plausible explanation for these findings. That is, the cognitive profiles of older people might be less heterogenous than that of younger people, which may be due to age-related central nervous system constraints.

Intraindividual Variability in Executive Function Performance in Healthy Adults: Cross-Sectional Analysis of the NAB Executive Functions Module

PubMed Central

Buczylowska, Dorota; Petermann, Franz

2018-01-01

The current study was aimed at investigating across-tasks intraindividual variability, also termed dispersion, in EF performance. The German adaptation of the Neuropsychological Assessment Battery (NAB) was used as a measure of EFs. Data of 444 participants aged 18–99 from six NAB Executive Functions Module subtests (i.e., Planning, Mazes, Letter Fluency, Judgment, Categories, and Word Generation) along with the NAB Total Index score as a measure of overall cognitive ability were analyzed. Maximum discrepancy (MD) was applied as a measure of dispersion. MD values ranged from 0.47 to 5.20 indicating substantial across-tasks dispersion in EF performance. Furthermore, dispersion moderately decreased with advancing age. Taking overall cognitive ability into account revealed that dispersion might be lower at older ages; especially, when associated with low overall ability levels. The dedifferentiation hypothesis offers a plausible explanation for these findings. That is, the cognitive profiles of older people might be less heterogenous than that of younger people, which may be due to age-related central nervous system constraints. PMID:29593624

Aging Effects on Whole-Brain Functional Connectivity in Adults Free of Cognitive and Psychiatric Disorders.

PubMed

Ferreira, Luiz Kobuti; Regina, Ana Carolina Brocanello; Kovacevic, Natasa; Martin, Maria da Graça Morais; Santos, Pedro Paim; Carneiro, Camila de Godoi; Kerr, Daniel Shikanai; Amaro, Edson; McIntosh, Anthony Randal; Busatto, Geraldo F

2016-09-01

Aging is associated with decreased resting-state functional connectivity (RSFC) within the default mode network (DMN), but most functional imaging studies have restricted the analysis to specific brain regions or networks, a strategy not appropriate to describe system-wide changes. Moreover, few investigations have employed operational psychiatric interviewing procedures to select participants; this is an important limitation since mental disorders are prevalent and underdiagnosed and can be associated with RSFC abnormalities. In this study, resting-state fMRI was acquired from 59 adults free of cognitive and psychiatric disorders according to standardized criteria and based on extensive neuropsychological and clinical assessments. We tested for associations between age and whole-brain RSFC using Partial Least Squares, a multivariate technique. We found that normal aging is not only characterized by decreased RSFC within the DMN but also by ubiquitous increases in internetwork positive correlations and focal internetwork losses of anticorrelations (involving mainly connections between the DMN and the attentional networks). Our results reinforce the notion that the aging brain undergoes a dedifferentiation processes with loss of functional diversity. These findings advance the characterization of healthy aging effects on RSFC and highlight the importance of adopting a broad, system-wide perspective to analyze brain connectivity. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Meditation and successful aging: can meditative practices counteract age-related cognitive decline?

PubMed

Sperduti, Marco; Makowski, Dominique; Blondé, Philippe; Piolino, Pascale

2017-06-01

Life expectancy is constantly increasing in the developed countries due to medical, hygiene and socio-economic advances. Unfortunately, a longer life not always corresponds to a healthier life. Indeed, aging is associated with growing risk factors for illness associated with societal conditions (isolation, maltreatment), and neurodegenerative diseases. Even normal aging is associated with a cognitive decline that can hinder independence and quality of life of elderly. Thus, one major societal challenge is to build policies that support people of all ages to maintain a maximum health and functional capacity throughout their lives. Meditation could be a promising intervention in contrasting the negative effects of aging. Indeed, it has been shown to enhance cognitive efficiency in several domains, such as attention and executive functions in young adults. Nevertheless, whether these effects extend to old participants is still a matter of debate. Few studies have directly investigated this issue, reporting encouraging results in a large panel of cognitive functions, such as: attention, executive functions and memory. However, a final conclusion about the causal role of meditation and the generalization of these results is made difficult due to several methodological limitations. We propose a roadmap for future studies to pass these limitations with the hope that the present work would contribute to the development of the young research field of meditation in gerontology.

Gray Matter Atrophy in the Cerebellum-Evidence of Increased Vulnerability of the Crus and Vermis with Advancing Age.

PubMed

Yu, Teresa; Korgaonkar, Mayuresh S; Grieve, Stuart M

2017-04-01

This study examined patterns of cerebellar volumetric gray matter (GM) loss across the adult lifespan in a large cross-sectional sample. Four hundred and seventy-nine healthy participants (age range: 7-86 years) were drawn from the Brain Resource International Database who provided T1-weighted MRI scans. The spatially unbiased infratentorial template (SUIT) toolbox in SPM8 was used for normalisation of the cerebellum structures. Global volumetric and voxel-based morphometry analyses were performed to evaluate age-associated trends and gender-specific age-patterns. Global cerebellar GM shows a cross-sectional reduction with advancing age of 2.5 % per decade-approximately half the rate seen in the whole brain. The male cerebellum is larger with a lower percentage of GM, however, after controlling for total brain volume, no gender difference was detected. Analysis of age-related changes in GM volume revealed large bilateral clusters involving the vermis and cerebellar crus where regional loss occurred at nearly twice the average cerebellar rate. No gender-specific patterns were detected. These data confirm that regionally specific GM loss occurs in the cerebellum with age, and form a solid base for further investigation to find functional correlates for this global and focal loss.

Asymmetry of Hemispheric Network Topology Reveals Dissociable Processes between Functional and Structural Brain Connectome in Community-Living Elders

PubMed Central

Sun, Yu; Li, Junhua; Suckling, John; Feng, Lei

2017-01-01

Human brain is structurally and functionally asymmetrical and the asymmetries of brain phenotypes have been shown to change in normal aging. Recent advances in graph theoretical analysis have showed topological lateralization between hemispheric networks in the human brain throughout the lifespan. Nevertheless, apparent discrepancies of hemispheric asymmetry were reported between the structural and functional brain networks, indicating the potentially complex asymmetry patterns between structural and functional networks in aging population. In this study, using multimodal neuroimaging (resting-state fMRI and structural diffusion tensor imaging), we investigated the characteristics of hemispheric network topology in 76 (male/female = 15/61, age = 70.08 ± 5.30 years) community-dwelling older adults. Hemispheric functional and structural brain networks were obtained for each participant. Graph theoretical approaches were then employed to estimate the hemispheric topological properties. We found that the optimal small-world properties were preserved in both structural and functional hemispheric networks in older adults. Moreover, a leftward asymmetry in both global and local levels were observed in structural brain networks in comparison with a symmetric pattern in functional brain network, suggesting a dissociable process of hemispheric asymmetry between structural and functional connectome in healthy older adults. Finally, the scores of hemispheric asymmetry in both structural and functional networks were associated with behavioral performance in various cognitive domains. Taken together, these findings provide new insights into the lateralized nature of multimodal brain connectivity, highlight the potentially complex relationship between structural and functional brain network alterations, and augment our understanding of asymmetric structural and functional specializations in normal aging. PMID:29209197

The accommodative ciliary muscle function is preserved in older humans

NASA Astrophysics Data System (ADS)

Tabernero, Juan; Chirre, Emmanuel; Hervella, Lucia; Prieto, Pedro; Artal, Pablo

2016-05-01

Presbyopia, the loss of the eye’s accommodation capability, affects all humans aged above 45-50 years old. The two main reasons for this to happen are a hardening of the crystalline lens and a reduction of the ciliary muscle functionality with age. While there seems to be at least some partial accommodating functionality of the ciliary muscle at early presbyopic ages, it is not yet clear whether the muscle is still active at more advanced ages. Previous techniques used to visualize the accommodation mechanism of the ciliary muscle are complicated to apply in the older subjects, as they typically require fixation stability during long measurement times and/or to have an ultrasound probe directly in contact with the eye. Instead, we used our own developed method based on high-speed recording of lens wobbling to study the ciliary muscle activity in a small group of pseudophakic subjects (around 80 years old). There was a significant activity of the muscle, clearly able to contract under binocular stimulation of accommodation. This supports a purely lenticular-based theory of presbyopia and it might stimulate the search for new solutions to presbyopia by making use of the remaining contraction force still presented in the aging eye.

Effects of real-time thermal aging on graphite/polyimide composites

NASA Technical Reports Server (NTRS)

Haskins, J. F.; Kerr, J. R.

1985-01-01

As part of a program to evaluate high-temperature advanced composites for use on supersonic cruise transport aircraft, two graphite/polyimide composites have been aged at elevated temperatures for times up to 5.7 years. Work on the first, HT-S/710 graphite/polyimide, was started in 1974. Evaluation of the second polyimide, Celion 6000/LARC-160, began in 1980. Baseline properties are presented, including unnotched and notched tensile data as a function of temperature, compression, flexure, shear, and constant-amplitude fatigue data at R = 0.1 and R = -1. Tensile specimens were aged in ovens where pressure and aging temperatures were controlled for various times up to and including 50,000 hours. Changes in tensile strength were determined and plotted as a function of aging time. The HT-S/710 composite aged at 450 F and 550 F if compared to the Celion 6000/LARC-160 composite aged at 350 F and 450 F. After tensile testing, many of the thermal aging specimens were examined using a scanning electron microscope. Results of these studies are presented, and changes in properties and degradation mechanisms during high-temperature aging are discussed and illustrated using metallographic techniques.

Application of skeletal age based on x-ray in selecting sports talents

NASA Astrophysics Data System (ADS)

Mao, Zongzhen; Xu, Guodong; Song, Tao

2012-01-01

Skeletal age has been studied and proved that for most elite athletes, it was coincident with the chronological ages when they were young. In order to explore the application of skeletal age in selecting sports talent, 32 athletes (female, chronological age 5-12 y) were chosen from the Gymnastics Training Base in this study. Their left hand-wrists were photographed with X-rays, and then the skeletal ages were estimated by Chinese version of the Tanner-Whitehouse Skeletal Maturity Assessment System. At the same time, their body shapes, functions, and sports ability were also measured. Results showed that 71.88% of the skeletal age was proportional to their chronological age (+/- 1 y); while 18.75% of the skeletal maturity was retarded by 1- 2 year, 9.37% of those was advanced more than 1 year. On the other hand, the body shape, functions and sports ability of the athletes were positively related with their skeletal maturity. This study proved that the determination of skeletal maturity is a reliable evaluation for selecting sports talent. A further study on the influence of gymnastics on the skeletal age is of great significance.

Age determination of mallards

USGS Publications Warehouse

Krapu, G.L.; Johnson, D.H.; Dane, C.W.

1979-01-01

A technique for distinguishing adult from yearling wild mallards (Anas platyrhynchos), from late winter through the nesting season, was developed by applying discriminant analysis procedures to selected wing feather characters of 126 yearlings and 76 adults (2-year-olds) hand-reared from wild eggs during 1974, 1975, and 1977. Average values for feather characters generally increased as the birds advanced from yearlings to adults. Black-white surface area of greater secondary covert 2 was the single most reliable aging character identified during the study. The error rate was lowest in females (3%) when discriminant functions were used with measurements of primary 1 weight and black-white area of greater secondary covert 2 and in males (9%) when the functions were used with black-white area of greater secondary coverts 1, 2, and 3. Methodology precludes aging of birds in the field during capture operations.

High dietary advanced glycation end products are associated with poorer spatial learning and accelerated Aβ deposition in an Alzheimer mouse model.

PubMed

Lubitz, Irit; Ricny, Jan; Atrakchi-Baranes, Dana; Shemesh, Chen; Kravitz, Efrat; Liraz-Zaltsman, Sigal; Maksin-Matveev, Anna; Cooper, Itzik; Leibowitz, Avshalom; Uribarri, Jaime; Schmeidler, James; Cai, Weijing; Kristofikova, Zdena; Ripova, Daniela; LeRoith, Derek; Schnaider-Beeri, Michal

2016-04-01

There is growing evidence of the involvement of advanced glycation end products (AGEs) in the pathogenesis of neurodegenerative processes including Alzheimer's disease (AD) and their function as a seed for the aggregation of Aβ, a hallmark feature of AD. AGEs are formed endogenously and exogenously during heating and irradiation of foods. We here examined the effect of a diet high in AGEs in the context of an irradiated diet on memory, insoluble Aβ42 , AGEs levels in hippocampus, on expression of the receptor for AGEs (RAGE), and on oxidative stress in the vasculature. We found that AD-like model mice on high-AGE diet due to irradiation had significantly poorer memory, higher hippocampal levels of insoluble Aβ42 and AGEs as well as higher levels of oxidative stress on vascular walls, compared to littermates fed an isocaloric diet. These differences were not due to weight gain. The data were further supported by the overexpression of RAGE, which binds to Aβ42 and regulates its transport across the blood-brain barrier, suggesting a mediating pathway. Because exposure to AGEs can be diminished, these insights provide an important simple noninvasive potential therapeutic strategy for alleviating a major lifestyle-linked disease epidemic. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Effect of Aging on Periodontal Inflammation, Microbial Colonization, and Disease Susceptibility

PubMed Central

Wu, Y.; Dong, G.; Xiao, W.; Xiao, E.; Miao, F.; Syverson, A.; Missaghian, N.; Vafa, R.; Cabrera-Ortega, A.A.; Rossa, C.; Graves, D.T.

2016-01-01

Periodontitis is a chronic inflammatory disease induced by a biofilm that forms on the tooth surface. Increased periodontal disease is associated with aging. We investigated the effect of aging on challenge by oral pathogens, examining the host response, colonization, and osteoclast numbers in aged versus young mice. We also compared the results with mice with lineage-specific deletion of the transcription factor FOXO1, which reduces dendritic cell (DC) function. Periodontitis was induced by oral inoculation of Porphyromonas gingivalis and Fusobacterium nucleatum in young (4 to 5 mo) and aged (14 to 15 mo) mice. Aged mice as well as mice with reduced DC function had decreased numbers of DCs in lymph nodes, indicative of a diminished host response. In vitro studies suggest that reduced DC numbers in lymph nodes of aged mice may involve the effect of advanced glycation end products on DC migration. Surprisingly, aged mice but not mice with genetically altered DC function had greater production of antibody to P. gingivalis, greater IL-12 expression, and more plasma cells in lymph nodes following oral inoculation as compared with young mice. The greater adaptive immune response in aged versus young mice was linked to enhanced levels of P. gingivalis and reduced bacterial diversity. Thus, reduced bacterial diversity in aged mice may contribute to increased P. gingivalis colonization following inoculation and increased periodontal disease susceptibility, reflected by higher TNF levels and osteoclast numbers in the periodontium of aged versus young mice. PMID:26762510

Effect of Aging on Periodontal Inflammation, Microbial Colonization, and Disease Susceptibility.

PubMed

Wu, Y; Dong, G; Xiao, W; Xiao, E; Miao, F; Syverson, A; Missaghian, N; Vafa, R; Cabrera-Ortega, A A; Rossa, C; Graves, D T

2016-04-01

Periodontitis is a chronic inflammatory disease induced by a biofilm that forms on the tooth surface. Increased periodontal disease is associated with aging. We investigated the effect of aging on challenge by oral pathogens, examining the host response, colonization, and osteoclast numbers in aged versus young mice. We also compared the results with mice with lineage-specific deletion of the transcription factor FOXO1, which reduces dendritic cell (DC) function. Periodontitis was induced by oral inoculation of Porphyromonas gingivalis and Fusobacterium nucleatum in young (4 to 5 mo) and aged (14 to 15 mo) mice. Aged mice as well as mice with reduced DC function had decreased numbers of DCs in lymph nodes, indicative of a diminished host response. In vitro studies suggest that reduced DC numbers in lymph nodes of aged mice may involve the effect of advanced glycation end products on DC migration. Surprisingly, aged mice but not mice with genetically altered DC function had greater production of antibody to P. gingivalis, greater IL-12 expression, and more plasma cells in lymph nodes following oral inoculation as compared with young mice. The greater adaptive immune response in aged versus young mice was linked to enhanced levels of P. gingivalis and reduced bacterial diversity. Thus, reduced bacterial diversity in aged mice may contribute to increased P. gingivalis colonization following inoculation and increased periodontal disease susceptibility, reflected by higher TNF levels and osteoclast numbers in the periodontium of aged versus young mice. © International & American Associations for Dental Research 2016.

Recent advances in female sexual dysfunction.

PubMed

Davis, A R

2000-06-01

Female sexuality has received little scientific study. Recently, increased interest in this field has generated new research in the epidemiology, pathophysiology, and pharmacotherapy of female sexual dysfunction (FSD). A new FSD classification system has been proposed. Although sexual difficulties are highly prevalent among women, the degree of associated distress is unknown. Risk factors for FSD are probably both psychologic and physiologic. Aging or menopause is associated with lubrication difficulties, which can be treated with hormone replacement. Hysterectomy seems more likely to result in improvement rather then deterioration of sexual functioning. Depression may be a predictor of sexual dysfunction after hysterectomy. Vasoactive agents are currently being evaluated as treatment for female sexual arousal disorder. The most important advance in the study of female sexual function is the recent surge of interest in this relatively unexplored field.

Driving with advanced vehicle technology: A qualitative investigation of older drivers' perceptions and motivations for use.

PubMed

Gish, Jessica; Vrkljan, Brenda; Grenier, Amanda; Van Miltenburg, Benita

2017-09-01

For older drivers, in-vehicle technology offers much potential to improve safety and increase longevity of retaining both licensure and community mobility. However, little is known about how older drivers perceive Advanced Vehicle Technologies (AVTs) based on everyday driving experience. Interviews with 35 older drivers (20 men; 15 women) aged 60-85 who owned a vehicle with at least two AVTs (e.g., back-up camera, lane departure warning) were conducted to explore the meanings that older drivers assigned to AVTs and motivations for use, including whether age-related functional changes were part of their automobile purchase decision. Findings indicate that age-related changes are not a primary reason for why older adults seek out AVTs, but they still perceived and experienced AVTs to counteract age-related changes in driving performance based upon changes they felt occurring within the body. Older drivers also described AVTs as generating a sense of comfort behind-the-wheel. Comfort with this technology was equated with convenience, ease of use, and increased feelings of safety. Discussion emphasizes how assessments of the quality of driving performance and value of technology occur in relation to an aging body. Copyright © 2016 Elsevier Ltd. All rights reserved.

Angiotensin II receptor blocker inhibits abnormal accumulation of advanced glycation end products and retinal damage in a rat model of type 2 diabetes.

PubMed

Sugiyama, Tetsuya; Okuno, Takashi; Fukuhara, Masayuki; Oku, Hidehiro; Ikeda, Tsunehiko; Obayashi, Hiroshi; Ohta, Mitsuhiro; Fukui, Michiaki; Hasegawa, Goji; Nakamura, Naoto

2007-09-01

The effects of an angiotensin II receptor blocker (ARB) on the accumulation of one of advanced glycation end products (AGEs), pentosidine, expression of vascular endothelial growth factor (VEGF) and retinal function were investigated in Spontaneously Diabetic Torii (SDT) rats. Candesartan, an ARB, was administered to SDT rats from 10 to 44 weeks of age and the results compared with untreated SDT rats and SD rats. Electroretinograms (ERGs) were recorded to evaluate retinal function. At 44 weeks of age, pentosidine was quantified in the vitreous, lens and plasma using high-performance liquid chromatography (HPLC). Real-time reverse transcription-PCR (RT-PCR) analysis was also performed in order to measure VEGF mRNA expression in the retina. Histological changes were examined and immunohistochemistry for pentosidine performed on the retina and retinal microvasculature. In untreated SDT rats, the amplitudes of a- and b-waves, oscillatory potentials were reduced significantly at 44 weeks of age compared with the 10-week levels, whereas they remained unchanged in SDT rats treated with candesartan. The concentration of pentosidine in the vitreous and lens did not change in treated SDT rats but increased in untreated SDT rats. Retinal VEGF mRNA expression was inhibited in treated SDT rats. Histologically, proliferative tissue was detected around the optic disc, with pentosidine being detected only in untreated SDT rats. Our findings indicate the ARB may inhibit the development of diabetic retinopathy by reducing the accumulation of pentosidine, one of AGEs and expression of VEGF in the retina.

Rejuvenation of human cardiac progenitor cells with Pim-1 kinase.

PubMed

Mohsin, Sadia; Khan, Mohsin; Nguyen, Jonathan; Alkatib, Monique; Siddiqi, Sailay; Hariharan, Nirmala; Wallach, Kathleen; Monsanto, Megan; Gude, Natalie; Dembitsky, Walter; Sussman, Mark A

2013-10-25

Myocardial function is enhanced by adoptive transfer of human cardiac progenitor cells (hCPCs) into a pathologically challenged heart. However, advanced age, comorbidities, and myocardial injury in patients with heart failure constrain the proliferation, survival, and regenerative capacity of hCPCs. Rejuvenation of senescent hCPCs will improve the outcome of regenerative therapy for a substantial patient population possessing functionally impaired stem cells. Reverse phenotypic and functional senescence of hCPCs by ex vivo modification with Pim-1. C-kit-positive hCPCs were isolated from heart biopsy samples of patients undergoing left ventricular assist device implantation. Growth kinetics, telomere lengths, and expression of cell cycle regulators showed significant variation between hCPC isolated from multiple patients. Telomere length was significantly decreased in hCPC with slow-growth kinetics concomitant with decreased proliferation and upregulation of senescent markers compared with hCPC with fast-growth kinetics. Desirable youthful characteristics were conferred on hCPCs by genetic modification using Pim-1 kinase, including increases in proliferation, telomere length, survival, and decreased expression of senescence markers. Senescence characteristics of hCPCs are ameliorated by Pim-1 kinase resulting in rejuvenation of phenotypic and functional properties. hCPCs show improved cellular properties resulting from Pim-1 modification, but benefits were more pronounced in hCPC with slow-growth kinetics relative to hCPC with fast-growth kinetics. With the majority of patients with heart failure presenting advanced age, infirmity, and impaired regenerative capacity, the use of Pim-1 modification should be incorporated into cell-based therapeutic approaches to broaden inclusion criteria and address limitations associated with the senescent phenotype of aged hCPC.

Rejuvenation of Human Cardiac Progenitor Cells With Pim-1 Kinase

PubMed Central

Mohsin, Sadia; Khan, Mohsin; Nguyen, Jonathan; Alkatib, Monique; Siddiqi, Sailay; Hariharan, Nirmala; Wallach, Kathleen; Monsanto, Megan; Gude, Natalie; Dembitsky, Walter; Sussman, Mark A.

2014-01-01

Rationale Myocardial function is enhanced by adoptive transfer of human cardiac progenitor cells (hCPCs) into a pathologically challenged heart. However, advanced age, comorbidities, and myocardial injury in patients with heart failure constrain the proliferation, survival, and regenerative capacity of hCPCs. Rejuvenation of senescent hCPCs will improve the outcome of regenerative therapy for a substantial patient population possessing functionally impaired stem cells. Objective Reverse phenotypic and functional senescence of hCPCs by ex vivo modification with Pim-1. Methods and Results C-kit–positive hCPCs were isolated from heart biopsy samples of patients undergoing left ventricular assist device implantation. Growth kinetics, telomere lengths, and expression of cell cycle regulators showed significant variation between hCPC isolated from multiple patients. Telomere length was significantly decreased in hCPC with slow-growth kinetics concomitant with decreased proliferation and upregulation of senescent markers compared with hCPC with fast-growth kinetics. Desirable youthful characteristics were conferred on hCPCs by genetic modification using Pim-1 kinase, including increases in proliferation, telomere length, survival, and decreased expression of senescence markers. Conclusions Senescence characteristics of hCPCs are ameliorated by Pim-1 kinase resulting in rejuvenation of phenotypic and functional properties. hCPCs show improved cellular properties resulting from Pim-1 modification, but benefits were more pronounced in hCPC with slow-growth kinetics relative to hCPC with fast-growth kinetics. With the majority of patients with heart failure presenting advanced age, infirmity, and impaired regenerative capacity, the use of Pim-1 modification should be incorporated into cell-based therapeutic approaches to broaden inclusion criteria and address limitations associated with the senescent phenotype of aged hCPC. PMID:24044948

Fine structural changes in the lateral vestibular nucleus of aging rats

NASA Technical Reports Server (NTRS)

Johnson, J. E., Jr.; Miquel, J.

1974-01-01

The fine structure of the lateral vestibular nucleus was investigated in Sprague-Dawley rats, that were sacrified at 4 weeks, 6-8 weeks, 6-8 months, and 18-20 months of age. In the neuronal perikaria, the following age-associated changes were seen with increasing frequency with advancing age: rodlike nuclear inclusions and nuclear membrane invaginations; cytoplasmic dense bodies with the characteristics of lipofuscin; and moderate disorganization of the granular endoplasmic reticulum. Dense bodies were also seen in glial cells. Rats 18 to 20 months old showed dendritic swellings, axonal degeneration, and an apparent increase in the number of axosomatic synaptic terminals containing flattened vesicles (presumed to be inhibitory in function).

Bone Marrow Adipocyte Developmental Origin and Biology.

PubMed

Bukowska, Joanna; Frazier, Trivia; Smith, Stanley; Brown, Theodore; Bender, Robert; McCarthy, Michelle; Wu, Xiying; Bunnell, Bruce A; Gimble, Jeffrey M

2018-06-01

This review explores how the relationships between bone marrow adipose tissue (BMAT) adipogenesis with advancing age, obesity, and/or bone diseases (osteopenia or osteoporosis) contribute to mechanisms underlying musculoskeletal pathophysiology. Recent studies have re-defined adipose tissue as a dynamic, vital organ with functions extending beyond its historic identity restricted solely to that of an energy reservoir or sink. "State of the art" methodologies provide novel insights into the developmental origin, physiology, and function of different adipose tissue depots. These include genetic tracking of adipose progenitors, viral vectors application, and sophisticated non-invasive imaging modalities. While constricted within the rigid bone cavity, BMAT vigorously contributes to local and systemic metabolic processes including hematopoiesis, osteogenesis, and energy metabolism and undergoes dynamic changes as a function of age, diet, bone topography, or sex. These insights will impact future research and therapies relating to osteoporosis.

Development of a high-temperature durable catalyst for use in catalytic combustors for advanced automotive gas turbine engines

NASA Astrophysics Data System (ADS)

Tong, H.; Snow, G. C.; Chu, E. K.; Chang, R. L. S.; Angwin, M. J.; Pessagno, S. L.

1981-09-01

Durable catalytic reactors for advanced gas turbine engines were developed. Objectives were: to evaluate furnace aging as a cost effective catalytic reactor screening test, measure reactor degradation as a function of furnace aging, demonstrate 1,000 hours of combustion durability, and define a catalytic reactor system with a high probability of successful integration into an automotive gas turbine engine. Fourteen different catalytic reactor concepts were evaluated, leading to the selection of one for a durability combustion test with diesel fuel for combustion conditions. Eight additional catalytic reactors were evaluated and one of these was successfully combustion tested on propane fuel. This durability reactor used graded cell honeycombs and a combination of noble metal and metal oxide catalysts. The reactor was catalytically active and structurally sound at the end of the durability test.

Development of a high-temperature durable catalyst for use in catalytic combustors for advanced automotive gas turbine engines

NASA Technical Reports Server (NTRS)

Tong, H.; Snow, G. C.; Chu, E. K.; Chang, R. L. S.; Angwin, M. J.; Pessagno, S. L.

1981-01-01

Durable catalytic reactors for advanced gas turbine engines were developed. Objectives were: to evaluate furnace aging as a cost effective catalytic reactor screening test, measure reactor degradation as a function of furnace aging, demonstrate 1,000 hours of combustion durability, and define a catalytic reactor system with a high probability of successful integration into an automotive gas turbine engine. Fourteen different catalytic reactor concepts were evaluated, leading to the selection of one for a durability combustion test with diesel fuel for combustion conditions. Eight additional catalytic reactors were evaluated and one of these was successfully combustion tested on propane fuel. This durability reactor used graded cell honeycombs and a combination of noble metal and metal oxide catalysts. The reactor was catalytically active and structurally sound at the end of the durability test.

Association of advanced glycation end products and chronic kidney disease with macroangiopathy in type 2 diabetes.

PubMed

Rigalleau, V; Cougnard-Gregoire, A; Nov, S; Gonzalez, C; Maury, E; Lorrain, S; Gin, H; Barberger-Gateau, P

2015-03-01

Accumulation of advanced glycation end-products (AGEs), may explain the major contribution of chronic kidney disease (CKD) to cardiovascular events in patients with type 2 diabetes (T2D) related to their impaired renal function. The aim of this study was to analyze the factors associated with AGE assessed by skin autofluorescence and their association with macroangiopathy in T2D. We measured skin autofluorescence in patients hospitalized for T2D. Glomerular filtration rates were estimated (eGFR) by the EPI-CKD formula. Associations between skin autofluorescence, renal function and macroangiopathy were explored by multivariate analyses adjusting for diabetes duration and control. The 418 patients had T2D since 13.3 (SD 9.8) years on average, high mean HbA1C: 8.9%, (SD 1.8), (74 mmol/mol, (SD 15)) and often renal complications (49.4% with CKD). Their mean skin autofluorescence was 2.53 (SD 0.62) A.U. In multivariate linear regression, skin autofluorescence was significantly associated with age (+0.20 for ten more years, p<0.0001), renal insufficiency (-0.07 for less 10 mL/min/1.73 m² eGFR, p<0.0001) and smoking (+0.21, p=0.0004). Autofluorescence (p=0.01), but not CKD, was associated with macroangiopathy independent of diabetes duration and control. Accumulation of AGEs is independently associated with renal insufficiency and macroangiopathy in patients with T2D. Copyright © 2015 Elsevier Inc. All rights reserved.

Molecular mechanisms of aging and immune system regulation in Drosophila.

PubMed

Eleftherianos, Ioannis; Castillo, Julio Cesar

2012-01-01

Aging is a complex process that involves the accumulation of deleterious changes resulting in overall decline in several vital functions, leading to the progressive deterioration in physiological condition of the organism and eventually causing disease and death. The immune system is the most important host-defense mechanism in humans and is also highly conserved in insects. Extensive research in vertebrates has concluded that aging of the immune function results in increased susceptibility to infectious disease and chronic inflammation. Over the years, interest has grown in studying the molecular interaction between aging and the immune response to pathogenic infections. The fruit fly Drosophila melanogaster is an excellent model system for dissecting the genetic and genomic basis of important biological processes, such as aging and the innate immune system, and deciphering parallel mechanisms in vertebrate animals. Here, we review the recent advances in the identification of key players modulating the relationship between molecular aging networks and immune signal transduction pathways in the fly. Understanding the details of the molecular events involved in aging and immune system regulation will potentially lead to the development of strategies for decreasing the impact of age-related diseases, thus improving human health and life span.

Molecular Mechanisms of Aging and Immune System Regulation in Drosophila

PubMed Central

Eleftherianos, Ioannis; Castillo, Julio Cesar

2012-01-01

Aging is a complex process that involves the accumulation of deleterious changes resulting in overall decline in several vital functions, leading to the progressive deterioration in physiological condition of the organism and eventually causing disease and death. The immune system is the most important host-defense mechanism in humans and is also highly conserved in insects. Extensive research in vertebrates has concluded that aging of the immune function results in increased susceptibility to infectious disease and chronic inflammation. Over the years, interest has grown in studying the molecular interaction between aging and the immune response to pathogenic infections. The fruit fly Drosophila melanogaster is an excellent model system for dissecting the genetic and genomic basis of important biological processes, such as aging and the innate immune system, and deciphering parallel mechanisms in vertebrate animals. Here, we review the recent advances in the identification of key players modulating the relationship between molecular aging networks and immune signal transduction pathways in the fly. Understanding the details of the molecular events involved in aging and immune system regulation will potentially lead to the development of strategies for decreasing the impact of age-related diseases, thus improving human health and life span. PMID:22949833

Critical Appraisal of Advanced Glycation End Products (AGEs) and Circulating Soluble Receptors for Advanced Glycation End Products (sRAGE) as a Predictive Biomarkers for Cardiovascular Disease in Hemodialysis Patients.

PubMed

Assiri, Adel M A; Kamel, Hala F M; ALrefai, Abeer A

2018-05-22

The interaction of advanced glycation end products (AGE) and their receptors promote vascular complications of diabetes in hemodialysis (HD) patients. The soluble form of the receptor for the advanced glycation end-products (sRAGE) has been studied as a vascular biomarker in various diseases with controversial results. Our aim was to evaluate the association of the serum levels of the AGEs and their receptor sRAGE with cardiovascular disease (CVD) and the cardiovascular risk factors among HD patients. There were 130 HD patients and 80 age and gender matched control subjects were involved; 31.5% of the HD group were diabetic, which was an underlying cause of renal impairment; 36.1% had CVD, which was comprising 44.7% of diabetics and 55.3% of non-diabetic patients. The AGEs and sRAGE were assessed by enzyme linked immunosorbent assay (ELISA). In addition, the lipid profile, glycemic indices, pre-dialysis renal function tests, and hemoglobin % (Hb) were evaluated. The results show that the circulating AGEs and sRAGE levels were significantly higher in the HD patients. Those with underlying diabetes displayed higher sRAGE levels, which were positively correlated with hyperglycemia, HbA1C, and total cholesterol (TC). The HD patients with an increased serum sRAGE exhibited more cardiovascular risk factors (hypercholesterolemia and anemia) with a high prevalence of CVD. Using a linear regression analysis, we found a significant association of sRAGE with CVD and TC among HD patients, regardless of whether associating diabetes was an underlying cause of renal impairment. Overall, the HD patients displayed significantly higher serum AGEs with a concomitant increase in the circulating sRAGE levels, mainly in the diabetic HD, which were significantly associated with the CVD (independent predictors) and CV risk factors (hypercholesterolemia), mainly sRAGEs, regardless of the underlying diabetes mellitus. This highlights the prognostic role of AGEs and sRAGE in HD patients regardless of underlying cause in order to predict the risk for CVD.

Far-infrared protects vascular endothelial cells from advanced glycation end products-induced injury via PLZF-mediated autophagy in diabetic mice

PubMed Central

Chen, Cheng-Hsien; Chen, Tso-Hsiao; Wu, Mei-Yi; Chou, Tz-Chong; Chen, Jia-Rung; Wei, Meng-Jun; Lee, San-Liang; Hong, Li-Yu; Zheng, Cai-Mei; Chiu, I-Jen; Lin, Yuh-Feng; Hsu, Ching-Min; Hsu, Yung-Ho

2017-01-01

The accumulation of advanced glycation end products (AGEs) in diabetic patients induces vascular endothelial injury. Promyelocytic leukemia zinc finger protein (PLZF) is a transcription factor that can be activated by low-temperature far-infrared (FIR) irradiation to exert beneficial effects on the vascular endothelium. In the present study, we investigated the influence of FIR-induced PLZF activation on AGE-induced endothelial injury both in vitro and in vivo. FIR irradiation inhibited AGE-induced apoptosis in human umbilical vein endothelial cells (HUVECs). PLZF activation increased the expression of phosphatidylinositol-3 kinases (PI3K), which are important kinases in the autophagic signaling pathway. FIR-induced PLZF activation led to autophagy in HUVEC, which was mediated through the upregulation of PI3K. Immunofluorescence staining showed that AGEs were engulfed by HUVECs and localized to lysosomes. FIR-induced autophagy promoted AGEs degradation in HUVECs. In nicotinamide/streptozotocin-induced diabetic mice, FIR therapy reduced serum AGEs and AGEs deposition at the vascular endothelium. FIR therapy also reduced diabetes-induced inflammatory markers in the vascular endothelium and improved vascular endothelial function. These protective effects of FIR therapy were not found in PLZF-knockout mice. Our data suggest that FIR-induced PLZF activation in vascular endothelial cells protects the vascular endothelium in diabetic mice from AGE-induced injury. PMID:28071754

Nifedipine, a calcium channel blocker, inhibits advanced glycation end product (AGE)-elicited mesangial cell damage by suppressing AGE receptor (RAGE) expression via peroxisome proliferator-activated receptor-gamma activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsui, Takanori; Yamagishi, Sho-ichi, E-mail: shoichi@med.kurume-u.ac.jp; Takeuchi, Masayoshi

2009-07-24

The interaction between advanced glycation end products (AGE) and their receptor RAGE mediates the progressive alteration in renal architecture and loss of renal function in diabetic nephropathy. Oxidative stress generation and inflammation also play a central role in diabetic nephropathy. This study investigated whether and how nifedipine, a calcium channel blocker (CCB), blocked the AGE-elicited mesangial cell damage in vitro. Nifedipine, but not amlodipine, a control CCB, down-regulated RAGE mRNA levels and subsequently reduced reactive oxygen species (ROS) generation in AGE-exposed mesangial cells. AGE increased mRNA levels of vascular cell adhesion molecule-1 (VCAM-1) and induced monocyte chemoattractant protein-1 (MCP-1) productionmore » in mesangial cells, both of which were prevented by the treatment with nifedipine, but not amlodipine. The beneficial effects of nifedipine on AGE-exposed mesangial cells were blocked by the simultaneous treatment of GW9662, an inhibitor of peroxisome proliferator-activated receptor-{gamma} (PPAR-{gamma}). Although nifedipine did not affect expression levels of PPAR-{gamma}, it increased the PPAR-{gamma} transcriptional activity in mesangial cells. Our present study provides a unique beneficial aspect of nifedipine on diabetic nephropathy; it could work as an anti-inflammatory agent against AGE by suppressing RAGE expression in cultured mesangial cells via PPAR-{gamma} activation.« less

Assessment of biochemical liver function tests in relation to age among steady state sickle cell anemia patients.

PubMed

Akuyam, S A; Abubakar, A; Lawal, N; Yusuf, R; Aminu, S M; Hassan, A; Musa, A; Bello, A K; Yahaya, I A; Okafor, P A

2017-11-01

Multiorgan failure including liver dysfunction is a common finding in sickle cell anemia (SCA) patients, the cause of which is multifactorial with advancing age said to be a major determinant. There is a paucity of data on liver function among SCA patients in relation to age in northern Nigerian hospitals, including Ahmadu Bello University Teaching Hospital (ABUTH), Zaria. This study was to assess the biochemical liver function tests (LFTs) as they relate to age among SCA patients in steady state, with a view to improving the overall monitoring of these patients. This study was carried out in ABUTH, Zaria, Northern Nigeria. LFTs were carried out in 100 SCA and 100 apparently healthy participants (controls). The SCA group was made up of fifty adults and fifty children diagnosed of SCA, whereas the control group was made up of fifty adults and fifty children who were apparently healthy and had hemoglobin AA. Paired two-tailed Student's t-test for matched samples and Pearson's linear correlation statistical methods were employed for the data analysis using Microsoft Office Excel 2007. A P ≤ 0.05 was considered as statistically significant. The serum concentrations of total bilirubin (TB), alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and AST/ALT ratio were significantly higher in SCA patients compared to the controls (P = 0.001, P = 0.001, P = 0.05, P = 0.05 and P = 0.001, respectively). Serum total protein (TP) and ALB were significantly lower (P = 0.01 and P < 0.05, respectively) in SCA patients compared with the controls. The levels of TB, ALT, AST, ALP, and AST/ALT were significantly lower in SCA adults compared to SCA children, whereas TP and ALB were higher in SCA adults compared to the SCA children. There were significant negative correlations between age and each of TB, ALT, AST, ALP, and AST/ALT, and significant positive correlations between age and each of TP and ALB in SCA patients. There are mild LFTs derangements in SCA patients even in steady state with the extent of the abnormalities decreasing with advancing age of the patients.

Advanced glycation end products: A link between metabolic and endothelial dysfunction in polycystic ovary syndrome?

PubMed

Pertynska-Marczewska, Magdalena; Diamanti-Kandarakis, Evanthia; Zhang, John; Merhi, Zaher

2015-11-01

Polycystic ovary syndrome (PCOS), a heterogeneous syndrome of reproductive and metabolic alterations, is associated with increased long-term risk of cardiovascular complications. This phenomenon has been linked to an increase in oxidative stress and inflammatory markers. Advanced glycation end products (AGEs) are pro-inflammatory molecules that trigger a state of intracellular oxidative stress and inflammation after binding to their cell membrane receptors RAGE. The activation of the AGE-RAGE axis has been well known to play a role in atherosclerosis in both men and women. Women with PCOS have systemic chronic inflammatory condition even at the ovarian level as represented by elevated levels of serum/ovarian AGEs and increased expression of the pro-inflammatory RAGE in ovarian tissue. Data also showed the presence of sRAGE in the follicular fluid and its potential protective role against the harmful effect of AGEs on ovarian function. Thus, whether AGE-RAGE axis constitutes a link between metabolic and endothelial dysfunction in women with PCOS is addressed in this review. Additionally, we discuss the role of hormonal changes observed in PCOS and how they are linked with the AGE-RAGE axis in order to better understand the nature of this complex syndrome whose consequences extend well beyond reproduction. Copyright © 2015 Elsevier Inc. All rights reserved.

Sex differences in vascular endothelial function and health in humans: impacts of exercise.

PubMed

Green, Daniel J; Hopkins, Nicola D; Jones, Helen; Thijssen, Dick H J; Eijsvogels, Thijs M H; Yeap, Bu B

2016-02-01

What is the topic of this review? This brief review discusses potential sex differences in arterial function across the age span, with special emphasis on the effects of oestrogen and testosterone on the vascular endothelium. What advances does it highlight? We discuss the relationship between the impacts of sex hormones on arterial function and health in the context of epidemiological evidence pertaining to the menopause and ageing. Studies performed in humans are emphasized, alongside insights from animal studies. Findings suggest that the combination of exercise and hormone administration should be potentially synergistic or additive in humans. This brief review presents historical evidence for the purported impacts of male and female sex hormones on the vasculature in humans, including effects on macro- and microvascular function and health. Impacts of ageing on hormonal changes and arterial function are considered in the context of the menopause. Physiological data are presented alongside clinical outcomes from large trials, in an attempt to rationalize disparate findings along the bench-to-bedside continuum. Finally, the theoretical likelihood that exercise and hormone treatment may induce synergistic and/or additive vascular adaptations is developed in the context of recent laboratory studies that have compared male and female responses to training. Differences between men and women in terms of the impact of age and cardiorespiratory fitness on endothelial function are addressed. Ultimately, this review highlights the paucity of high-quality and compelling evidence regarding the fundamental impact, in humans, of sex differences on arterial function and the moderating impacts of exercise on arterial function, adaptation and health at different ages in either sex. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.

The association between radiographic severity and pre-operative function in patients undergoing primary knee replacement for osteoarthritis.

PubMed

Dowsey, Michelle M; Dieppe, Paul; Lohmander, Stefan; Castle, David; Liew, Danny; Choong, Peter F M

2012-12-01

To determine the association between radiographic osteoarthritis (OA) and pre-operative function in patients undergoing primary knee replacement. Single centre study examining pre-operative outcomes in a consecutive series of 525 patients who underwent primary knee replacement for OA between January 2006 and December 2007. Pre-operative data included: demographics, American Society of Anaesthesiologists (ASA) status and OA in the contralateral knee. The International Knee Society (IKS) rating and Short Form-12 (SF-12) were recorded for each patient. Pre-operative radiographs were read by a single observer for Kellgren and Lawrence (K&L) grading and Osteoarthritis Research Society International (OARSI) atlas features. Multiple linear regression was used to assess the strength of associations between radiographic OA severity and function, adjusting for clinically relevant variables. Lateral tibiofemoral osteophyte grade was an independent predictor of pre-operative function as determined by the functional sub-scale of the IKS in patients undergoing primary knee replacement (coefficient=2.58, p=0.033). No associations were evident between pre-operative function and modified K&L, joint space narrowing, Ahlbäck attrition and coronal plane deformity. Other statistically significant predictors of poorer pre-operative function included: advancing age, female gender, knee pain and poorer SF-12 mental component summary scores which including osteophyte grade accounted for 24.6% of the variation in functional scores, (r=0.496). Osteophytes in the lateral compartment of the knee were associated with pre-operative function in patients with advanced knee OA. Further studies are required which examine individual radiographic features specifically in patients with advanced knee OA to determine their relationship to pre-operative pain and function. Copyright © 2012 Elsevier B.V. All rights reserved.

Food-advanced glycation end products aggravate the diabetic vascular complications via modulating the AGEs/RAGE pathway.

PubMed

Lv, Xing; Lv, Gao-Hong; Dai, Guo-Ying; Sun, Hong-Mei; Xu, Hui-Qin

2016-11-01

The aim of this study was to investigate the effects of high-advanced glycation end products (AGEs) diet on diabetic vascular complications. The Streptozocin (STZ)-induced diabetic mice were fed with high-AGEs diet. Diabetic characteristics, indicators of renal and cardiovascular functions, and pathohistology of pancreas, heart and renal were evaluated. AGEs/RAGE/ROS pathway parameters were determined. During the experiments, the diabetic mice exhibited typical characteristics including weight loss, polydipsia, polyphagia, polyuria, high-blood glucose, and low-serum insulin levels. However, high-AGEs diet effectively aggravated these diabetic characteristics. It also increased the 24-h urine protein levels, serum levels of urea nitrogen, creatinine, c-reactive protein (CRP), low density lipoprotein (LDL), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the diabetic mice. High-AGEs diet deteriorated the histology of pancreas, heart, and kidneys, and caused structural alterations of endothelial cells, mesangial cells and podocytes in renal cortex. Eventually, high-AGEs diet contributed to the high-AGE levels in serum and kidneys, high-levels of reactive oxygen species (ROS) and low-levels of superoxide dismutase (SOD) in serum, heart, and kidneys. It also upregulated RAGE mRNA and protein expression in heart and kidneys. Our results showed that high-AGEs diet deteriorated vascular complications in the diabetic mice. The activation of AGEs/RAGE/ROS pathway may be involved in the pathogenesis of vascular complications in diabetes. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

The pathological role of advanced glycation end products-downregulated heat shock protein 60 in islet β-cell hypertrophy and dysfunction.

PubMed

Guan, Siao-Syun; Sheu, Meei-Ling; Yang, Rong-Sen; Chan, Ding-Cheng; Wu, Cheng-Tien; Yang, Ting-Hua; Chiang, Chih-Kang; Liu, Shing-Hwa

2016-04-26

Heat shock protein 60 (HSP60) is a mitochondrial chaperone. Advanced glycation end products (AGEs) have been shown to interfere with the β-cell function. We hypothesized that AGEs induced β-cell hypertrophy and dysfunction through a HSP60 dysregulation pathway during the stage of islet/β-cell hypertrophy of type-2-diabetes. We investigated the role of HSP60 in AGEs-induced β-cell hypertrophy and dysfunction using the models of diabetic mice and cultured β-cells. Hypertrophy, increased levels of p27Kip1, AGEs, and receptor for AGEs (RAGE), and decreased levels of HSP60, insulin, and ATP content were obviously observed in pancreatic islets of 12-week-old db/db diabetic mice. Low-concentration AGEs significantly induced the cell hypertrophy, increased the p27Kip1 expression, and decreased the HSP60 expression, insulin secretion, and ATP content in cultured β-cells, which could be reversed by RAGE neutralizing antibody. HSP60 overexpression significantly reversed AGEs-induced hypertrophy, dysfunction, and ATP reduction in β-cells. Oxidative stress was also involved in the AGEs-decreased HSP60 expression in β-cells. Pancreatic sections from diabetic patient showed islet hypertrophy, increased AGEs level, and decreased HSP60 level as compared with normal subject. These findings highlight a novel mechanism by which a HSP60-correlated signaling pathway contributes to the AGEs-RAGE axis-induced β-cell hypertrophy and dysfunction under diabetic hyperglycemia.

The pathological role of advanced glycation end products-downregulated heat shock protein 60 in islet β-cell hypertrophy and dysfunction

PubMed Central

Wu, Cheng-Tien; Yang, Ting-Hua; Chiang, Chih-Kang; Liu, Shing-Hwa

2016-01-01

Heat shock protein 60 (HSP60) is a mitochondrial chaperone. Advanced glycation end products (AGEs) have been shown to interfere with the β-cell function. We hypothesized that AGEs induced β-cell hypertrophy and dysfunction through a HSP60 dysregulation pathway during the stage of islet/β-cell hypertrophy of type-2-diabetes. We investigated the role of HSP60 in AGEs-induced β-cell hypertrophy and dysfunction using the models of diabetic mice and cultured β-cells. Hypertrophy, increased levels of p27Kip1, AGEs, and receptor for AGEs (RAGE), and decreased levels of HSP60, insulin, and ATP content were obviously observed in pancreatic islets of 12-week-old db/db diabetic mice. Low-concentration AGEs significantly induced the cell hypertrophy, increased the p27Kip1 expression, and decreased the HSP60 expression, insulin secretion, and ATP content in cultured β-cells, which could be reversed by RAGE neutralizing antibody. HSP60 overexpression significantly reversed AGEs-induced hypertrophy, dysfunction, and ATP reduction in β-cells. Oxidative stress was also involved in the AGEs-decreased HSP60 expression in β-cells. Pancreatic sections from diabetic patient showed islet hypertrophy, increased AGEs level, and decreased HSP60 level as compared with normal subject. These findings highlight a novel mechanism by which a HSP60-correlated signaling pathway contributes to the AGEs-RAGE axis-induced β-cell hypertrophy and dysfunction under diabetic hyperglycemia. PMID:27056903

Advanced lipid peroxidation end products in oxidative damage to proteins. Potential role in diseases and therapeutic prospects for the inhibitors.

PubMed

Negre-Salvayre, A; Coatrieux, C; Ingueneau, C; Salvayre, R

2008-01-01

Reactive carbonyl compounds (RCCs) formed during lipid peroxidation and sugar glycoxidation, namely Advanced lipid peroxidation end products (ALEs) and Advanced Glycation end products (AGEs), accumulate with ageing and oxidative stress-related diseases, such as atherosclerosis, diabetes or neurodegenerative diseases. RCCs induce the 'carbonyl stress' characterized by the formation of adducts and cross-links on proteins, which progressively leads to impaired protein function and damages in all tissues, and pathological consequences including cell dysfunction, inflammatory response and apoptosis. The prevention of carbonyl stress involves the use of free radical scavengers and antioxidants that prevent the generation of lipid peroxidation products, but are inefficient on pre-formed RCCs. Conversely, carbonyl scavengers prevent carbonyl stress by inhibiting the formation of protein cross-links. While a large variety of AGE inhibitors has been developed, only few carbonyl scavengers have been tested on ALE-mediated effects. This review summarizes the signalling properties of ALEs and ALE-precursors, their role in the pathogenesis of oxidative stress-associated diseases, and the different agents efficient in neutralizing ALEs effects in vitro and in vivo. The generation of drugs sharing both antioxidant and carbonyl scavenger properties represents a new therapeutic challenge in the treatment of carbonyl stress-associated diseases.

Computer-based symptom assessment is feasible in patients with advanced cancer: results from an international multicenter study, the EPCRC-CSA.

PubMed

Hjermstad, Marianne Jensen; Lie, Hanne C; Caraceni, Augusto; Currow, David C; Fainsinger, Robin L; Gundersen, Odd Erik; Haugen, Dagny Faksvaag; Heitzer, Ellen; Radbruch, Lukas; Stone, Patrick C; Strasser, Florian; Kaasa, Stein; Loge, Jon Håvard

2012-11-01

Symptom assessment by computers is only effective if it provides valid results and is perceived as useful for clinical use by the end users: patients and health care providers. To identify factors associated with discontinuation, time expenditure, and patient preferences of the computerized symptom assessment used in an international multicenter data collection project: the European Palliative Care Research Collaborative-Computerized Symptom Assessment. Cancer patients with incurable metastatic or locally advanced disease were recruited from 17 centers in eight countries, providing 1017 records for analyses. Observer-based registrations and patient-reported measures on pain, depression, and physical function were entered on touch screen laptop computers. The entire assessment was completed by 94.9% (n = 965), with median age 63 years (range 18-91 years) and median Karnofsky Performance Status (KPS) score of 70 (range 20-100). Predictive factors for noncompletion were higher age, lower KPS, and more pain (P ≤ 0.012). Time expenditure among completers increased with higher age, male gender, Norwegian nationality, number of comorbidities, and lower physical functioning (P ≤ 0.007) but was inversely related to pain levels and tiredness (P ≤ 0.03). Need for assistance was predicted by higher age, nationality other than Norwegian, lower KPS, and lower educational level (P < 0.001). More than 50% of patients preferred computerized assessment to a paper and pencil version. The high completion rate shows that symptom assessment by computers is feasible in patients with advanced cancer. However, reduced performance status reduces compliance and increases the need for assistance. Future work should aim at identifying the minimum set of valid screening questions and refine the software to optimize symptom assessment and reduce respondent burden in frail patients. Copyright © 2012 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Influence of physical exercise on microRNAs in skeletal muscle regeneration, aging and diseases

PubMed Central

Ultimo, Simona; Zauli, Giorgio; Martelli, Alberto M.; Vitale, Marco; McCubrey, James A.; Capitani, Silvano; Neri, Luca M.

2018-01-01

Skeletal muscle is a dynamic tissue with remarkable plasticity and its growth and regeneration are highly organized, with the activation of specific transcription factors, proliferative pathways and cytokines. The decline of skeletal muscle tissue with age, is one of the most important causes of functional loss of independence in older adults. Maintaining skeletal muscle function throughout the lifespan is a prerequisite for good health and independent living. Physical activity represents one of the most effective preventive agents for muscle decay in aging. Several studies have underlined the importance of microRNAs (miRNAs) in the control of myogenesis and of skeletal muscle regeneration and function. In this review, we reported an overview and recent advances about the role of miRNAs expressed in the skeletal muscle, miRNAs regulation by exercise in skeletal muscle, the consequences of different physical exercise training modalities in the skeletal muscle miRNA profile, their regulation under pathological conditions and the role of miRNAs in age-related muscle wasting. Specific miRNAs appear to be involved in response to different types of exercise and therefore to play an important role in muscle fiber identity and myofiber gene expression in adults and elder population. Understanding the roles and regulation of skeletal muscle miRNAs during muscle regeneration may result in new therapeutic approaches in aging or diseases with impaired muscle function or re-growth. PMID:29682218

Glycation of antibodies: Modification, methods and potential effects on biological functions.

PubMed

Wei, Bingchuan; Berning, Kelsey; Quan, Cynthia; Zhang, Yonghua Taylor

Glycation is an important protein modification that could potentially affect bioactivity and molecular stability, and glycation of therapeutic proteins such as monoclonal antibodies should be well characterized. Glycated protein could undergo further degradation into advance glycation end (AGE) products. Here, we review the root cause of glycation during the manufacturing, storage and in vivo circulation of therapeutic antibodies, and the current analytical methods used to detect and characterize glycation and AGEs, including boronate affinity chromatography, charge-based methods, liquid chromatography-mass spectrometry and colorimetric assay. The biological effects of therapeutic protein glycation and AGEs, which ranged from no affect to loss of activity, are also discussed.

Serum pentosidine as an indicator of Alzheimer's disease.

PubMed

Meli, M; Perier, C; Ferron, C; Parssegny, F; Denis, C; Gonthier, R; Laurent, B; Reynaud, E; Frey, J; Chamson, A

2002-04-01

Pentosidine, an advanced glycation end product (AGE), was assayed by HPLC in serum proteins from patients with Alzheimer type dementia (AD), patients with diabetes mellitus (D), and healthy (C) age-matched old subjects (mean age from each group = 84 years). Serum pentosidine was significantly different between the three groups despite similar renal function (serum creatinine < 160 micromol/L). In all groups of patients, pentosidine was independent of glycated hemoglobin (HbA1C) and the early glycation marker fructosamine and appeared to be an independent marker, mainly bound to serum albumin. Pentosidine could be an important factor useful for the diagnosis of Alzheimer's disease.

A new measure for assessing executive function across a wide age range: children and adults find happy-sad more difficult than day-night.

PubMed

Lagattuta, Kristin Hansen; Sayfan, Liat; Monsour, Michael

2011-05-01

Two experiments examined 4- to 11-year-olds' and adults' performance (N = 350) on two variants of a Stroop-like card task: the day-night task (say 'day' when shown a moon and 'night' when shown a sun) and a new happy-sad task (say 'happy' for a sad face and 'sad' for a happy face). Experiment 1 featured colored cartoon drawings. In Experiment 2, the happy-sad task featured photographs, and pictures for both measures were gray scale. All age groups made more errors and took longer to respond to the happy-sad versus the day-night versions. Unlike the day-night task, the happy-sad task did not suffer from ceiling effects, even in adults. The happy-sad task provides a methodological advance for measuring executive function across a wide age range.

Rates of decline in Alzheimer disease decrease with age.

PubMed

Holland, Dominic; Desikan, Rahul S; Dale, Anders M; McEvoy, Linda K

2012-01-01

Age is the strongest risk factor for sporadic Alzheimer disease (AD), yet the effects of age on rates of clinical decline and brain atrophy in AD have been largely unexplored. Here, we examined longitudinal rates of change as a function of baseline age for measures of clinical decline and structural MRI-based regional brain atrophy, in cohorts of AD, mild cognitive impairment (MCI), and cognitively healthy (HC) individuals aged 65 to 90 years (total n = 723). The effect of age was modeled using mixed effects linear regression. There was pronounced reduction in rates of clinical decline and atrophy with age for AD and MCI individuals, whereas HCs showed increased rates of clinical decline and atrophy with age. This resulted in convergence in rates of change for HCs and patients with advancing age for several measures. Baseline cerebrospinal fluid densities of AD-relevant proteins, Aβ(1-42), tau, and phospho-tau(181p) (ptau), showed a similar pattern of convergence with advanced age across cohorts, particularly for ptau. In contrast, baseline clinical measures did not differ by age, indicating uniformity of clinical severity at baseline. These results imply that the phenotypic expression of AD is relatively mild in individuals older than approximately 85 years, and this may affect the ability to distinguish AD from normal aging in the very old. Our findings show that inclusion of older individuals in clinical trials will substantially reduce the power to detect disease-modifying therapeutic effects, leading to dramatic increases in required clinical trial sample sizes with age of study sample.

Correlation of pulmonary function and usual interstitial pneumonia computed tomography patterns in idiopathic pulmonary fibrosis.

PubMed

Arcadu, Antonella; Byrne, Suzanne C; Pirina, Pietro; Hartman, Thomas E; Bartholmai, Brian J; Moua, Teng

2017-08-01

Little is known about presenting 'inconsistent' or 'possible' usual interstitial pneumonia (UIP) computed tomography (CT) patterns advancing to 'consistent' UIP as disease progresses in idiopathic pulmonary fibrosis (IPF). We hypothesized that if 'consistent' UIP represented more advanced disease, such a pattern on presentation should also correlate with more severe pulmonary function test (PFT) abnormalities. Consecutive IPF patients (2005-2013) diagnosed by international criteria with baseline PFT and CT were included. Presenting CTs were assessed by three expert radiologists for consensus UIP pattern ('consistent', 'possible', and 'inconsistent'). Approximation of individual and combined interstitial abnormalities was also performed with correlation of interstitial abnormalities and UIP CT pattern made with PFT findings and survival. Three-hundred and fifty patients (70% male) were included with a mean age of 68.3 years. Mean percent predicted forced vital capacity (FVC%) and diffusion capacity (DLCO%) was 64% and 45.5% respectively. Older age and male gender correlated more with 'consistent' UIP CT pattern. FVC% was not associated with any UIP pattern but did correlate with total volume of radiologist assessed interstitial abnormalities. DLCO% was lower in those with 'consistent' UIP pattern. A 'consistent' UIP CT pattern was also not independently predictive of survival after correction for age, gender, FVC%, and DLCO%. PFT findings appear to correlate with extent of radiologic disease but not specific morphologic patterns. Whether such UIP patterns represent different stages of disease severity or radiologic progression is not supported by coinciding pulmonary function decline. Copyright © 2017 Elsevier Ltd. All rights reserved.

Relationships between regional cerebellar volume and sensorimotor and cognitive function in young and older adults

PubMed Central

Bernard, Jessica A.; Seidler, Rachael D.

2013-01-01

The cerebellum has been implicated in both sensorimotor and cognitive function, but is known to undergo volumetric declines with advanced age. Individual differences in regional cerebellar volume may therefore provide insight into performance variability across the lifespan, as has been shown with other brain structures and behaviors. Here, we investigated whether there are regional age differences in cerebellar volume in young and older adults, and whether these volumes explain, in part, individual differences in sensorimotor and cognitive task performance. We found that older adults had smaller cerebellar volume than young adults; specifically, lobules in the anterior cerebellum were more impacted by age. Multiple regression analyses for both age groups revealed associations between sensorimotor task performance in several domains (balance, choice reaction time, and timing) and regional cerebellar volume. There were also relationships with working memory, but none with measures of general cognitive or executive function. Follow-up analyses revealed several differential relationships with age between regional volume and sensorimotor performance. These relationships were predominantly selective to cerebellar regions that have been implicated in cognitive functions. Therefore, it may be the cognitive aspects of sensorimotor task performance that are best explained by individual differences in regional cerebellar volumes. In sum, our results demonstrate the importance of regional cerebellar volume with respect to both sensorimotor and cognitive performance, and we provide additional insight into the role of the cerebellum in age-related performance declines. PMID:23625382

Visual impairment in Finnish Usher syndrome type III.

PubMed

Plantinga, Rutger F; Pennings, Ronald J E; Huygen, Patrick L M; Sankila, Eeva-Marja; Tuppurainen, Kaija; Kleemola, Leenamaija; Cremers, Cor W R J; Deutman, August F

2006-02-01

To evaluate visual impairment in Finnish Usher syndrome type 3 (USH3) and compare this with visual impairment in Usher syndrome types 1b (USH1b) and 2a (USH2a). We carried out a retrospective study of 28 Finnish USH3 patients, 24 Dutch USH2a patients and 17 Dutch USH1b patients. Cross-sectional regression analyses of the functional acuity score (FAS), functional field score (FFS*) and functional vision score (FVS*) related to age were performed for all patients. The FFS* and FVS* were calculated using the isoptre V-4 test target instead of the usual III-4 target. Statistical tests relating to regression lines and Student's t-test were used to compare between USH3 patients and the other genetic subtypes of Usher syndrome. Cross-sectional analyses revealed significant deterioration in the FAS (1.3% per year), FFS* (1.4% per year) and FVS* (1.8% per year) with advancing age in the USH3 patient group. At a given age the USH3 patients showed significantly poorer visual field function than the USH2a patients. The rate of deterioration in visual function in Finnish USH3 patients was fairly similar to that in Dutch USH1b or USH2a patients. At a given age, visual field impairment in USH3 patients was similar to that in USH1b patients but poorer than in USH2a patients.

The Hallmarks of Aging

PubMed Central

López-Otín, Carlos; Blasco, Maria A.; Partridge, Linda; Serrano, Manuel; Kroemer, Guido

2013-01-01

Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contribution to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging with minimal side-effects. PMID:23746838

Longitudinal alterations in health-related quality of life and its impact on the clinical course of patients with advanced hepatocellular carcinoma receiving sorafenib treatment.

PubMed

Shomura, Masako; Kagawa, Tatehiro; Okabe, Haruka; Shiraishi, Koichi; Hirose, Shunji; Arase, Yoshitaka; Tsuruya, Kota; Takahira, Sachiko; Mine, Tetsuya

2016-11-11

This study aimed to identify the health-related quality of life (HRQOL) domains associated with prognosis by assessing longitudinal alterations in HRQOL in patients with advanced hepatocellular carcinoma receiving sorafenib. We prospectively assessed HRQOL by administering the SF-36 questionnaire 3-monthly to consecutive patients with advanced hepatocellular carcinoma receiving sorafenib. We evaluated the impact of HRQOL on their overall survival and duration of treatment with sorafenib using Cox's proportional hazards model. There were 54 participants: 42 (78 %) were male, the median age was 71 years, 24 (44 %) had hepatitis C virus infection, 33 (61 %) had Child-Pugh scores of 5, and 30 (56 %) had TNM stage IV hepatocellular carcinoma. The median overall survival and treatment duration were 9 and 5 months, respectively, and 40 patients (74 %) died. Thirteen patients receiving sorafenib over a 1-year period maintained all domain scores >40, without a significant decline during the treatment period. In contrast, physical functioning, physical role, and vitality scores declined continuously and significantly in the year before death (in the 40 patients who died). Previous curative treatment and physical functioning scores ≥40 at baseline were significantly associated with longer overall survival by multivariate analysis. Social functioning scores ≥40, absence of vascular invasion, and lower DCP value were significant predictors of longer treatment duration. HRQOL was not significantly impaired in those patients who were able to complete a 1-year course of sorafenib treatment. Baseline physical functioning scores ≥40 and social functioning scores ≥40 were significantly associated with longer overall survival and longer treatment duration, respectively. Thus, HRQOL could be a valuable marker to predict the clinical course of patients with advanced hepatocellular carcinoma receiving sorafenib.

Gait kinematics and kinetics are affected more by peripheral arterial disease than age

PubMed Central

Myers, Sara A.; Applequist, Bryon C.; Huisinga, Jessie M.; Pipinos, Iraklis I.; Johanning, Jason M.

2016-01-01

Peripheral arterial disease (PAD) produces abnormal gait and disproportionately affects older individuals. The current study investigated PAD gait biomechanics in young and older subjects. Sixty-one (31 < 65 years, age: 57.4 ± 5.3 years and 30 ≥ 65 years; age: 72.2 ± 5.4 years) patients with PAD and 52 healthy age matched controls were included. Patients with PAD were tested during pain free walking and compared to matched healthy controls. Joint kinematics and kinetics (torques) were compared using a 2 × 2 ANOVA (Groups: PAD vs. Control, Age: Younger vs. Older). Patients with PAD had significantly increased ankle and decreased hip range of motion during the stance phase as well as decreased ankle dorsiflexor torque compared to controls. Gait changes in older individuals are largely constrained to time-distance parameters. Joint kinematics and kinetics are significantly altered in patients with PAD during pain free ambulation. Symptomatic PAD produces a consistent ambulatory deficit across ages definable by advanced biomechanical analysis. The most important finding of the current study is that gait, in the absence of PAD and other ambulatory comorbidities, does not decline significantly with age based on advanced biomechanical analysis. Therefore, previous studies must be examined in the context of potential PAD patients being present in the population and future ambulatory studies must include PAD as a confounding factor when assessing the gait function of elderly individuals. PMID:27149635

Therapeutic uses of drug-carrier systems for imidazole-containing dipeptide compounds that act as pharmacological chaperones and have significant impact on the treatment of chronic diseases associated with increased oxidative stress and the formation of advanced glycation end products.

PubMed

Babizhayev, Mark A; Yegorov, Yegor E

2010-01-01

The purpose of this study was to determine how the naturally occurring molecules N-acetylcarnosine, L-carnosine, and carcinine, which are chemical or pharmacological chaperones, affect the cells and biomolecules of patients with skin diseases, cosmetic skin lesions, or underlying clinically significant visual impairment such as age-related cataracts, age-related retinal degeneration, and ocular complications of diabetes. We evaluated and characterized the effects of cited pharmacological chaperones on enzyme activity, protein structure in tissues, and other biomarkers of diseases in skin cells and tissues or in ocular tissues (human cataractous and normal lenses) derived from ophthalmic patients or age-matched donors. The samples were used to test imidazole-containing peptidomimetic chemical/pharmacological chaperones in relation to oxidative stress induced by reaction with lipid peroxides or advanced non-enzymatic glycation processes. Chaperone function is characterized by interaction with other proteins, mediating their folding, transport, and interaction with other molecules, lipid peroxidation products, and membranes. Although these therapies remain on hold pending further investigation, we present growing evidence demonstrating the ability of N-acetylcarnosine (lubricant eye drops) or carcinine pharmacological chaperone therapy to act as novel treatments for age-related cataracts, age-related macular degeneration, and ocular complications of diabetes. Finally, we examine strategies for identifying potential chaperone compounds and for experimentally demonstrating chaperone and transglycating (de-glycation) types of activity in in vitro and in vivo models of human age-related eye diseases, such as cataracts, and advanced glycation tissue protein-engineered systems.

Association between imagined and actual functional reach (FR): a comparison of young and older adults.

PubMed

Gabbard, Carl; Cordova, Alberto

2013-01-01

Recent studies indicate that the ability to mentally represent action using motor imagery declines with advanced age (>64 years). As the ability to represent action declines, the elderly may experience increasing difficulty with movement planning and execution. Here, we determined the association between estimation of reach via use of motor imagery and actual FR. Young adults (M=22 years) and older adults (M=66 years) estimated reach while standing with targets randomly presented in peripersonal (within actual reach) and extrapersonal (beyond reach) space. Imagined responses were compared to the individual's scaled maximum reach. FR, also while standing, was assessed using the standardized Functional Reach Test (FRT). Results for total score estimation accuracy showed that there was no difference for age; however, results for mean bias and distribution of error revealed that the older group underestimated while the younger group overestimated. In reference to FR, younger adults outperformed older adults (30 versus 14in.) and most prominent, only the younger group showed a significant relationship between estimation and FR. In addition to gaining insight to the effects of advanced age on the ability to mentally represent action and its association with movement execution, these results although preliminary, may have clinical implications based on the question of whether motor imagery training could improve movement estimations and how that might affect actual reach. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Effect of renal function on serum concentration of 1,5-anhydroglucitol in type 2 diabetic patients in chronic kidney disease stages I-III: A comparative study with HbA1c and glycated albumin.

PubMed

Hasslacher, Christoph; Kulozik, Felix

2016-09-01

1,5-Anhydroglucitol (1,5-AG) is a new blood glucose control marker reflecting temporary glucose elevations. However, 1,5-AG is of limited value in patients with advanced renal insufficiency. The aim of the present study was to assess the correlation between 1,5-AG levels and renal function in patients with earlier stages of nephropathy compared with another two markers of diabetes control, namely HbA1c and glycated albumin (GA). The following parameters were measured in 377 patients with type 2 diabetes: HbA1c, serum concentrations of 1,5-AG, GA and creatinine, hemoglobin, urinary albumin/creatinine ratio, and urinary excretion of α1 -microglobulin (A1M). Estimated glomerular filtration rate (eGFR) was calculated according to the Cockgroft-Gault formula. There was a negative correlation between 1,5-AG and renal function (r = -0.18; P < 0.001). Concentrations of 1,5-AG were, on average, 27.2% lower in patients with glomerular hyperfiltration (eGFR >120 mL/min) compared with patients with moderate renal impairment (eGFR 30-59 mL/min; P = 0.016). In contrast, HbA1c, GA levels and urinary A1M excretion did not differ between the two patient groups. The mean age of patients with eGFR 30-59 mL/min was substantially higher than that of patients with glomerular hyperfiltration (P < 0.001). Thus, an age-related change in the renal glucose threshold could be the reason for the observed correlation between 1,5-AG and renal function. In clinical practice, age and renal function must be taken into consideration when interpreting 1,5-AG levels, even in the absence of advanced renal impairment. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Mitochondrial Energy Metabolism and Redox Signaling in Brain Aging and Neurodegeneration

PubMed Central

Yin, Fei; Boveris, Alberto

2014-01-01

Abstract Significance: The mitochondrial energy-transducing capacity is essential for the maintenance of neuronal function, and the impairment of energy metabolism and redox homeostasis is a hallmark of brain aging, which is particularly accentuated in the early stages of neurodegenerative diseases. Recent Advances: The communications between mitochondria and the rest of the cell by energy- and redox-sensitive signaling establish a master regulatory device that controls cellular energy levels and the redox environment. Impairment of this regulatory devise is critical for aging and the early stages of neurodegenerative diseases. Critical Issues: This review focuses on a coordinated metabolic network—cytosolic signaling, transcriptional regulation, and mitochondrial function—that controls the cellular energy levels and redox status as well as factors which impair this metabolic network during brain aging and neurodegeneration. Future Directions: Characterization of mitochondrial function and mitochondria-cytosol communications will provide pivotal opportunities for identifying targets and developing new strategies aimed at restoring the mitochondrial energy-redox axis that is compromised in brain aging and neurodegeneration. Antioxid. Redox Signal. 20, 353–371. PMID:22793257

Maternal IL-6 during pregnancy can be estimated from newborn brain connectivity and predicts future working memory in offspring.

PubMed

Rudolph, Marc D; Graham, Alice M; Feczko, Eric; Miranda-Dominguez, Oscar; Rasmussen, Jerod M; Nardos, Rahel; Entringer, Sonja; Wadhwa, Pathik D; Buss, Claudia; Fair, Damien A

2018-05-01

Several lines of evidence support the link between maternal inflammation during pregnancy and increased likelihood of neurodevelopmental and psychiatric disorders in offspring. This longitudinal study seeks to advance understanding regarding implications of systemic maternal inflammation during pregnancy, indexed by plasma interleukin-6 (IL-6) concentrations, for large-scale brain system development and emerging executive function skills in offspring. We assessed maternal IL-6 during pregnancy, functional magnetic resonance imaging acquired in neonates, and working memory (an important component of executive function) at 2 years of age. Functional connectivity within and between multiple neonatal brain networks can be modeled to estimate maternal IL-6 concentrations during pregnancy. Brain regions heavily weighted in these models overlap substantially with those supporting working memory in a large meta-analysis. Maternal IL-6 also directly accounts for a portion of the variance of working memory at 2 years of age. Findings highlight the association of maternal inflammation during pregnancy with the developing functional architecture of the brain and emerging executive function.

[Glycation, glycoxidation and diabetes mellitus].

PubMed

Boulanger, Eric; Wautier, Jean-Luc; Dequiedt, Philippe; Schmidt, Anne-Marie

2006-01-01

Advanced glycation end-products (AGEs) result from a reaction between carbohydrates and the free amino groups of proteins, lipids, and DNA. Non enzymatic glycation, glycoxidation with glucose auto-oxidation and the polyol pathway are involved in glycated protein formation. AGEs also named glycotoxins are found in excess in pathological situations such as diabetes mellitus, renal failure, and aging or after absorption of food containing glycated products. Three major pathophysiological mechanisms are described to explain AGE toxicity, first AGEs can accumulate in the vessel wall and in collagen of different tissues; second in situ glycation is possible; third, AGEs bind to cell receptors inducing deleterious consequences. AGE receptor RAGE is a multiligand member of the immunoglobulin superfamily of cell surface molecules. AGE-receptor interaction can alter, macrophage, endothelial cell, mesangial and mesothelial cell functions and can induce inflammation. Oxidant stress, vascular hyperpermeability, vascular cell adhesion molecule-1 (VCAM-1) overexpression and monocytes chemotactic Protein-1 (MCP-1) production have been observed after cell activation by AGEs. AGEs appear to be involved in the genesis of diabetic macro but also microangiopathy such as retinopathy and glomerulosclerosis. New drugs are tested to prevent or break the AGE-protein cross-linkage, or to control the AGE-receptor interaction and their consequences. Dietary treatment, strict glycemic control and preservation of renal function remain the best approach for preventing AGE formation and limiting their deleterious effects.

Hand grip strength and dexterity function in children aged 6-12 years: A cross-sectional study.

PubMed

Omar, Mohammed T A; Alghadir, Ahmad H; Zafar, Hamayun; Al Baker, Shaheerah

Cross-sectional and clinical measurement. Assessment of hand function considers an essential part in clinical practice. To develop normative values of hand grip strength and dexterity function for 6-12-year-old children in Saudi Arabia. Grip strength and dexterity function was measured in 525 children using Grip Track hand dynamometer (JTECH Medical, Midvale, UT, USA) and 9-hole pegboard test respectively. The grip strength and dexterity function was improved as age progressed regardless of gender. Across all age groups, the hand grip strength of boys was significantly higher than girls for dominant hand (31.75 ± 10.33 vs 28.24 ± 9.35; P < .001) and nondominant hand (31.01 ± 10.27 vs 27.27 ± 9.30; P < .001). The girls performed slightly faster than boys for dominant hand (19.70 vs 20.68; P < .05) and nondominant hand (21.79 vs 23.46; P < .05). In general, girls completed a 9-HPT faster than boys in the 2 of 7 age groups: 11 years (9-HPT scores = 2.10 seconds; P < .01) and 12 years (9-HPT scores = 1.93 seconds; P < .01). The overall patterns of hand grip strength and dexterity function observed in the present study are similar to the previous studies that established acceleration of grip strength with advanced age, and faster performance scores in older children than younger children in both genders. Norms of hand grip strength and dexterity enable therapists to identify some developmental characteristics of hand function among Saudi children, determine the presence of impairment, and compare scores from children in different clinical settings. Not applicable. Copyright © 2017 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

Plasticity of the aging brain: new directions in cognitive neuroscience.

PubMed

Gutchess, Angela

2014-10-31

Cognitive neuroscience has revealed aging of the human brain to be rich in reorganization and change. Neuroimaging results have recast our framework around cognitive aging from one of decline to one emphasizing plasticity. Current methods use neurostimulation approaches to manipulate brain function, providing a direct test of the ways that the brain differently contributes to task performance for younger and older adults. Emerging research into emotional, social, and motivational domains provides some evidence for preservation with age, suggesting potential avenues of plasticity, alongside additional evidence for reorganization. Thus, we begin to see that aging of the brain, amidst interrelated behavioral and biological changes, is as complex and idiosyncratic as the brain itself, qualitatively changing over the life span. Copyright © 2014, American Association for the Advancement of Science.

Theories of Memory and Aging: A Look at the Past and a Glimpse of the Future

PubMed Central

Festini, Sara B.

2017-01-01

The present article reviews theories of memory and aging over the past 50 years. Particularly notable is a progression from early single-mechanism perspectives to complex multifactorial models proposed to account for commonly observed age deficits in memory function. The seminal mechanistic theories of processing speed, limited resources, and inhibitory deficits are discussed and viewed as especially important theories for understanding age-related memory decline. Additionally, advances in multivariate techniques including structural equation modeling provided new tools that led to the development of more complex multifactorial theories than existed earlier. The important role of neuroimaging is considered, along with the current prevalence of intervention studies. We close with predictions about new directions that future research on memory and aging will take. PMID:27257229

Gastrointestinal tract and the elderly: functional foods, gut microflora and healthy ageing.

PubMed

Saunier, K; Doré, J

2002-09-01

Advances in science and medicine as well as improved living standards have led to a steady increase in life expectancy. Yet ageing is associated with increased susceptibility to degenerative or infectious diseases, which may be exacerbated by a poor nutritional status. The intestinal microflora will mediate crucial events towards the protection or degradation of health. It is hence essential and timely that strategies of preventive nutrition aimed at maintaining or improving the quality of life of the ageing population be developed. "CROWNALIFE" is a newly funded EuropeanUnion project, so called because of its emphasis on the preservation of the period of independence of the elderly, recognised as the "crown of life". The project aims at assessing age-related alterations and exploring strategies to restore and maintain a balanced healthy intestinal environment. Current knowledge on the composition and function of the human intestinal microflora is still improving with the use of better methodologies and yet their evolution with ageing has not been investigated in detail. There have been a few reports that putatively protective lactic acid bacteria, in general, and bifidobacteria, in particular, seem less represented in the elderly faecal flora. We have also observed an increase in species diversity of the dominant faecal microflora with ageing. This certainly warrants confirmation and is being addressed by the investigation of age-related changes in the structure and function of the intestinal flora of the elderly in countries across Europe. Ensuing results will constitute a baseline for functional-food based strategies aimed at providing health benefits for the elderly.

Immunochemical detection of advanced glycosylation end products in vivo.

PubMed

Makita, Z; Vlassara, H; Cerami, A; Bucala, R

1992-03-15

Reducing sugars react with protein amino groups to form a diverse group of protein-bound moieties with fluorescent and cross-linking properties. These compounds, called advanced glycosylation end products (AGEs), have been implicated in the structural and functional alterations of proteins that occur during aging and long-term diabetes. Although several AGEs have been identified on the basis of de novo synthesis and tissue isolation procedures, the measurement of AGE compounds in vivo has remained difficult. As an approach to the study of AGE formation in vivo, we prepared polyclonal antiserum to an AGE epitope(s) which forms in vitro after incubation of glucose with ribonuclease (RNase). This antiserum proved suitable for the detection of AGEs which form in vivo. Both diabetic tissue and serum known to contain elevated levels of AGEs readily competed for antibody binding. Cross-reactivity studies revealed the presence of a common AGE epitope(s) which forms after the incubation of diverse proteins with glucose. Cross-reactive epitopes also formed with glucose 6-phosphate or fructose. These data suggest that tissue AGEs which form in vivo appear to contain a common immunological epitope which cross-reacts with AGEs prepared in vitro, supporting the concept that immunologically similar AGE structures form from the incubation of sugars with different proteins (Horiuchi, S., Araki, N., and Morino, Y. (1991) J. Biol. Chem. 266, 7329-7332). None of the known AGEs, such as 4-furanyl-2-furoyl-1H-imidazole, 1-alkyl-2-formyl-3,4-diglycosylpyrrole, pyrraline, carboxymethyllysine, or pentosidine, were found to compete for binding to anti-AGE antibody. These data further suggest that the dominant AGE epitope which forms from the reaction of glucose with proteins under native conditions is immunologically distinct from the structurally defined AGEs described to date.

Exo-organoplasty interventions: A brief review of past, present and future directions for advance heart failure management.

PubMed

Nawaz, Waqas; Khan, Farhan Ullah; Khan, Muhammad Zahid; Gang, Wang; Yang, Mengqi; Liao, Xiaoqian; Zhang, Li; Ihsan, Awais Ullah; Khan, Amjad; Han, Lei; Zhou, Xiaohui

2017-04-01

Heart failure (HF) is a debilitating disease in which abnormal function of the heart leads to imbalance of blood demand to tissues and organs. The pathogenesis of HF is very complex and various factors can contribute including myocardial infarction, ischemia, hypertension and genetic cardiomyopathies. HF is the leading cause of death and its prevalence is expected to increase in parallel with the population age. Different kind of therapeutic approaches including lifestyle modification, medication and pacemakers are used for HF patients in NYHA I-III functional class. However, for advance stage HF patient's (NYHA IV), ventricle assist devices are clinically use and stem cells are under active investigation. Most of these therapies leads to modest symptoms relief and have no significant role in long-term survival rate. Currently there is no effective treatment for advance HF except heart transplantation, which is still remain clinically insignificant because of donor pool limitation. As HF is a result of multiple etiologies therefore multi-functional therapeutic platform is needed. Exo-organoplasty interventions are studied from almost one century. The major goals of these interventions are to treat various kind of heart disease from outside the heart muscle without having direct contact with blood. Various kind of interventions (devices and techniques) are developed in this arena with the passage of time. The purpose of this review is to describe the theory behind intervention devices, the devices themselves, their clinical results, advantages and limitations. Furthermore, to present a future multi-functional therapeutic platform (ASD) for advance stage HF management. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Lung function and blood markers of nutritional status in non-COPD aging men with smoking history: a cross-sectional study.

PubMed

Shiozawa, Nobuyoshi; Hayashimoto, Kanae; Suzuki, Etsuji; Kikuchi, Hiroshi; Takata, Shingo; Ashida, Kozo; Watanabe, Masutaka; Hosaki, Yasuhiro; Mitsunobu, Fumihiro

2010-08-09

Cigarette smoking and advanced age are well known as risk factors for chronic obstructive pulmonary disease (COPD), and nutritional abnormalities are important in patients with COPD. However, little is known about the nutritional status in non-COPD aging men with smoking history. We therefore investigated whether reduced lung function is associated with lower blood markers of nutritional status in those men. This association was examined in a cross-sectional study of 65 Japanese male current or former smokers aged 50 to 80 years: 48 without COPD (non-COPD group), divided into tertiles according to forced expiratory volume in one second as percent of forced vital capacity (FEV(1)/FVC), and 17 with COPD (COPD group). After adjustment for potential confounders, lower FEV(1)/FVC was significantly associated with lower red blood cell count (RBCc), hemoglobin, and total protein (TP); not with total energy intake. The difference in adjusted RBCc and TP among the non-COPD group tertiles was greater than that between the bottom tertile in the non-COPD group and the COPD group. In non-COPD aging men with smoking history, trends toward reduced nutritional status and anemia may independently emerge in blood components along with decreased lung function even before COPD onset.

Beneath the floor: re-analysis of neurodevelopmental outcomes in untreated Hurler syndrome.

PubMed

Shapiro, Elsa G; Whitley, Chester B; Eisengart, Julie B

2018-05-11

Hurler syndrome (MPS IH), the severe, neurodegenerative form of type one mucopolysaccharidosis, is associated with rapid neurocognitive decline during toddlerhood and multi-system dysfunction. It is now standardly treated with hematopoietic cell transplantation (HCT), which halts accumulating disease pathology and prevents early death. While norm-based data on developmental functioning in untreated children have previously demonstrated neurocognitive decline, advances in methodology for understanding the cognitive functioning of children with neurodegenerative diseases have highlighted that the previous choice of scores to report results was not ideal. Specifically, the lowest possible norm-based score is 50, which obscures the complete range of cognitive functioning at more advanced stages of neurodeterioration. To a set of cognitive data collected on a sample of untreated children, we applied a modern method of score analysis, calculating a developmental quotient based on age equivalent scores, to reveal the full range of cognitive functioning beneath this cutoff of 50, uncovering new information about the rapidity of decline and the profound impairment in these children. Among 39 observations for 32 patients with untreated Hurler syndrome, the full array of cognitive functioning below 50 includes many children in the severely to profoundly impaired range. The loss of skills per time unit was 14 points between age 1 and 2. There was a very large range of developmental quotients corresponding to the norm-based cutoff of 50. This report enables clarification of functioning at levels that extend beneath the floor of 50 in previous work. At the dawn of newborn screening and amidst a proliferation of new therapies for MPS I, these data can provide crucial benchmark information for developing treatments, particularly for areas of the world where transplant may not be available.

The Emerging Role of IGF-1 Deficiency in Cardiovascular Aging: Recent Advances

PubMed Central

Csiszar, Anna

2012-01-01

This review focuses on cardiovascular protective effects of insulin-like growth factor (IGF)-1, provides a landscape of molecular mechanisms involved in cardiovascular alterations in patients and animal models with congenital and adult-onset IGF-1 deficiency, and explores the link between age-related IGF-1 deficiency and the molecular, cellular, and functional changes that occur in the cardiovascular system during aging. Microvascular protection conferred by endocrine and paracrine IGF-1 signaling, its implications for the pathophysiology of cardiac failure and vascular cognitive impairment, and the role of impaired cellular stress resistance in cardiovascular aging considered here are based on emerging knowledge of the effects of IGF-1 on Nrf2-driven antioxidant response. PMID:22451468

Aging and Family Life: A Decade Review

PubMed Central

Silverstein, Merril; Giarrusso, Roseann

2010-01-01

In this review, we summarize and critically evaluate the major empirical, conceptual, and theoretical directions that studies of aging families have taken during the first decade of the 21st century. The field has benefited from an expanded perspective based on four overarching themes: (a) complexity in emotional relations, (b) diversity in family structures and households, (c) interdependence of family roles and functions, and (d) patterns and outcomes of caregiving. Although research on aging families has advanced theory and applied innovative statistical techniques, the literature has fallen short in fully representing diverse populations and in applying the broadest set of methodological tools available. We discuss these and other frontier areas of scholarship in light of the aging of baby boomers and their families. PMID:22930600

Molecular mechanism of sarcopenia and cachexia: recent research advances.

PubMed

Sakuma, Kunihiro; Aoi, Wataru; Yamaguchi, Akihiko

2017-06-01

Skeletal muscle provides a fundamental basis for human function, enabling locomotion and respiration. Muscle loss occurs as a consequence of several chronic diseases (cachexia) and normal aging (sarcopenia). Although many negative regulators (atrogin-1, muscle ring finger-1, nuclear factor-kappaB (NF-κB), myostatin, etc.) have been proposed to enhance protein degradation during both sarcopenia and cachexia, the adaptation of these mediators markedly differs within both conditions. Sarcopenia and cachectic muscles have been demonstrated to be abundant in myostatin-linked molecules. The ubiquitin-proteasome system (UPS) is activated during rapid atrophy model (cancer cachexia), but few mediators of the UPS change during sarcopenia. NF-κB signaling is activated in cachectic, but not in sarcopenic, muscle. Recent studies have indicated the age-related defect of autophagy signaling in skeletal muscle, whereas autophagic activation occurs in cachectic muscle. This review provides recent research advances dealing with molecular mediators modulating muscle mass in both sarcopenia and cachexia.

Aquatic exercise for residential aged care adults with dementia: benefits and barriers to participation.

PubMed

Henwood, Timothy; Neville, Christine; Baguley, Chantelle; Beattie, Elizabeth

2017-09-01

Pilot work by our group has demonstrated that aquatic exercise has valuable functional and psychosocial benefits for adults living in the residential aged care setting with dementia. The aim of the currents study was to advance this work by delivering the Watermemories Swimming Club aquatic exercise program to a more representative population of older, institutionalized adults with dementia. The benefits of 12 weeks of twice weekly participation in the Watermemories Swimming Club aquatic exercise program were assessed among an exercise and usual care control group of residential aged care adults with advanced dementia. A battery of physical and psychosocial measures were collected before and after the intervention period, and program implementation was also investigated. Seven residential aged care facilities of 24 approached, agreed to participate and 56 residents were purposefully allocated to exercise or control. Twenty-three participants per group were included in the final analysis. Both groups experienced decreases in skeletal muscle index and lean mass (p < 0.001), but exercise stifled losses in muscle strength and transition into sarcopenic. Behavioral and psychological symptoms of dementia and activities of daily living approached significance (p = 0.06) with positive trends observed across other psychosocial measures. This study demonstrates the value of exercise participation, and specifically aquatic exercise in comparison to usual care for older, institutionalized adults with advanced dementia. However, it also highlights a number of barriers to participation. To overcome these barriers and ensure opportunity to residents increased provider and sector support is required.

Video Self-Modeling Applications With Students With Autism Spectrum Disorder in a Small Private School Setting

ERIC Educational Resources Information Center

Tom, Buggey

2005-01-01

Videotaped self-modeling (VSM) was developed as a means to allow participants to view themselves in situations where they are performing at a more advanced level than they typically function. VSM has been used effectively to train positive behaviors and reduce unwanted behaviors across a range of ages and behaviors; however, few studies of VSM…

The Infant Audience: The Impact and Implications of Child Development Research on Performing Arts Practice for the Very Young

ERIC Educational Resources Information Center

Drury, Rachel C.; Fletcher-Watson, Ben

2017-01-01

The advances of scientific techniques such as magnetic resonance imaging and functional magnetic resonance imaging have led to an enormous increase in understanding of the physical, neurological and cognitive developments in infancy. Alongside this, radical new forms of theatre, dance and music have emerged, aimed at this same age group. Many…

Defining how aging Pseudotsuga and Abies compensate for multiple stresses through multi-criteria assessment of a functional-structural model

Treesearch

Maureen C. Kennedy; E. David Ford; Thomas M. Hinckley

2009-01-01

Many hypotheses have been advanced about factors that control tree longevity. We use a simulation model with multi-criteria optimization and Pareto optimality to determine branch morphologies in the Pinaceae that minimize the effect of growth limitations due to water stress while simultaneously maximizing carbohydrate gain. Two distinct branch morphologies in the...

Stem cell therapies for age-related macular degeneration: the past, present, and future.

PubMed

Dang, Yalong; Zhang, Chun; Zhu, Yu

2015-01-01

In the developed world, age-related macular degeneration (AMD) is one of the major causes of irreversible blindness in the elderly. Although management of neovascular AMD (wet AMD) has dramatically progressed, there is still no effective treatment for nonneovascular AMD (dry AMD), which is characterized by retinal pigment epithelial (RPE) cell death (or dysfunction) and microenvironmental disruption in the retina. Therefore, RPE replacement and microenvironmental regulation represent viable treatments for dry AMD. Recent advances in cell biology have demonstrated that RPE cells can be easily generated from several cell types (pluripotent stem cells, multipotent stem cells, or even somatic cells) by spontaneous differentiation, coculturing, defined factors or cell reprogramming, respectively. Additionally, in vivo studies also showed that the restoration of visual function could be obtained by transplanting functional RPE cells into the subretinal space of recipient. More importantly, clinical trials approved by the US government have shown promising prospects in RPE transplantation. However, key issues such as implantation techniques, immune rejection, and xeno-free techniques are still needed to be further investigated. This review will summarize recent advances in cell transplantation for dry AMD. The obstacles and prospects in this field will also be discussed.

Effects of Age on Auditory and Cognitive Processing: Implications for Hearing Aid Fitting and Audiologic Rehabilitation

PubMed Central

Pichora-Fuller, M. Kathleen; Singh, Gurjit

2006-01-01

Recent advances in research and clinical practice concerning aging and auditory communication have been driven by questions about age-related differences in peripheral hearing, central auditory processing, and cognitive processing. A “site-of-lesion” view based on anatomic levels inspired research to test competing hypotheses about the contributions of changes at these three levels of the nervous system. A “processing” view based on psychologic functions inspired research to test alternative hypotheses about how lower-level sensory processes and higher-level cognitive processes interact. In the present paper, we suggest that these two views can begin to be unified following the example set by the cognitive neuroscience of aging. The early pioneers of audiology anticipated such a unified view, but today, advances in science and technology make it both possible and necessary. Specifically, we argue that a synthesis of new knowledge concerning the functional neuroscience of auditory cognition is necessary to inform the design and fitting of digital signal processing in “intelligent” hearing devices, as well as to inform best practices for resituating hearing aid fitting in a broader context of audiologic rehabilitation. Long-standing approaches to rehabilitative audiology should be revitalized to emphasize the important role that training and therapy play in promoting compensatory brain reorganization as older adults acclimatize to new technologies. The purpose of the present paper is to provide an integrated framework for understanding how auditory and cognitive processing interact when older adults listen, comprehend, and communicate in realistic situations, to review relevant models and findings, and to suggest how new knowledge about age-related changes in audition and cognition may influence future developments in hearing aid fitting and audiologic rehabilitation. PMID:16528429

Accumulation of advanced glycation end products and beta 2-microglobulin in fibrotic thickening of the peritoneum in long-term peritoneal dialysis patients.

PubMed

Nakamoto, Hirotaka; Hamada, Chieko; Shimaoka, Tetsutaro; Sekiguchi, Yoshimi; Io, Hiroaki; Kaneko, Kayo; Horikoshi, Satoshi; Tomino, Yasuhiko

2014-03-01

Characteristics of pathological alterations in long-term peritoneal dialysis (PD) are thickening of submesothelial compact (SMC) zone, small-vessel vasculopathy, and loss of mesothelial cells. Bioincompatible PD fluid plays crucial roles in peritoneal injury. Encapsulating peritoneal sclerosis (EPS), a rare and serious complication, occurred in patients on long-term PD or frequent peritonitis episodes, and ~50 % of EPS developed after PD cessation. We hypothesized that PD-related peritoneal injury factors induced by bioincompatible PD fluid accumulated in the peritoneum and might induce EPS. We therefore examined the accumulation of advanced glycation end products (AGE) and beta 2-microglobulin (β2M) in peritoneum and evaluated the relationship between their accumulation, clinical parameters, and outcome after PD cessation. Forty-five parietal peritoneal specimens were obtained from 28 PD patients, 14 uremic patients, and three patients with normal kidney function. The peritoneal equilibration test was used for peritoneal function. AGE- and β2M-expressing areas were found in vascular walls, perivascular areas, and the deep layer of the SMC in short-term PD patients and extended over the entire SMC in long-term patients. Peritonitis and prolonged PD treatment aggravated peritoneal thickening and the proportion of AGE-expressing areas. The proportion of β2M-expressing areas was increased in long-term PD patients. Thickening of the SMC and the proportions of AGE- and β2M-expressing areas were not related to ascites or EPS after PD withdrawal. It appears that the increased proportion of AGE and β2M deposition induced by long-term exposure of PD fluid may be a marker of peritoneal injury.

Management of pancreatic cancer in the elderly.

PubMed

Higuera, Oliver; Ghanem, Ismael; Nasimi, Rula; Prieto, Isabel; Koren, Laura; Feliu, Jaime

2016-01-14

Currently, pancreatic adenocarcinoma mainly occurs after 60 years of age, and its prognosis remains poor despite modest improvements in recent decades. The aging of the population will result in a rise in the incidence of pancreatic adenocarcinoma within the next years. Thus, the management of pancreatic cancer in the elderly population is gaining increasing relevance. Older cancer patients represent a heterogeneous group with different biological, functional and psychosocial characteristics that can modify the usual management of this disease, including pharmacokinetic and pharmacodynamic changes, polypharmacy, performance status, comorbidities and organ dysfunction. However, the biological age, not the chronological age, of the patient should be the limiting factor in determining the most appropriate treatment for these patients. Unfortunately, despite the increased incidence of this pathology in older patients, there is an underrepresentation of these patients in clinical trials, and the management of older patients is thus determined by extrapolation from the results of studies performed in younger patients. In this review, the special characteristics of the elderly, the multidisciplinary management of localized and advanced ductal adenocarcinoma of the pancreas and the most recent advances in the management of this condition will be discussed, focusing on surgery, chemotherapy, radiation and palliative care.

Different Impact of Essential Hypertension on Structural and Functional Age-Related Vascular Changes.

PubMed

Bruno, Rosa Maria; Duranti, Emiliano; Ippolito, Chiara; Segnani, Cristina; Bernardini, Nunzia; Di Candio, Giulio; Chiarugi, Massimo; Taddei, Stefano; Virdis, Agostino

2017-01-01

We evaluated whether vascular remodeling is present in physiological aging and whether hypertension accelerates the aging process for vascular function and structure. Small arteries from 42 essential hypertensive patients (HT) and 41 normotensive individuals (NT) were dissected after subcutaneous biopsy. Endothelium-dependent vasodilation (pressurized myograph) was assessed by acetylcholine, repeated under the nitric oxide synthase inhibitor N-nitro-l-arginine methylester or the antioxidant tempol. Structure was evaluated by media-lumen ratio (M/L). Intravascular oxidative generation and collagen deposition were assessed. Inhibition by N-nitro-l-arginine methylester on ACh was inversely related to age in both groups (P<0.0001) and blunted in HT versus NT for each age range. In NT, tempol enhanced endothelial function in the oldest subgroup; in HT, the potentiating effect started earlier. HT showed an increased M/L (P<0.001) versus control. In both groups, M/L was directly related to age (P<0.0001). M/L was greater in HT, starting from 31 to 45 years range. A significant age-hypertension interaction occurred (P=0.0009). In NT, intravascular superoxide emerged in the oldest subgroup, whereas it appeared earlier among HT. Among NT, aged group displayed an increment of collagen fibers versus young group. In HT, collagen deposition was already evident in youngest, with a further enhancement in the aged group. In small arteries, ageing shows a eutrophic vascular remodeling and a reduced nitric oxide availability. Oxidative stress and fibrosis emerge in advanced age. In HT, nitric oxide availability is early reduced, but the progression rate with age is similar. Structural alterations include wide collagen deposition and intravascular reactive oxygen species, and the progression rate with age is steeper. © 2016 American Heart Association, Inc.

Increased gray-matter volume in medication-naive high-functioning children with autism spectrum disorder.

PubMed

Palmen, Saskia J M C; Hulshoff Pol, Hilleke E; Kemner, Chantal; Schnack, Hugo G; Durston, Sarah; Lahuis, Bertine E; Kahn, René S; Van Engeland, Herman

2005-04-01

To establish whether high-functioning children with autism spectrum disorder (ASD) have enlarged brains in later childhood, and if so, whether this enlargement is confined to the gray and/or to the white matter and whether it is global or more prominent in specific brain regions. Brain MRI scans were acquired from 21 medication-naive, high-functioning children with ASD between 7 and 15 years of age and 21 comparison subjects matched for gender, age, IQ, height, weight, handedness, and parental education, but not pubertal status. Patients showed a significant increase of 6% in intracranium, total brain, cerebral gray matter, cerebellum, and of more than 40% in lateral and third ventricles compared to controls. The cortical gray-matter volume was evenly affected in all lobes. After correction for brain volume, ventricular volumes remained significantly larger in patients. High-functioning children with ASD showed a global increase in gray-matter, but not white-matter and cerebellar volume, proportional to the increase in brain volume, and a disproportional increase in ventricular volumes, still present after correction for brain volume. Advanced pubertal development in the patients compared to the age-matched controls may have contributed to the findings reported in the present study.

Medical challenges at the end of the first ten decades of life.

PubMed

Münzer, Thomas

2017-07-11

Demographic changes worldwide challenge the healthcare system. Advanced age is associated with a number of biological alterations that, together with concomitant comorbidities, increase the risk for functional decline by inducing functional disintegration. In this concept frailty and sarcopenia play an important role. Consequently the preservation of muscle mass and function are prominent targets of medicine in old age. In order to professionally care for persons in their last years of life several other factors influencing medical decisions regarding diagnostic and treatments are important. These factors concern the life expectancy, the person`s functional status the physicians involved in care and the family system. Balancing between over- and undertreatment in very old patients can be optimised by a goal-oriented decision making approach. Very old persons with poor decision making capacity might benefit from decisions made in a team. To be able to manage the challenges associated with the last decade of life, we need physicians who have the knowledge, the appropriate attitude towards frail old patients and the skills to communicate with different groups involved in care. Ideally old age medicine should become an integrative part of a unified national medical curriculum.

Do Older Adults Need Sleep? A Review of Neuroimaging, Sleep, and Aging Studies.

PubMed

Scullin, Michael K

2017-09-01

Sleep habits, sleep physiology, and sleep disorders change with increasing age. However, there is a longstanding debate regarding whether older adults need sleep to maintain health and daily functioning (reduced-sleep-need view). An alternative possibility is that all older adults need sleep, but that many older adults have lost the ability to obtain restorative sleep (reduced-sleep-ability view). Prior research using behavioral and polysomnography outcomes has not definitively disentangled the reduced-sleep-need and reduced-sleep-ability views. Therefore, this review examines the neuroimaging literature to determine whether age-related changes in sleep cause-or are caused by-age-related changes in brain structure, function, and pathology. In middle-aged and older adults, poorer sleep quality, greater nighttime hypoxia, and shorter sleep duration related to cortical thinning in frontal regions implicated in slow wave generation, in frontoparietal networks implicated in cognitive control, and in hippocampal regions implicated in memory consolidation. Furthermore, poor sleep quality was associated with higher amyloid burden and decreased connectivity in the default mode network, a network that is disrupted in the pathway to Alzheimer's disease. All adults need sleep, but cortical thinning and amyloidal deposition with advancing age may weaken the brain's ability to produce restorative sleep. Therefore, sleep in older adults may not always support identical functions for physical, mental, and cognitive health as in young adults.

Antioxidant Defence, Oxidative Stress and Oxidative Damage in Saliva, Plasma and Erythrocytes of Dementia Patients. Can Salivary AGE be a Marker of Dementia?

PubMed Central

Choromańska, Magdalena; Klimiuk, Anna; Kostecka-Sochoń, Paula; Wilczyńska, Karolina; Kwiatkowski, Mikołaj; Okuniewska, Natalia; Waszkiewicz, Napoleon; Zalewska, Anna

2017-01-01

Oxidative stress plays a crucial role in dementia pathogenesis; however, its impact on salivary secretion and salivary qualities is still unknown. This study included 80 patients with moderate dementia and 80 healthy age- and sex-matched individuals. Salivary flow, antioxidants (salivary peroxidase, catalase, superoxide dismutase, uric acid and total antioxidant capacity), and oxidative damage products (advanced oxidation protein products, advanced glycation end products (AGE), 8-isoprostanes, 8-hydroxy-2’-deoxyguanosine and total oxidant status) were estimated in non-stimulated and stimulated saliva, as well as in plasma and erythrocytes. We show that in dementia patients the concentration/activity of major salivary antioxidants changes, and the level of oxidative damage to DNA, proteins and lipids is increased compared to healthy controls. Non-stimulated and stimulated salivary secretions were significantly reduced in dementia patients. The deterioration in mini mental state examination (MMSE) score correlated with salivary AGE levels, which when considered with receiver operating characteristic (ROC) analysis, suggests their potential role in the non-invasive diagnosis of dementia. In conclusion, dementia is associated with disturbed salivary redox homeostasis and impaired secretory function of the salivary glands. Salivary AGE may be useful in the diagnosis of dementia. PMID:29053628

GxE interactions between FOXO genotypes and drinking tea are significantly associated with prevention of cognitive decline in advanced age in China.

PubMed

Zeng, Yi; Chen, Huashuai; Ni, Ting; Ruan, Rongping; Feng, Lei; Nie, Chao; Cheng, Lingguo; Li, Yang; Tao, Wei; Gu, Jun; Land, Kenneth C; Yashin, Anatoli; Tan, Qihua; Yang, Ze; Bolund, Lars; Yang, Huanming; Hauser, Elizabeth; Willcox, D Craig; Willcox, Bradley J; Tian, Xiao-Li; Vaupel, James W

2015-04-01

Logistic regression analysis based on data from 822 Han Chinese oldest old aged 92+ demonstrated that interactions between carrying FOXO1A-266 or FOXO3-310 or FOXO3-292 and tea drinking at around age 60 or at present time were significantly associated with lower risk of cognitive disability at advanced ages. Associations between tea drinking and reduced cognitive disability were much stronger among carriers of the genotypes of FOXO1A-266 or FOXO3-310 or FOXO3-292 compared with noncarriers, and it was reconfirmed by analysis of three-way interactions across FOXO genotypes, tea drinking at around age 60, and at present time. Based on prior findings from animal and human cell models, we postulate that intake of tea compounds may activate FOXO gene expression, which in turn may positively affect cognitive function in the oldest old population. Our empirical findings imply that the health benefits of particular nutritional interventions, including tea drinking, may, in part, depend upon individual genetic profiles. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The possible impact of advanced glycation end products on pregnancy outcome in women with diabetes mellitus type 1.

PubMed

Pertynska-Marczewska, Magdalena; Cypryk, Katarzyna

2017-09-01

Diabetes mellitus (DM) is a group of metabolic disorders of carbohydrate metabolism in which glucose is underutilized, resulting in hyperglycemia. Reproductive impairment in poorly controlled diabetes mellitus type 1 (T1DM) results from a combined effect of insulin deficiency and hyperglycemia that disrupt the functioning of metabolic signals participating in the regulation of the reproductive system. Good metabolic control as a result of intensive insulin therapy has a great impact on the fertility and childbearing possibilities in the T1DM females. Advanced glycation end products (AGEs) are formed by nonenzymatic modification of proteins, lipids, and nucleic acids by glucose. The formation and accumulation of AGEs are known to progress at an accelerated rate in diabetes. AGEs either act on the pro-inflammatory cell surface receptors called RAGE or bind to the circulating anti-inflammatory sRAGE that prevents activation of cell-surface RAGE by AGEs and other proinflammatory ligands. Pregnancy has been found to induce a significant increase in RAGE protein levels in both myometrium and omental vasculature. This review will focus on the role of AGEs and RAGE in pregnancy complicated by DM type 1 as well as ways to reduce the rate of congenital malformations in the offspring of diabetic type 1 women.

N-acetylcysteine Counteracts Adipose Tissue Macrophage Infiltration and Insulin Resistance Elicited by Advanced Glycated Albumin in Healthy Rats.

PubMed

da Silva, Karolline S; Pinto, Paula R; Fabre, Nelly T; Gomes, Diego J; Thieme, Karina; Okuda, Ligia S; Iborra, Rodrigo T; Freitas, Vanessa G; Shimizu, Maria H M; Teodoro, Walcy R; Marie, Suely K N; Woods, Tom; Brimble, Margaret A; Pickford, Russell; Rye, Kerry-Anne; Okamoto, Maristela; Catanozi, Sergio; Correa-Giannela, Maria L; Machado, Ubiratan F; Passarelli, Marisa

2017-01-01

Background: Advanced glycation endproducts elicit inflammation. However, their role in adipocyte macrophage infiltration and in the development of insulin resistance, especially in the absence of the deleterious biochemical pathways that coexist in diabetes mellitus, remains unknown. We investigated the effect of chronic administration of advanced glycated albumin (AGE-albumin) in healthy rats, associated or not with N-acetylcysteine (NAC) treatment, on insulin sensitivity, adipose tissue transcriptome and macrophage infiltration and polarization. Methods: Male Wistar rats were intraperitoneally injected with control (C) or AGE-albumin alone, or, together with NAC in the drinking water. Biochemical parameters, lipid peroxidation, gene expression and protein contents were, respectively, determined by enzymatic techniques, reactive thiobarbituric acid substances, RT-qPCR and immunohistochemistry or immunoblot. Carboxymethyllysine (CML) and pyrraline (PYR) were determined by LC/mass spectrometry (LC-MS/MS) and ELISA. Results: CML and PYR were higher in AGE-albumin as compared to C. Food consumption, body weight, systolic blood pressure, plasma lipids, glucose, hepatic and renal function, adipose tissue relative weight and adipocyte number were similar among groups. In AGE-treated animals, insulin resistance, adipose macrophage infiltration and Col12a1 mRNA were increased with no changes in M1 and M2 phenotypes as compared to C-albumin-treated rats. Total GLUT4 content was reduced by AGE-albumin as compared to C-albumin. NAC improved insulin sensitivity, reduced urine TBARS, adipose macrophage number and Itgam and Mrc mRNA and increased Slc2a4 and Ppara . CD11b, CD206, Ager, Ddost, Cd36, Nfkb1, Il6, Tnf , Adipoq, Retn, Arg, and Il12 expressions were similar among groups. Conclusions: AGE-albumin sensitizes adipose tissue to inflammation due to macrophage infiltration and reduces GLUT4, contributing to insulin resistance in healthy rats. NAC antagonizes AGE-albumin and prevents insulin resistance. Therefore, it may be a useful tool in the prevention of AGE action on insulin resistance and long-term complications of DM.

Impacts on employment, finances, and lifestyle for working age people facing an expected premature death: A systematic review.

PubMed

Kochovska, Slavica; Luckett, Tim; Agar, Meera; Phillips, Jane L

2018-06-01

ABSTRACTObjective:The working ages (25-65 years) are a period when most people have significant work, financial, and family responsibilities. A small proportion of working age people will face an expected premature death from cancer or other life-limiting illness. Understanding the impact an expected premature death has on this population is important for informing support. The current study set out to summarize research describing the effects that facing an expected premature death has on employment, financial, and lifestyle of working age people and their families. A systematic review using narrative synthesis approach. Four electronic databases were searched in July 2016 for peer-reviewed, English language studies focusing on the financial, employment, and lifestyle concerns of working age adults living with an advanced life-limiting illness and/or their carers and/or children. Fifteen quantitative and 12 qualitative studies were included. Two-thirds (n = 18) were focused on cancer. All studies identified adverse effects on workforce participation, finances, and lifestyle. Many patients were forced to work less or give up work/retire early because of symptoms and reduced functioning. In addition to treatment costs, patients and families were also faced with child care, travel, and home/car modification costs. Being younger was associated with greater employment and financial burden, whereas having children was associated with lower functional well-being. Changes in family roles were identified as challenging regardless of diagnosis, whereas maintaining normalcy and creating stability was seen as a priority by parents with advanced cancer. This review is limited by the smaller number of studies focussing on the needs of working age people with nonmalignant disease. Working age people facing an expected premature death and their families have significant unmet financial, employment, and lifestyle needs. Comparing and contrasting their severity, timing, and priority for people with nonmalignant conditions is required to better understand their unique needs.

Simple noninvasive measurement of skin autofluorescence.

PubMed

Meerwaldt, Robbert; Links, Thera; Graaff, Reindert; Thorpe, Suzannne R; Baynes, John W; Hartog, Jasper; Gans, Reinold; Smit, Andries

2005-06-01

Accumulation of advanced glycation end products (AGEs) is thought to play a role in the pathogenesis of chronic complications of diabetes mellitus and renal failure. Several studies indicate that AGE accumulation in tissue may reflect the cumulative effect of hyperglycemia and oxidative stress over many years. Simple quantitation of AGE accumulation in tissue could provide a tool for assessing the risk of long-term complications. Because several AGEs exhibit autofluorescence, we developed a noninvasive autofluorescence reader (AFR). Skin autofluorescence measured with the AFR correlates with collagen-linked fluorescence and specific skin AGE levels from skin biopsy samples. Furthermore, skin autofluorescence correlates with long-term glycemic control and renal function, and preliminary results show correlations with the presence of long-term complications in diabetes. The AFR may be useful as a clinical tool for rapid assessment of risk for AGE-related long-term complications in diabetes and in other conditions associated with AGE accumulation.

Hitting a Moving Target: Basic Mechanisms of Recovery from Acquired Developmental Brain Injury

PubMed Central

Giza, Christopher C.; Kolb, Bryan; Harris, Neil G.; Asarnow, Robert F.; Prins, Mayumi L.

2009-01-01

Acquired brain injuries represent a major cause of disability in the pediatric population. Understanding responses to developmental acquired brain injuries requires knowledge of the neurobiology of normal development, age-at-injury effects and experience-dependent neuroplasticity. In the developing brain, full recovery cannot be considered as a return to the premorbid baseline, since ongoing maturation means that cerebral functioning in normal individuals will continue to advance. Thus, the recovering immature brain has to ‘hit a moving target’ to achieve full functional recovery, defined as parity with age-matched uninjured peers. This review will discuss the consequences of developmental injuries such as focal lesions, diffuse hypoxia and traumatic brain injury (TBI). Underlying cellular and physiological mechanisms relevant to age-at-injury effects will be described in considerable detail, including but not limited to alterations in neurotransmission, connectivity/network functioning, the extracellular matrix, response to oxidative stress and changes in cerebral metabolism. Finally, mechanisms of experience-dependent plasticity will be reviewed in conjunction with their effects on neural repair and recovery. PMID:19956795

Advanced Glycation End Products Predict Loss of Renal Function and Correlate With Lesions of Diabetic Kidney Disease in American Indians With Type 2 Diabetes.

PubMed

Saulnier, Pierre-Jean; Wheelock, Kevin M; Howell, Scott; Weil, E Jennifer; Tanamas, Stephanie K; Knowler, William C; Lemley, Kevin V; Mauer, Michael; Yee, Berne; Nelson, Robert G; Beisswenger, Paul J

2016-12-01

We examined associations of advanced glycation end products (AGEs) with renal function loss (RFL) and its structural determinants in American Indians with type 2 diabetes. Data were from a 6-year clinical trial that assessed renoprotective efficacy of losartan. Participants remained under observation after the trial concluded. Glomerular filtration rate (GFR) was measured annually. Kidney biopsies were performed at the end of the trial. Five AGEs were measured in serum collected at enrollment and at kidney biopsy. RFL was defined as ≥40% decline of measured GFR from baseline. Of 168 participants (mean baseline age 41 years, HbA 1c 9.2%, GFR 164 mL/min, and albumin-to-creatinine ratio 31 mg/g), 104 reached the RFL end point during median follow-up of 8.0 years. After multivariable adjustment, each doubling of carboxyethyl lysine (hazard ratio [HR] 1.60 [95% CI 1.08-2.37]) or methylglyoxal hydroimidazolone (HR 1.30 [95% CI 1.02-1.65]) concentration was associated with RFL. Carboxyethyl lysine, carboxymethyl lysine, and methylglyoxal hydroimidazolone correlated positively with cortical interstitial fractional volume (partial r = 0.23, P = 0.03; partial r = 0.25, P = 0.02; and partial r = 0.31, P = 0.003, respectively). Glyoxyl hydroimidazolone and methylglyoxal hydroimidazolone correlated negatively with total filtration surface per glomerulus (partial r = -0.26, P = 0.01; and partial r = -0.21, P = 0.046, respectively). AGEs improve prediction of RFL and its major structural correlates. © 2016 by the American Diabetes Association.

Advanced Glycation End Products Predict Loss of Renal Function and Correlate With Lesions of Diabetic Kidney Disease in American Indians With Type 2 Diabetes

PubMed Central

Saulnier, Pierre-Jean; Wheelock, Kevin M.; Howell, Scott; Weil, E. Jennifer; Tanamas, Stephanie K.; Knowler, William C.; Lemley, Kevin V.; Mauer, Michael; Yee, Berne; Beisswenger, Paul J.

2016-01-01

We examined associations of advanced glycation end products (AGEs) with renal function loss (RFL) and its structural determinants in American Indians with type 2 diabetes. Data were from a 6-year clinical trial that assessed renoprotective efficacy of losartan. Participants remained under observation after the trial concluded. Glomerular filtration rate (GFR) was measured annually. Kidney biopsies were performed at the end of the trial. Five AGEs were measured in serum collected at enrollment and at kidney biopsy. RFL was defined as ≥40% decline of measured GFR from baseline. Of 168 participants (mean baseline age 41 years, HbA1c 9.2%, GFR 164 mL/min, and albumin-to-creatinine ratio 31 mg/g), 104 reached the RFL end point during median follow-up of 8.0 years. After multivariable adjustment, each doubling of carboxyethyl lysine (hazard ratio [HR] 1.60 [95% CI 1.08–2.37]) or methylglyoxal hydroimidazolone (HR 1.30 [95% CI 1.02–1.65]) concentration was associated with RFL. Carboxyethyl lysine, carboxymethyl lysine, and methylglyoxal hydroimidazolone correlated positively with cortical interstitial fractional volume (partial r = 0.23, P = 0.03; partial r = 0.25, P = 0.02; and partial r = 0.31, P = 0.003, respectively). Glyoxyl hydroimidazolone and methylglyoxal hydroimidazolone correlated negatively with total filtration surface per glomerulus (partial r = −0.26, P = 0.01; and partial r = −0.21, P = 0.046, respectively). AGEs improve prediction of RFL and its major structural correlates. PMID:27609106

Physical activity, function, and longevity among the very old.

PubMed

Stessman, Jochanan; Hammerman-Rozenberg, Robert; Cohen, Aaron; Ein-Mor, Eliana; Jacobs, Jeremy M

2009-09-14

Recommendations encouraging physical activity (PA) set no upper age limit, yet evidence supporting the benefits of PA among the very old is sparse. We examined the effects of continuing, increasing, or decreasing PA levels on survival, function, and health status among the very old. Mortality data from ages 70 to 88 years and health, comorbidity, and functional status at ages 70, 78, and 85 years were assessed through the Jerusalem Longitudinal Cohort Study (1990-2008). A representative sample of 1861 people born in 1920 and 1921 enrolled in this prospective study, resulting in 17 109 person-years of follow-up for all-cause mortality. Among physically active vs sedentary participants, respectively, at age 70, the 8-year mortality was 15.2% vs 27.2% (P < .001); at age 78, the 8-year mortality was 26.1% vs 40.8% (P <.001); and at age 85 years, the 3-year mortality was 6.8% vs 24.4% (P < .001). In Cox proportional-hazards models adjusting for mortality risk factors, lower mortality was associated with PA level at ages 70 (hazard ratio, 0.61; 95% confidence interval, 0.38-0.96), 78 (0.69; 0.48-0.98), and 85 (0.42; 0.25-0.68). A significant survival benefit was associated with initiating PA between ages 70 and 78 years (P = .04) and ages 78 and 85 years (P < .001). Participation in higher levels of PA, compared with being sedentary, did not show a dose-dependent association with mortality. The PA level at age 78 was associated with remaining independent while performing activities of daily living at age 85 (odds ratio, 1.92; 95% confidence interval, 1.11-3.33). Among the very old, not only continuing but also initiating PA was associated with better survival and function. This finding supports the encouragement of PA into advanced old age.

Age-related increase of resting metabolic rate in the human brain

PubMed Central

Peng, Shin-Lei; Dumas, Julie A.; Park, Denise C.; Liu, Peiying; Filbey, Francesca M.; McAdams, Carrie J.; Pinkham, Amy E.; Adinoff, Bryon; Zhang, Rong; Lu, Hanzhang

2014-01-01

With age, many aspects of the brain structure undergo a pronounced decline, yet individuals generally function well until advanced old age. There appear to be several compensatory mechanisms in brain aging, but their precise nature is not well characterized. Here we provide evidence that the brain of older adults expends more energy when compared to younger adults, as manifested by an age-related increase (P=0.03) in cerebral metabolic rate of oxygen (CMRO2) (N=118, men=56, ages 18 to 74). We further showed that, before the mean menopausal age of 51 years old, female and male groups have similar rates of CMRO2 increase (P=0.015) and there was no interaction between age and sex effects (P=0.85). However, when using data from the entire age range, women have a slower rate of CMRO2 change when compared to men (P<0.001 for age × sex interaction term). Thus, menopause and estrogen level may have played a role in this sex difference. Our data also revealed a possible circadian rhythm of CMRO2 in that brain metabolic rate is greater at noon than in the morning (P=0.02). This study reveals a potential neurobiological mechanism for age-related compensation in brain function and also suggests a sex-difference in its temporal pattern. PMID:24814209

Sibling composition, executive function, and children's thinking about mental diversity.

PubMed

Kennedy, Katie; Lagattuta, Kristin Hansen; Sayfan, Liat

2015-04-01

Prior investigations of relations between sibling composition and theory of mind have focused almost exclusively on false belief understanding in children 6 years of age and younger. The current work expands previous research by examining whether sibling composition predicts 4- to 11-year-olds' (N=192) more advanced mental state reasoning on interpretive theory of mind tasks. Even when controlling for age and executive function, children with a greater number of older siblings or with more same-sex siblings demonstrated stronger knowledge in both their predictions and explanations that people with different past experiences can have diverse interpretations of ambiguous stimuli. These data provide some of the first documentation of sibling constellations that predict individual differences in theory of mind during middle childhood. Copyright © 2014 Elsevier Inc. All rights reserved.

Advanced skeletal maturity in children and adolescents with myelomeningocele.

PubMed

Roiz, Ronald; Mueske, Nicole M; Van Speybroeck, Alexander; Ryan, Deirdre D; Gilsanz, Vicente; Wren, Tishya A L

2017-12-11

Atypical skeletal development is common in youth with myelomeningocele (MM), though the underlying reasons have not been fully elucidated. This study assessed skeletal maturity in children and adolescents with MM and examined the effects of sex, age, sexual development, ethnicity, anthropometrics and shunt status. Forty-three males and 35 females with MM, 6-16 years old, underwent hand radiographs for bone age determination. The difference between bone age and chronological age was evaluated using Wilcoxon sign rank tests. Relationships between age discrepancy (skeletal-chronological) and participant characteristics were assessed using multiple linear regression with forward selection. Overall, forty percent (31/78) of MM participants had an advanced bone age of 1 year or greater (median: 2.5 years), while 47% (37/78) were within 1 year above or below their chronological age (-0.001 years) and 13% (10/78) were delayed by more than 1 year (-1.4 years). Bone age was advanced compared to chronologic age in both males and females (p⩽ 0.024). Advanced bone age was observed in early to late puberty and after maturation (p⩽ 0.07), as well as in Hispanic participants (p= 0.003) and in those with a shunt (p= 0.0004). Advanced bone age was positively correlated with height, weight and body mass index (BMI) percentiles (p= 0.004). In multiple linear regression analysis, advanced bone age was most strongly associated with higher Tanner stage of sexual development, and higher weight, height or BMI percentile. Advanced skeletal maturity is common in children/adolescents with MM over 8 years of age who have reached puberty (65%), particularly those who are overweight (80%). Hormonal effects associated with adiposity and sexual maturity likely influence skeletal maturation. Clinicians may use Tanner stage and weight or BMI to gain insight into skeletal maturity.

Advancing innovation in health care leadership: a collaborative experience.

PubMed

Garcia, Victor H; Meek, Kevin L; Wilson, Kimburli A

2011-01-01

The changing framework of today's health care system requires leaders to be increasingly innovative in how they approach their daily functions and responsibilities. Sustaining and advancing a level of innovation that already exists can be challenging for health care administrators with the demands of time and resource limitations. Using collaboration to bring new-age teaching and disciplines to front-line leadership, one hospital was able to reinvigorate a culture of innovation through multiple levels and disciplines of the organization. The Innovation Certification Course provided nursing leaders and other managers' an evidence-drive approach, new principles and useful strategies of innovative leadership and graduate program education.

Age-related accumulation of Maillard reaction products in human articular cartilage collagen.

PubMed

Verzijl, N; DeGroot, J; Oldehinkel, E; Bank, R A; Thorpe, S R; Baynes, J W; Bayliss, M T; Bijlsma, J W; Lafeber, F P; Tekoppele, J M

2000-09-01

Non-enzymic modification of tissue proteins by reducing sugars, the so-called Maillard reaction, is a prominent feature of aging. In articular cartilage, relatively high levels of the advanced glycation end product (AGE) pentosidine accumulate with age. Higher pentosidine levels have been associated with a stiffer collagen network in cartilage. However, even in cartilage, pentosidine levels themselves represent <1 cross-link per 20 collagen molecules, and as such cannot be expected to contribute substantially to the increase in collagen network stiffness. In the present study, we investigated a broad range of Maillard reaction products in cartilage collagen in order to determine whether pentosidine serves as an adequate marker for AGE levels. Not only did the well-characterized AGEs pentosidine, N(epsilon)-(carboxymethyl)lysine, and N(epsilon)-(carboxyethyl)lysine increase with age in cartilage collagen (all P<0.0001), but also general measures of AGE cross-linking, such as browning and fluorescence (both P<0.0001), increased. The levels of these AGEs are all higher in cartilage collagen than in skin collagen. As a functional measure of glycation the digestibility of articular collagen by bacterial collagenase was investigated; digestibility decreased linearly with age, proportional to the extent of glycation. Furthermore, the arginine content and the sum of the hydroxylysine and lysine content of cartilage collagen decrease significantly with age (P<0.0001 and P<0. 01 respectively), possibly due to modification by the Maillard reaction. The observed relationship between glycation and amino acid modification has not been reported previously in vivo. Our present results indicate that extensive accumulation of a variety of Maillard reaction products occurs in cartilage collagen with age. Altogether our results support the hypothesis that glycation contributes to stiffer and more brittle cartilage with advancing age.

Age-related accumulation of Maillard reaction products in human articular cartilage collagen.

PubMed Central

Verzijl, N; DeGroot, J; Oldehinkel, E; Bank, R A; Thorpe, S R; Baynes, J W; Bayliss, M T; Bijlsma, J W; Lafeber, F P; Tekoppele, J M

2000-01-01

Non-enzymic modification of tissue proteins by reducing sugars, the so-called Maillard reaction, is a prominent feature of aging. In articular cartilage, relatively high levels of the advanced glycation end product (AGE) pentosidine accumulate with age. Higher pentosidine levels have been associated with a stiffer collagen network in cartilage. However, even in cartilage, pentosidine levels themselves represent <1 cross-link per 20 collagen molecules, and as such cannot be expected to contribute substantially to the increase in collagen network stiffness. In the present study, we investigated a broad range of Maillard reaction products in cartilage collagen in order to determine whether pentosidine serves as an adequate marker for AGE levels. Not only did the well-characterized AGEs pentosidine, N(epsilon)-(carboxymethyl)lysine, and N(epsilon)-(carboxyethyl)lysine increase with age in cartilage collagen (all P<0.0001), but also general measures of AGE cross-linking, such as browning and fluorescence (both P<0.0001), increased. The levels of these AGEs are all higher in cartilage collagen than in skin collagen. As a functional measure of glycation the digestibility of articular collagen by bacterial collagenase was investigated; digestibility decreased linearly with age, proportional to the extent of glycation. Furthermore, the arginine content and the sum of the hydroxylysine and lysine content of cartilage collagen decrease significantly with age (P<0.0001 and P<0. 01 respectively), possibly due to modification by the Maillard reaction. The observed relationship between glycation and amino acid modification has not been reported previously in vivo. Our present results indicate that extensive accumulation of a variety of Maillard reaction products occurs in cartilage collagen with age. Altogether our results support the hypothesis that glycation contributes to stiffer and more brittle cartilage with advancing age. PMID:10947951

Vaginal reconstruction following resection of primary locally advanced and recurrent colorectal malignancies.

PubMed

D'Souza, Dougal N; Pera, Miguel; Nelson, Heidi; Finical, Stephan J; Tran, Nho V

2003-12-01

Vertical rectus abdominus myocutaneous flap reconstruction facilitates healing within the radiated pelvis and preserves the possibility of subsequent sexual function in patients with colorectal cancer who require partial or complete resection of the vagina. A retrospective review of a consecutive series of patients. A tertiary referral center. All patients undergoing surgical treatment of locally advanced or recurrent colorectal cancer and vertical rectus abdominus myocutaneous flap reconstruction of the vagina. Vertical rectus abdominus myocutaneous flap reconstruction. Operative feasibility, complications, and sexual function. Twelve patients underwent extended resection for primary locally advanced or recurrent colorectal cancer including total or near total vaginectomy. Median age was 47 years. Tumors included 9 rectal adenocarcinomas, 2 anal squamous cell carcinomas, and 1 recurrent cecal adenocarcinoma. Surgical procedures included 8 abdominoperineal resections with posterior exenteration; resection of pelvic tumor and partial vaginectomy in 2 patients with previous abdominoperineal resection; 1 total exenteration; and 1 total proctocolectomy with posterior exenteration. The average operative time for tumor extirpation, irradiation, and reconstruction was more than 9 hours and all patients required blood transfusions. Despite 2 patients having superficial necrosis and 4 having mild wound infections, no patient required reoperation and all achieved complete healing. Five patients reported resuming sexual intercourse. The vertical rectus abdominus myocutaneous flap can be successfully used for vaginal reconstruction following resection of locally advanced colorectal cancer. It provides nonirradiated, vascularized tissue that fills the pelvic dead space, allows for stomal placement, and provides a chance for sexual function.

Liquid Medication Dosing Errors in Children: Role of Provider Counseling Strategies

PubMed Central

Yin, H. Shonna; Dreyer, Benard P.; Moreira, Hannah A.; van Schaick, Linda; Rodriguez, Luis; Boettger, Susanne; Mendelsohn, Alan L.

2014-01-01

Objective To examine the degree to which recommended provider counseling strategies, including advanced communication techniques and dosing instrument provision, are associated with reductions in parent liquid medication dosing errors. Methods Cross-sectional analysis of baseline data on provider communication and dosing instrument provision from a study of a health literacy intervention to reduce medication errors. Parents whose children (<9 years) were seen in two urban public hospital pediatric emergency departments (EDs) and were prescribed daily dose liquid medications self-reported whether they received counseling about their child’s medication, including advanced strategies (teachback, drawings/pictures, demonstration, showback) and receipt of a dosing instrument. Primary dependent variable: observed dosing error (>20% deviation from prescribed). Multivariate logistic regression analyses performed, controlling for: parent age, language, country, ethnicity, socioeconomic status, education, health literacy (Short Test of Functional Health Literacy in Adults); child age, chronic disease status; site. Results Of 287 parents, 41.1% made dosing errors. Advanced counseling and instrument provision in the ED were reported by 33.1% and 19.2%, respectively; 15.0% reported both. Advanced counseling and instrument provision in the ED were associated with decreased errors (30.5 vs. 46.4%, p=0.01; 21.8 vs. 45.7%, p=0.001). In adjusted analyses, ED advanced counseling in combination with instrument provision was associated with a decreased odds of error compared to receiving neither (AOR 0.3; 95% CI 0.1–0.7); advanced counseling alone and instrument alone were not significantly associated with odds of error. Conclusion Provider use of advanced counseling strategies and dosing instrument provision may be especially effective in reducing errors when used together. PMID:24767779

Liquid medication dosing errors in children: role of provider counseling strategies.

PubMed

Yin, H Shonna; Dreyer, Benard P; Moreira, Hannah A; van Schaick, Linda; Rodriguez, Luis; Boettger, Susanne; Mendelsohn, Alan L

2014-01-01

To examine the degree to which recommended provider counseling strategies, including advanced communication techniques and dosing instrument provision, are associated with reductions in parent liquid medication dosing errors. Cross-sectional analysis of baseline data on provider communication and dosing instrument provision from a study of a health literacy intervention to reduce medication errors. Parents whose children (<9 years) were seen in 2 urban public hospital pediatric emergency departments (EDs) and were prescribed daily dose liquid medications self-reported whether they received counseling about their child's medication, including advanced strategies (teachback, drawings/pictures, demonstration, showback) and receipt of a dosing instrument. The primary dependent variable was observed dosing error (>20% deviation from prescribed). Multivariate logistic regression analyses were performed, controlling for parent age, language, country, ethnicity, socioeconomic status, education, health literacy (Short Test of Functional Health Literacy in Adults); child age, chronic disease status; and site. Of 287 parents, 41.1% made dosing errors. Advanced counseling and instrument provision in the ED were reported by 33.1% and 19.2%, respectively; 15.0% reported both. Advanced counseling and instrument provision in the ED were associated with decreased errors (30.5 vs. 46.4%, P = .01; 21.8 vs. 45.7%, P = .001). In adjusted analyses, ED advanced counseling in combination with instrument provision was associated with a decreased odds of error compared to receiving neither (adjusted odds ratio 0.3; 95% confidence interval 0.1-0.7); advanced counseling alone and instrument alone were not significantly associated with odds of error. Provider use of advanced counseling strategies and dosing instrument provision may be especially effective in reducing errors when used together. Copyright © 2014 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Dietary intake of advanced glycation endproducts is associated with higher levels of advanced glycation endproducts in plasma and urine: The CODAM study.

PubMed

Scheijen, Jean L J M; Hanssen, Nordin M J; van Greevenbroek, Marleen M; Van der Kallen, Carla J; Feskens, Edith J M; Stehouwer, Coen D A; Schalkwijk, Casper G

2018-06-01

Advanced glycation endproducts (AGEs) are formed by the reaction between reducing sugars and proteins. AGEs in the body have been associated with several age-related diseases. High-heat treated and most processed foods are rich in AGEs. The aim of our study was to investigate whether dietary AGEs, are associated with plasma and urinary AGE levels. In 450 participants of the Cohort on Diabetes and Atherosclerosis Maastricht study (CODAM study) we measured plasma and urine concentrations of the AGEs Nε-(carboxymethyl)lysine (CML), Nε-(1-carboxyethyl)lysine (CEL) and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) using UPLC-MS/MS. We also estimated dietary intake of CML, CEL and MG-H1 with the use of a dietary AGE database and a food frequency questionnaire (FFQ). We used linear regression to investigate the association between standardized dietary AGE intake and standardized plasma or urinary AGE levels, after adjustment for age, sex, glucose metabolism status, waist circumference, kidney function, energy- and macro-nutrient intake, smoking status, physical activity, alcohol intake, LDL-cholesterol and markers of oxidative stress. We found that higher intake of dietary CML, CEL and MG-H1 was associated with significantly higher levels of free plasma and urinary CML, CEL and MG-H1 (βCML = 0.253 (95% CI 0.086; 0.415), βCEL = 0.194 (95% CI 0.040; 0.339), βMG-H1 = 0.223 (95% CI 0.069; 0.373) for plasma and βCML = 0.223 (95% CI 0.049; 0.393), βCEL = 0.180 (95% CI 0.019; 0.332), βMG-H1 = 0.196 (95% CI 0.037; 0.349) for urine, respectively). In addition, we observed non-significant associations of dietary AGEs with their corresponding protein bound plasma AGEs. We demonstrate that higher intake of dietary AGEs is associated with higher levels of AGEs in plasma and urine. Our findings may have important implications for those who ingest a diet rich in AGEs. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

The Fall in Older Adults: Physical and Cognitive Problems.

PubMed

Laurence, Bernard Demanze; Michel, Lacour

2017-01-01

The aging of posture and balance function alters the quality of life in older people and causes serious problems in terms of public health and socio-economic costs for our modern societies. This article reviews the various causes of imbalance and dizziness in the elderly, and considers how to prevent falls, and how to rehabilitate a faller subject in order to regain a good quality of life. Two effective ways of intervention are discussed, emphasizing the crucial role of physical activity and cognitive stimulation, classic or using the latest technical advances in virtual reality and video games. Fall in the elderly result from aging mechanisms acting on both the sensorimotor and cognitive spheres. The structural and functional integrity of the peripheral sensory receptors and the musculoskeletal system deteriorate with age. The brain ages and the executive functions, memory, learning, cortical processing of information, sharing of attentional resources and concentration, are modified in the elderly. Psychological affective factors such as depression, anxiety and stress contribute also to speed up the sensorimotor and cognitive decline. The rehabilitation of the postural balance in the elderly must take into account all of these components. The aging of the population and the increased of lifespan are a challenge for our modern societies regarding the major health and socio-economic questions they raise. The fall in the elderly being one of the dramatic consequences of the aging equilibration function, it is therefore imperative to develop rehabilitation procedures of balance. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Human umbilical cord plasma proteins revitalize hippocampal function in aged mice

PubMed Central

Castellano, Joseph M.; Mosher, Kira I.; Abbey, Rachelle J.; McBride, Alisha A.; James, Michelle L.; Berdnik, Daniela; Shen, Jadon C.; Zou, Bende; Xie, Xinmin S.; Tingle, Martha; Hinkson, Izumi V.; Angst, Martin S.; Wyss-Coray, Tony

2017-01-01

Ageing drives changes in neuronal and cognitive function, the decline of which is a major feature of many neurological disorders. The hippocampus, a brain region subserving roles of spatial and episodic memory and learning, is sensitive to the detrimental effects of ageing at morphological and molecular levels. With advancing age, synapses in various hippocampal subfields exhibit impaired long-term potentiation1, an electrophysiological correlate of learning and memory. At the molecular level, immediate early genes are among the synaptic plasticity genes that are both induced by long-term potentiation2, 3, 4 and downregulated in the aged brain5, 6, 7, 8. In addition to revitalizing other aged tissues9, 10, 11, 12, 13, exposure to factors in young blood counteracts age-related changes in these central nervous system parameters14, 15, 16, although the identities of specific cognition-promoting factors or whether such activity exists in human plasma remains unknown17. We hypothesized that plasma of an early developmental stage, namely umbilical cord plasma, provides a reservoir of such plasticity-promoting proteins. Here we show that human cord plasma treatment revitalizes the hippocampus and improves cognitive function in aged mice. Tissue inhibitor of metalloproteinases 2 (TIMP2), a blood-borne factor enriched in human cord plasma, young mouse plasma, and young mouse hippocampi, appears in the brain after systemic administration and increases synaptic plasticity and hippocampal-dependent cognition in aged mice. Depletion experiments in aged mice revealed TIMP2 to be necessary for the cognitive benefits conferred by cord plasma. We find that systemic pools of TIMP2 are necessary for spatial memory in young mice, while treatment of brain slices with TIMP2 antibody prevents long-term potentiation, arguing for previously unknown roles for TIMP2 in normal hippocampal function. Our findings reveal that human cord plasma contains plasticity-enhancing proteins of high translational value for targeting ageing- or disease-associated hippocampal dysfunction. PMID:28424512

Cellular changes in the enteric nervous system during ageing.

PubMed

Saffrey, M Jill

2013-10-01

The intrinsic neurons of the gut, enteric neurons, have an essential role in gastrointestinal functions. The enteric nervous system is plastic and continues to undergo changes throughout life, as the gut grows and responds to dietary and other environmental changes. Detailed analysis of changes in the ENS during ageing suggests that enteric neurons are more vulnerable to age-related degeneration and cell death than neurons in other parts of the nervous system, although there is considerable variation in the extent and time course of age-related enteric neuronal loss reported in different studies. Specific neuronal subpopulations, particularly cholinergic myenteric neurons, may be more vulnerable than others to age-associated loss or damage. Enteric degeneration and other age-related neuronal changes may contribute to gastrointestinal dysfunction that is common in the elderly population. Evidence suggests that caloric restriction protects against age-associated loss of enteric neurons, but recent advances in the understanding of the effects of the microbiota and the complex interactions between enteric ganglion cells, mucosal immune system and intestinal epithelium indicate that other factors may well influence ageing of enteric neurons. Much remains to be understood about the mechanisms of neuronal loss and damage in the gut, although there is evidence that reactive oxygen species, neurotrophic factor dysregulation and/or activation of a senescence associated phenotype may be involved. To date, there is no evidence for ongoing neurogenesis that might replace dying neurons in the ageing gut, although small local sites of neurogenesis would be difficult to detect. Finally, despite the considerable evidence for enteric neurodegeneration during ageing, and evidence for some physiological changes in animal models, the ageing gut appears to maintain its function remarkably well in animals that exhibit major neuronal loss, indicating that the ENS has considerable functional reserve. © 2013 Elsevier Inc. All rights reserved.

Evaluation and Validation of Organic Materials for Advanced Stirling Convertors (ASCs): Overview

NASA Technical Reports Server (NTRS)

Shin, Euy-Sik Eugene

2015-01-01

Various organic materials are used as essential parts in Stirling Convertors for their unique properties and functionalities such as bonding, potting, sealing, thread locking, insulation, and lubrication. More efficient Advanced Stirling Convertors (ASC) are being developed for future space applications especially with a long mission cycle, sometimes up to 17 years, such as deep space exploration or lunar surface power or Mars rovers, and others. Thus, performance, durability, and reliability of those organics should be critically evaluated in every possible material-process-fabrication-service environment relations based on their mission specifications. In general, thermal stability, radiation hardness, outgassing, and material compatibility of the selected organics have been systematically evaluated while their process and fabrication conditions and procedures were being optimized. Service environment-simulated long term aging tests up to 4 years were performed as a function of temperature for durability assessment of the most critical organic material systems.

A biopsychosocial approach to women’s sexual function and dysfunction at midlife: A narrative review

PubMed Central

Thomas, Holly N.; Thurston, Rebecca C.

2016-01-01

A satisfying sex life is an important component of overall well-being, but sexual dysfunction is common, especially in midlife women. The aim of this review is (a) to define sexual function and dysfunction, (b) to present theoretical models of female sexual response, (c) to examine longitudinal studies of how sexual function changes during midlife, and (d) to review treatment options. Four types of female sexual dysfunction are currently recognized: Female Orgasmic Disorder, Female Sexual Interest/Arousal Disorder, Genito-Pelvic Pain/Penetration Disorder, and Substance/Medication-Induced Sexual Dysfunction. However, optimal sexual function transcends the simple absence of dysfunction. A biopsychosocial approach that simultaneously considers physical, psychological, sociocultural, and interpersonal factors is necessary to guide research and clinical care regarding women’s sexual function. Most longitudinal studies reveal an association between advancing menopause status and worsening sexual function. Psychosocial variables, such as availability of a partner, relationship quality, and psychological functioning, also play an integral role. Future directions for research should include deepening our understanding of how sexual function changes with aging and developing safe and effective approaches to optimizing women’s sexual function with aging. Overall, holistic, biopsychosocial approaches to women’s sexual function are necessary to fully understand and treat this key component of midlife women’s well-being. PMID:27013288

A biopsychosocial approach to women's sexual function and dysfunction at midlife: A narrative review.

PubMed

Thomas, Holly N; Thurston, Rebecca C

2016-05-01

A satisfying sex life is an important component of overall well-being, but sexual dysfunction is common, especially in midlife women. The aim of this review is (a) to define sexual function and dysfunction, (b) to present theoretical models of female sexual response, (c) to examine longitudinal studies of how sexual function changes during midlife, and (d) to review treatment options. Four types of female sexual dysfunction are currently recognized: Female Orgasmic Disorder, Female Sexual Interest/Arousal Disorder, Genito-Pelvic Pain/Penetration Disorder, and Substance/Medication-Induced Sexual Dysfunction. However, optimal sexual function transcends the simple absence of dysfunction. A biopsychosocial approach that simultaneously considers physical, psychological, sociocultural, and interpersonal factors is necessary to guide research and clinical care regarding women's sexual function. Most longitudinal studies reveal an association between advancing menopause status and worsening sexual function. Psychosocial variables, such as availability of a partner, relationship quality, and psychological functioning, also play an integral role. Future directions for research should include deepening our understanding of how sexual function changes with aging and developing safe and effective approaches to optimizing women's sexual function with aging. Overall, holistic, biopsychosocial approaches to women's sexual function are necessary to fully understand and treat this key component of midlife women's well-being. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Correlates of Social Functioning in Autism Spectrum Disorder: The Role of Social Cognition.

PubMed

Bishop-Fitzpatrick, Lauren; Mazefsky, Carla A; Eack, Shaun M; Minshew, Nancy J

2017-03-01

Individuals with autism spectrum disorder (ASD) experience marked challenges with social function by definition, but few modifiable predictors of social functioning in ASD have been identified in extant research. This study hypothesized that deficits in social cognition and motor function may help to explain poor social functioning in individuals with ASD. Cross-sectional data from 108 individuals with ASD and without intellectual disability ages 9 through 27.5 were used to assess the relationship between social cognition and motor function, and social functioning. Results of hierarchical multiple regression analyses revealed that greater social cognition, but not motor function, was significantly associated with better social functioning when controlling for sex, age, and intelligence quotient. Post-hoc analyses revealed that, better performance on second-order false belief tasks was associated with higher levels of socially adaptive behavior and lower levels of social problems. Our findings support the development and testing of interventions that target social cognition in order to improve social functioning in individuals with ASD. Interventions that teach generalizable skills to help people with ASD better understand social situations and develop competency in advanced perspective taking have the potential to create more durable change because their effects can be applied to a wide and varied set of situations and not simply a prescribed set of rehearsed situations.

Advanced glycation end‑products affect the cytoskeletal structure of rat glomerular endothelial cells via the Ras‑related C3 botulinum toxin substrate 1 signaling pathway.

PubMed

Lan, Lei; Han, Yongsheng; Ren, Wei; Jiang, Jielong; Wang, Peng; Hu, Zhao

2015-06-01

The present study aimed to determine the molecular mechanisms leading to the production of advanced glycation end‑products (AGEs) and their effect on the morphology and function of rat glomerular capillary endothelial cells (GECs). Primary rat GECs were treated with AGE‑modified human serum albumin (AGE‑HSA) and divided into groups according to AGE concentration and treatment time. The structure and distribution of cytoskeletal protein F‑actin and the cortical actin binding protein, cortactin, were analyzed using immunofluorescence and confocal microscopy. As the Ras‑related C3 botulinum toxin substrate 1 (Rac1) signaling pathway was previously identified to be involved in mediating the contraction of endothelial actin‑myosin activity, Rac1 was examined subsequent to treatment of the cells with the Rac1 agonist 2'‑O‑methyladenosine‑3',5'‑cyclic monophosphate (O‑Me‑cAMP) for 1 h using a pull‑down assay. Cell permeability was determined by the leakage rate of a fluorescein isothiocyanate fluorescent marker protein. AGE‑HSA treatment resulted in alterations in the structure and distribution of F‑actin and cortactin in a dose‑ and time‑dependent manner, while no effect was observed with HSA alone. The effect of AGE on the cytoskeleton was inhibited by the addition of O‑Me‑cAMP. AGE‑HSA significantly reduced the level of Rac1 activity (P<0.05); however, no effect was observed on total protein levels. Furthermore, AGE‑HSA treatment led to a significant increase in the permeability of endothelial cells (P<0.01), which was inhibited by O‑Me‑cAMP (P<0.01). The Rac1 signaling pathway is thus suggested to serve an important function in mediating AGE‑induced alterations in GEC morphology and function.

Children and older adults exhibit distinct sub-optimal cost-benefit functions when preparing to move their eyes and hands.

PubMed

Gonzalez, Claudia C; Mon-Williams, Mark; Burke, Melanie R

2015-01-01

Numerous activities require an individual to respond quickly to the correct stimulus. The provision of advance information allows response priming but heightened responses can cause errors (responding too early or reacting to the wrong stimulus). Thus, a balance is required between the online cognitive mechanisms (inhibitory and anticipatory) used to prepare and execute a motor response at the appropriate time. We investigated the use of advance information in 71 participants across four different age groups: (i) children, (ii) young adults, (iii) middle-aged adults, and (iv) older adults. We implemented 'cued' and 'non-cued' conditions to assess age-related changes in saccadic and touch responses to targets in three movement conditions: (a) Eyes only; (b) Hands only; (c) Eyes and Hand. Children made less saccade errors compared to young adults, but they also exhibited longer response times in cued versus non-cued conditions. In contrast, older adults showed faster responses in cued conditions but exhibited more errors. The results indicate that young adults (18-25 years) achieve an optimal balance between anticipation and execution. In contrast, children show benefits (few errors) and costs (slow responses) of good inhibition when preparing a motor response based on advance information; whilst older adults show the benefits and costs associated with a prospective response strategy (i.e., good anticipation).

How Do Concept-Maps Function for Reading Comprehension Improvement of Iranian Advanced EFL Learners of Both Genders?

ERIC Educational Resources Information Center

Khaghaninejad, Mohammad Saber; Arefinejad, Mansour

2015-01-01

This study was an attempt to examine the effect of concept mapping on reading comprehension of Iranian EFL learners. Pretest-posttest design was employed to scrutinize the possible improvement of the study's participants who were male and female learners whose ages ranged from 19 to 40 and had taken general English courses at Islamic Azad…

Triage of patients with moderate to severe heart failure: who should be referred to a heart failure center?

PubMed

Thorvaldsen, Tonje; Benson, Lina; Ståhlberg, Marcus; Dahlström, Ulf; Edner, Magnus; Lund, Lars H

2014-02-25

The purpose of this study was to evaluate simple criteria for referral of patients from the general practitioner to a heart failure (HF) center. In advanced HF, the criteria for heart transplantation, left ventricular assist device, and palliative care are well known among HF specialists, but criteria for referral to an advanced HF center have not been developed for generalists. We assessed observed and expected all-cause mortality in 10,062 patients with New York Heart Association (NYHA) functional class III to IV HF and ejection fraction <40% registered in the Swedish Heart Failure Registry between 2000 and 2013. Next, 5 pre-specified universally available risk factors were assessed as potential triggers for referral, using multivariable Cox regression: systolic blood pressure ≤90 mm Hg; creatinine ≥160 μmol/l; hemoglobin ≤120 g/l; no renin-angiotensin system antagonist; and no beta-blocker. In NYHA functional class III to IV and age groups ≤65 years, 66 to 80 years, and >80 years, there were 2,247, 4,632, and 3,183 patients, with 1-year observed versus expected survivals of 90% versus 99%, 79% versus 97%, and 61% versus 89%, respectively. In the age ≤80 years group, the presence of 1, 2, or 3 to 5 of these risk factors conferred an independent hazard ratio for all-cause mortality of 1.40, 2.30, and 4.07, and a 1-year survival of 79%, 60%, and 39%, respectively (p < 0.001). In patients ≤80 years of age with NYHA functional class III to IV HF and ejection fraction <40%, mortality is predominantly related to HF or its comorbidities. Potential heart transplantation/left ventricular assist device candidacy is suggested by ≥1 risk factor and potential palliative care by multiple universally available risk factors. These patients may benefit from referral to an advanced HF center. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Practical and Ethical Aspects of Advance Research Directives for Research on Healthy Aging: German and Israeli Professionals' Perspectives.

PubMed

Werner, Perla; Schicktanz, Silke

2018-01-01

Healthy aging is the development and maintenance of optimal cognitive, social and physical well-being, and function in older adults. Preventing or minimizing disease is one of the main ways of achieving healthy aging. Dementia is one of the most prevalent and life-changing diseases of old age. Thus, dementia prevention research is defined as one of the main priorities worldwide. However, conducting research with persons who lack the capacity to give consent is a major ethical issue. Our study attempts to explore if and how advance research directives (ARDs) may be used as a future tool to deal with the ethical and practical issues in dementia research. We conducted focus groups and in-depth interviews with German and Israeli professional stakeholders from the fields of gerontology, ethics, medical law, psychiatry, neurology and policy advice ( n  = 16), and analyzed the main topics discussed regarding cross-national similarities and controversies within the groups, as well as across the two national contexts. While both countries are in the midst of a developmental process and have recognized the importance and need for ARD as a tool for expanding healthy aging, Germany is in a more advanced stage than Israel because of the EU regulation process, which indicates the influence of international harmonization on these research-related ethical issues. Consensual themes within the qualitative material were identified: the need for a broader debate on ARD, the ethical importance of autonomy and risk-benefit assessment for ARD implementation, the role of the proxy and the need for the differentiation of types of dementia research. Controversies and dilemmas aroused around themes such as the current role of IRBs in each country, the need for limits, and how to guaranty safeguarding and control. Implementing a new tool is a step-by-step procedure requiring a thorough understanding of the current state of knowledge as well as of the challenges and hurdles ahead. As long as improving quality of life and promoting autonomy continue to be core elements in the process of healthy aging, efforts to advance knowledge and solve dilemmas associated with the implementation of ARD is of the utmost importance.

Analysis of clinically important factors on the performance of advanced hydraulic, microprocessor-controlled exo-prosthetic knee joints based on 899 trial fittings

PubMed Central

Hahn, Andreas; Lang, Michael; Stuckart, Claudia

2016-01-01

Abstract The objective of this work is to evaluate whether clinically important factors may predict an individual's capability to utilize the functional benefits provided by an advanced hydraulic, microprocessor-controlled exo-prosthetic knee component. This retrospective cross-sectional cohort analysis investigated the data of above knee amputees captured during routine trial fittings. Prosthetists rated the performance indicators showing the functional benefits of the advanced maneuvering capabilities of the device. Subjects were asked to rate their perception. Simple and multiple linear and logistic regression was applied. Data from 899 subjects with demographics typical for the population were evaluated. Ability to vary gait speed, perform toileting, and ascend stairs were identified as the most sensitive performance predictors. Prior C-Leg users showed benefits during advanced maneuvering. Variables showed plausible and meaningful effects, however, could not claim predictive power. Mobility grade showed the largest effect but also failed to be predictive. Clinical parameters such as etiology, age, mobility grade, and others analyzed here do not suffice to predict individual potential. Daily walking distance may pose a threshold value and be part of a predictive instrument. Decisions based solely on single parameters such as mobility grade rating or walking distance seem to be questionable. PMID:27828871

Analysis of clinically important factors on the performance of advanced hydraulic, microprocessor-controlled exo-prosthetic knee joints based on 899 trial fittings.

PubMed

Hahn, Andreas; Lang, Michael; Stuckart, Claudia

2016-11-01

The objective of this work is to evaluate whether clinically important factors may predict an individual's capability to utilize the functional benefits provided by an advanced hydraulic, microprocessor-controlled exo-prosthetic knee component.This retrospective cross-sectional cohort analysis investigated the data of above knee amputees captured during routine trial fittings. Prosthetists rated the performance indicators showing the functional benefits of the advanced maneuvering capabilities of the device. Subjects were asked to rate their perception. Simple and multiple linear and logistic regression was applied.Data from 899 subjects with demographics typical for the population were evaluated. Ability to vary gait speed, perform toileting, and ascend stairs were identified as the most sensitive performance predictors. Prior C-Leg users showed benefits during advanced maneuvering. Variables showed plausible and meaningful effects, however, could not claim predictive power. Mobility grade showed the largest effect but also failed to be predictive.Clinical parameters such as etiology, age, mobility grade, and others analyzed here do not suffice to predict individual potential. Daily walking distance may pose a threshold value and be part of a predictive instrument. Decisions based solely on single parameters such as mobility grade rating or walking distance seem to be questionable.

Characteristics of first-time fathers of advanced age: a Norwegian population-based study

PubMed Central

2013-01-01

Background The modern phenomenon of delayed parenthood applies not only to women but also to men, but less is known about what characterises men who are expecting their first child at an advanced age. This study investigates the sociodemographic characteristics, health behaviour, health problems, social relationships and timing of pregnancy in older first-time fathers. Methods A cross-sectional study was conducted of 14 832 men who were expecting their first child, based on data from the Norwegian Mother and Child Cohort Study (MoBa) carried out by the Norwegian Institute of Public Health. Data were collected in 2005–2008 by means of a questionnaire in gestational week 17–18 of their partner’s pregnancy, and from the Norwegian Medical Birth Register. The distribution of background variables was investigated across the age span of 25 years and above. Men of advanced age (35–39 years) and very advanced age (40 years or more) were compared with men aged 25–34 years by means of bivariate and multivariate logistic regression analyses. Results The following factors were found to be associated with having the first child at an advanced or very advanced age: being unmarried or non-cohabitant, negative health behaviour (overweight, obesity, smoking, frequent alcohol intake), physical and mental health problems (lower back pain, cardiovascular diseases, high blood pressure, sleeping problems, previous depressive symptoms), few social contacts and dissatisfaction with partner relationship. There were mixed associations for socioeconomic status: several proxy measures of high socioeconomic status (e.g. income >65 000 €, self-employment) were associated with having the first child at an advanced or very advanced age, as were several other proxy measures of low socioeconomic status (e.g. unemployment, low level of education, immigrant background).The odds of the child being conceived after in vitro fertilisation were threefold in men aged 34–39 and fourfold from 40 years and above. Conclusions Men who expect their first baby at an advanced or very advanced age constitute a socioeconomically heterogeneous group with more health problems and more risky health behaviour than younger men. Since older men often have their first child with a woman of advanced age, in whom similar characteristics have been reported, their combined risk of adverse perinatal outcomes needs further attention by clinicians and researchers. PMID:23363654

[Effects of exercise and physical activity on vital age].

PubMed

Tanaka, Kiyoji; Matsuo, Tomoaki

2009-07-01

Advances in medical care have enabled many middle-aged and older adults to live for long periods of time. However, considerable variability is present among those people with regards to both longevity and physical health status. Physical inactivity is a significant risk factor for many chronic diseases, while exercise habituation is beneficial for the maintenance of good health and high vitality. The authors have developed the concept of so-called vital age for the assessment of health and functional status in middle-aged and older adults. The vital age is estimated using a variety of bio-medical, primarily cardiovascular risk factor parameters. Previous research has compared vital age between sedentary persons and those with obesity and chronic diseases and between sedentary persons and those with exercise habituation, and found that exercise habituation can certainly contribute to better physical vitality in previously sedentary persons as well as diseased persons.

Adult Age Differences and the Role of Cognitive Resources in Perceptual–Motor Skill Acquisition: Application of a Multilevel Negative Exponential Model

PubMed Central

Kennedy, Kristen M.; Rodrigue, Karen M.; Lindenberger, Ulman; Raz, Naftali

2010-01-01

The effects of advanced age and cognitive resources on the course of skill acquisition are unclear, and discrepancies among studies may reflect limitations of data analytic approaches. We applied a multilevel negative exponential model to skill acquisition data from 80 trials (four 20-trial blocks) of a pursuit rotor task administered to healthy adults (19–80 years old). The analyses conducted at the single-trial level indicated that the negative exponential function described performance well. Learning parameters correlated with measures of task-relevant cognitive resources on all blocks except the last and with age on all blocks after the second. Thus, age differences in motor skill acquisition may evolve in 2 phases: In the first, age differences are collinear with individual differences in task-relevant cognitive resources; in the second, age differences orthogonal to these resources emerge. PMID:20047985

Potentiation of cGMP signaling increases oxygen delivery and oxidative metabolism in contracting skeletal muscle of older but not young humans

PubMed Central

Nyberg, Michael; Piil, Peter; Egelund, Jon; Sprague, Randy S; Mortensen, Stefan P; Hellsten, Ylva

2015-01-01

Aging is associated with progressive loss of cardiovascular and skeletal muscle function. The impairment in physical capacity with advancing age could be related to an insufficient peripheral O2 delivery to the exercising muscles. Furthermore, the mechanisms underlying an impaired blood flow regulation remain unresolved. Cyclic guanosine monophosphate (cGMP) is one of the main second messengers that mediate smooth muscle vasodilation and alterations in cGMP signaling could, therefore, be one mechanism by which skeletal muscle perfusion is impaired with advancing age. The current study aimed to evaluate the effect of inhibiting the main enzyme involved in cGMP degradation, phosphodiesterase 5 (PDE5), on blood flow and O2 delivery in contracting skeletal muscle of young and older humans. A group of young (23 ± 1 years) and a group of older (72 ± 2 years) male human subjects performed submaximal knee-extensor exercise in a control setting and following intake of the highly selective PDE5 inhibitor sildenafil. Sildenafil increased leg O2 delivery (6–9%) and leg O2 uptake (10–12%) at all three exercise intensities in older but not young subjects. The increase in leg O2 delivery with sildenafil in the older subjects correlated with the increase in leg O2 uptake (r2 = 0.843). These findings suggest an insufficient O2 delivery to the contracting skeletal muscle of aged individuals and that reduced cGMP availability is a novel mechanism underlying impaired skeletal muscle perfusion with advancing age. PMID:26272735

Quantitative measures of healthy aging and biological age

PubMed Central

Kim, Sangkyu; Jazwinski, S. Michal

2015-01-01

Numerous genetic and non-genetic factors contribute to aging. To facilitate the study of these factors, various descriptors of biological aging, including ‘successful aging’ and ‘frailty’, have been put forth as integrative functional measures of aging. A separate but related quantitative approach is the ‘frailty index’, which has been operationalized and frequently used. Various frailty indices have been constructed. Although based on different numbers and types of health variables, frailty indices possess several common properties that make them useful across different studies. We have been using a frailty index termed FI34 based on 34 health variables. Like other frailty indices, FI34 increases non-linearly with advancing age and is a better indicator of biological aging than chronological age. FI34 has a substantial genetic basis. Using FI34, we found elevated levels of resting metabolic rate linked to declining health in nonagenarians. Using FI34 as a quantitative phenotype, we have also found a genomic region on chromosome 12 that is associated with healthy aging and longevity. PMID:26005669

Microglial aging in the healthy CNS: phenotypes, drivers, and rejuvenation

PubMed Central

Wong, Wai T.

2013-01-01

Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and age-related macular degeneration (AMD), share two characteristics in common: (1) a disease prevalence that increases markedly with advancing age, and (2) neuroinflammatory changes in which microglia, the primary resident immune cell of the CNS, feature prominently. These characteristics have led to the hypothesis that pathogenic mechanisms underlying age-related neurodegenerative disease involve aging changes in microglia. If correct, targeting features of microglial senescence may constitute a feasible therapeutic strategy. This review explores this hypothesis and its implications by considering the current knowledge on how microglia undergo change during aging and how the emergence of these aging phenotypes relate to significant alterations in microglial function. Evidence and theories on cellular mechanisms implicated in driving senescence in microglia are reviewed, as are “rejuvenative” measures and strategies that aim to reverse or ameliorate the aging microglial phenotype. Understanding and controlling microglial aging may represent an opportunity for elucidating disease mechanisms and for formulating novel therapies. PMID:23493481

Temporal Information Processing and its Relation to Executive Functions in Elderly Individuals.

PubMed

Nowak, Kamila; Dacewicz, Anna; Broczek, Katarzyna; Kupisz-Urbanska, Malgorzata; Galkowski, Tadeusz; Szelag, Elzbieta

2016-01-01

Normal aging triggers deterioration in cognitive functions. Evidence has shown that these age-related changes concern also executive functions (EF) as well as temporal information processing (TIP) in a millisecond range. A considerable amount of literature data has indicated that each of these two functions sets a frame for our mental activity and may be considered in terms of embodied cognition due to advanced age. The present study addresses the question whether in elderly subjects the efficiency of TIP is related to individual differences in EF. The study involved 53 normal healthy participants aged from 65 to 78. In these subjects TIP was assessed by sequencing abilities measured with temporal-order threshold (TOT). It is defined as the minimum time gap separating two auditory stimuli presented in rapid succession which is necessary for a subject to report correctly their temporal order, thus the relation 'before-after.' The EF were assessed with regard to the efficiency of the executive planning measured with the Tower of London-Drexel University (TOL DX ) which has become a well-known EF task. Using Spearman's rank correlations we observed two main results. Firstly, the indices of the TOL DX indicated a coherent construct reflecting the effectiveness of executive planning in the elderly. Initiation time seemed dissociated from these coherent indices, which suggested a specific strategy of mental planning in the elderly based on on-line planning rather than on preplanning. Secondly, TOT was significantly correlated with the indices of TOL DX . Although some of these correlations were modified by subject's age, the correlation between TOT and the main index of TOL DX ( 'Total Move Score' ) was rather age resistant. These results suggest that normal aging may be characterized by an overlapping of deteriorated TIP and deteriorated EF.

Temporal Information Processing and its Relation to Executive Functions in Elderly Individuals

PubMed Central

Nowak, Kamila; Dacewicz, Anna; Broczek, Katarzyna; Kupisz-Urbanska, Malgorzata; Galkowski, Tadeusz; Szelag, Elzbieta

2016-01-01

Normal aging triggers deterioration in cognitive functions. Evidence has shown that these age-related changes concern also executive functions (EF) as well as temporal information processing (TIP) in a millisecond range. A considerable amount of literature data has indicated that each of these two functions sets a frame for our mental activity and may be considered in terms of embodied cognition due to advanced age. The present study addresses the question whether in elderly subjects the efficiency of TIP is related to individual differences in EF. The study involved 53 normal healthy participants aged from 65 to 78. In these subjects TIP was assessed by sequencing abilities measured with temporal-order threshold (TOT). It is defined as the minimum time gap separating two auditory stimuli presented in rapid succession which is necessary for a subject to report correctly their temporal order, thus the relation ‘before-after.’ The EF were assessed with regard to the efficiency of the executive planning measured with the Tower of London-Drexel University (TOLDX) which has become a well-known EF task. Using Spearman’s rank correlations we observed two main results. Firstly, the indices of the TOLDX indicated a coherent construct reflecting the effectiveness of executive planning in the elderly. Initiation time seemed dissociated from these coherent indices, which suggested a specific strategy of mental planning in the elderly based on on-line planning rather than on preplanning. Secondly, TOT was significantly correlated with the indices of TOLDX. Although some of these correlations were modified by subject’s age, the correlation between TOT and the main index of TOLDX (‘Total Move Score’) was rather age resistant. These results suggest that normal aging may be characterized by an overlapping of deteriorated TIP and deteriorated EF. PMID:27807426

[The sense of smell in daily life].

PubMed

Steinbach, S; Hundt, W; Zahnert, T

2008-09-01

An intact olfactory system affects all areas of life including the creation of new life, partner selection, daily hygiene, food intake, and the perception of danger from gas and smoke. The olfactory system is most effective from adolescence to middle age. With advancing age the regeneration of olfactory receptor cells decreases, often resulting in an increasing loss of smell. Functional anosmia affects 5% of the general population and 10% of those over 65. Therefore, olfactory dysfunctions are not uncommon. The following provides an overview of the physiology of smell, olfactory testing, special olfactory dysfunctions as well as treatment and general recommendations.

[Role of Maillard products in the chronic complications of diabetes mellitus. Bioclinical applications].

PubMed

Trivin, F

1998-01-01

The formation of Maillard products is increased in the diabetes mellitus. These advanced glycated end products (AGEs) alter metabolic functions of macromolecules and increase free radical formation while decreasing free radical-scavenging enzyme activity. The elimination of AGEs is insured by the macrophage cells equipped with appropriate receptors (RAGE) and cleared by kidneys. The knowledge of these molecular mechanisms had allowed the emergence of biochemical analytes such as 3-deoxyglucosone, pentosidine, and carboxymethyl-lysine, as markers of the ris of micro- and macro-angiopathy, the main chronic complications of the diabetes mellitus.

Racial and Ethnic Differences in Advance Directive Possession: Role of Demographic Factors, Religious Affiliation, and Personal Health Values in a National Survey of Older Adults

PubMed Central

Neuhaus, John M.; Chiong, Winston

2016-01-01

Abstract Background: Black and Hispanic older Americans are less likely than white older Americans to possess advance directives. Understanding the reasons for this racial and ethnic difference is necessary to identify targets for future interventions to improve advance care planning in these populations. Methods: The aim of the study was to evaluate whether racial and ethnic differences in advance directive possession are explained by other demographic factors, religious characteristics, and personal health values. A general population survey was conducted in a nationally representative sample using a web-enabled survey panel of American adults aged 50 and older (n = 2154). Results: In a sample of older Americans, white participants are significantly more likely to possess advance directives (44.0%) than black older Americans (24.0%, p < 0.001) and Hispanic older Americans (29.0%, p = 0.006). Gender, age, retired or disabled employment status, educational attainment, religious affiliation, Internet access, preferences for physician-centered decision making, and desiring longevity regardless of functional status were independent predictors of advance directive possession. In fully adjusted multivariable models with all predictors included, black older Americans remained significantly less likely than white older Americans to have an advance directive (odds ratio [OR] = 0.42, 95% confidence interval [CI] = 0.24–0.75), whereas the effect of Hispanic ethnicity was no longer statistically significant (OR = 0.65, 95% CI = 0.39–1.1). Conclusion: In a nationally representative sample, black race is an independent predictor for advance directive possession. This association remains even after adjustment for other demographic variables, religious characteristics, and personal health values. These findings support targeted efforts to mitigate racial disparities in access to advance care planning. PMID:26840850

Long-term administration of advanced glycation end-product stimulates the activation of NLRP3 inflammasome and sparking the development of renal injury.

PubMed

Yeh, Wan-Ju; Yang, Hsin-Yi; Pai, Man-Hui; Wu, Chi-Hao; Chen, Jiun-Rong

2017-01-01

The accumulation of advanced glycation end-products (AGEs) and the enhanced interaction of AGE with their cellular receptor (RAGE) have been implicated in the progression of chronic kidney disease. The purpose of this study was to examine whether the AGE/RAGE-induced nephrotoxic effects are associated with inflammasome activation and endothelial dysfunction. Chronic renal injury was examined in BALB/c mice by the long-term administration of carbonyl-AGE for 16 weeks. Endothelial dysfunction was detected by measuring the number of circulating endothelial progenitor cells (EPCs) and the levels of nitric oxide synthase (eNOS) and nitric oxide (NO) in kidneys. Results showed that administration of methylglyoxal-bovine serum albumin (MG-BSA) AGE accelerated renal MG, carboxyethyl lysine, carboxymethyl lysine and malondialdehyde formation and, in parallel, the levels of serum creatinine and blood urea nitrogen (BUN) were significantly increased. Expression of RAGE and NLRP3 inflammasome-related proteins (TXNIP, NLRP3, procaspase-1 and caspase-1) and IL (interleukin)-1β secretion were upregulated, whereas the levels of EPCs, eNOS and NO were lower in MG-BSA-treated mice. This induction by MG-BSA was significantly inhibited by RAGE antagonist. Our results firstly reveal a possible mechanism of AGE-mediated renal dysfunction upon NLRP3 inflammasome activation. Therapeutic blockade of RAGE may ameliorate renal and endothelial functions in subjects under high AGE burden. Copyright © 2016 Elsevier Inc. All rights reserved.

Advanced glycation end products in children with chronic renal failure and type 1 diabetes.

PubMed

Misselwitz, Joachim; Franke, Sybille; Kauf, Eberhard; John, Ulrike; Stein, Günter

2002-05-01

Serum levels of advanced glycation end products (AGEs) are markedly elevated in adults with chronic renal failure (CRF) and diabetes mellitus. Accumulation of AGEs in tissues contributes to the development of long-term complications. Up to now little has been known about the formation of AGEs in childhood. We determined serum levels of the well known AGEs pentosidine and Nvarepsilon-carboxymethyllysine (CML) in children with CRF (n=12), end-stage renal disease (ESRD) (n=9), renal transplantation (n=12), and type 1 diabetes mellitus (n=42) and in healthy children (n=20). Pentosidine was measured by high-performance liquid chromatography (HPLC), CML by a competitive enzyme-linked immunosorbent assay (ELISA) system. Serum levels of pentosidine and CML were significantly higher in the children with CRF and ESRD than in controls (P< 0.001), but nearly within the normal range after transplantation. Both AGEs showed a significant negative correlation with creatinine clearance (P< 0.001). During a single session of low-flux hemodialysis, total pentosidine and CML levels did not change. Free pentosidine, however, was reduced by 78% (P=0.04). Diabetic children showed significantly elevated pentosidine levels (P< 0.001) despite normal renal function. We conclude that, similar to adults, increased formation and accumulation of AGEs also exist in children with CRF and type 1 diabetes mellitus. At present the best prevention of AGE-related complications is an early renal transplantation in children with ESRD, as well as a careful metabolic monitoring of diabetics.

Healthy adolescents' neural response to reward: associations with puberty, positive affect, and depressive symptoms.

PubMed

Forbes, Erika E; Ryan, Neal D; Phillips, Mary L; Manuck, Stephen B; Worthman, Carol M; Moyles, Donna L; Tarr, Jill A; Sciarrillo, Samantha R; Dahl, Ronald E

2010-02-01

Changes in reward-related behavior are an important component of normal adolescent affective development. Understanding the neural underpinnings of these normative changes creates a foundation for investigating adolescence as a period of vulnerability to affective disorders, substance use disorders, and health problems. Studies of reward-related brain function have revealed conflicting findings regarding developmental change in the reactivity of the striatum and medial prefrontal cortex (mPFC) and have not considered puberty. The current study focused on puberty-specific changes in brain function and their association with mood. A sample of 77 healthy adolescents (26 pre-/early pubertal, 51 mid-/late pubertal) recruited in a narrow age range (mean = 11.94 years, SD = 0.75) were assessed for sexual maturation and circulating testosterone, completed a functional magnetic resonance imaging (fMRI) guessing task with monetary reward, and underwent experience sampling of mood in natural environments. For comparison, 19 healthy adults completed the fMRI assessment. Adolescents with more advanced pubertal maturation exhibited less striatal and more mPFC reactivity during reward outcome than similarly aged adolescents with less advanced maturation. Testosterone was positively correlated with striatal reactivity in boys during reward anticipation and negatively correlated with striatal reactivity in girls and boys during reward outcome. Striatal reactivity was positively correlated with real-world subjective positive affect and negatively correlated with depressive symptoms. mPFC reactivity was positively correlated with depressive symptoms. Reward-related brain function changes with puberty and is associated with adolescents' positive affect and depressive symptoms. Increased reward-seeking behavior at this developmental point could serve to compensate for these changes.

Effect of Carnosine on Renal Function, Oxidation and Glycation Products in the Kidneys of High-Fat Diet/Streptozotocin-Induced Diabetic Rats.

PubMed

Fatih Aydın, Abdurrahman; Küçükgergin, Canan; Bingül, İlknur; Doğan-Ekici, Işın; Doğru-Abbasoğlu, Semra; Uysal, Müjdat

2017-05-01

High fat diet (HFD) and low dose of streptozotocin (STZ)-treated rats provide an animal model for type 2 Diabetes Mellitus (T2DM). Oxidative stress plays a role in the development of diabetic complications. Carnosine (CAR) has antioxidant and antiglycating properties. We investigated effects of CAR on renal function, oxidation and glycation products in HFD+STZ-rats. Rats were fed with HFD (60% of total calories from fat) for 4 weeks and then a single dose STZ (40 mg/kg; i.p.) was applied. Rats with blood glucose levels above 200 mg/dL were fed with HFD until the end of the 12 th week. CAR (250 mg/kg body weight; i.p.; 5 times a week) was administered to rats for the last 4 weeks. Glycated hemoglobin (HbA1c), glucose, lipids, and andrenal function tests in serum as well as reactive oxygen species, malondialdehyde, protein carbonyl, advanced oxidation protein products, advanced glycation end products (AGEs), antioxidant power, and antioxidant enzyme activities and their mRNA expressions in kidneys were determined. CAR treatment did not alter glucose and HbA1c, but it decreased serum lipids, creatinine, and urea levels in HFD+STZ rats. Oxidation products of lipids and proteins and AGEs levels decreased, but antioxidant enzyme activities and their mRNA expressions remained unchanged due to CAR treatment. Our results indicate that CAR treatment alleviated renal function and decreased accumulation of oxidation and glycation products in kidneys in HFD+STZ-rats. © Georg Thieme Verlag KG Stuttgart · New York.

Differential effects of cardiovascular and resistance exercise on functional mobility in individuals with advanced cancer: a randomized trial.

PubMed

Litterini, Amy J; Fieler, Vickie K; Cavanaugh, James T; Lee, Jeannette Q

2013-12-01

To compare the effects of resistance and cardiovascular exercise on functional mobility in individuals with advanced cancer. Prospective, 2-group pretest-posttest pilot study with randomization to either resistance or cardiovascular exercise mode. Comprehensive community cancer center and a hospital-based fitness facility. Volunteer sample of individuals (N=66; 30 men; 36 women; mean age, 62y) with advanced cancer recruited through the cancer center, palliative care service, rehabilitation department, and a local hospice. Ten weeks of individualized resistance or cardiovascular exercise, prescribed and monitored by oncology-trained exercise personnel. Functional mobility was assessed using the Short Physical Performance Battery (SPPB); self-reported pain and fatigue were assessed secondarily using visual analog scales. Data were analyzed using a split plot 2×2 analysis of variance (α=.05). Fifty-two patients (78.8%) completed the study: 23 (67.7%) of 34 patients in the resistance arm and 29 (90.6%) of 32 patients in the cardiovascular arm. No participant withdrew because of study adverse events. Ten-week outcomes (n=52) included a significant increase in SPPB total score (P<.001), increase in gait speed (P=.001), and reduction in fatigue (P=.05). Although cardiovascular exercise participants had a modestly greater improvement in SPPB total score than resistance training participants (F1,49=4.21, P=.045), the difference was not confirmed in a subsequent intention-to-treat analysis (N=66). Individuals with advanced cancer appear to benefit from exercise for improving functional mobility. Neither resistance nor cardiovascular exercise appeared to have a strong differential effect on outcome. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Pyrrolidine Dithiocarbamate Prevents Neuroinflammation and Cognitive Dysfunction after Endotoxemia in Rats

PubMed Central

Kan, Min Hui; Yang, Ting; Fu, Hui Qun; Fan, Long; Wu, Yan; Terrando, Niccolò; Wang, Tian-Long

2016-01-01

Systemic inflammation, for example as a result of infection, often contributes to long-term complications. Neuroinflammation and cognitive decline are key hallmarks of several neurological conditions, including advance age. The contribution of systemic inflammation to the central nervous system (CNS) remains not fully understood. Using a model of peripheral endotoxemia with lipopolysaccharide (LPS) we investigated the role of nuclear factor-κB (NF-κB) activity in mediating long-term neuroinflammation and cognitive dysfunction in aged rats. Herein we describe the anti-inflammatory effects of pyrrolidine dithiocarbamate (PDTC), a selective NF-κB inhibitor, in modulating systemic cytokines including tumor necrosis factor (TNF)-α and interleukin-1β (IL-1β) and CNS markers after LPS exposure in aged rats. In the hippocampus, PDTC not only reduced neuroinflammation by modulating canonical NF-κB activity but also affected IL-1β expression in astrocytes. Parallel effects were observed on behavior and postsynaptic density-95 (PSD95), a marker of synaptic function. Taken together these changes improved acute and long-term cognitive function in aged rats after LPS exposure. PMID:27493629

The evolution of senescence through decelerating selection for system reliability.

PubMed

Laird, R A; Sherratt, T N

2009-05-01

Senescence is a universal phenomenon in organisms, characterized by increasing mortality and decreasing fecundity with advancing chronological age. Most proximate agents of senescence, such as reactive oxygen species and UV radiation, are thought to operate by causing a gradual build-up of bodily damage. Yet most current evolutionary theories of senescence emphasize the deleterious effects of functioning genes in late life, leaving a gap between proximate and ultimate explanations. Here, we present an evolutionary model of senescence based on reliability theory, in which beneficial genes or gene products gradually get damaged and thereby fail, rather than actively cause harm. Specifically, the model allows organisms to evolve multiple redundant copies of a gene product (or gene) that performs a vital function, assuming that organisms can avoid condition-dependent death so long as at least one copy remains undamaged. We show that organisms with low levels of extrinsic mortality, and high levels of genetic damage, tend to evolve high levels of redundancy, and that mutation-selection balance results in a stable population distribution of the number of redundant elements. In contrast to previous evolutionary models of senescence, the mortality curves that emerge from such populations match empirical senescence patterns in three key respects: they exhibit: (1) an initially low, but rapidly increasing mortality rate at young ages, (2) a plateau in mortality at advanced ages and (3) 'mortality compensation', whereby the height of the mortality plateau is independent of the environmental conditions under which different populations evolved.

Post-partum trend in blood pressure levels, renal function and proteinuria in women with severe preeclampsia and eclampsia in Sub-Saharan Africa: a 6-months cohort study.

PubMed

Kaze, Francois Folefack; Njukeng, Francis A; Kengne, Andre-Pascal; Ashuntantang, Gloria; Mbu, Robinson; Halle, Marie Patrice; Asonganyi, Tazoacha

2014-04-09

Preeclampsia and eclampsia, which are the most frequent hypertensive disorders in pregnancy, are associated with renal involvements. We aimed to assess the time trend in blood pressure levels, renal function and proteinuria after delivery, and investigate their determinants in Cameroonian women with severe preeclampsia and eclampsia. This was a prospective cohort study involving 54 women with severe preeclampsia and eclampsia, conducted between July 2010 and February 2012 at the central maternity unit of the Yaoundé Central Hospital. Clinical and laboratory parameters were recorded from day-1 to 6 months after delivery. Mixed-linear and logistic regression models were used to relate baseline and within follow-up levels of covariates, with changes in blood pressure levels, renal function and proteinuria, as well as persisting hypertension, renal failure and proteinuria. During follow-up, a significant improvement was observed in blood pressure, renal function and proteinuria (all p < 0.002). Thirteen (24.1%) patients with renal failure at delivery recovered completely within six weeks. Twenty-six (48.1%), 17 (31.5%) and 1 (1.8%) patients had persisting proteinuria at 6 weeks, 3 months and 6 months post-delivery, respectively. Corresponding figures for persisting hypertension were 23 (42.6%), 15 (27.8%) and 8 (14.8%). Advanced age, higher body mass index, low gestational age at delivery, low fetal birth weight, and proteinuria at delivery were the main risk factors for persisting hypertension at 3 months, meanwhile low fetal birth weight, severe preeclampsia and proteinuria at delivery were correlated with persisting proteinuria at 3 months. Advanced age and higher body mass index were the only determinants of the composite outcome of persisting hypertension or proteinuria at three and six months. Hypertension and proteinuria are very common beyond the postpartum period in Cameroonian women with severe preeclampsia and eclampsia. Long-term follow-up of these women will help preventing and controlling related complications.

Multispecificity of Immunoglobulin M Antibodies Raised against Advanced Glycation End Products

PubMed Central

Chikazawa, Miho; Otaki, Natsuki; Shibata, Takahiro; Miyashita, Hiroaki; Kawai, Yoshichika; Maruyama, Shoichi; Toyokuni, Shinya; Kitaura, Yasuyuki; Matsuda, Tsukasa; Uchida, Koji

2013-01-01

Advanced glycation end products (AGEs) are a heterogeneous and complex group of compounds that are formed when reducing sugars, such as dehydroascorbic acid, react in a nonenzymatic way with amino acids in proteins and other macromolecules. AGEs are prevalent in the diabetic vasculature and contribute to the development of atherosclerosis. The presence and accumulation of AGEs in many different cell types affect the extracellular and intracellular structure and function. In the present study, we studied the immune response to the dehydroascorbic acid-derived AGEs and provide multiple lines of evidence suggesting that the AGEs could be an endogenous source of innate epitopes recognized by natural IgM antibodies. Prominent IgM titers to the AGEs were detected in the sera of normal mice and were significantly accelerated by the immunization with the AGEs. Patients with systemic lupus erythematosus (SLE), a potentially fatal systemic autoimmune disease characterized by the increased production of autoantibodies, showed significantly higher serum levels of the IgM titer against the AGEs than healthy individuals. A progressive increase in the IgM response against the AGEs was also observed in the SLE-prone mice. Strikingly, a subset of monoclonal antibodies, showing a specificity toward the AGEs, prepared from normal mice immunized with the AGEs and from the SLE mice cross-reacted with the double-stranded DNA. Moreover, they also cross-reacted with several other modified proteins, including the acetylated proteins, suggesting that the multiple specificity of the antibodies might be ascribed, at least in part, to the increased electronegative potential of the proteins. These findings suggest that the protein modification by the endogenous carbonyl compounds, generating electronegative proteins, could be a source of multispecific natural antibodies. PMID:23543734

Later endogenous circadian temperature nadir relative to an earlier wake time in older people

NASA Technical Reports Server (NTRS)

Duffy, J. F.; Dijk, D. J.; Klerman, E. B.; Czeisler, C. A.

1998-01-01

The contribution of the circadian timing system to the age-related advance of sleep-wake timing was investigated in two experiments. In a constant routine protocol, we found that the average wake time and endogenous circadian phase of 44 older subjects were earlier than that of 101 young men. However, the earlier circadian phase of the older subjects actually occurred later relative to their habitual wake time than it did in young men. These results indicate that an age-related advance of circadian phase cannot fully account for the high prevalence of early morning awakening in healthy older people. In a second study, 13 older subjects and 10 young men were scheduled to a 28-h day, such that they were scheduled to sleep at many circadian phases. Self-reported awakening from scheduled sleep episodes and cognitive throughput during the second half of the wake episode varied markedly as a function of circadian phase in both groups. The rising phase of both rhythms was advanced in the older subjects, suggesting an age-related change in the circadian regulation of sleep-wake propensity. We hypothesize that under entrained conditions, these age-related changes in the relationship between circadian phase and wake time are likely associated with self-selected light exposure at an earlier circadian phase. This earlier exposure to light could account for the earlier clock hour to which the endogenous circadian pacemaker is entrained in older people and thereby further increase their propensity to awaken at an even earlier time.

Age-related macular degeneration.

PubMed

Cheung, Lily K; Eaton, Angie

2013-08-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, and the prevalence of the disease increases exponentially with every decade after age 50 years. It is a multifactorial disease involving a complex interplay of genetic, environmental, metabolic, and functional factors. Besides smoking, hypertension, obesity, and certain dietary habits, a growing body of evidence indicates that inflammation and the immune system may play a key role in the development of the disease. AMD may progress from the early form to the intermediate form and then to the advanced form, where two subtypes exist: the nonneovascular (dry) type and the neovascular (wet) type. The results from the Age-Related Eye Disease Study have shown that for the nonneovascular type of AMD, supplementation with high-dose antioxidants (vitamin C, vitamin E, and β-carotene) and zinc is recommended for those with the intermediate form of AMD in one or both eyes or with advanced AMD or vision loss due to AMD in one eye. As for the neovascular type of the advanced AMD, the current standard of therapy is intravitreal injections of vascular endothelial growth factor inhibitors. In addition, lifestyle and dietary modifications including improved physical activity, reduced daily sodium intake, and reduced intake of solid fats, added sugars, cholesterol, and refined grain foods are recommended. To date, no study has demonstrated that AMD can be cured or effectively prevented. Clearly, more research is needed to fully understand the pathophysiology as well as to develop prevention and treatment strategies for this devastating disease. © 2013 Pharmacotherapy Publications, Inc.

Recommendations for managing cutaneous disorders associated with advancing age

PubMed Central

Humbert, Philippe; Dréno, Brigitte; Krutmann, Jean; Luger, Thomas Anton; Triller, Raoul; Meaume, Sylvie; Seité, Sophie

2016-01-01

The increasingly aged population worldwide means more people are living with chronic diseases, reduced autonomy, and taking various medications. Health professionals should take these into consideration when managing dermatological problems in elderly patients. Accordingly, current research is investigating the dermatological problems associated with the loss of cutaneous function with age. As cell renewal slows, the physical and chemical barrier function declines, cutaneous permeability increases, and the skin becomes increasingly vulnerable to external factors. In geriatric dermatology, the consequences of cutaneous aging lead to xerosis, skin folding, moisture-associated skin damage, and impaired wound healing. These problems pose significant challenges for both the elderly and their carers. Most often, nurses manage skin care in the elderly. However, until recently, little attention has been paid to developing appropriate, evidence-based, skincare protocols. The objective of this paper is to highlight common clinical problems with aging skin and provide some appropriate advice on cosmetic protocols for managing them. A review of the literature from 2004 to 2014 using PubMed was performed by a working group of six European dermatologists with clinical and research experience in dermatology. Basic topical therapy can restore and protect skin barrier function, which relieves problems associated with xerosis, prevents aggravating moisture-associated skin damage, and enhances quality of life. In conclusion, the authors provide physicians with practical recommendations to assist them in implementing basic skin care for the elderly in an integrated care approach. PMID:26929610

Strength training in the elderly: effects on risk factors for age-related diseases.

PubMed

Hurley, B F; Roth, S M

2000-10-01

Strength training (ST) is considered a promising intervention for reversing the loss of muscle function and the deterioration of muscle structure that is associated with advanced age. This reversal is thought to result in improvements in functional abilities and health status in the elderly by increasing muscle mass, strength and power and by increasing bone mineral density (BMD). In the past couple of decades, many studies have examined the effects of ST on risk factors for age-related diseases or disabilities. Collectively, these studies indicate that ST in the elderly: (i) is an effective intervention against sarcopenia because it produces substantial increases in the strength, mass, power and quality of skeletal muscle; (ii) can increase endurance performance; (iii) normalises blood pressure in those with high normal values; (iv) reduces insulin resistance; (v) decreases both total and intra-abdominal fat; (vi) increases resting metabolic rate in older men; (vii) prevents the loss of BMD with age; (viii) reduces risk factors for falls; and (ix) may reduce pain and improve function in those with osteoarthritis in the knee region. However, contrary to popular belief, ST does not increase maximal oxygen uptake beyond normal variations, improve lipoprotein or lipid profiles, or improve flexibility in the elderly.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wesnousky, Steven G.; Briggs, Richard W.; Caffee, Marc W.

Deposits near Lamoille in the Ruby Mountains-East Humboldt Range of central Nevada and at Woodfords on the eastern edge of the Sierra Nevada each record two distinct glacial advances. In this paper, we compare independent assessments of terrestrial cosmogenic nuclide (TCN) surface exposure ages for glacial deposits that we have determined to those obtained by others at the two sites. At each site, TCN ages of boulders on moraines of the younger advance are between 15 and 30 ka and may be associated with marine oxygen isotope stage (MIS) 2. At Woodfords, TCN ages of boulders on the moraine ofmore » the older advance are younger than ~ 60 ka and possibly formed during MIS 4, whereas boulders on the correlative outwash surface show ages approaching 140 ka (~ MIS 6). The TCN ages of boulders on older glacial moraine at Woodfords thus appear to severely underestimate the true age of the glacial advance responsible for the deposit. The same is possibly true at Lamoille where clasts sampled from the moraine of the oldest advance have ages ranging between 20 and 40 ka with a single outlier age of ~ 80 ka. The underestimations are attributed to the degradation and denudation of older moraine crests. Noting that boulder ages on the older advances at each site overlap significantly with MIS 2. Finally, we speculate that erosion of the older moraines has been episodic, with a pulse of denudation accompanying the inception of MIS 2 glaciation.« less

Longitudinal Changes in Sexual Functioning as Women Transition Through Menopause: Results from the Study of Women’s Health Across the Nation (SWAN)

PubMed Central

Avis, Nancy E.; Brockwell, Sarah; Randolph, John F.; Shen, Shunhua; Cain, Virginia S.; Ory, Marcia; Greendale, Gail A.

2009-01-01

Objective Sexual functioning is an important component of women’s lives. The extent to which the menopause transition is associated with decreased sexual functioning remains inconclusive. This study seeks to determine if advancing through the menopause transition is associated with changes in sexual functioning. Design A prospective, longitudinal cohort study of women aged 42–52 at baseline recruited at 7 US sites (N=3302) in the Study of Women’s Health Across the Nation (SWAN). Cohort eligible women had an intact uterus, at least one ovary, were not currently using exogenous hormones, were either pre- or early perimenopausal, and self-identified as one of the study’s designated racial/ethnic groups. Data from the baseline interview and six annual follow-up visits are reported. Outcomes are self-reported ratings of importance of sex; frequency of sexual desire, arousal, masturbation, sexual intercourse, and pain during intercourse; degree of emotional satisfaction and physical pleasure. Results Adjusting for baseline age, chronological aging, and relevant social, health, and psychological parameters, the odds of reporting vaginal or pelvic pain increased and desire decreased by late perimenopause. Masturbation increased at early perimenopause, but declined during postmenopause. Menopausal transition was unrelated to other outcomes. Health, psychological functioning, and importance of sex were related to all sexual function outcomes. Age, race/ethnicity, marital status, change in relationship, and vaginal dryness were also associated with sexual functioning. Conclusions Pain during sexual intercourse increases and sexual desire decreases over the menopausal transition. Masturbation increases during the early transition, but then declines in postmenopause. Adjusting for other factors, the menopausal transition was not independently associated with reports of the importance of sex, sexual arousal, frequency of sexual intercourse, emotional satisfaction with partner, or physical pleasure. PMID:19212271

Longitudinal changes in sexual functioning as women transition through menopause: results from the Study of Women's Health Across the Nation.

PubMed

Avis, Nancy E; Brockwell, Sarah; Randolph, John F; Shen, Shunhua; Cain, Virginia S; Ory, Marcia; Greendale, Gail A

2009-01-01

Sexual functioning is an important component of women's lives. The extent to which the menopausal transition is associated with decreased sexual functioning remains inconclusive. This study seeks to determine if advancing through the menopausal transition is associated with changes in sexual functioning. This was a prospective, longitudinal cohort study of women aged 42 to 52 years at baseline recruited at seven US sites (N = 3,302) in the Study of Women's Health Across the Nation (SWAN). Cohort-eligible women had an intact uterus, had at least one ovary, were not currently using exogenous hormones, were either premenopausal or early perimenopausal, and self-identified as one of the study's designated racial/ethnic groups. Data from the baseline interview and six annual follow-up visits are reported. Outcomes are self-reported ratings of importance of sex; frequency of sexual desire, arousal, masturbation, sexual intercourse, and pain during intercourse; and degree of emotional satisfaction and physical pleasure. With adjustment for baseline age, chronological aging, and relevant social, health, and psychological parameters, the odds of reporting vaginal or pelvic pain increased and desire decreased by late perimenopause. Masturbation increased at early perimenopause but declined during postmenopause. The menopausal transition was unrelated to other outcomes. Health, psychological functioning, and importance of sex were related to all sexual function outcomes. Age, race/ethnicity, marital status, change in relationship, and vaginal dryness were also associated with sexual functioning. Pain during sexual intercourse increases and sexual desire decreases over the menopausal transition. Masturbation increases during the early transition, but then declines in postmenopause. With adjustment for other factors, the menopausal transition was not independently associated with reports of the importance of sex, sexual arousal, frequency of sexual intercourse, emotional satisfaction with partner, or physical pleasure.

Age as a Confounding Factor for the Accurate Non-Invasive Diagnosis of Advanced NAFLD Fibrosis.

PubMed

McPherson, Stuart; Hardy, Tim; Dufour, Jean-Francois; Petta, Salvatore; Romero-Gomez, Manuel; Allison, Mike; Oliveira, Claudia P; Francque, Sven; Van Gaal, Luc; Schattenberg, Jörn M; Tiniakos, Dina; Burt, Alastair; Bugianesi, Elisabetta; Ratziu, Vlad; Day, Christopher P; Anstee, Quentin M

2017-05-01

Non-invasive fibrosis scores are widely used to identify/exclude advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). However, these scores were principally developed and validated in patients aged between 35 and 65 years of age. The objective of this study was to assess the effect of age on the performance of non-invasive fibrosis tests in NAFLD. Patients were recruited from European specialist hepatology clinics. The cohort was divided into five age-based groups: ≤35 (n=74), 36-45 (n=96), 46-55 (n=197), 56-64 (n=191), and ≥65 years (n=76), and the performance of the aspartate aminotransferase (AST)/alanine transaminase (ALT) ratio, fibrosis 4 (FIB-4), and NAFLD fibrosis score (NFS) for advanced fibrosis (stage F3-F4) for each group was assessed using liver biopsy as the standard. Six hundred and thirty-four patients were included. The diagnostic accuracy of the AST/ALT ratio was lower than NFS and FIB-4 in all the age groups. The AST/ALT ratio, NFS, and FIB-4 score performed poorly for a diagnosis of advanced fibrosis in those aged ≤35 years (area under the receiver operating characteristic curves (AUROCs 0.52, 0.52, and 0.60, respectively). For all groups >35 years, AUROCs for advanced fibrosis were similar for the NFS and FIB-4 score (range 0.77-0.84). However, the specificity for advanced fibrosis using the FIB-4 and NFS declined with age, becoming unacceptably low in those aged ≥65 years (35% for FIB-4 and 20% for NFS). New cutoffs were derived (and validated) for those aged ≥65 years, which improved specificity to 70% without adversely affecting sensitivity (FIB-4 2.0, sensitivity 77%; NFS 0.12, sensitivity 80%). The NFS and FIB-4 scores have similar accuracy for advanced fibrosis in patients aged >35 years. However, the specificity for advanced fibrosis is unacceptably low in patients aged ≥65 years, resulting in a high false positive rate. New thresholds for use in patients aged ≥65 years are proposed to address this issue.

Age as a Confounding Factor for the Accurate Non-Invasive Diagnosis of Advanced NAFLD Fibrosis

PubMed Central

McPherson, Stuart; Hardy, Tim; Dufour, Jean-Francois; Petta, Salvatore; Romero-Gomez, Manuel; Allison, Mike; Oliveira, Claudia P; Francque, Sven; Van Gaal, Luc; Schattenberg, Jörn M; Tiniakos, Dina; Burt, Alastair; Bugianesi, Elisabetta; Ratziu, Vlad; Day, Christopher P; Anstee, Quentin M

2017-01-01

OBJECTIVES: Non-invasive fibrosis scores are widely used to identify/exclude advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). However, these scores were principally developed and validated in patients aged between 35 and 65 years of age. The objective of this study was to assess the effect of age on the performance of non-invasive fibrosis tests in NAFLD. METHODS: Patients were recruited from European specialist hepatology clinics. The cohort was divided into five age-based groups: ≤35 (n=74), 36–45 (n=96), 46–55 (n=197), 56–64 (n=191), and ≥65 years (n=76), and the performance of the aspartate aminotransferase (AST)/alanine transaminase (ALT) ratio, fibrosis 4 (FIB-4), and NAFLD fibrosis score (NFS) for advanced fibrosis (stage F3–F4) for each group was assessed using liver biopsy as the standard. RESULTS: Six hundred and thirty-four patients were included. The diagnostic accuracy of the AST/ALT ratio was lower than NFS and FIB-4 in all the age groups. The AST/ALT ratio, NFS, and FIB-4 score performed poorly for a diagnosis of advanced fibrosis in those aged ≤35 years (area under the receiver operating characteristic curves (AUROCs 0.52, 0.52, and 0.60, respectively). For all groups >35 years, AUROCs for advanced fibrosis were similar for the NFS and FIB-4 score (range 0.77–0.84). However, the specificity for advanced fibrosis using the FIB-4 and NFS declined with age, becoming unacceptably low in those aged ≥65 years (35% for FIB-4 and 20% for NFS). New cutoffs were derived (and validated) for those aged ≥65 years, which improved specificity to 70% without adversely affecting sensitivity (FIB-4 2.0, sensitivity 77% NFS 0.12, sensitivity 80%). CONCLUSIONS: The NFS and FIB-4 scores have similar accuracy for advanced fibrosis in patients aged >35 years. However, the specificity for advanced fibrosis is unacceptably low in patients aged ≥65 years, resulting in a high false positive rate. New thresholds for use in patients aged ≥65 years are proposed to address this issue. PMID:27725647

Speed, not magnitude, of knee extensor torque production is associated with self-reported knee function early after anterior cruciate ligament reconstruction.

PubMed

Hsieh, Chao-Jung; Indelicato, Peter A; Moser, Michael W; Vandenborne, Krista; Chmielewski, Terese L

2015-11-01

To examine the magnitude and speed of knee extensor torque production at the initiation of advanced anterior cruciate ligament (ACL) reconstruction rehabilitation and the associations with self-reported knee function. Twenty-eight subjects who were 12 weeks post-ACL reconstruction and 28 age- and sex-matched physically active controls participated in this study. Knee extensor torque was assessed bilaterally with an isokinetic dynamometer at 60°/s. The variables of interest were peak torque, average rate of torque development, time to peak torque and quadriceps symmetry index. Knee function was assessed with the International Knee Documentation Committee Subjective Knee Form (IKDC-SKF). Peak torque and average rate of torque development were lower on the surgical side compared to the non-surgical side and controls. Quadriceps symmetry index was lower in subjects with ACL reconstruction compared to controls. On the surgical side, average rate of torque development was positively correlated with IKDC-SKF score (r = 0.379) while time to peak torque was negatively correlated with IKDC-SKF score (r = -0.407). At the initiation of advanced ACL reconstruction rehabilitation, the surgical side displayed deficits in peak torque and average rate of torque development. A higher rate of torque development and shorter time to peak torque were associated with better self-reported knee function. The results suggest that the rate of torque development should be addressed during advanced ACL reconstruction rehabilitation and faster knee extensor torque generation may lead to better knee function. III.

The role of weight loss and exercise in correcting skeletal muscle mitochondrial abnormalities in obesity, diabetes and aging.

PubMed

Toledo, Frederico G S; Goodpaster, Bret H

2013-10-15

Mitochondria within skeletal muscle have been implicated in insulin resistance of obesity and type 2 diabetes mellitus as well as impaired muscle function with normal aging. Evaluating the potential of interventions to improve mitochondria is clearly relevant to the prevention or treatment of metabolic diseases and age-related dysfunction. This review provides an overview and critical evaluation of the effects of weight loss and exercise interventions on skeletal muscle mitochondria, along with implications for insulin resistance, obesity, type 2 diabetes and aging. The available literature strongly suggests that the lower mitochondrial capacity associated with obesity, type 2 diabetes and aging is not an irreversible lesion. However, weight loss does not appear to affect this response, even when the weight loss is extreme. In contrast, increasing physical activity improves mitochondrial content and perhaps the function of individual mitochondrion. Despite the consistent effect of exercise to improve mitochondrial capacity, studies mechanistically linking mitochondria to insulin resistance, reductions in intramyocellular lipid or improvement in muscle function remain inconclusive. In summary, studies of diet and exercise training have advanced our understanding of the link between mitochondrial oxidative capacity and insulin resistance in obesity, type 2 diabetes and aging. Nevertheless, additional inquiry is necessary to establish the significance and clinical relevance of those perturbations, which could lead to targeted therapies for a myriad of conditions and diseases involving mitochondria. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The Effects of Age at Cleft Palate Repair on Middle Ear Function and Hearing Level.

PubMed

Lou, Qun; Zhu, Hongping; Luo, Yi; Zhou, Zhibo; Ma, Lian; Ma, Xiaoran; Fu, Yuan

2018-05-01

To investigate the age effects of cleft palate repair on middle ear function and hearing level in patients who underwent cleft palate repair at different ages by audiologic examination. Medical histories were gathered in detail, and audiologic tests (ie, tympanometry and pure tone hearing threshold) were conducted in 126 patients after palatoplasty. The patients were divided into the following 4 groups according to their ages when they underwent cleft palate repair: group I (0-3 years, 73 patients), group II (4-7 years, 29 patients), group III (8-11 years, 16 patients), and group IV (12 years and older, 8 patients). The data regarding tympanograms, hearing levels, and the average hearing thresholds of each group were analyzed using chi-square tests. The prevalence of middle ear dysfunction and hearing loss in the patients who underwent palatoplasty before 3 years old (27.4% and 2.0% respectively) was significantly lower than that in patients who underwent palatopalsty at 12 years or older (75.0% and 43.7%, respectively). Linear-by-linear association revealed that the prevalences of middle ear dysfunction and hearing loss among the 4 groups were significantly different ( P < .05). The prevalence of middle ear dysfunction and hearing loss tended to increase with advancing age at the time of cleft palate repair. From an audiologist's perspective, palatoplasty at an early age is very beneficial in helping children with cleft palates acquire better middle ear function and hearing level.

Effect of ageing on neurocognitive function by stage of HIV infection: evidence from the Multicenter AIDS Cohort Study.

PubMed

Goodkin, Karl; Miller, Eric N; Cox, Christopher; Reynolds, Sandra; Becker, James T; Martin, Eileen; Selnes, Ola A; Ostrow, David G; Sacktor, Ned C

2017-09-01

The demographics of the HIV epidemic in the USA have shifted towards older age. We aimed to establish the relationship between the processes of ageing and HIV infection in neurocognitive impairment. With longitudinal data from the Multicenter AIDS Cohort Study, a long-term prospective cohort study of the natural and treated history of HIV infection among men who have sex with men in the USA, we examined the effect of ageing, HIV infection (by disease stage), and their interaction on five neurocognitive domains: information processing speed, executive function, episodic memory, working memory, and motor function. We controlled for duration of serostatus in a subanalysis, as well as comorbidities and other factors that affect cognition. Analyses were by linear mixed models for longitudinal data. 5086 participants (47 886 visits) were included in the analytic sample (2278 HIV-seropositive participants contributed 20 477 visits and 2808 HIV-seronegative control participants contributed 27 409 visits). In an a-priori multivariate analysis with control variables including comorbidities and time since seroconversion, significant, direct negative effects of ageing were noted on all neurocognitive domains (p<0·0001 for all). Similar effects were noted for late-stage HIV disease progression on information processing speed (p=0·002), executive function (p<0·0001), motor function (p<0·0001), and working memory (p=0·001). Deleterious interaction effects were also noted in the domains of episodic memory (p=0·03) and motor function (p=0·02). A greater than expected effect of ageing on episodic memory and motor function with advanced stages of HIV infection suggests that these two domains are most susceptible to the progression of neurocognitive impairment caused by ageing in individuals with HIV. This deficit pattern suggests differential damage to the hippocampus and basal ganglia (specifically nigrostriatal pathways). Older individuals with HIV infection should be targeted for regular screening for HIV-associate neurocognitive disorder, particularly with tests referable to the episodic memory and motor domains. National Institute of Mental Health. Copyright © 2017 Elsevier Ltd. All rights reserved.

Long-term effects of peroxisome proliferator-activated receptor ligand bezafibrate on N-terminal pro-B type natriuretic peptide in patients with advanced functional capacity impairment

PubMed Central

Node, Koichi; Inoue, Teruo; Boyko, Valentin; Goldberg, Ilan; Fisman, Enrique Z; Adler, Yehuda; Schwammenthal, Ehud; Matas, Zipora; Behar, Solomon; Tenenbaum, Alexander

2009-01-01

Background The effects of pan-peroxisome proliferator-activated receptor (PPAR) ligand bezafibrate on N-terminal pro-B type natriuretic peptide (ProBNP) level in patients with coronary artery disease (CAD) is unknown. The current study aimed to investigate the long-term effects of bezafibrate on ProBNP level in patients with pre-existing CAD and advanced functional capacity impairment. Methods Metabolic and inflammatory parameters were analyzed from stored frozen serum samples obtained from 108 patients enrolled in the Bezafibrate Infarction Prevention (BIP) Study. They presented with New York Heart Association (NYHA) functional class III, comprising 58 patients in the bezafibrate group and 50 in the placebo groups, and completed a 2-year prospective, double-blind, placebo-controlled follow-up. Results During follow-up ProBNP level did not change significantly in the placebo group, whereas it increased slightly in the bezafibrate group, which was older and with lower baseline ProBNP values. No significant differences between the groups were found for ProBNP levels after 2 year of follow-up. Analysis-of-covariance (ANCOVA) -taking into account age and baseline ProBNP level- showed that bezafibrate was not associated with longitudinal ProBNP changes during the follow-up period (p = 0.3). Conclusion Long-term treatment by bezafibrate was not associated with longitudinal ProBNP changes in patients with pre-existing CAD and advanced functional capacity impairment. PMID:19173749

[Advanced glycation end products: A risk factor for human health].

PubMed

Wautier, M-P; Tessier, F J; Wautier, J-L

2014-11-01

Advanced glycation end products (AGE) result from a chemical reaction between the carbonyl group of reducing sugar and the nucleophilic NH2 of a free amino acid or a protein; lysine and arginine being the main reactive amino acids on proteins. Following this first step, a molecular rearrangement occurs, rearrangement of Amadori resulting to the formation of Maillard products. Glycation can cause the clouding of the lens by inducing reactions crosslinking proteins. Specialized receptors (RAGE, Galectin 3…) bind AGE. The binding to the receptor causes the formation of free radicals, which have a deleterious effect because they are powerful oxidizing agents, but also play the role of intracellular messenger, altering the cell functions. This is especially true at the level of endothelial cells: the attachment of AGE to RAGE receptor causes an increase in vascular permeability. AGE binding to endothelium RAGE and to monocytes-macrophages, led to the production of cytokines, growth factors, to the expression of adhesion molecules, and the production of procoagulant activity. Diabetic retinopathy is related to excessive secretion of vascular growth factor (vascular endothelial growth factor [VEGF]). AGE-RAGE receptor binding causes the synthesis and secretion of VEGF. Increased permeability, facilitation of leukocyte migration, the production of reactive oxygen species, cytokines and VEGF suggest that the AGE could be an element of a cascade of reactions responsible for the diabetic angiopathy and vascular damages observed during aging and chronic renal failure. Balanced diet or some drugs can limit the deleterious effect of AGE. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

AGEs, RAGEs and s-RAGE; friend or foe for cancer.

PubMed

Ahmad, Saheem; Khan, Hamda; Siddiqui, Zeba; Khan, Mohd Yasir; Rehman, Shahnawaz; Shahab, Uzma; Godovikova, Tatyana; Silnikov, Vladimir; Moinuddin

2018-04-01

Impaired awareness of glycation biology in cancer initiation and progression is one of the fundamental reasons for its meticulous investigation of the molecules involved in signalling pathway. Glycation of biological macromolecules results in the progression of advanced glycation end-products (AGEs) that proliferates the process of carcinogenesis by activation of transcription factors and release of cytokines. The receptor for advanced glycation end-products (RAGEs) with the binding of its different ligands like; AGEs, HMGB1 and S100 activate the signalling arrays. The activation of downstream signalling pathway ultimately leads to the pathophysiological conditions of diabetes, ageing, neurological disorders and cancers as well as a result of the activation of transcription factors which is discussed in the main body text of this review. However, there might be a likelihood of the positive effect of the HMGB1 and S100 proteins in cancer. Still, some untouched mechanisms might be responsible for the establishment of the function of AGE-RAGE or AGE-sRAGE axis activation that leads to the friend-foe association with the cancers. The levels of RAGE and s-RAGE may be a useful biomarker of ligand-RAGE pathway activation and cancer. Thus, the possibility of providing a potential complement to carcinogenesis is very high which might be an interesting target for therapeutic interventions. This article is an insightful assessment on AGE, RAGE and s-RAGE for its possible role in cancer onset and progression. The novel therapeutic targets for cancer prevention or inhibition are also explained in brief in relation to AGE and RAGE. Copyright © 2017 Elsevier Ltd. All rights reserved.

Korean preschoolers' advanced inhibitory control and its relation to other executive skills and mental state understanding.

PubMed

Oh, Seungmi; Lewis, Charlie

2008-01-01

This study assessed executive function and mental state understanding in Korean preschoolers. In Experiment 1, forty 3.5- and 4-year-old Koreans showed ceiling performance on inhibition and switching measures, although their performance on working memory and false belief was comparable to that of Western children. Experiment 2 revealed a similar advantage in a sample of seventy-six 3- and 4-year-old Koreans compared with sixty-four age-matched British children. Korean children younger than 3.5 years of age showed ceiling effects on some inhibition measures despite more stringent protocols and the link between executive function and mental state understanding was not as strong as in the British sample. The results raise key questions about the nature and development of the executive system and its relation to social understanding.

The aging musculoskeletal system and obesity-related considerations with exercise

PubMed Central

Vincent, Heather K.; Raiser, Sara N.; Vincent, Kevin R.

2012-01-01

Advancing age and adiposity contribute to musculoskeletal degenerative diseases and the development of sarcopenic obesity. The etiology of muscle loss is multifactorial, and includes inflammation, oxidative stress and hormonal changes, and is worsened by activity avoidance due to fear of pain. The risk for mobility disability and functional impairment rises with severity of obesity in the older adult. Performance measures of walking distance, walking speed, chair rise, stair climb, body transfers and ability to navigate obstacles on a course are adversely affected in this population, and this reflects decline in daily physical functioning. Exercise training is an ideal intervention to counteract the effects of aging and obesity. The 18 randomized controlled trials of exercise studies with or without diet components reviewed here indicate that 3–18 month programs that included aerobic and strengthening exercise (2–3 days per week) with caloric restriction (typically 750 kcal deficit/day), induced the greatest change in functional performance measures compared with exercise or diet alone. Importantly, resistance exercise attenuates muscle mass loss with the interventions. These interventions can also combat factors that invoke sarcopenia, including inflammation, oxidative stress and insulin resistance. Therefore, regular multimodal exercise coupled with diet appears to be very effective for counteracting sarocpenic obesity and improving mobility and function in the older, obese adult. PMID:22440321

Diagnostic Pathology and Laboratory Medicine in the Age of “Omics”

PubMed Central

Finn, William G.

2007-01-01

Functional genomics and proteomics involve the simultaneous analysis of hundreds or thousands of expressed genes or proteins and have spawned the modern discipline of computational biology. Novel informatic applications, including sophisticated dimensionality reduction strategies and cancer outlier profile analysis, can distill clinically exploitable biomarkers from enormous experimental datasets. Diagnostic pathologists are now charged with translating the knowledge generated by the “omics” revolution into clinical practice. Food and Drug Administration-approved proprietary testing platforms based on microarray technologies already exist and will expand greatly in the coming years. However, for diagnostic pathology, the greatest promise of the “omics” age resides in the explosion in information technology (IT). IT applications allow for the digitization of histological slides, transforming them into minable data and enabling content-based searching and archiving of histological materials. IT will also allow for the optimization of existing (and often underused) clinical laboratory technologies such as flow cytometry and high-throughput core laboratory functions. The state of pathology practice does not always keep up with the pace of technological advancement. However, to use fully the potential of these emerging technologies for the benefit of patients, pathologists and clinical scientists must embrace the changes and transformational advances that will characterize this new era. PMID:17652635

The Science of Vascular Contributions to Cognitive Impairment and Dementia (VCID): A Framework for Advancing Research Priorities in the Cerebrovascular Biology of Cognitive Decline.

PubMed

Corriveau, Roderick A; Bosetti, Francesca; Emr, Marian; Gladman, Jordan T; Koenig, James I; Moy, Claudia S; Pahigiannis, Katherine; Waddy, Salina P; Koroshetz, Walter

2016-03-01

The World Health Organization reports that 47.5 million people are affected by dementia worldwide. With aging populations and 7.7 million new cases each year, the burden of illness due to dementia approaches crisis proportions. Despite significant advances in our understanding of the biology of Alzheimer's disease (AD), the leading dementia diagnosis, the actual causes of dementia in affected individuals are unknown except for rare fully penetrant genetic forms. Evidence from epidemiology and pathology studies indicates that damage to the vascular system is associated with an increased risk of many types of dementia. Both Alzheimer's pathology and cerebrovascular disease increase with age. How AD affects small blood vessel function and how vascular dysfunction contributes to the molecular pathology of Alzheimer's are areas of intense research. The science of vascular contributions to cognitive impairment and dementia (VCID) integrates diverse aspects of biology and incorporates the roles of multiple cell types that support the function of neural tissue. Because of the proven ability to prevent and treat cardiovascular disease and hypertension with population benefits for heart and stroke outcomes, it is proposed that understanding and targeting the biological mechanisms of VCID can have a similarly positive impact on public health.

Early complications after pneumonectomy: retrospective study of 168 patients.

PubMed

Alloubi, Ihsan; Jougon, Jacques; Delcambre, Frédéric; Baste, Jean Marc; Velly, Jean François

2010-08-01

The purpose of this study was to assess the mortality and risk factors of complications after pneumonectomy for lung cancer. Between 1996 and 2001, we reviewed and analysed the demographic, clinical, functional, and surgical variables of 168 patients to identify risk factors of postoperative complications by univariate and multivariate analyses with Medlog software system. The mean age was 60+/-10 years, overall mortality and morbidity rates were 4.17% and 41.6%, respectively. All frequencies of respiratory complications were 1.2% for acute respiratory failure, 10.1% for pneumonia, 2.4% for acute pulmonary oedema, 4.17% for bronchopleural fistula, 2.4% for thoracic empyema and 18.5% for left recurrent nerve injuries. Postoperative arrhythmias developed in 46% of our patients. The risk factors for cardiopulmonary morbidity and mortality with univariate analysis were advanced age (P<0.01), preoperative poor performance status (P<0.015), and chronic artery disease (P<0.008). Factors adversely affecting morbidity with multivariate analysis included age (P=0.0001), associated cardiovascular disease (P=0.001), and altered forced expiratory volume in 1 s (P=0.0005). Complications after pneumonectomy are associated with high mortality. Careful attention must be paid to patients with advanced age and heart disease. Chest physiotherapy is paramount to have uneventful outcomes.

Motor function is associated with 1,25(OH)(2)D and indices of insulin-glucose dynamics in non-diabetic older adults.

PubMed

Justice, Jamie N; Pierpoint, Lauren A; Mani, Diba; Schwartz, Robert S; Enoka, Roger M

2014-06-01

Advancing age is accompanied by changes in metabolic characteristics, such as reduced insulin sensitivity and low levels of vitamin D, which may exacerbate age-related declines in physical function. The aim of the present study was to determine the associations between insulin-glucose dynamics, vitamin D metabolites, and performance on a battery of motor tasks in healthy, non-diabetic older adults. Sixty-nine community-dwelling men and women (65-90 years) were recruited. Insulin-glucose dynamics were determined by an intravenous glucose tolerance test, and vitamin D metabolites were measured. Motor function was characterized by the time to walk 500 m, chair-rise time, lower body strength, dorsiflexor steadiness and endurance time, and muscle coactivation. Significant unadjusted correlations were found between insulin-glucose dynamics and 1,25-dihydroxyvitamin D [1,25(OH)2D] with walk time, strength, steadiness, endurance time, and muscle activation (p < 0.05). A significant amount of the variance in walking endurance was explained by the sex of the individual, 1,25(OH)2D, and fasting blood insulin (R (2) = 0.36, p < 0.001). Strength could be partially explained by age, body fatness, and fasting glucose (R (2) = 0.55, p < 0.001). Poor motor function in non-diabetic older men and women was associated with indices of insulin-glucose dynamics and the bio-active vitamin D metabolite 1,25(OH)2D. Walking endurance and strength were explained by 1,25(OH)2D and fasting blood glucose and insulin, even after adjusting for age, sex, and body fat. Motor function in a relatively small sample of non-diabetic older men and women was associated with metabolic factors that increase in prevalence with aging.

Age-Related Changes in the Expression of the Circadian Clock Protein PERIOD in Drosophila Glial Cells

PubMed Central

Long, Dani M.; Giebultowicz, Jadwiga M.

2018-01-01

Circadian clocks consist of molecular negative feedback loops that coordinate physiological, neurological, and behavioral variables into “circa” 24-h rhythms. Rhythms in behavioral and other circadian outputs tend to weaken during aging, as evident in progressive disruptions of sleep-wake cycles in aging organisms. However, less is known about the molecular changes in the expression of clock genes and proteins that may lead to the weakening of circadian outputs. Western blot studies have demonstrated that the expression of the core clock protein PERIOD (PER) declines in the heads of aged Drosophila melanogaster flies. This age-related decline in PER does not occur in the central pacemaker neurons but has been demonstrated so far in retinal photoreceptors. Besides photoreceptors, clock proteins are also expressed in fly glia, which play important roles in neuronal homeostasis and are further categorized into subtypes based on morphology and function. While previous studies of mammalian glial cells have demonstrated the presence of functional clocks in astrocytes and microglia, it is not known which glial cell types in Drosophila express clock proteins and how their expression may change in aged individuals. Here, we conducted immunocytochemistry experiments to identify which glial subtypes express PER protein suggestive of functional circadian clocks. Glial cell subtypes that showed night-time accumulation and day-time absence in PER consistent with oscillations reported in the pacemaker neurons were selected to compare the level of PER protein between young and old flies. Our data demonstrate that some glial subtypes show rhythmic PER expression and the relative PER levels become dampened with advanced age. Identification of glial cell types that display age-related dampening of PER levels may help to understand the cellular changes that contribute to the loss of homeostasis in the aging brain. PMID:29375400

Age Drives Distortion of Brain Metabolic, Vascular and Cognitive Functions, and the Gut Microbiome

PubMed Central

Hoffman, Jared D.; Parikh, Ishita; Green, Stefan J.; Chlipala, George; Mohney, Robert P.; Keaton, Mignon; Bauer, Bjoern; Hartz, Anika M. S.; Lin, Ai-Ling

2017-01-01

Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer’s disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in brain metabolism, cerebral blood flow (CBF), gut microbiome and cognition in aging, and potential implications for AD development. We conducted our study with a group of young mice (5–6 months of age) and compared those to old mice (18–20 months of age) by utilizing metabolic profiling, neuroimaging, gut microbiome analysis, behavioral assessments and biochemical assays. We found that compared to young mice, old mice had significantly increased levels of numerous amino acids and fatty acids that are highly associated with inflammation and AD biomarkers. In the gut microbiome analyses, we found that old mice had increased Firmicutes/Bacteroidetes ratio and alpha diversity. We also found impaired blood-brain barrier (BBB) function and reduced CBF as well as compromised learning and memory and increased anxiety, clinical symptoms often seen in AD patients, in old mice. Our study suggests that the aging process involves deleterious changes in brain metabolic, vascular and cognitive functions, and gut microbiome structure and diversity, all which may lead to inflammation and thus increase the risk for AD. Future studies conducting comprehensive and integrative characterization of brain aging, including crosstalk with peripheral systems and factors, will be necessary to define the mechanisms underlying the shift from normal aging to pathological processes in the etiology of AD. PMID:28993728

Visual search and the aging brain: discerning the effects of age-related brain volume shrinkage on alertness, feature binding, and attentional control.

PubMed

Müller-Oehring, Eva M; Schulte, Tilman; Rohlfing, Torsten; Pfefferbaum, Adolf; Sullivan, Edith V

2013-01-01

Decline in visuospatial abilities with advancing age has been attributed to a demise of bottom-up and top-down functions involving sensory processing, selective attention, and executive control. These functions may be differentially affected by age-related volume shrinkage of subcortical and cortical nodes subserving the dorsal and ventral processing streams and the corpus callosum mediating interhemispheric information exchange. Fifty-five healthy adults (25-84 years) underwent structural MRI and performed a visual search task to test perceptual and attentional demands by combining feature-conjunction searches with "gestalt" grouping and attentional cueing paradigms. Poorer conjunction, but not feature, search performance was related to older age and volume shrinkage of nodes in the dorsolateral processing stream. When displays allowed perceptual grouping through distractor homogeneity, poorer conjunction-search performance correlated with smaller ventrolateral prefrontal cortical and callosal volumes. An alerting cue attenuated age effects on conjunction search, and the alertness benefit was associated with thalamic, callosal, and temporal cortex volumes. Our results indicate that older adults can capitalize on early parallel stages of visual information processing, whereas age-related limitations arise at later serial processing stages requiring self-guided selective attention and executive control. These limitations are explained in part by age-related brain volume shrinkage and can be mitigated by external cues.

Progranulin, lysosomal regulation and neurodegenerative disease.

PubMed

Kao, Aimee W; McKay, Andrew; Singh, Param Priya; Brunet, Anne; Huang, Eric J

2017-06-01

The discovery that heterozygous and homozygous mutations in the gene encoding progranulin are causally linked to frontotemporal dementia and lysosomal storage disease, respectively, reveals previously unrecognized roles of the progranulin protein in regulating lysosome biogenesis and function. Given the importance of lysosomes in cellular homeostasis, it is not surprising that progranulin deficiency has pleiotropic effects on neural circuit development and maintenance, stress response, innate immunity and ageing. This Progress article reviews recent advances in progranulin biology emphasizing its roles in lysosomal function and brain innate immunity, and outlines future avenues of investigation that may lead to new therapeutic approaches for neurodegeneration.

Quality of life in Malaysian colorectal cancer patients.

PubMed

Wan Puteh, Sharifa Ezat; Saad, Natrah Mohd; Aljunid, Syed Mohd; Abdul Manaf, Mohd Rizal; Sulong, Saperi; Sagap, Ismail; Ismail, Fuad; Muhammad Annuar, Muhd Azrif

2013-04-01

The rapidly increasing of incidence colorectal cancer (CRC) in Malaysia and the introduction of new treatments that prolong survival advocating treatment outcome measures such as patients' quality of life (QOL) are evaluated in this study. The study aims to determine QOL in CRC patients according to cancer stage and age. A cross-sectional study was performed from June to December 2011 at four public tertiary hospitals. The European Organization for Research and Treatment in Cancer (EORTC) Quality of Life Questionnaire Core-30 (EORTC QLQ C-30) questionnaire was used through face-to-face interview and the medical records of 160 respondents were reviewed. The mean age of respondents was 58.47 ± 12.04 years with 57.5% of respondents being male and 42.5% female. The majority of respondents were in CRC stages III and IV. Median global health status (GHS) score was 83.33 (IQR 16.67). Sikhs and Indians had a higher median GHS score compared to other ethnicities (Kruskal-Wallis, χ(2)  = 12.12, p = 0.007). Emotional, cognitive and social functions were higher in respondents with earlier stage of disease (Kruskal-Wallis, χ2 = 6.06, 6.36, 10.58, p = 0.048, 0.042, 0.005). Median pain, dyspnea, diarrhea and financial implication scores were significantly higher in advanced stage of disease (Kruskal-Wallis, χ(2)  = 9.31, 6.26,6.77, 7.28, p = 0.010, 0.044,0.034,0.026). Median diarrhea score (p = 0.012) was significantly different between age groups. Emotional, cognitive and social functions deteriorate with advanced stage of disease. Patients with advanced stage disease experience more pain, dyspnea, diarrhea and financial implications. A systematic screening program to detect cases as early as possible is essential nationwide. Copyright © 2013 Wiley Publishing Asia Pty Ltd.

Aging increases cell-to-cell transcriptional variability upon immune stimulation.

PubMed

Martinez-Jimenez, Celia Pilar; Eling, Nils; Chen, Hung-Chang; Vallejos, Catalina A; Kolodziejczyk, Aleksandra A; Connor, Frances; Stojic, Lovorka; Rayner, Timothy F; Stubbington, Michael J T; Teichmann, Sarah A; de la Roche, Maike; Marioni, John C; Odom, Duncan T

2017-03-31

Aging is characterized by progressive loss of physiological and cellular functions, but the molecular basis of this decline remains unclear. We explored how aging affects transcriptional dynamics using single-cell RNA sequencing of unstimulated and stimulated naïve and effector memory CD4 + T cells from young and old mice from two divergent species. In young animals, immunological activation drives a conserved transcriptomic switch, resulting in tightly controlled gene expression characterized by a strong up-regulation of a core activation program, coupled with a decrease in cell-to-cell variability. Aging perturbed the activation of this core program and increased expression heterogeneity across populations of cells in both species. These discoveries suggest that increased cell-to-cell transcriptional variability will be a hallmark feature of aging across most, if not all, mammalian tissues. Copyright © 2017, American Association for the Advancement of Science.

Proteomic Profiling of Mitochondrial Enzymes during Skeletal Muscle Aging.

PubMed

Staunton, Lisa; O'Connell, Kathleen; Ohlendieck, Kay

2011-03-07

Mitochondria are of central importance for energy generation in skeletal muscles. Expression changes or functional alterations in mitochondrial enzymes play a key role during myogenesis, fibre maturation, and various neuromuscular pathologies, as well as natural fibre aging. Mass spectrometry-based proteomics suggests itself as a convenient large-scale and high-throughput approach to catalogue the mitochondrial protein complement and determine global changes during health and disease. This paper gives a brief overview of the relatively new field of mitochondrial proteomics and discusses the findings from recent proteomic surveys of mitochondrial elements in aged skeletal muscles. Changes in the abundance, biochemical activity, subcellular localization, and/or posttranslational modifications in key mitochondrial enzymes might be useful as novel biomarkers of aging. In the long term, this may advance diagnostic procedures, improve the monitoring of disease progression, help in the testing of side effects due to new drug regimes, and enhance our molecular understanding of age-related muscle degeneration.

The Light and Shadow of Senescence and Inflammation in Cardiovascular Pathology and Regenerative Medicine

PubMed Central

Dal Sasso, Eleonora; Schirone, Leonardo; Forte, Maurizio; Palmerio, Silvia; Gerosa, Gino; Sciarretta, Sebastiano

2017-01-01

Recent epidemiologic studies evidence a dramatic increase of cardiovascular diseases, especially associated with the aging of the world population. During aging, the progressive impairment of the cardiovascular functions results from the compromised tissue abilities to protect the heart against stress. At the molecular level, in fact, a gradual weakening of the cellular processes regulating cardiovascular homeostasis occurs in aging cells. Atherosclerosis and heart failure are particularly correlated with aging-related cardiovascular senescence, that is, the inability of cells to progress in the mitotic program until completion of cytokinesis. In this review, we explore the intrinsic and extrinsic causes of cellular senescence and their role in the onset of these cardiovascular pathologies. Additionally, we dissect the effects of aging on the cardiac endogenous and exogenous reservoirs of stem cells. Finally, we offer an overview on the strategies of regenerative medicine that have been advanced in the quest for heart rejuvenation. PMID:29118467

Physiology of ageing of the musculoskeletal system.

PubMed

Boros, Katalin; Freemont, Tony

2017-04-01

This review aims to provide a summary of current concepts of ageing in relation to the musculoskeletal system, highlighting recent advances in the understanding of the mechanisms involved in the development of age-related changes in bone, skeletal muscle, chondroid and fibrous tissues. The key components of the musculoskeletal system and their functions are introduced together with a general overview of the molecular hallmarks of ageing. A brief description of the normal architecture of each of these tissue types is followed by a summary of established and developing concepts of mechanisms contributing to the age-related alterations in each. Extensive detailed description of these changes is beyond the scope of this review; instead, we aim to highlight some of the most significant processes and, where possible, the molecular changes underlying these and refer the reader to in-depth, subspecialist reviews of the individual components for further details. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

FAmily CEntered (FACE) advance care planning: Study design and methods for a patient-centered communication and decision-making intervention for patients with HIV/AIDS and their surrogate decision-makers.

PubMed

Kimmel, Allison L; Wang, Jichuan; Scott, Rachel K; Briggs, Linda; Lyon, Maureen E

2015-07-01

Although the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has become a chronic illness, disease-specific advance care planning has not yet been evaluated for the palliative care needs of adults with HIV/AIDS. This prospective, longitudinal, randomized, two-arm controlled clinical trial aims to test the efficacy of FAmily CEntered advance care planning among adults living with AIDS and/or HIV with co-morbidities on congruence in treatment preferences, healthcare utilization, and quality of life. The FAmily CEntered intervention arm is two face-to-face sessions with a trained, certified facilitator: Session 1) Disease-Specific Advance Care Planning Respecting Choices Interview; Session 2) Completion of advance directive. The Healthy Living Control arm is: Session 1) Developmental/Relationship History; Session 2) Nutrition. Follow-up data will be collected at 3, 6, 12, and 18 months post-intervention. A total of 288 patient/surrogate dyads will be enrolled from five hospital-based, out-patient clinics in Washington, District of Columbia. Participants will be HIV positive and ≥ 21 years of age; surrogates will be ≥ 18 years of age. Exclusion criteria are homicidality, suicidality, psychosis, and impaired cognitive functioning. We hypothesize that this intervention will enhance patient-centered communication with a surrogate decision-maker about end of life treatment preferences over time, enhance patient quality of life and decrease health care utilization. We further hypothesize that this intervention will decrease health disparities for Blacks in completion of advance directives. If proposed aims are achieved, the benefits of palliative care, particularly increased treatment preferences about end-of-life care and enhanced quality of life, will be extended to people living with AIDS. Copyright © 2015 Elsevier Inc. All rights reserved.

Tailoring peripartum nursing care for women of advanced maternal age.

PubMed

Suplee, Patricia Dunphy; Dawley, Katy; Bloch, Joan Rosen

2007-01-01

Births to women of advanced maternal age have increased dramatically over the last decade in both the United States. The majority of women who deliver their first baby after age 35 are healthy and experience positive birth outcomes. According to current research, primigravidas over 35 tend to be educated consumers. Their physical and psychosocial needs differ from those of the mother in her 20s, due to advanced age and factors related to difficulty conceiving and life circumstances. This paper presents (a) an overview of the possible risks to outcomes of childbearing for women over the age of 35; (b) a discussion of how women of advanced maternal age may differ from younger women related to developmental stage, stress or anxiety or both, decision making, and support systems; and (c) an exploration of tailoring nursing care strategies during the peripartum period specifically for this age cohort.

Flight duration and flight muscle ultrastructure of unfed hawk moths.

PubMed

Wone, Bernard W M; Pathak, Jaika; Davidowitz, Goggy

2018-06-13

Flight muscle breakdown has been reported for many orders of insects, but the basis of this breakdown in insects with lifelong dependence on flight is less clear. Lepidopterans show such muscle changes across their lifespans, yet how this change affects the ability of these insects to complete their life cycles is not well documented. We investigated the changes in muscle function and ultrastructure of unfed aging adult hawk moths (Manduca sexta). Flight duration was examined in young, middle-aged, and advanced-aged unfed moths. After measurement of flight duration, the main flight muscle (dorsolongitudinal muscle) was collected and histologically prepared for transmission electron microscopy to compare several measurements of muscle ultrastructure among moths of different ages. Muscle function assays revealed significant positive correlations between muscle ultrastructure and flight distance that were greatest in middle-aged moths and least in young moths. In addition, changes in flight muscle ultrastructure were detected across treatment groups. The number of mitochondria in muscle cells peaked in middle-aged moths. Many wild M. sexta do not feed as adults; thus, understanding the changes in flight capacity and muscle ultrastructure in unfed moths provides a more complete understanding of the ecophysiology and resource allocation strategies of this species. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cross-hemispheric functional connectivity in the human fetal brain.

PubMed

Thomason, Moriah E; Dassanayake, Maya T; Shen, Stephen; Katkuri, Yashwanth; Alexis, Mitchell; Anderson, Amy L; Yeo, Lami; Mody, Swati; Hernandez-Andrade, Edgar; Hassan, Sonia S; Studholme, Colin; Jeong, Jeong-Won; Romero, Roberto

2013-02-20

Compelling evidence indicates that psychiatric and developmental disorders are generally caused by disruptions in the functional connectivity (FC) of brain networks. Events occurring during development, and in particular during fetal life, have been implicated in the genesis of such disorders. However, the developmental timetable for the emergence of neural FC during human fetal life is unknown. We present the results of resting-state functional magnetic resonance imaging performed in 25 healthy human fetuses in the second and third trimesters of pregnancy (24 to 38 weeks of gestation). We report the presence of bilateral fetal brain FC and regional and age-related variation in FC. Significant bilateral connectivity was evident in half of the 42 areas tested, and the strength of FC between homologous cortical brain regions increased with advancing gestational age. We also observed medial to lateral gradients in fetal functional brain connectivity. These findings improve understanding of human fetal central nervous system development and provide a basis for examining the role of insults during fetal life in the subsequent development of disorders in neural FC.

Alcohol, aging, and innate immunity.

PubMed

Boule, Lisbeth A; Kovacs, Elizabeth J

2017-07-01

The global population is aging: in 2010, 8% of the population was older than 65 y, and that is expected to double to 16% by 2050. With advanced age comes a heightened prevalence of chronic diseases. Moreover, elderly humans fair worse after acute diseases, namely infection, leading to higher rates of infection-mediated mortality. Advanced age alters many aspects of both the innate and adaptive immune systems, leading to impaired responses to primary infection and poor development of immunologic memory. An often overlooked, yet increasingly common, behavior in older individuals is alcohol consumption. In fact, it has been estimated that >40% of older adults consume alcohol, and evidence reveals that >10% of this group is drinking more than the recommended limit by the National Institute on Alcohol Abuse and Alcoholism. Alcohol consumption, at any level, alters host immune responses, including changes in the number, phenotype, and function of innate and adaptive immune cells. Thus, understanding the effect of alcohol ingestion on the immune system of older individuals, who are already less capable of combating infection, merits further study. However, there is currently almost nothing known about how drinking alters innate immunity in older subjects, despite innate immune cells being critical for host defense, resolution of inflammation, and maintenance of immune homeostasis. Here, we review the effects of aging and alcohol consumption on innate immune cells independently and highlight the few studies that have examined the effects of alcohol ingestion in aged individuals. © Society for Leukocyte Biology.

Micronutrient intake in advanced age: Te Puāwaitanga o Ngā Tapuwae Kia ora Tonu, Life and Living in Advanced Age: A Cohort Study in New Zealand (LiLACS NZ).

PubMed

Wham, Carol; Teh, Ruth; Moyes, Simon A; Rolleston, Anna; Muru-Lanning, Marama; Hayman, Karen; Kerse, Ngaire; Adamson, Ashley

2016-11-09

A high prevalence of undernutrition has previously been reported in indigenous Māori (49 %) and non-Māori (38 %) octogenarians and may be associated with risk of micronutrient deficiencies. We examined vitamin and mineral intakes and the contributing food sources among 216 Māori and 362 non-Māori participating in Life and Living to Advanced age a Cohort Study in New Zealand, using a repeat 24-h multiple-pass recall. More than half of the Māori and non-Māori participants had intakes below the estimated average requirement from food alone for Ca, Mg and Se. Vitamin B6 (Māori women only), folate (women only), vitamin E (Māori women; all men) and Zn (men only) were low in these ethnic and sex subgroups. Women had intakes of higher nutrient density in folate, vitamin C, Ca, Mg, K, vitamin A (non-Māori) and β-carotene (Māori) compared with men (P<0·05). When controlling for age and physical function, β-carotene, folate, vitamin C, Ca and Mg were no longer significantly different, but vitamins B2, B12, E and D, Fe, Na, Se and Zn became significantly different for Māori between men and women. When controlling for age and physical function, vitamins A and C and Ca were no longer significantly different, but vitamin B2, Fe, Na and Zn became significantly different for non-Māori between men and women. For those who took nutritional supplements, Māori were less likely to be deficient in food alone intake of vitamin A, folate and Mg, whereas non-Maori were less likely to be deficient in intakes of Mg, K and Zn, but more likely to be deficient in vitamin B12 intake. A lack of harmonisation in nutrient recommendations hinders the interpretation of nutrient adequacy; nonetheless, Ca, Mg and Se are key micronutrients of concern. Milk and cheese were important contributions to Ca intake, whereas bread was a key source of Mg and Se. Examination of dietary intake related to biochemical status and health outcomes will establish the utility of these observations.

Progeroid syndromes: models for stem cell aging?

PubMed

Bellantuono, I; Sanguinetti, G; Keith, W N

2012-02-01

Stem cells are responsible for tissue repair and maintenance and it is assumed that changes observed in the stem cell compartment with age underlie the concomitant decline in tissue function. Studies in murine models have highlighted the importance of intrinsic changes occurring in stem cells with age. They have also drawn the attention to other factors, such as changes in the local or systemic environment as the primary cause of stem cell dysfunction. Whilst knowledge in murine models has been advancing rapidly there has been little translation of these data to human aging. This is most likely due to the difficulties of testing the regenerative capacity of human stem cells in vivo and to substantial differences in the aging phenotype within humans. Here we summarize evidence to show how progeroid syndromes, integrated with other models, can be valuable tools in addressing questions about the role of stem cell aging in human degenerative diseases of older age and the molecular pathways involved.

Prevalence and correlates of physical disability and functional limitation among community dwelling older people in rural Malaysia, a middle income country

PubMed Central

2010-01-01

Background The prevalence and correlates of physical disability and functional limitation among older people have been studied in many developed countries but not in a middle income country such as Malaysia. The present study investigated the epidemiology of physical disability and functional limitation among older people in Malaysia and compares findings to other countries. Methods A population-based cross sectional study was conducted in Alor Gajah, Malacca. Seven hundred and sixty five older people aged 60 years and above underwent tests of functional limitation (Tinetti Performance Oriented Mobility Assessment Tool). Data were also collected for self reported activities of daily living (ADL) using the Barthel Index (ten items). To compare prevalence with other studies, ADL disability was also defined using six basic ADL's (eating, bathing, dressing, transferring, toileting and walking) and five basic ADL's (eating, bathing, dressing, transferring and toileting). Results Ten, six and five basic ADL disability was reported by 24.7% (95% CI 21.6-27.9), 14.4% (95% CI 11.9-17.2) and 10.6% (95% CI 8.5-13.1), respectively. Functional limitation was found in 19.5% (95% CI 16.8-22.5) of participants. Variables independently associated with 10 item ADL disability physical disability, were advanced age (≥ 75 years: prevalence ratio (PR) 7.9; 95% CI 4.8-12.9), presence of diabetes (PR 1.8; 95% CI 1.4-2.3), stroke (PR 1.5; 95% CI 1.1-2.2), depressive symptomology (PR 1.3; 95% CI 1.1-1.8) and visual impairment (blind: PR 2.0; 95% CI 1.1-3.6). Advancing age (≥ 75 years: PR 3.0; 95% CI 1.7-5.2) being female (PR 2.7; 95% CI 1.2-6.1), presence of arthritis (PR 1.6; 95% CI 1.2-2.1) and depressive symptomology (PR 2.0; 95% CI 1.5-2.7) were significantly associated with functional limitation. Conclusions The prevalence of physical disability and functional limitation among older Malaysians appears to be much higher than in developed countries but is comparable to developing countries. Associations with socio-demographic and other health related variables were consistent with other studies. PMID:20716377

A conserved NAD+ binding pocket that regulates protein-protein interactions during aging.

PubMed

Li, Jun; Bonkowski, Michael S; Moniot, Sébastien; Zhang, Dapeng; Hubbard, Basil P; Ling, Alvin J Y; Rajman, Luis A; Qin, Bo; Lou, Zhenkun; Gorbunova, Vera; Aravind, L; Steegborn, Clemens; Sinclair, David A

2017-03-24

DNA repair is essential for life, yet its efficiency declines with age for reasons that are unclear. Numerous proteins possess Nudix homology domains (NHDs) that have no known function. We show that NHDs are NAD + (oxidized form of nicotinamide adenine dinucleotide) binding domains that regulate protein-protein interactions. The binding of NAD + to the NHD domain of DBC1 (deleted in breast cancer 1) prevents it from inhibiting PARP1 [poly(adenosine diphosphate-ribose) polymerase], a critical DNA repair protein. As mice age and NAD + concentrations decline, DBC1 is increasingly bound to PARP1, causing DNA damage to accumulate, a process rapidly reversed by restoring the abundance of NAD + Thus, NAD + directly regulates protein-protein interactions, the modulation of which may protect against cancer, radiation, and aging. Copyright © 2017, American Association for the Advancement of Science.

Stem cell ageing: does it happen and can we intervene?

PubMed

Bellantuono, Ilaria; Keith, W Nicol

2007-11-19

Adult stem cells have become the focus of intense research in recent years as a result of their role in the maintenance and repair of tissues. They exert this function through their extensive expansion (self-renewal) and multipotent differentiation capacity. Understanding whether adult stem cells retain this capacity throughout the lifespan of the individual, or undergo a process of ageing resulting in a decreased stem cell pool, is an important area of investigation. Progress in this area has been hampered by lack of suitable models and of appropriate markers and assays to identify stem cells. However, recent data suggest that an understanding of the mechanisms governing stem cell ageing can give insight into the mechanism of tissue ageing and, most importantly, advance our ability to use stem cells in cell and gene therapy strategies.

Use of specular microscopy to determine corneal endothelial cell morphology and morphometry in enucleated cat eyes.

PubMed

Franzen, Angela A; Pigatto, João A T; Abib, Fernando C; Albuquerque, Luciane; Laus, José L

2010-07-01

The purpose of this study was to investigate the effect of age on endothelial morphology and morphometry in cats. The corneal endothelium was studied using a contact specular microscope. A total of 18 cats (Felis catus Linnaeus, 1758) were evaluated in this study. The subjects were divided into three groups of six cats each in function of age: G1 (1 to 3 months old), G2 (5 to 12 months old), and G3 (24 to 40 months old). The examination presented data as endothelial cell density (ECD), average cell area, corneal thickness, polymegathism, and pleomorphism. Results revealed ECD decrease in corneas of normal cats with age, as well as a corresponding increase in endothelial cell area and pleomorphism. The present work suggests that the endothelial parameters evaluated change with advancing age.

Advanced Glycation End Product (AGE) Accumulation in the Skin is Associated with Depression: The Maastricht Study.

PubMed

van Dooren, Fleur E P; Pouwer, Frans; Schalkwijk, Casper G; Sep, Simone J S; Stehouwer, Coen D A; Henry, Ronald M A; Dagnelie, Pieter C; Schaper, Nicolaas C; van der Kallen, Carla J H; Koster, Annemarie; Denollet, Johan; Verhey, Frans R J; Schram, Miranda T

2017-01-01

Depression is a highly prevalent disease with a high morbidity and mortality risk. Its pathophysiology is not entirely clear. However, type 2 diabetes is an important risk factor for depression. One mechanism that may explain this association may include the formation of advanced glycation end products (AGEs). We therefore investigated the association of AGEs with depressive symptoms and depressive disorder. In addition, we examined whether the potential association was present for somatic and/or cognitive symptoms of depression. Cross-sectional data were used from the Maastricht Study (N = 862, mean age 59.8 ± 8.5 years, 55% men). AGE accumulation was measured with skin autofluorescence (SAF) by use of the AGE Reader. Plasma levels of protein-bound pentosidine were measured with high-performance liquid chromatography and fluorescence detection. Nε-(carboxymethyl)lysine (CML) and Nε-(carboxyethyl)lysine (CEL) were measured with ultraperformance liquid chromatography and tandem mass spectrometry. Depressive symptoms and depressive disorder were assessed by the nine-item Patient Health Questionnaire and the Mini-International Neuropsychiatric Interview. Higher SAF was associated with depressive symptoms (β = 0.42, 95% CI 0.12-0.73, P = .007) and depressive disorder (OR = 1.42, 95% CI 1.04-1.95, P = .028) after adjustment for age, sex, type 2 diabetes, smoking, BMI, and kidney function. Plasma pentosidine, CML, and CEL were not independently associated with depressive symptoms and depressive disorder. This study shows that AGE accumulation in the skin is independently associated with higher levels of depressive symptoms and depressive disorder. This association is present for both somatic and cognitive symptoms of depression. This might suggest that AGEs are involved in the development of depression. © 2016 Wiley Periodicals, Inc.

Differential impact of glucose levels and advanced glycation end-products on tubular cell viability and pro-inflammatory/profibrotic functions.

PubMed

Franko, Benoit; Brault, Julie; Jouve, Thomas; Beaumel, Sylvain; Benhamou, Pierre-Yves; Zaoui, Philippe; Stasia, Marie José

2014-09-05

High glucose (HG) or synthetic advanced glycation end-products (AGE) conditions are generally used to mimic diabetes in cellular models. Both models have shown an increase of apoptosis, oxidative stress and pro-inflammatory cytokine production in tubular cells. However, the impact of the two conditions combined has rarely been studied. In addition, the impact of glucose level variation due to cellular consumption is not clearly characterized in such experiments. Therefore, the aim of this study was to compare the effect of HG and AGE separately and of both on tubular cell phenotype changes in the HK2 cell line. Moreover, glucose consumption was monitored every hour to maintain the glucose level by supplementation throughout the experiments. We thus observed a significant decrease of apoptosis and H2O2 production in the HK2 cell. HG or AGE treatment induced an increase of total and mitochondrial apoptosis as well as TGF-β release compared to control conditions; however, AGE or HG led to apoptosis preferentially involving the mitochondria pathway. No cumulative effect of HG and AGE treatment was observed on apoptosis. However, a pretreatment with RAGE antibodies partially abolished the apoptotic effect of HG and completely abolished the apoptotic effect of AGE. In conclusion, tubular cells are sensitive to the lack of glucose as well as to the HG and AGE treatments, the AGE effect being more deleterious than the HG effect. Absence of a potential synergistic effect of HG and AGE could indicate that they act through a common pathway, possibly via the activation of the RAGE receptors. Copyright © 2014 Elsevier Inc. All rights reserved.

Correlates of Social Functioning in Autism Spectrum Disorder: The Role of Social Cognition

PubMed Central

Bishop-Fitzpatrick, Lauren; Mazefsky, Carla A.; Eack, Shaun M.; Minshew, Nancy J.

2017-01-01

Background Individuals with autism spectrum disorder (ASD) experience marked challenges with social function by definition, but few modifiable predictors of social functioning in ASD have been identified in extant research. This study hypothesized that deficits in social cognition and motor function may help to explain poor social functioning in individuals with ASD. Method Cross-sectional data from 108 individuals with ASD and without intellectual disability ages 9 through 27.5 were used to assess the relationship between social cognition and motor function, and social functioning. Results Results of hierarchical multiple regression analyses revealed that greater social cognition, but not motor function, was significantly associated with better social functioning when controlling for sex, age, and intelligence quotient. Post-hoc analyses revealed that, better performance on second-order false belief tasks was associated with higher levels of socially adaptive behavior and lower levels of social problems. Conclusions Our findings support the development and testing of interventions that target social cognition in order to improve social functioning in individuals with ASD. Interventions that teach generalizable skills to help people with ASD better understand social situations and develop competency in advanced perspective taking have the potential to create more durable change because their effects can be applied to a wide and varied set of situations and not simply a prescribed set of rehearsed situations. PMID:28839456

The epigenetic landscape of age-related diseases: the geroscience perspective.

PubMed

Gensous, Noémie; Bacalini, Maria Giulia; Pirazzini, Chiara; Marasco, Elena; Giuliani, Cristina; Ravaioli, Francesco; Mengozzi, Giacomo; Bertarelli, Claudia; Palmas, Maria Giustina; Franceschi, Claudio; Garagnani, Paolo

2017-08-01

In this review, we summarize current knowledge regarding the epigenetics of age-related diseases, focusing on those studies that have described DNA methylation landscape in cardio-vascular diseases, musculoskeletal function and frailty. We stress the importance of adopting the conceptual framework of "geroscience", which starts from the observation that advanced age is the major risk factor for several of these pathologies and aims at identifying the mechanistic links between aging and age-related diseases. DNA methylation undergoes a profound remodeling during aging, which includes global hypomethylation of the genome, hypermethylation at specific loci and an increase in inter-individual variation and in stochastic changes of DNA methylation values. These epigenetic modifications can be an important contributor to the development of age-related diseases, but our understanding on the complex relationship between the epigenetic signatures of aging and age-related disease is still poor. The most relevant results in this field come from the use of the so called "epigenetics clocks" in cohorts of subjects affected by age-related diseases. We report these studies in final section of this review.

Basic consensus document on late-onset hypogonadism.

PubMed

Becerra Fernández, Antonio; Enríquez Acosta, Luis

2008-01-01

One of the most important elements in men's live is the ability to engage in normal sexual activity; loss of this activity has always been considered especially important. The relationship between sexual activity, as well as other masculine characteristics, and the testicles has been well known since ancient times and has been related to the slow decrease in testosterone secretion with advanced age. Male hypogonadism is one of the most frequent and under-diagnosed endocrine diseases. Several terms have been proposed to refer to clinical situations caused by the age-related decline in male gonadal function; currently, the most widely accepted term is late-onset hypogonadism (LOH). LOH consists of a clinical and biochemical syndrome associated with advanced age (in men), characterized by typical symptoms and reduced serum testosterone concentrations, which can affect multiple organs and systems and reduce quality of life. This syndrome can be treated and the alterations produced can be reversed. To achieve this, a diagnostic protocol that approaches the multiple factors related to the risks and benefits of treatment is required. Copyright © 2008 Sociedad Española de Endocrinología y Nutrición. Published by Elsevier Espana. All rights reserved.

Age-specific reproductive success in a long-lived bird: do older parents resist stress better?

PubMed

Angelier, Frederic; Moe, Børge; Weimerskirch, Henri; Chastel, Olivier

2007-11-01

In many vertebrates, reproductive performance increases with advancing age but mechanisms involved in such a pattern remain poorly studied. One potential mechanism may be the hormonal stress response, which shifts energy investment away from reproduction and redirects it towards survival. In birds, this stress response is achieved through a release of corticosterone and is also accompanied by a decrease in circulating prolactin, a hormone involved widely in regulating parental cares. It has been predicted that, when the value of the current reproduction is high relative to the value of future reproduction and survival, as it is expected to be in older adults, the stress response should be attenuated to ensure that reproduction is not inhibited. We tested this hypothesis by measuring the corticosterone and prolactin responses of known-age (8-36 years old) incubating snow petrels (Pagadroma nivea) to a standardized capture/handling stress protocol. We also investigated whether an attenuation of the stress responses will correlate with a lower occurrence of egg neglect, a frequently observed behaviour in snow petrels. The probability of successfully fledging a chick increased from 6 years to 12 years before stabilizing after 12 years of age. Corticosterone response to stress was unaffected by age. Prolactin response to stress, however, was influenced clearly by age: in both sexes older breeders had higher stress-induced prolactin levels than younger ones. This was due to an increasing attenuation of the prolactin response to stress with advancing age in females, and in males this was due to a probably higher intrinsic capacity of older males to secrete prolactin. Moreover, higher stress-induced prolactin levels were correlated with a lower probability of neglecting the egg. In young breeders, the combination of a robust corticosterone increase with a lower ability to maintain prolactin secretion during acute stress is probably one of the functional causes of their lower incubation commitment. We suggest that the ability to maintain a threshold level of prolactin during a stressful situation may be an important physiological mechanism involved in the improvement of reproductive performance with advancing age in long-lived birds.

N-acetylcysteine Counteracts Adipose Tissue Macrophage Infiltration and Insulin Resistance Elicited by Advanced Glycated Albumin in Healthy Rats

PubMed Central

da Silva, Karolline S.; Pinto, Paula R.; Fabre, Nelly T.; Gomes, Diego J.; Thieme, Karina; Okuda, Ligia S.; Iborra, Rodrigo T.; Freitas, Vanessa G.; Shimizu, Maria H. M.; Teodoro, Walcy R.; Marie, Suely K. N.; Woods, Tom; Brimble, Margaret A.; Pickford, Russell; Rye, Kerry-Anne; Okamoto, Maristela; Catanozi, Sergio; Correa-Giannela, Maria L.; Machado, Ubiratan F.; Passarelli, Marisa

2017-01-01

Background: Advanced glycation endproducts elicit inflammation. However, their role in adipocyte macrophage infiltration and in the development of insulin resistance, especially in the absence of the deleterious biochemical pathways that coexist in diabetes mellitus, remains unknown. We investigated the effect of chronic administration of advanced glycated albumin (AGE-albumin) in healthy rats, associated or not with N-acetylcysteine (NAC) treatment, on insulin sensitivity, adipose tissue transcriptome and macrophage infiltration and polarization. Methods: Male Wistar rats were intraperitoneally injected with control (C) or AGE-albumin alone, or, together with NAC in the drinking water. Biochemical parameters, lipid peroxidation, gene expression and protein contents were, respectively, determined by enzymatic techniques, reactive thiobarbituric acid substances, RT-qPCR and immunohistochemistry or immunoblot. Carboxymethyllysine (CML) and pyrraline (PYR) were determined by LC/mass spectrometry (LC-MS/MS) and ELISA. Results: CML and PYR were higher in AGE-albumin as compared to C. Food consumption, body weight, systolic blood pressure, plasma lipids, glucose, hepatic and renal function, adipose tissue relative weight and adipocyte number were similar among groups. In AGE-treated animals, insulin resistance, adipose macrophage infiltration and Col12a1 mRNA were increased with no changes in M1 and M2 phenotypes as compared to C-albumin-treated rats. Total GLUT4 content was reduced by AGE-albumin as compared to C-albumin. NAC improved insulin sensitivity, reduced urine TBARS, adipose macrophage number and Itgam and Mrc mRNA and increased Slc2a4 and Ppara. CD11b, CD206, Ager, Ddost, Cd36, Nfkb1, Il6, Tnf, Adipoq, Retn, Arg, and Il12 expressions were similar among groups. Conclusions: AGE-albumin sensitizes adipose tissue to inflammation due to macrophage infiltration and reduces GLUT4, contributing to insulin resistance in healthy rats. NAC antagonizes AGE-albumin and prevents insulin resistance. Therefore, it may be a useful tool in the prevention of AGE action on insulin resistance and long-term complications of DM. PMID:29018354

Antibody-directed myostatin inhibition in 21-mo-old mice reveals novel roles for myostatin signaling in skeletal muscle structure and function.

PubMed

Murphy, Kate T; Koopman, René; Naim, Timur; Léger, Bertrand; Trieu, Jennifer; Ibebunjo, Chikwendu; Lynch, Gordon S

2010-11-01

Sarcopenia is the progressive loss of skeletal muscle mass and function with advancing age, leading to reduced mobility and quality of life. We tested the hypothesis that antibody-directed myostatin inhibition would attenuate the decline in mass and function of muscles of aged mice and that apoptosis would be reduced. Eighteen-month-old C57BL/6 mice were treated for 14 wk with a once-weekly injection of saline (control, n=9) or a mouse chimera of anti-human myostatin antibody (PF-354, 10 mg/kg; n=12). PF-354 prevented the age-related reduction in body mass and increased soleus, gastrocnemius, and quadriceps muscle mass (P<0.05). PF-354 increased fiber cross-sectional area by 12% and enhanced maximum in situ force of tibialis anterior (TA) muscles by 35% (P<0.05). PF-354 increased the proportion of type IIa fibers by 114% (P<0.01) and enhanced activity of oxidative enzymes (SDH) by 39% (P<0.01). PF-354 reduced markers of apoptosis in TA muscle cross-sections by 56% (P<0.03) and reduced caspase3 mRNA by 65% (P<0.04). Antibody-directed myostatin inhibition attenuated the decline in mass and function of muscles of aging mice, in part, by reducing apoptosis. These observations identify novel roles for myostatin in regulation of muscle mass and highlight the therapeutic potential of antibody-directed myostatin inhibition for sarcopenia.

Characteristics of positive-interaction parenting style among primiparous teenage, optimal age, and advanced age mothers in Canada.

PubMed

Kim, Theresa H M; Connolly, Jennifer A; Rotondi, Michael; Tamim, Hala

2018-01-08

Positive-interaction parenting early in childhood is encouraged due to its association with behavioural development later in life. The objective of this study was to examine if the level of positive-interaction parenting style differs among teen, optimal age, and advanced age mothers in Canada, and to identify the characteristics associated with positive-interaction parenting style separately for each age group. This was a cross-sectional secondary analysis of the National Longitudinal Survey of Children and Youth. First-time mothers with children 0-23 months were grouped into: teen (15-19 years, N = 53,409), optimal age (20-34 years, N = 790,960), and advanced age (35 years and older, N = 106,536). The outcome was positive-interaction parenting style (Parenting Practices Scale); maternal socio-demographics, health, social, and child characteristics were considered for backward stepwise multiple linear regression modeling, stratified for each of the age groups. Teen, optimal age, and advanced age mothers reported similar levels of positive- interaction parenting style. Covariates differed across the three age groups. Among optimal age mothers, being an ever-landed immigrant, childcare use, and being devoted to religion were found to decrease positive-interaction parenting style, whereas, higher education was found to increase positive-interaction parenting style. Teen mothers were not found to have any characteristics uniquely associated with positive-interaction parenting. Among advanced age mothers, social support was uniquely associated with an increase in positive-interaction parenting. Very good/excellent health was found to be positively associated with parenting in teens but negatively associated with parenting in advanced age mothers. Characteristics associated with positive-interaction parenting varied among the three age groups. Findings may have public health implications through information dissemination to first-time mothers, clinicians, researchers, and public health facilities.

Ageing and inflammation in patients with HIV infection.

PubMed

Nasi, M; De Biasi, S; Gibellini, L; Bianchini, E; Pecorini, S; Bacca, V; Guaraldi, G; Mussini, C; Pinti, M; Cossarizza, A

2017-01-01

Nowadays, HIV + patients have an expected lifespan that is only slightly shorter than healthy individuals. For this reason, along with the fact that infection can be acquired at a relatively advanced age, the effects of ageing on HIV + people have begun to be evident. Successful anti-viral treatment is, on one hand, responsible for the development of side effects related to drug toxicity; on the other hand, it is not able to inhibit the onset of several complications caused by persistent immune activation and chronic inflammation. Therefore, patients with a relatively advanced age, i.e. aged more than 50 years, can experience pathologies that affect much older citizens. HIV + individuals with non-AIDS-related complications can thus come to the attention of clinicians because of the presence of neurocognitive disorders, cardiovascular diseases, metabolic syndrome, bone abnormalities and non-HIV-associated cancers. Chronic inflammation and immune activation, observed typically in elderly people and defined as 'inflammaging', can be present in HIV + patients who experience a type of premature ageing, which affects the quality of life significantly. This relatively new condition is extremely complex, and important factors have been identified as well as the traditional behavioural risk factors, e.g. the toxicity of anti-retroviral treatments and the above-mentioned chronic inflammation leading to a functional decline and a vulnerability to injury or pathologies. Here, we discuss the role of inflammation and immune activation on the most important non-AIDS-related complications of chronic HIV infection, and the contribution of aging per se to this scenario. © 2016 British Society for Immunology.

Brief report: Predictors of outcomes in the Early Start Denver Model delivered in a group setting.

PubMed

Vivanti, Giacomo; Dissanayake, Cheryl; Zierhut, Cynthia; Rogers, Sally J

2013-07-01

There is a paucity of studies that have looked at factors associated with responsiveness to interventions in preschoolers with autism spectrum disorder (ASD). We investigated learning profiles associated with response to the early start Denver model delivered in a group setting. Our preliminary results from 21 preschool children with an ASD aged 2- to 5-years suggest that the children with more advanced skills in functional use of objects, goal understanding and imitation made the best developmental gains after 1 year of treatment. Cognitive abilities, social attention, intensity of the treatment and chronological age were not associated with treatment gains.

Mesenchymal Stem Cells from Adipose Tissue in Clinical Applications for Dermatological Indications and Skin Aging.

PubMed

Gaur, Meenakshi; Dobke, Marek; Lunyak, Victoria V

2017-01-20

Operating at multiple levels of control, mesenchymal stem cells from adipose tissue (ADSCs) communicate with organ systems to adjust immune response, provide signals for differentiation, migration, enzymatic reactions, and to equilibrate the regenerative demands of balanced tissue homeostasis. The identification of the mechanisms by which ADSCs accomplish these functions for dermatological rejuvenation and wound healing has great potential to identify novel targets for the treatment of disorders and combat aging. Herein, we review new insights into the role of adipose-derived stem cells in the maintenance of dermal and epidermal homeostasis, and recent advances in clinical applications of ADSCs related to dermatology.

Mesenchymal Stem Cells from Adipose Tissue in Clinical Applications for Dermatological Indications and Skin Aging

PubMed Central

Gaur, Meenakshi; Dobke, Marek; Lunyak, Victoria V.

2017-01-01

Operating at multiple levels of control, mesenchymal stem cells from adipose tissue (ADSCs) communicate with organ systems to adjust immune response, provide signals for differentiation, migration, enzymatic reactions, and to equilibrate the regenerative demands of balanced tissue homeostasis. The identification of the mechanisms by which ADSCs accomplish these functions for dermatological rejuvenation and wound healing has great potential to identify novel targets for the treatment of disorders and combat aging. Herein, we review new insights into the role of adipose-derived stem cells in the maintenance of dermal and epidermal homeostasis, and recent advances in clinical applications of ADSCs related to dermatology. PMID:28117680

Web-Altairis: An Internet-Enabled Ground System

NASA Technical Reports Server (NTRS)

Miller, Phil; Coleman, Jason; Gemoets, Darren; Hughes, Kevin

2000-01-01

This paper describes Web-Altairis, an Internet-enabled ground system software package funded by the Advanced Automation and Architectures Branch (Code 588) of NASA's Goddard Space Flight Center. Web-Altairis supports the trend towards "lights out" ground systems, where the control center is unattended and problems are resolved by remote operators. This client/server software runs on most popular platforms and provides for remote data visualization using the rich functionality of the VisAGE toolkit. Web-Altairis also supports satellite commanding over the Internet. This paper describes the structure of Web-Altairis and VisAGE, the underlying technologies, the provisions for security, and our experiences in developing and testing the software.

The genetic pleiotropy of musculoskeletal aging

PubMed Central

Karasik, David; Cohen-Zinder, Miri

2012-01-01

Musculoskeletal aging is detrimental to multiple bodily functions and starts early, probably in the fourth decade of an individual's life. Sarcopenia is a health problem that is expected to only increase as a greater portion of the population lives longer; prevalence of the related musculoskeletal diseases is similarly expected to increase. Unraveling the biological and biomechanical associations and molecular mechanisms underlying these diseases represents a formidable challenge. There are two major problems making disentangling the biological complexity of musculoskeletal aging difficult: (a) it is a systemic, rather than “compartmental,” problem, which should be approached accordingly, and (b) the aging per se is neither well defined nor reliably measurable. A unique challenge of studying any age-related condition is a need of distinguishing between the “norm” and “pathology,” which are interwoven throughout the aging organism. We argue that detecting genes with pleiotropic functions in musculoskeletal aging is needed to provide insights into the potential biological mechanisms underlying inter-individual differences insusceptibility to the musculoskeletal diseases. However, exploring pleiotropic relationships among the system's components is challenging both methodologically and conceptually. We aimed to focus on genetic aspects of the cross-talk between muscle and its “neighboring” tissues and organs (tendon, bone, and cartilage), and to explore the role of genetics to find the new molecular links between skeletal muscle and other parts of the “musculoskeleton.” Identification of significant genetic variants underlying the musculoskeletal system's aging is now possible more than ever due to the currently available advanced genomic technologies. In summary, a “holistic” genetic approach is needed to study the systems's normal functioning and the disease predisposition in order to improve musculoskeletal health. PMID:22934054

Lifestyle Modulators of Neuroplasticity: How Physical Activity, Mental Engagement, and Diet Promote Cognitive Health during Aging.

PubMed

Phillips, Cristy

2017-01-01

The number of the elderly across the globe will approximate 2.1 billion by 2050. Juxtaposed against this burgeoning segment of the population is evidence that nonpathological aging is associated with an increased risk for cognitive decline in a variety of domains, changes that can cause mild disability even before the onset of dementia. Given that pharmacological treatments that mitigate dementia are still outstanding, alternative therapeutic options are being investigated increasingly. The results from translational studies have shown that modifiable lifestyle factors-including physical activity, cognitive engagement, and diet-are a key strategy for maintaining brain health during aging. Indeed, a multiplicity of studies has demonstrated relationships between lifestyle factors, brain structure and function, and cognitive function in aging adults. For example, physical activity and diet modulate common neuroplasticity substrates (neurotrophic signaling, neurogenesis, inflammation, stress response, and antioxidant defense) in the brain whereas cognitive engagement enhances brain and cognitive reserve. The aims of this review are to evaluate the relationship between modifiable lifestyle factors, neuroplasticity, and optimal brain health during aging; to identify putative mechanisms that contribute positive brain aging; and to highlight future directions for scientists and clinicians. Undoubtedly, the translation of cutting-edge knowledge derived from the field of cognitive neuroscience will advance our understanding and enhance clinical treatment interventions as we endeavor to promote brain health during aging.

Lifestyle Modulators of Neuroplasticity: How Physical Activity, Mental Engagement, and Diet Promote Cognitive Health during Aging

PubMed Central

2017-01-01

The number of the elderly across the globe will approximate 2.1 billion by 2050. Juxtaposed against this burgeoning segment of the population is evidence that nonpathological aging is associated with an increased risk for cognitive decline in a variety of domains, changes that can cause mild disability even before the onset of dementia. Given that pharmacological treatments that mitigate dementia are still outstanding, alternative therapeutic options are being investigated increasingly. The results from translational studies have shown that modifiable lifestyle factors—including physical activity, cognitive engagement, and diet—are a key strategy for maintaining brain health during aging. Indeed, a multiplicity of studies has demonstrated relationships between lifestyle factors, brain structure and function, and cognitive function in aging adults. For example, physical activity and diet modulate common neuroplasticity substrates (neurotrophic signaling, neurogenesis, inflammation, stress response, and antioxidant defense) in the brain whereas cognitive engagement enhances brain and cognitive reserve. The aims of this review are to evaluate the relationship between modifiable lifestyle factors, neuroplasticity, and optimal brain health during aging; to identify putative mechanisms that contribute positive brain aging; and to highlight future directions for scientists and clinicians. Undoubtedly, the translation of cutting-edge knowledge derived from the field of cognitive neuroscience will advance our understanding and enhance clinical treatment interventions as we endeavor to promote brain health during aging. PMID:28695017

Age-associated changes in cardiovascular structure and function: a fertile milieu for future disease

PubMed Central

Strait, James

2015-01-01

Important changes occur in the cardiovascular system with advancing age, even in apparently healthy individuals. Thickening and stiffening of the large arteries develop due to collagen and calcium deposition and loss of elastic fibers in the medial layer. These arterial changes cause systolic blood pressure to rise with age, while diastolic blood pressure generally declines after the sixth decade. In the left ventricle, modest concentric wall thickening occurs due to cellular hypertrophy, but cavity size does not change. Although left ventricular systolic function is preserved across the age span, early diastolic filling rate declines 30–50% between the third and ninth decades. Conversely, an age-associated increase in late diastolic filling due to atrial contraction preserves end-diastolic volume. Aerobic exercise capacity declines approximately 10% per decade in cross-sectional studies; in longitudinal studies, however, this decline is accelerated in the elderly. Reductions in peak heart rate and peripheral oxygen utilization but not stroke volume appear to mediate the age-associated decline in aerobic capacity. Deficits in both cardiac b-adrenergic receptor density and in the efficiency of postsynaptic b-adrenergic signaling contribute significantly to the reduced cardiovascular performance during exercise in older adults. Although these cardiovascular aging changes are considered “normative”, they lower the threshold for the development of cardiovascular disease, which affects the majority of older adults. PMID:21809160

Cognitive Function in Normal-Weight, Overweight, and Obese Older Adults: An Analysis of the Advanced Cognitive Training for Independent and Vital Elderly Cohort

PubMed Central

Kuo, Hsu-Ko; Jones, Richard N.; Milberg, William P.; Tennstedt, Sharon; Talbot, Laura; Morris, John N.; Lipsitz, Lewis A.

2010-01-01

OBJECTIVES To assess how elevated body mass index (BMI) affects cognitive function in elderly people. DESIGN Cross-sectional study. SETTING Data for this cross-sectional study were taken from a multicenter randomized controlled trial, the Advanced Cognitive Training for Independent and Vital Elderly trial. PARTICIPANTS The analytic sample included 2,684 normal-weight, overweight, or obese subjects aged 65 to 94. MEASUREMENTS Evaluation of cognitive abilities was performed in several domains: global cognition, memory, reasoning, and speed of processing. Cross-sectional association between body weight status and cognitive functions was analyzed using multiple linear regression. RESULTS Overweight subjects had better performance on a reasoning task (β = 0.23, standard error (SE) = 0.11, P = .04) and the Useful Field of View (UFOV) measure (β = −39.46, SE = 12.95, P = .002), a test of visuospatial speed of processing, after controlling for age, sex, race, years of education, intervention group, study site, and cardiovascular risk factors. Subjects with class I (BMI 30.0–34.9 kg/m2) and class II (BMI>35.0 kg/m2) obesity had better UFOV measure scores (β = −38.98, SE = 14.77, P = .008; β = −35.75, SE = 17.65, and P = .04, respectively) in the multivariate model than normal-weight subjects. The relationships between BMI and individual cognitive domains were nonlinear. CONCLUSION Overweight participants had better cognitive performance in terms of reasoning and visuospatial speed of processing than normal-weight participants. Obesity was associated with better performance in visuospatial speed of processing than normal weight. The relationship between BMI and cognitive function should be studied prospectively. PMID:16420204

First-time fathers' expectations and experiences of childbirth in relation to age.

PubMed

Schytt, Erica; Bergström, Malin

2014-01-01

to investigate first-time fathers' expectations and experiences of childbirth and satisfaction with care in relation to paternal age. data from a randomised controlled trial of antenatal education were used for secondary analysis. Data were collected by questionnaires in mid-pregnancy and at three months after the birth. Comparisons by χ(2)-tests and Student's t-tests were made between men in three age groups: young men aged ≤27 years (n=188), men of average age 28-33 years (n=389) and men of advanced age ≥34 years (n=200). the expectant fathers were recruited from 15 antenatal clinics spread over Sweden. 777 first-time fathers. antenatal expectations and postnatal memory of the childbirth experience varied by paternal age. In mid-pregnancy, mixed or negative feelings about the upcoming birth were more prevalent in men of advanced age (29%) compared with men of average (26%) and young (18%) age (p<0.01), and they feared the event more than the youngest (mean on the Wijma Delivery Expectancy Questionnaire: advanced age 43.3; average age 42.9; young 38.7; p<0.01). The older men also assessed their partner's labour and birth as more difficult (advanced age 43%; average age 41%; young 32%; p=0.05) and had a less positive overall birth experience (advanced age 30%; average age 36%; young 43%; p<0.05). However, older fathers were more satisfied with care given during the intrapartum period: 52% were overall satisfied compared with 46% of the men of average age and 39% of young age (p=0.03). men of advanced age had more fearful and negative expectations during their partner's pregnancies and postnatally assessed the births as less positive and more difficult than younger men did. Despite this, older men were more satisfied with intrapartum care. knowledge about age-related differences in the expectations and experiences of first-time fathers may help midwives and doctors give more individualised information and support, with special attention to older men's expectations and experiences of the birth as such, and to younger men's perception of care. Copyright © 2013 Elsevier Ltd. All rights reserved.

Transpiration during life cycle in controlled wheat growth

NASA Technical Reports Server (NTRS)

Volk, Tyler; Rummel, John D.

1990-01-01

A previously developed model of wheat growth, designed for convenient incorporation into system level models of advanced space life support systems is described. The model is applied to data from an experiment that grew wheat under controlled conditions and measured fresh biomass and cumulated transpiration as a function of time. The adequacy of modeling the transpiration as proportional to the inedible biomass and an age factor that varies during the life cycle are discussed.

Red blood cells open promising avenues for longitudinal studies of ageing in laboratory, non-model and wild animals.

PubMed

Stier, Antoine; Reichert, Sophie; Criscuolo, Francois; Bize, Pierre

2015-11-01

Ageing is characterized by a progressive deterioration of multiple physiological and molecular pathways, which impair organismal performance and increase risks of death with advancing age. Hence, ageing studies must identify physiological and molecular pathways that show signs of age-related deterioration, and test their association with the risk of death and longevity. This approach necessitates longitudinal sampling of the same individuals, and therefore requires a minimally invasive sampling technique that provides access to the larger spectrum of physiological and molecular pathways that are putatively associated with ageing. The present paper underlines the interest in using red blood cells (RBCs) as a promising target for longitudinal studies of ageing in vertebrates. RBCs provide valuable information on the following six pathways: cell maintenance and turnover (RBC number, size, and heterogeneity), glucose homeostasis (RBC glycated haemoglobin), oxidative stress parameters, membrane composition and integrity, mitochondrial functioning, and telomere dynamics. The last two pathways are specific to RBCs of non-mammalian species, which possess a nucleus and functional mitochondria. We present the current knowledge about RBCs and age-dependent changes in these pathways in non-model and wild species that are especially suitable to address questions related to ageing using longitudinal studies. We discuss how the different pathways relate with survival and lifespan and give information on their genetic and environmental determinants to appraise their evolutionary potential. Copyright © 2015 Elsevier Inc. All rights reserved.

Glycation & Insulin Resistance: Novel Mechanisms and Unique Targets?

PubMed Central

Song, Fei; Schmidt, Ann Marie

2012-01-01

Objectives Multiple biochemical, metabolic and signal transduction pathways contribute to insulin resistance. In this review, we present the evidence that the post-translational process of protein glycation may play role in insulin resistance. The post-translational modifications, the advanced glycation endproducts (AGEs), are formed and accumulate by endogenous and exogenous mechanisms. Methods and Results AGEs may contribute to insulin resistance by a variety of mechanisms, including generation of tumor necrosis factor-alpha, direct modification of the insulin molecule thereby leading to its impaired action, generation of oxidative stress, and impairment of mitochondrial function, as examples. AGEs may stimulate signal transduction via engagement of cellular receptors, such as RAGE, or receptor for AGE. AGE-RAGE interaction perpetuates AGE formation and cellular stress via induction of inflammation, oxidative stress and reduction in the expression and activity of the enzyme, glyoxalase I that detoxifies the AGE precursor, methylglyoxal, or MG. Conclusions Once set in motion, glycation-promoting mechanisms may stimulate ongoing AGE production and target tissue stresses that reduce insulin responsiveness. Strategies to limit AGE accumulation and action may contribute to prevention of insulin resistance and its consequences. PMID:22815341

Age-associated Cognitive Decline: Insights into Molecular Switches and Recovery Avenues.

PubMed

Konar, Arpita; Singh, Padmanabh; Thakur, Mahendra K

2016-03-01

Age-associated cognitive decline is an inevitable phenomenon that predisposes individuals for neurological and psychiatric disorders eventually affecting the quality of life. Scientists have endeavored to identify the key molecular switches that drive cognitive decline with advancing age. These newly identified molecules are then targeted as recovery of cognitive aging and related disorders. Cognitive decline during aging is multi-factorial and amongst several factors influencing this trajectory, gene expression changes are pivotal. Identifying these genes would elucidate the neurobiological underpinnings as well as offer clues that make certain individuals resilient to withstand the inevitable age-related deteriorations. Our laboratory has focused on this aspect and investigated a wide spectrum of genes involved in crucial brain functions that attribute to senescence induced cognitive deficits. We have recently identified master switches in the epigenome regulating gene expression alteration during brain aging. Interestingly, these factors when manipulated by chemical or genetic strategies successfully reverse the age-related cognitive impairments. In the present article, we review findings from our laboratory and others combined with supporting literary evidences on molecular switches of brain aging and their potential as recovery targets.

Alterations in Mouse Hypothalamic Adipokine Gene Expression and Leptin Signaling following Chronic Spinal Cord Injury and with Advanced Age

PubMed Central

Bigford, Gregory E.; Bracchi-Ricard, Valerie C.; Nash, Mark S.; Bethea, John R.

2012-01-01

Chronic spinal cord injury (SCI) results in an accelerated trajectory of several cardiovascular disease (CVD) risk factors and related aging characteristics, however the molecular mechanisms that are activated have not been explored. Adipokines and leptin signaling are known to play a critical role in neuro-endocrine regulation of energy metabolism, and are now implicated in central inflammatory processes associated with CVD. Here, we examine hypothalamic adipokine gene expression and leptin signaling in response to chronic spinal cord injury and with advanced age. We demonstrate significant changes in fasting-induced adipose factor (FIAF), resistin (Rstn), long-form leptin receptor (LepRb) and suppressor of cytokine-3 (SOCS3) gene expression following chronic SCI and with advanced age. LepRb and Jak2/stat3 signaling is significantly decreased and the leptin signaling inhibitor SOCS3 is significantly elevated with chronic SCI and advanced age. In addition, we investigate endoplasmic reticulum (ER) stress and activation of the uncoupled protein response (UPR) as a biological hallmark of leptin resistance. We observe the activation of the ER stress/UPR proteins IRE1, PERK, and eIF2alpha, demonstrating leptin resistance in chronic SCI and with advanced age. These findings provide evidence for adipokine-mediated inflammatory responses and leptin resistance as contributing to neuro-endocrine dysfunction and CVD risk following SCI and with advanced age. Understanding the underlying mechanisms contributing to SCI and age related CVD may provide insight that will help direct specific therapeutic interventions. PMID:22815920

Computed tomographic colonography for colorectal cancer screening: risk factors for the detection of advanced neoplasia.

PubMed

Hassan, Cesare; Pooler, B Dustin; Kim, David H; Rinaldi, Antonio; Repici, Alessandro; Pickhardt, Perry J

2013-07-15

The objective of this study was to determine whether age, sex, a positive family history of colorectal cancer, and body mass index (BMI) are important predictors of advanced neoplasia in the setting of screening computed tomographic colonography (CTC). Consecutive patients who were referred for first-time screening CTC from 2004 to 2011 at a single medical center were enrolled. Results at pathology were recorded for all patients who underwent polypectomy. Logistic regression was used to identify significant predictor variables for advanced neoplasia (any adenoma ≥ 10 mm or with villous component, high-grade dysplasia, or adenocarcinoma). Odds ratios (ORs) were used to express associations between the study variables (age, sex, BMI, and a positive family history of colorectal cancer) and advanced neoplasia. In total, 7620 patients underwent CTC screening. Of these, 276 patients (3.6%; 95% confidence interval [CI], 3.2%-4.1%) ultimately were diagnosed with advanced neoplasia. At multivariate analysis, age (mean OR per 10-year increase, 1.8; 95% CI, 1.6-2.0) and being a man (OR, 1.7; 95% CI, 1.3-2.2) were independent predictors of advanced neoplasia, whereas BMI and a positive family history of colorectal cancer were not. The number needed to screen to detect 1 case of advanced neoplasia varied from 51 among women aged ≤ 55 years to 10 among men aged >65 years. The number of post-CTC colonoscopies needed to detect 1 case of advanced neoplasia varied from 2 to 4. Age and sex were identified as important independent predictors of advanced neoplasia risk in individuals undergoing screening CTC, whereas BMI and a positive family history of colorectal cancer were not. These results have implications for appropriate patient selection. © 2013 American Cancer Society.

Impact of Fermented Foods on Human Cognitive Function-A Review of Outcome of Clinical Trials.

PubMed

Sivamaruthi, Bhagavathi Sundaram; Kesika, Periyanaina; Chaiyasut, Chaiyavat

2018-05-31

Food is an essential need for all living creatures which provides the energy to maintain life and grow further. Fermentation is a process used to preserve and advance the quality of foods, and those foods are known as fermented foods. Some foods offer health benefits to consumers apart from nutrition, and such foods are called as functional foods. Most functional foods are fermented foods, and the fermenting microorganism plays a precious role in the functional property of the food. Cognitive decline is closely associated with the productivity of an individual and the society. Even though cognitive decline is connected to aging, dietary pattern influences memory, anxiety and other social behaviors. Many scientific studies have explained the link between food habits and cognitive functions by in vitro and in vivo models. The present review compiled the clinical data on the impact of fermented foods on human cognitive function.

Relationship of demographic and health factors to cognition in older adults in the ACTIVE study.

PubMed

Rexroth, Daniel F; Tennstedt, Sharon L; Jones, Richard N; Guey, Lin T; Rebok, George W; Marsiske, Michael M; Xu, Yan; Unverzagt, Frederick W

2013-12-01

Examine the relationship of demographics and health conditions, alone and in combination, on objective measures of cognitive function in a large sample of community-dwelling older adults. Baseline data from 2,782 participants in the Advanced Cognitive Training in Independent and Vital Elderly (ACTIVE) study were used to examine relationships of demographics and health conditions with composite scores of memory, reasoning, and speed of processing. Younger age, increased education, and White race were independently associated with better performance in each cognitive domain after adjusting for gender and health conditions. Male gender, diabetes, and suspected clinical depression were associated with poorer cognitive functioning; suspected clinical depression was associated with lower reasoning and diabetes and history of stroke with slower speed of processing. Age, education, and race are consistently associated with cognitive performance in this sample of older community-dwelling adults. Diabetes, stroke, and suspected clinical depression had independent but weaker effects on cognition.

Reconstruction for chronic Achilles tendinopathy: comparison of flexor hallucis longus (FHL) transfer versus V-Y advancement.

PubMed

Staggers, Jackson R; Smith, Kenneth; de C Netto, Cesar; Naranje, Sameer; Prasad, Krishna; Shah, Ashish

2018-04-01

Several operative techniques exist for Achilles tendinopathy. The purpose of our study was to compare the clinical and functional outcomes of flexor hallucis longus (FHL) transfer and V-Y advancement for the treatment of chronic insertional Achilles tendinopathy. Retrospective chart review from 2010 to 2016 of patients that underwent FHL transfer or V-Y advancement for chronic insertional Achilles tendinopathy. Outcome measures were compared for these two procedures. In total, 46 patients (49 ankles) with a mean age of 55.0 (range 33-73) years. Mean follow-up time 44.7 +/- 25.5 months. FHL group had 21 patients (21 ankles) with 89% satisfaction, 14% complication rate, final VAS of 0.4, final VISA-A of 89.1, subjective strength improvement following surgery of 78%, and 94% would recommend the procedure. V-Y group had 25 patients (28 ankles) with 74% subjective satisfaction, 21% complication rate, final VAS of 1.4, final VISA-A of 78.4, subjective strength improvement following surgery of 67%, and 84% would recommend the procedure. There was no significant difference in any of the results rates between the two groups (p > .05). V-Y advancement is comparable to FHL transfer for the operative management of insertional Achilles tendinopathy. Though our results trend towards less satisfactory results following V-Y advancement, we found high satisfaction rates with similar functional outcomes and complication rates in both operative groups. We suggest considering V-Y advancement as a viable option for the primary treatment of chronic insertional Achilles tendinopathy in patients who may not be an ideal candidate for FHL transfer.

Terrestrial cosmogenic surface exposure dating of glacial and associated landforms in the Ruby Mountains-East Humboldt Range of central Nevada and along the northeastern flank of the Sierra Nevada

DOE PAGES

Wesnousky, Steven G.; Briggs, Richard W.; Caffee, Marc W.; ...

2016-05-07

Deposits near Lamoille in the Ruby Mountains-East Humboldt Range of central Nevada and at Woodfords on the eastern edge of the Sierra Nevada each record two distinct glacial advances. In this paper, we compare independent assessments of terrestrial cosmogenic nuclide (TCN) surface exposure ages for glacial deposits that we have determined to those obtained by others at the two sites. At each site, TCN ages of boulders on moraines of the younger advance are between 15 and 30 ka and may be associated with marine oxygen isotope stage (MIS) 2. At Woodfords, TCN ages of boulders on the moraine ofmore » the older advance are younger than ~ 60 ka and possibly formed during MIS 4, whereas boulders on the correlative outwash surface show ages approaching 140 ka (~ MIS 6). The TCN ages of boulders on older glacial moraine at Woodfords thus appear to severely underestimate the true age of the glacial advance responsible for the deposit. The same is possibly true at Lamoille where clasts sampled from the moraine of the oldest advance have ages ranging between 20 and 40 ka with a single outlier age of ~ 80 ka. The underestimations are attributed to the degradation and denudation of older moraine crests. Noting that boulder ages on the older advances at each site overlap significantly with MIS 2. Finally, we speculate that erosion of the older moraines has been episodic, with a pulse of denudation accompanying the inception of MIS 2 glaciation.« less

Terrestrial cosmogenic surface exposure dating of glacial and associated landforms in the Ruby Mountains-East Humboldt Range of central Nevada and along the northeastern flank of the Sierra Nevada

USGS Publications Warehouse

Wesnousky, Steven G.; Briggs, Richard; Caffee, Marc W.; Ryerson, Rick J.; Finkel, Robert C.; Owen, Lewis A.

2016-01-01

Deposits near Lamoille in the Ruby Mountains-East Humboldt Range of central Nevada and at Woodfords on the eastern edge of the Sierra Nevada each record two distinct glacial advances. We compare independent assessments of terrestrial cosmogenic nuclide (TCN) surface exposure ages for glacial deposits that we have determined to those obtained by others at the two sites. At each site, TCN ages of boulders on moraines of the younger advance are between 15 and 30 ka and may be associated with marine oxygen isotope stage (MIS) 2. At Woodfords, TCN ages of boulders on the moraine of the older advance are younger than ~ 60 ka and possibly formed during MIS 4, whereas boulders on the correlative outwash surface show ages approaching 140 ka (~ MIS 6). The TCN ages of boulders on older glacial moraine at Woodfords thus appear to severely underestimate the true age of the glacial advance responsible for the deposit. The same is possibly true at Lamoille where clasts sampled from the moraine of the oldest advance have ages ranging between 20 and 40 ka with a single outlier age of ~ 80 ka. The underestimations are attributed to the degradation and denudation of older moraine crests. Noting that boulder ages on the older advances at each site overlap significantly with MIS 2. We speculate that erosion of the older moraines has been episodic, with a pulse of denudation accompanying the inception of MIS 2 glaciation.

Oxidants produced by methylglyoxal-modified collagen trigger ER stress and apoptosis in skin fibroblasts.

PubMed

Nowotny, Kerstin; Castro, José Pedro; Hugo, Martín; Braune, Sabine; Weber, Daniela; Pignitter, Marc; Somoza, Veronika; Bornhorst, Julia; Schwerdtle, Tanja; Grune, Tilman

2018-05-20

Methylglyoxal (MG), a highly reactive dicarbonyl, interacts with proteins to form advanced glycation end products (AGEs). AGEs include a variety of compounds which were shown to have damaging potential and to accumulate in the course of different conditions such as diabetes mellitus and aging. After confirming collagen as a main target for MG modifications in vivo within the extracellular matrix, we show here that MG-collagen disrupts fibroblast redox homeostasis and induces endoplasmic reticulum (ER) stress and apoptosis. In particular, MG-collagen-induced apoptosis is associated with the activation of the PERK-eIF2α pathway and caspase-12. MG-collagen contributes to altered redox homeostasis by directly generating hydrogen peroxide and oxygen-derived free radicals. The induction of ER stress in human fibroblasts was confirmed using collagen extracts isolated from old mice in which MG-derived AGEs were enriched. In conclusion, MG-derived AGEs represent one factor contributing to diminished fibroblast function during aging. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Delivery strategies for treatment of age-related ocular diseases: From a biological understanding to biomaterial solutions.

PubMed

Delplace, Vianney; Payne, Samantha; Shoichet, Molly

2015-12-10

Age-related ocular diseases, such as age-related macular degeneration (AMD), diabetic retinopathy, and glaucoma, result in life-long functional deficits and enormous global health care costs. As the worldwide population ages, vision loss has become a major concern for both economic and human health reasons. Due to recent research into biomaterials and nanotechnology major advances have been gained in the field of ocular delivery. This review provides a summary and discussion of the most recent strategies employed for the delivery of both drugs and cells to the eye to treat a variety of age-related diseases. It emphasizes the current challenges and limitations to ocular delivery and how the use of innovative materials can overcome these issues and ultimately provide treatment for age-related degeneration and regeneration of lost tissues. This review also provides critical considerations and an outlook for future studies in the field of ophthalmic delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

Aging and Parkinson's disease: Different sides of the same coin?

PubMed

Collier, Timothy J; Kanaan, Nicholas M; Kordower, Jeffrey H

2017-07-01

Despite abundant epidemiological evidence in support of aging as the primary risk factor for PD, biological correlates of a connection have been elusive. In this article, we address the following question: does aging represent biology accurately characterized as pre-PD? We present evidence from our work on midbrain dopamine neurons of aging nonhuman primates that demonstrates that markers of known correlates of dopamine neuron degeneration in PD, including impaired proteasome/lysosome function, oxidative/nitrative damage, and inflammation, all increase with advancing age and are exaggerated in the ventral tier substantia nigra dopamine neurons most vulnerable to degeneration in PD. Our findings support the view that aging-related changes in the dopamine system approach the biological threshold for parkinsonism, actively producing a vulnerable pre-parkinsonian state. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Advanced Computational Methods for Optimization of Non-Periodic Inspection Intervals for Aging Infrastructure

DTIC Science & Technology

2017-01-05

AFRL-AFOSR-JP-TR-2017-0002 Advanced Computational Methods for Optimization of Non-Periodic Inspection Intervals for Aging Infrastructure Manabu...Computational Methods for Optimization of Non-Periodic Inspection Intervals for Aging Infrastructure 5a.  CONTRACT NUMBER 5b.  GRANT NUMBER FA2386...UNLIMITED: PB Public Release 13. SUPPLEMENTARY NOTES 14. ABSTRACT This report for the project titled ’Advanced Computational Methods for Optimization of

Impact of androgen and dietary advanced glycation end products on female rat liver.

PubMed

Palioura, Eleni; Palimeri, Sotiria; Piperi, Christina; Sakellariou, Stratigoula; Kandaraki, Eleni; Sergentanis, Theodoros; Levidou, Georgia; Agrogiannis, George; Papalois, Apostolos; Korkolopoulou, Penelope; Diamanti-Kandarakis, Evanthia; Papavassiliou, Athanasios G

2015-01-01

Advanced glycation end products (AGEs) have been related to a wide range of liver disorders including hyperandrogenic states such as the Polycystic Ovary Syndrome (PCOS). The aim of the present study is to evaluate the potential impact of dietary glycotoxins exposure and androgen excess on hepatic histology and biochemistry in an androgenized female rat model. The study population consisted of 80 female Wistar rats, divided in 3 groups, a group of prepubertal (Group A, n=30) and adult rats (Group B, n=20) that were androgenized via subcutaneous implantation of dihydrotestosterone-containing pellets as well as a group of adult non-androgenized rodents (Group C, n=30). All groups were randomly assigned either to a high-AGE or low-AGE diet for 3 months. Rats fed with a high-AGE diet exhibited significantly elevated levels of gamma-glutamyl transferase (x03B3;GT) (p≤0.0002) and indices of AGE immunostaining in liver tissue (p<0.01) when compared to the respective low-AGE group, while aspartate aminotransferase (AST) levels were affected only in non-androgenized animals (p=0.0002). Androgenization per se constitutes an aggravating factor as demonstrated by the elevated x03B3;GT levels in adult androgenized animals compared to non-androgenized, independent of diet content (p=0.0002) and by the elevated AST and alanine aminotransferase (ALT) levels in low-AGE subgroups (adult androgenized vs. non-androgenized, p=0.0002) followed by increased immunohistochemical AGE deposition in hepatocytes of the latter categories (p=0.0007). The present study suggests that androgens and glycotoxins may contribute synergistically to distort hepatic physiology and function as observed in hyperandrogenic conditions. © 2015 The Author(s) Published by S. Karger AG, Basel.

Electronic Assessment of Physical Decline in Geriatric Cancer Patients.

PubMed

Fallahzadeh, Ramin; Ghasemzadeh, Hassan; Shahrokni, Armin

2018-03-08

The purpose of this review is to explore state-of-the-art remote monitoring and emerging new sensing technologies for in-home physical assessment and their application/potential in cancer care. In addition, we discuss the main functional and non-functional requirements and research challenges of employing such technologies in real-world settings. With rapid growth in aging population, effective and efficient patient care has become an important topic. Advances in remote monitoring and in its forefront in-home physical assessment technologies play a fundamental role in reducing the cost and improving the quality of care by complementing the traditional in-clinic healthcare. However, there is a gap in medical research community regarding the applicability and potential outcomes of such systems. While some studies reported positive outcomes using remote assessment technologies, such as web/smart phone-based self-reports and wearable sensors, the cancer research community is still lacking far behind. Thorough investigation of more advanced technologies in cancer care is warranted.

Recent trends in electrochemical biosensors of superoxide dismutases.

PubMed

Balamurugan, Murugesan; Santharaman, Paulraj; Madasamy, Thangamuthu; Rajesh, Seenivasan; Sethy, Niroj Kumar; Bhargava, Kalpana; Kotamraju, Srigiridhar; Karunakaran, Chandran

2018-09-30

Superoxide dismutases (SODs), a family of ubiquitous enzymes, provide essential protection to biological systems against uncontrolled reactions with oxygen- and nitrogen- based radical species. We review first the role of SODs in oxidative stress and the other biological functions such as peroxidase, nitrite oxidase, thiol oxidase activities etc., implicating its role in neurodegenerative, cardiovascular diseases, and ageing. Also, this review focuses on the development of electrochemical label-free immunosensor for SOD1 and the recent advances in biosensing assay methods based on their catalytic and biological functions with various substrates including reactive oxygen species (superoxide anion radical, hydrogen peroxide), nitric oxide metabolites (nitrite, nitrate) and thiols using thiol oxidase activity. Furthermore, we emphasize the progress made in improving the detection performance through incorporation of the SOD into conducting polymers and nanocomposite matrices. In addition, we address the potential opportunities, challenges, advances in electrochemical-sensing platforms and development of portable analyzer for point-of-care applications. Copyright © 2018 Elsevier B.V. All rights reserved.

Mutations in WNT1 Cause Different Forms of Bone Fragility

PubMed Central

Keupp, Katharina; Beleggia, Filippo; Kayserili, Hülya; Barnes, Aileen M.; Steiner, Magdalena; Semler, Oliver; Fischer, Björn; Yigit, Gökhan; Janda, Claudia Y.; Becker, Jutta; Breer, Stefan; Altunoglu, Umut; Grünhagen, Johannes; Krawitz, Peter; Hecht, Jochen; Schinke, Thorsten; Makareeva, Elena; Lausch, Ekkehart; Cankaya, Tufan; Caparrós-Martín, José A.; Lapunzina, Pablo; Temtamy, Samia; Aglan, Mona; Zabel, Bernhard; Eysel, Peer; Koerber, Friederike; Leikin, Sergey; Garcia, K. Christopher; Netzer, Christian; Schönau, Eckhard; Ruiz-Perez, Victor L.; Mundlos, Stefan; Amling, Michael; Kornak, Uwe; Marini, Joan; Wollnik, Bernd

2013-01-01

We report that hypofunctional alleles of WNT1 cause autosomal-recessive osteogenesis imperfecta, a congenital disorder characterized by reduced bone mass and recurrent fractures. In consanguineous families, we identified five homozygous mutations in WNT1: one frameshift mutation, two missense mutations, one splice-site mutation, and one nonsense mutation. In addition, in a family affected by dominantly inherited early-onset osteoporosis, a heterozygous WNT1 missense mutation was identified in affected individuals. Initial functional analysis revealed that altered WNT1 proteins fail to activate canonical LRP5-mediated WNT-regulated β-catenin signaling. Furthermore, osteoblasts cultured in vitro showed enhanced Wnt1 expression with advancing differentiation, indicating a role of WNT1 in osteoblast function and bone development. Our finding that homozygous and heterozygous variants in WNT1 predispose to low-bone-mass phenotypes might advance the development of more effective therapeutic strategies for congenital forms of bone fragility, as well as for common forms of age-related osteoporosis. PMID:23499309

Metabolism of AGEs – Bacterial AGEs Are Degraded by Metallo-Proteases

PubMed Central

Cohen-Or, Ifat; Katz, Chen; Ron, Eliora Z.

2013-01-01

Advanced Glycation End Products (AGEs) are the final products of non-enzymatic protein glycation that results in loss of protein structure and function. We have previously shown that in E. coli AGEs are continually formed as high-molecular weight protein complexes. Moreover, we showed that AGEs are removed from the cells by an active, ATP-dependent secretion and that these secreted molecules have low molecular weight. Taken together, these results indicate that E. coli contains a fraction of low molecular weight AGEs, in addition to the high-molecular weight AGEs. Here we show that the low-molecular weight AGEs originate from high-molecular weight AGEs by proteolytic degradation. Results of in-vitro and in vivo experiments indicated that this degradation is carried out not by the major ATP-dependent proteases that are responsible for the main part of bacterial protein quality control but by an alternative metal-dependent proteolysis. This proteolytic reaction is essential for the further secretion of AGEs from the cells. As the biochemical reactions involving AGEs are not yet understood, the implication of a metalloprotease in breakdown of high molecular weight AGEs and their secretion constitutes an important step in the understanding of AGEs metabolism. PMID:24130678

Metabolism of AGEs--bacterial AGEs are degraded by metallo-proteases.

PubMed

Cohen-Or, Ifat; Katz, Chen; Ron, Eliora Z

2013-01-01

Advanced Glycation End Products (AGEs) are the final products of non-enzymatic protein glycation that results in loss of protein structure and function. We have previously shown that in E. coli AGEs are continually formed as high-molecular weight protein complexes. Moreover, we showed that AGEs are removed from the cells by an active, ATP-dependent secretion and that these secreted molecules have low molecular weight. Taken together, these results indicate that E. coli contains a fraction of low molecular weight AGEs, in addition to the high-molecular weight AGEs. Here we show that the low-molecular weight AGEs originate from high-molecular weight AGEs by proteolytic degradation. Results of in-vitro and in vivo experiments indicated that this degradation is carried out not by the major ATP-dependent proteases that are responsible for the main part of bacterial protein quality control but by an alternative metal-dependent proteolysis. This proteolytic reaction is essential for the further secretion of AGEs from the cells. As the biochemical reactions involving AGEs are not yet understood, the implication of a metalloprotease in breakdown of high molecular weight AGEs and their secretion constitutes an important step in the understanding of AGEs metabolism.

Redox theory of aging: implications for health and disease

PubMed Central

Go, Young-Mi; Jones, Dean P.

2017-01-01

Genetics ultimately defines an individual, yet the phenotype of an adult is extensively determined by the sequence of lifelong exposures, termed the exposome. The redox theory of aging recognizes that animals evolved within an oxygen-rich environment, which created a critical redox interface between an organism and its environment. Advances in redox biology show that redox elements are present throughout metabolic and structural systems and operate as functional networks to support the genome in adaptation to environmental resources and challenges during lifespan. These principles emphasize that physical and functional phenotypes of an adult are determined by gene–environment interactions from early life onward. The principles highlight the critical nature of cumulative exposure memories in defining changes in resilience progressively during life. Both plasma glutathione and cysteine systems become oxidized with aging, and the recent finding that cystine to glutathione ratio in human plasma predicts death in coronary artery disease (CAD) patients suggests this could provide a way to measure resilience of redox networks in aging and disease. The emerging concepts of cumulative gene–environment interactions warrant focused efforts to elucidate central mechanisms by which exposure memory governs health and etiology, onset and progression of disease. PMID:28667066

Advanced myopia, prevalence and incidence analysis.

PubMed

Greene, Peter R; Greene, Judith M

2018-04-01

Various high-percentage high-incidence medical conditions, acute or chronic, start at a particular age of onset t1 (years), accumulate or progress rapidly, with a system time constant t0 (years), typically from 1 week to 5 years, and then level off at a plateau level [Formula: see text], ultimately affecting 10-95% of the population. This report investigates the prevalence and incidence functions for myopia and high myopia as a function of age. Fundamental prevalence versus time and incidence versus time results allow continuous prediction of myopia and high myopia population fractions as a function of age. This is a retrospective study. Nine reports are calculated with N = 444,600 subjects. There were no interventions other than usual regular eye examinations and subsequent indicated refraction change. The main result is continuous prediction of myopia prevalence-time data along with incidence rate data (%/year), age of onset (years), system plateau level, and system time constant (years). These parameters apply to progressive myopia and high myopia (R < -6 D), useful over several decades. The primary finding of this research is that the prevalence ratio of high myopes (R < -6.0 D) to common myopes is expected to increase from 15% entering college to 45% or more after college and graduate school. These statistics are particularly relevant to the many years of study required by M.D., Ph.D., and M.D./Ph.D. programs.

Deciphering death: a commentary on Gompertz (1825) ‘On the nature of the function expressive of the law of human mortality, and on a new mode of determining the value of life contingencies’

PubMed Central

Kirkwood, Thomas B. L.

2015-01-01

In 1825, the actuary Benjamin Gompertz read a paper, ‘On the nature of the function expressive of the law of human mortality, and on a new mode of determining the value of life contingencies’, to the Royal Society in which he showed that over much of the adult human lifespan, age-specific mortality rates increased in an exponential manner. Gompertz's work played an important role in shaping the emerging statistical science that underpins the pricing of life insurance and annuities. Latterly, as the subject of ageing itself became the focus of scientific study, the Gompertz model provided a powerful stimulus to examine the patterns of death across the life course not only in humans but also in a wide range of other organisms. The idea that the Gompertz model might constitute a fundamental ‘law of mortality’ has given way to the recognition that other patterns exist, not only across the species range but also in advanced old age. Nevertheless, Gompertz's way of representing the function expressive of the pattern of much of adult mortality retains considerable relevance for studying the factors that influence the intrinsic biology of ageing. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society. PMID:25750242

Deciphering death: a commentary on Gompertz (1825) 'On the nature of the function expressive of the law of human mortality, and on a new mode of determining the value of life contingencies'.

PubMed

Kirkwood, Thomas B L

2015-04-19

In 1825, the actuary Benjamin Gompertz read a paper, 'On the nature of the function expressive of the law of human mortality, and on a new mode of determining the value of life contingencies', to the Royal Society in which he showed that over much of the adult human lifespan, age-specific mortality rates increased in an exponential manner. Gompertz's work played an important role in shaping the emerging statistical science that underpins the pricing of life insurance and annuities. Latterly, as the subject of ageing itself became the focus of scientific study, the Gompertz model provided a powerful stimulus to examine the patterns of death across the life course not only in humans but also in a wide range of other organisms. The idea that the Gompertz model might constitute a fundamental 'law of mortality' has given way to the recognition that other patterns exist, not only across the species range but also in advanced old age. Nevertheless, Gompertz's way of representing the function expressive of the pattern of much of adult mortality retains considerable relevance for studying the factors that influence the intrinsic biology of ageing. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.

Inflammation and premature aging in advanced chronic kidney disease.

PubMed

Kooman, Jeroen P; Dekker, Marijke J; Usvyat, Len A; Kotanko, Peter; van der Sande, Frank M; Schalkwijk, Casper G; Shiels, Paul G; Stenvinkel, Peter

2017-10-01

Systemic inflammation in end-stage renal disease is an established risk factor for mortality and a catalyst for other complications, which are related to a premature aging phenotype, including muscle wasting, vascular calcification, and other forms of premature vascular disease, depression, osteoporosis, and frailty. Uremic inflammation is also mechanistically related to mechanisms involved in the aging process, such as telomere shortening, mitochondrial dysfunction, and altered nutrient sensing, which can have a direct effect on cellular and tissue function. In addition to uremia-specific causes, such as abnormalities in the phosphate-Klotho axis, there are remarkable similarities between the pathophysiology of uremic inflammation and so-called "inflammaging" in the general population. Potentially relevant, but still somewhat unexplored in this respect, are abnormal or misplaced protein structures, as well as abnormalities in tissue homeostasis, which evoke danger signals through damage-associated molecular patterns, as well as the senescence-associated secretory phenotype. Systemic inflammation, in combination with the loss of kidney function, can impair the resilience of the body to external and internal stressors by reduced functional and structural tissue reserves, and by impairing normal organ crosstalk, thus providing an explanation for the greatly increased risk of homeostatic breakdown in this population. In this review, the relationship between uremic inflammation and a premature aging phenotype, as well as potential causes and consequences, are discussed. Copyright © 2017 the American Physiological Society.

CE: Can Your Older Patients Drive Safely?

PubMed

Staplin, Loren; Lococo, Kathy H; Mastromatto, Tia; Sifrit, Kathy J; Trazzera, Kathleen M

2017-09-01

: In many areas of the world, driving is an essential part of life and for reasons of comfort, convenience, and security remains the primary mode of transportation among older adults. Both normal aging and diseases that are more prevalent in advanced age can substantially reduce older drivers' functional abilities, elevating their risk of involvement in motor vehicle accidents and serious injury or death. Identifying and intervening with older drivers at increased crash risk is an important aspect of preventive medicine. The authors discuss the specific driving risks adults face as they age and how nurses can raise older patients' awareness of these risks. They also discuss the importance of connecting older adults to community resources that may help them continue driving safely for a longer period or find alternative transportation options.

Glenohumeral instability and rotator cuff tear.

PubMed

Porcellini, Giuseppe; Caranzano, Francesco; Campi, Fabrizio; Pellegrini, Andrea; Paladini, Paolo

2011-12-01

The prevalence of rotator cuff tears after traumatic dislocation increases with advancing age, a likely consequence of the age-associated deterioration of the structure and mechanical properties of the tendons of the rotator cuff. These are the effective stabilizers of the glenohumeral joint, compressing the humeral head in the 3-dimensional concavity of the glenohumeral joint. It is impossible to establish whether a lesion of the capsular-labrum complex or of the rotator cuff causes or follows a dislocation, regardless of whether it is anterior or posterior. A peripheral nerve or a brachial plexus injury can be associated with tendon lesion and instability, developing the "terrible triad" of the shoulder. Both conservative and surgical management are possible, and surgeons must choose the most appropriate management modality according to the biologic age, functional demands, and type of lesion.

Mobile Health Applications to Promote Active and Healthy Ageing

PubMed Central

Helbostad, Jorunn L.; Vereijken, Beatrix; Becker, Clemens; Todd, Chris; Taraldsen, Kristin; Pijnappels, Mirjam; Aminian, Kamiar; Mellone, Sabato

2017-01-01

The European population is ageing, and there is a need for health solutions that keep older adults independent longer. With increasing access to mobile technology, such as smartphones and smartwatches, the development and use of mobile health applications is rapidly growing. To meet the societal challenge of changing demography, mobile health solutions are warranted that support older adults to stay healthy and active and that can prevent or delay functional decline. This paper reviews the literature on mobile technology, in particular wearable technology, such as smartphones, smartwatches, and wristbands, presenting new ideas on how this technology can be used to encourage an active lifestyle, and discusses the way forward in order further to advance development and practice in the field of mobile technology for active, healthy ageing. PMID:28335475

Mobile Health Applications to Promote Active and Healthy Ageing.

PubMed

Helbostad, Jorunn L; Vereijken, Beatrix; Becker, Clemens; Todd, Chris; Taraldsen, Kristin; Pijnappels, Mirjam; Aminian, Kamiar; Mellone, Sabato

2017-03-18

The European population is ageing, and there is a need for health solutions that keep older adults independent longer. With increasing access to mobile technology, such as smartphones and smartwatches, the development and use of mobile health applications is rapidly growing. To meet the societal challenge of changing demography, mobile health solutions are warranted that support older adults to stay healthy and active and that can prevent or delay functional decline. This paper reviews the literature on mobile technology, in particular wearable technology, such as smartphones, smartwatches, and wristbands, presenting new ideas on how this technology can be used to encourage an active lifestyle, and discusses the way forward in order further to advance development and practice in the field of mobile technology for active, healthy ageing.

Positive associations between physical and cognitive performance measures in fibromyalgia.

PubMed

Cherry, Barbara J; Zettel-Watson, Laura; Chang, Jennifer C; Shimizu, Renee; Rutledge, Dana N; Jones, C Jessie

2012-01-01

To investigate the associations between perceived physical function (self-report) and physical and cognitive performance (objective assessments) in persons with fibromyalgia (FM). Correlational study. Exercise testing laboratory in Southern California. Community-residing ambulatory adults meeting the American College of Rheumatology 1990 criteria for FM (N=68; mean age, 59.5y). Not applicable. Composite Physical Function scale, Senior Fitness Test (3 items), Fullerton Advanced Balance scale, 30-foot walk, Trail Making Test parts A and B, Digit Symbol Substitution Test, a composite score of these 3 cognitive measures, attention/executive function composite, processing speed composite, problem solving, inhibition, and episodic memory composite. Hierarchical regression analyses showed that after controlling for age and FM symptoms, better physical performance (based on assessments, not self-report) was associated with higher cognitive function in attention/executive function, processing speed, problem solving, and inhibition. Researchers should continue to investigate the relationship between physical and cognitive function in both clinical and nonclinical populations, as well as explore changes across time. Because physical activity has been associated with neural improvements, further research may identify whether particular mechanisms, such as neurogenesis, synaptogenesis, or changes in inflammatory marker levels, are involved. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.