Advanced glycation end-products: a biological consequence of lifestyle contributing to cancer disparity.

PubMed

Turner, David P

2015-05-15

Low income, poor diet, obesity, and a lack of exercise are interrelated lifestyle factors that can profoundly alter our biologic make up to increase cancer risk, growth, and development. We recently reported a potential mechanistic link between carbohydrate-derived metabolites and cancer, which may provide a biologic consequence of lifestyle that can directly affect tumor biology. Advanced glycation end-products (AGE) are reactive metabolites produced as a by-product of sugar metabolism. Failure to remove these highly reactive metabolites can lead to protein damage, aberrant cell signaling, increased stress responses, and decreased genetic fidelity. Critically, AGE accumulation is also directly affected by our lifestyle choices and shows a race-specific, tumor-dependent pattern of accumulation in cancer patients. This review will discuss the contribution of AGEs to the cancer phenotype, with a particular emphasis on their biologic links with the socioeconomic and environmental risk factors that drive cancer disparity. Given the potential benefits of lifestyle changes and the potential biologic role of AGEs in promoting cancer, opportunities exist for collaborations affecting basic, translational, epidemiologic, and cancer prevention initiatives. ©2015 American Association for Cancer Research.

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.

Subacute ibuprofen treatment rescues the synaptic and cognitive deficits in advanced-aged mice

PubMed Central

Rogers, Justin T.; Liu, Chia-Chen; Zhao, Na; Wang, Jian; Putzke, Travis; Yang, Longyu; Shinohara, Mitsuru; Fryer, John D.; Kanekiyo, Takahisa; Bu, Guojun

2017-01-01

Aging is accompanied by increased neuroinflammation, synaptic dysfunction and cognitive deficits both in rodents and humans, yet the onset and progression of these deficits throughout the life span remain unknown. These aging-related deficits affect the quality of life and present challenges to our aging society. Here, we defined age-dependent and progressive impairments of synaptic and cognitive functions and showed that reducing astrocyte-related neuroinflammation through anti-inflammatory drug treatment in aged mice reverses these events. By comparing young (3 months), middle-aged (18 months), aged (24 months) and advanced-aged wild-type mice (30 months), we found that the levels of an astrocytic marker, GFAP, progressively increased after 18 months of age, which preceded the decreases of the synaptic marker PSD-95. Hippocampal long-term potentiation (LTP) was also suppressed in an age-dependent manner, where significant deficits were observed after 24 months of age. Fear conditioning tests demonstrated that associative memory in the context and cued conditions was decreased starting at the ages of 18 and 30 months, respectively. When the mice were tested on hidden platform water maze, spatial learning memory was significantly impaired after 24 months of age. Importantly, subacute treatment with the anti-inflammatory drug ibuprofen suppressed astrocyte activation, and restored synaptic plasticity and memory function in advanced-aged mice. These results support the critical contribution of aging-related inflammatory responses to hippocampal-dependent cognitive function and synaptic plasticity, in particular during advanced aging. Our findings provide strong evidence that suppression of neuroinflammation could be a promising treatment strategy to preserve cognition during aging. PMID:28254590

Uremic Toxicity of Advanced Glycation End Products in CKD

PubMed Central

Stinghen, Andréa E.M.; Massy, Ziad A.; Vlassara, Helen; Striker, Gary E.

2016-01-01

Advanced glycation end products (AGEs), a heterogeneous group of compounds formed by nonenzymatic glycation reactions between reducing sugars and amino acids, lipids, or DNA, are formed not only in the presence of hyperglycemia, but also in diseases associated with high levels of oxidative stress, such as CKD. In chronic renal failure, higher circulating AGE levels result from increased formation and decreased renal clearance. Interactions between AGEs and their receptors, including advanced glycation end product–specific receptor (RAGE), trigger various intracellular events, such as oxidative stress and inflammation, leading to cardiovascular complications. Although patients with CKD have a higher burden of cardiovascular disease, the relationship between AGEs and cardiovascular disease in patients with CKD is not fully characterized. In this paper, we review the various deleterious effects of AGEs in CKD that lead to cardiovascular complications and the role of these AGEs in diabetic nephropathy. We also discuss potential pharmacologic approaches to circumvent these deleterious effects by reducing exogenous and endogenous sources of AGEs, increasing the breakdown of existing AGEs, or inhibiting AGE-induced inflammation. Finally, we speculate on preventive and therapeutic strategies that focus on the AGE-RAGE axis to prevent vascular complications in patients with CKD. PMID:26311460

beta-Aminoalcohols as Potential Reactivators of Aged Sarin-/Soman-Inhibited Acetylcholinesterase

DTIC Science & Technology

2017-02-08

This approach includes high - quality quantum mechanical/molecular mechanical calcula- tions, providing reliable reactivation steps and energetics...I. V. Khavrutskii Department of Defense Biotechnology High Performance Computing Software Applications Institute Telemedicine and Advanced...b] Dr. A. Wallqvist Department of Defense Biotechnology High Performance Computing Software Applications Institute Telemedicine and Advanced

Paternal age at childbirth and eating disorders in offspring.

PubMed

Javaras, K N; Rickert, M E; Thornton, L M; Peat, C M; Baker, J H; Birgegård, A; Norring, C; Landén, M; Almqvist, C; Larsson, H; Lichtenstein, P; Bulik, C M; D'Onofrio, B M

2017-02-01

Advanced paternal age at childbirth is associated with psychiatric disorders in offspring, including schizophrenia, bipolar disorder and autism. However, few studies have investigated paternal age's relationship with eating disorders in offspring. In a large, population-based cohort, we examined the association between paternal age and offspring eating disorders, and whether that association remains after adjustment for potential confounders (e.g. parental education level) that may be related to late/early selection into fatherhood and to eating disorder incidence. Data for 2 276 809 individuals born in Sweden 1979-2001 were extracted from Swedish population and healthcare registers. The authors used Cox proportional hazards models to examine the effect of paternal age on the first incidence of healthcare-recorded anorexia nervosa (AN) and all eating disorders (AED) occurring 1987-2009. Models were adjusted for sex, birth order, maternal age at childbirth, and maternal and paternal covariates including country of birth, highest education level, and lifetime psychiatric and criminal history. Even after adjustment for covariates including maternal age, advanced paternal age was associated with increased risk, and younger paternal age with decreased risk, of AN and AED. For example, the fully adjusted hazard ratio for the 45+ years (v. the 25-29 years) paternal age category was 1.32 [95% confidence interval (CI) 1.14-1.53] for AN and 1.26 (95% CI 1.13-1.40) for AED. In this large, population-based cohort, paternal age at childbirth was positively associated with eating disorders in offspring, even after adjustment for potential confounders. Future research should further explore potential explanations for the association, including de novo mutations in the paternal germline.

Implication of advanced glycation end products (Ages) and their receptor (Rage) on myocardial contractile and mitochondrial functions.

PubMed

Neviere, Remi; Yu, Yichi; Wang, Lei; Tessier, Frederic; Boulanger, Eric

2016-08-01

Advanced glycation end products (AGEs) play an important role for the development and/or progression of cardiovascular diseases, mainly through induction of oxidative stress and inflammation. AGEs are a heterogeneous group of molecules formed by non-enzymatic reaction of reducing sugars with amino acids of proteins, lipids and nucleic acids. AGEs are mainly formed endogenously, while recent studies suggest that diet constitutes an important exogenous source of AGEs. The presence and accumulation of AGEs in various cardiac cell types affect extracellular and intracellular structure and function. AGEs contribute to a variety of microvascular and macrovascular complications through the formation of cross-links between molecules in the basement membrane of the extracellular matrix and by engaging the receptor for advanced glycation end products (RAGE). Activation of RAGE by AGEs causes up regulation of the transcription factor nuclear factor-κB and its target genes. of the RAGE engagement stimulates oxidative stress, evokes inflammatory and fibrotic reactions, which all contribute to the development and progression of devastating cardiovascular disorders. This review discusses potential targets of glycation in cardiac cells, and underlying mechanisms that lead to heart failure with special interest on AGE-induced mitochondrial dysfunction in the myocardium.

Insights into neurogenesis and aging: potential therapy for degenerative disease?

PubMed Central

Marr, Robert A; Thomas, Rosanne M; Peterson, Daniel A

2010-01-01

Neurogenesis is the process by which new neural cells are generated from a small population of multipotent stem cells in the adult CNS. This natural generation of new cells is limited in its regenerative capabilities and also declines with age. The use of stem cells in the treatment of neurodegenerative disease may hold great potential; however, the age-related incidence of many CNS diseases coincides with reduced neurogenesis. This review concisely summarizes current knowledge related to adult neurogenesis and its alteration with aging and examines the feasibility of using stem cell and gene therapies to combat diseases of the CNS with advancing age. PMID:20806052

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

Dietary Advanced Glycation End Products and their Potential role in Cardiometabolic Disease in Children

PubMed Central

Gupta, Anshu; Uribarri, Jaime

2016-01-01

The rising incidence of obesity and metabolic diseases such as diabetes mellitus and cardiovascular disease in adolescents and young adults is of grave concern. Recent studies favor role of lifestyle factors over genetics in perpetuation of inflammation, insulin resistance and oxidative stress, which are pathophysiologic processes common to above diseases; furthermore, the importance of dietary factors in addition to calories and physical activity in these processes is being increasingly recognized. Advanced glycation end products (AGEs) belong to a category of dietary oxidants which have been implicated in the pathogenesis of inflammation, oxidative stress, insulin resistance, β-cell failure and endothelial dysfunction. This paper reviews the studies of AGEs with focus on their role in cardiometabolic disease in children. A MEDLINE search was performed using the keywords childhood obesity, metabolic syndrome and advanced glycation end products. Articles published in English between 1975 and 2015 and their references were reviewed. While most studies were performed in adults, a few studies also demonstrated a role of AGEs in obesity and associated cardiometabolic comorbidities in the younger population. Available evidence suggests involvement of AGEs in pathogenesis of adiposity and β-cell failure in children. Potential areas for further research to investigate underlying mechanisms are proposed. PMID:27008270

DEVELOPING THE TRANSDISCIPLINARY AGING RESEARCH AGENDA: NEW DEVELOPMENTS IN BIG DATA.

PubMed

Callaghan, Christian William

2017-07-19

In light of dramatic advances in big data analytics and the application of these advances in certain scientific fields, new potentialities exist for breakthroughs in aging research. Translating these new potentialities to research outcomes for aging populations, however, remains a challenge, as underlying technologies which have enabled exponential increases in 'big data' have not yet enabled a commensurate era of 'big knowledge,' or similarly exponential increases in biomedical breakthroughs. Debates also reveal differences in the literature, with some arguing big data analytics heralds a new era associated with the 'end of theory' or which makes the scientific method obsolete, where correlation supercedes causation, whereby science can advance without theory and hypotheses testing. On the other hand, others argue theory cannot be subordinate to data, no matter how comprehensive data coverage can ultimately become. Given these two tensions, namely between exponential increases in data absent exponential increases in biomedical research outputs, and between the promise of comprehensive data coverage and data-driven inductive versus theory-driven deductive modes of enquiry, this paper seeks to provide a critical review of certain theory and literature that offers useful perspectives of certain developments in big data analytics and their theoretical implications for aging research. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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...

Coptis chinensis Polysaccharides Inhibit Advanced Glycation End Product Formation.

PubMed

Yang, Ye; Li, Yun; Yin, Dengke; Chen, Song; Gao, Xiangdong

2016-06-01

Coptis chinensis Franch (Huanglian) is commonly used to treat diabetes in China. In this study, the effects of the C. chinensis Franch polysaccharides (CCP) on advanced glycation end product (AGE) formation in vitro and in streptozotocin-induced diabetic mice were investigated. CCP significantly inhibited all the three periods of nonenzymatic protein glycation in vitro, including Amadori product, dicarbonyl compound, and AGE formation (P < .01). In diabetic mice, the administration of CCP not only improved both bodyweight and serum insulin and decreased fasting blood glucose and glycated serum protein concentrations but also decreased the AGE accumulations and morphological abnormalities in pancreas and liver. The inhibitory effects of CCP on AGE formation afford a potential therapeutic use in the prevention and treatment of diabetes.

Should Andover College Add a Distance Education Program?

ERIC Educational Resources Information Center

Woodbury, Amanda L.

Adding distance education would provide Andover College with unlimited growth and potentially increased revenue. Andover has three groups of students: nontraditional evening students aged 25-59 who want a degree to advance in their careers; traditional students aged 17-24; and certificate candidates. A distance program would make classes more…

[AGEs and RAGE - advanced glycation end-products and their receptor in questions and answers].

PubMed

Kalousová, Marta; Zima, Tomáš

2014-09-01

Advanced glycation end products (AGEs) play an important role in the pathogenesis of chronic diseases and their complications, especially diabetic complications, atherosclerosis, complications of chronic kidney diseases and neurodegenerative diseases. These substances are formed via non-enzymatic glycation and their formation is potentiated in case of carbonyl stress. AGEs are represented by a heterogeneous group of compounds, e.g. carboxymethyllysine, pentosine, methylglyoxallysin dimer, vesperlysine, imidazolones etc. AGEs can modify proteins and so change their physical and chemical properties and can act also via specific receptors, among them RAGE (receptor for advanced glycation end products) is the best known but not the unique one. RAGE is a multiligand receptor capable to bind also HMGB1 (high mobility group box protein 1), S100 proteins or amyloid fibrils. RAGE - ligand interactions results to activation of a variety of signaling pathways including oxidative stress and activation of nuclear factor κB and subsequent proinflammatory response depending on the cell type. AGEs and RAGE together with further mechanisms - hexosamine pathway, polyol pathway, lipid metabolism disorder, activation of proteinkinase C, oxidative stress and inflammatory reaction take part in the pathogenesis of diabetic complications. Terapeuticaly it is possible to decrease endogenous formation of AGEs, influence the AGEs intake to the organism and their absorption in the intestine or stimulate their degradation.Key words: AGEs - advanced glycation end-products - carbonyl stress - diabetes mellitus - inflammation - oxidative stress - RAGE - receptor for AGEs - sRAGE.

Emerging nondestructive inspection methods for aging aircraft

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

Beattie, A; Dahlke, L; Gieske, J

This report identifies and describes emerging nondestructive inspection (NDI) methods that can potentially be used to inspect commercial transport and commuter aircraft for structural damage. The nine categories of emerging NDI techniques are: acoustic emission, x-ray computed tomography, backscatter radiation, reverse geometry x-ray, advanced electromagnetics, including magnetooptic imaging and advanced eddy current techniques, coherent optics, advanced ultrasonics, advanced visual, and infrared thermography. The physical principles, generalized performance characteristics, and typical applications associated with each method are described. In addition, aircraft inspection applications are discussed along with the associated technical considerations. Finally, the status of each technique is presented, with amore » discussion on when it may be available for use in actual aircraft maintenance programs. It should be noted that this is a companion document to DOT/FAA/CT-91/5, Current Nondestructive Inspection Methods for Aging Aircraft.« less

Dietary Advanced Glycation End Products and Their Role in Health and Disease12

PubMed Central

Uribarri, Jaime; del Castillo, María Dolores; de la Maza, María Pía; Filip, Rosana; Gugliucci, Alejandro; Luevano-Contreras, Claudia; Macías-Cervantes, Maciste H; Markowicz Bastos, Deborah H; Medrano, Alejandra; Menini, Teresita; Portero-Otin, Manuel; Rojas, Armando; Sampaio, Geni Rodrigues; Wrobel, Kazimierz; Wrobel, Katarzyna; Garay-Sevilla, Ma Eugenia

2015-01-01

Over the past 2 decades there has been increasing evidence supporting an important contribution from food-derived advanced glycation end products (AGEs) to the body pool of AGEs and therefore increased oxidative stress and inflammation, processes that play a major role in the causation of chronic diseases. A 3-d symposium (1st Latin American Symposium of AGEs) to discuss this subject took place in Guanajuato, Mexico, on 1–3 October 2014 with the participation of researchers from several countries. This review is a summary of the different presentations and subjects discussed, and it is divided into 4 sections. The first section deals with current general knowledge about AGEs. The second section dwells on mechanisms of action of AGEs, with special emphasis on the receptor for advanced glycation end products and the potential role of AGEs in neurodegenerative diseases. The third section discusses different approaches to decrease the AGE burden. The last section discusses current methodologic problems with measurement of AGEs in different samples. The subject under discussion is complex and extensive and cannot be completely covered in a short review. Therefore, some areas of interest have been left out because of space. However, we hope this review illustrates currently known facts about dietary AGEs as well as pointing out areas that require further research. PMID:26178030

Telling a (good?) counterstory of aging: natural bodybuilding meets the narrative of decline.

PubMed

Phoenix, Cassandra; Smith, Brett

2011-09-01

In Western society, the narrative of decline dominates the aging process. We know very little about the complexities of how people resist this narrative. The purpose of this article is to understand how a group of mature natural bodybuilders resisted the narrative of decline. In-depth life story interviews were conducted with 13 natural bodybuilders aged between 50 and 73 years. Verbatim transcripts were produced and the data analyzed using a structural narrative analysis. A dialogical analysis was also utilized. The participants' experiences did not fit with stereotypical assumptions about decline and deterioration in older age. They all told counterstories to "natural" aging, yet what differed was how the participants' counterstories resisted the narrative of decline and the level of resistance that they provided. We advance knowledge in the fields of aging and narrative inquiry by revealing the multidimensionality of resistance. We demonstrated how participants storied resistance in different ways and the important implications this had for the way aging was understood and acted upon-by themselves and potentially by others. In addition to advancing theoretical knowledge, in this article, we also significantly contribute to understandings of the potential of narrative for changing human lives and behavior across the life course in more positive and nuanced ways.

The Challenge of a Knowledge Society. A Philippine Plan of Action.

ERIC Educational Resources Information Center

Diaz, Rony V.; And Others

This volume explores the potentials of advanced technologies as they apply to education and training and looks at efforts to exploit these potentials in three areas: vocational-technical training, formal education, and corporate programs. An introduction, "The Age of Knowledge Work" (Emmanuel T. Velasco, Gayla C. Carreon), defines…

A Commentary on Age Segregation for Older Prisoners

PubMed Central

Kerbs, John J.; Jolley, Jennifer M.

2014-01-01

The growing number of older prisoners in state and federal prisons has fostered an important discussion in literature regarding the potential benefits of age-segregated living arrangements for older inmates. This article begins with a brief review of the reasons for America's aging prison population. Thereafter, it uses a multidisciplinary literature review to clarify a 4-point rationale for age-segregated prisons: (a) cost savings via centralized health care for older prisoners; (b) the reduction of civil liabilities for correctional systems that centralize disability services as per requirements of the Americans with Disabilities Act of 1990; (c) the advancement of prisoner safety for older inmates; and (d) the promotion of rehabilitation by advancing treatment opportunities with a group that is most likely to desist from future criminal activity (in part) due to age-related desistance from crime. Conclusions focus on age segregation within the historical context of segregation in prison based on sociodemographic characteristics. PMID:28316366

Oocyte or embryo donation to women of advanced reproductive age: an Ethics Committee opinion.

PubMed

2016-10-01

Advanced reproductive age (ARA) is a risk factor for female infertility, pregnancy loss, fetal anomalies, stillbirth, and obstetric complications. Oocyte donation reverses the age-related decline in implantation and birth rates of women in their 40s and 50s and restores pregnancy potential beyond menopause. However, obstetrical complications in older patients remain high, particularly related to operative delivery and hypertensive and cardiovascular risks. Physicians should perform a thorough medical evaluation designed to assess the physical fitness of a patient for pregnancy before deciding to attempt transfer of embryos to any woman of advanced reproductive age (>45 years). Embryo transfer should be strongly discouraged or denied to women of ARA with underlying conditions that increase or exacerbate obstetrical risks. Because of concerns related to the high-risk nature of pregnancy, as well as longevity, treatment of women over the age of 55 should generally be discouraged. This statement replaces the earlier ASRM Ethics Committee document of the same name, last published in 2013 (Fertil Steril 2013;100:337-40). Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

What Can ADHD without Comorbidity Teach Us about Comorbidity?

ERIC Educational Resources Information Center

Takeda, Toshinobu; Ambrosini, Paul J.; deBerardinis, Rachel; Elia, Josephine

2012-01-01

Neuropsychiatric comorbidity in ADHD is frequent, impairing and poorly understood. In this report, characteristics of comorbid and comorbid-free ADHD subjects are investigated in an attempt to identify differences that could potentially advance our understanding of risk factors. In a clinically-referred ADHD cohort of 449 youths (ages 6-18), age,…

Some observations on age relationships in spruce-fir regeneration

Treesearch

Barton M. Blum

1973-01-01

Measurement of the ages of seedlings of balsam fir (Abies balsamea (L) Mill.), red spruce (Picea rubens Sarg.), and white spruce (Picea glauca (Moench) Voss) 15 years after the first harvest of a two-cut shelterwood operation revealed that very few potential crop-tree seedlings in the sample occurred as advance...

Cinnamon bark proanthocyanidins as reactive carbonyl scavengers to prevent the formation of advanced glycation endproducts.

PubMed

Peng, Xiaofang; Cheng, Ka-Wing; Ma, Jinyu; Chen, Bo; Ho, Chi-Tang; Lo, Clive; Chen, Feng; Wang, Mingfu

2008-03-26

Cinnamon bark has been reported to be effective in the alleviation of diabetes through its antioxidant and insulin-potentiating activities. In this study, the inhibitory effect of cinnamon bark on the formation of advanced glycation endproducts (AGEs) was investigated in a bovine serum albumin (BSA)-glucose model. Several phenolic compounds, such as catechin, epicatechin, and procyanidin B2, and phenol polymers were identified from the subfractions of aqueous cinnamon extract. These compounds showed significant inhibitory effects on the formation of AGEs. Their antiglycation activities were not only brought about by their antioxidant activities but also related to their trapping abilities of reactive carbonyl species such as methylglyoxal (MGO), an intermediate reactive carbonyl of AGE formation. Preliminary study on the reaction between MGO and procyanidin B2 revealed that MGO-procyanidin B2 adducts are primary products which are supposed to be stereoisomers. This is the first report that proanthocyanidins can effectively scavenge reactive carbonyl species and thus inhibit the formation of AGEs. As proanthocyanidins behave in a similar fashion as aminoguanidine (AG), the first AGE inhibitor explored in clinical trials, they show great potential to be developed as agents to alleviate diabetic complications.

Skin autofluorescence as a measure of advanced glycation endproduct deposition: a novel risk marker in chronic kidney disease.

PubMed

Smit, Andries J; Gerrits, Esther G

2010-11-01

Skin autofluorescence (SAF) is a new method to noninvasively assess accumulation of advanced glycation endproducts (AGEs) in a tissue with low turnover. Recent progress in the clinical application of SAF as a risk marker for diabetic nephropathy as well as cardiovascular disease in nondiabetic end-stage kidney disease, less advanced chronic kidney disease, and renal transplant recipients is reviewed. Experimental studies highlight the fundamental role of the interaction of AGEs with the receptor for AGEs (RAGEs), also called the AGE-RAGE axis, in the pathogenesis of vascular and chronic kidney disease. SAF predicts (cardiovascular) mortality in renal failure and also chronic renal transplant dysfunction. Long-term follow-up results from the Diabetes Control and Complications Trial and UK Prospective Diabetes Study suggest that AGE accumulation is a key carrier of metabolic memory and oxidative stress. Short-term intervention studies in diabetic nephropathy with thiamine, benfotiamine and angiotensin-receptor blockers aimed at reducing AGE formation have reported mixed results. SAF is a noninvasive marker of AGE accumulation in a tissue with low turnover, and thereby of metabolic memory and oxidative stress. SAF independently predicts cardiovascular and renal risk in diabetes, as well as in chronic kidney disease. Further long-term studies are required to assess the potential benefits of interventions to reduce AGE accumulation.

Relationship of Advanced Glycation End Products With Cardiovascular Disease in Menopausal Women.

PubMed

Pertynska-Marczewska, Magdalena; Merhi, Zaher

2015-07-01

Cardiovascular disease (CVD) represents the most significant cause of death in postmenopausal women. Advanced glycation end products (AGEs) are formed by nonenzymatic modification of proteins, lipids, and nucleic acids by glucose. This review focuses on the contribution of AGEs and their receptors to the development of CVD in menopause. Advanced glycation end products circulate and activate the proinflammatory endothelial cell surface receptor called RAGE, bind to the extracellular matrix of the cardiovascular system, or bind to the circulating anti-inflammatory soluble form of RAGE (sRAGE). Data emerging from human and animal studies suggest that AGEs and both receptors (RAGE and sRAGE) are implicated in the pathophysiology of CVD. Particular emphasis has been given to the role of AGE-RAGE axis in oxidative stress, inflammation, endothelial cell toxicity, and progression of atherosclerosis in menopause. Data accruing from human and animal studies suggest that RAGE expression level and circulating sRAGE level are associated with estradiol and are correlated with CVD risk factors, such as adiposity, dyslipidemia, insulin resistance, diabetes, and metabolic syndrome. By recognizing the impact of AGEs on atherosclerosis, pharmacological strategies targeting the AGE-RAGE pathway hold therapeutic potential for CVD in menopausal women. © The Author(s) 2014.

Lack of association of CFD polymorphisms with advanced age-related macular degeneration.

PubMed

Zeng, Jiexi; Chen, Yuhong; Tong, Zongzhong; Zhou, Xinrong; Zhao, Chao; Wang, Kevin; Hughes, Guy; Kasuga, Daniel; Bedell, Matthew; Lee, Clara; Ferreyra, Henry; Kozak, Igor; Haw, Weldon; Guan, Jean; Shaw, Robert; Stevenson, William; Weishaar, Paul D; Nelson, Mark H; Tang, Luosheng; Zhang, Kang

2010-11-03

Age-related macular degeneration (AMD) is the most common cause of irreversible central vision loss worldwide. Research has linked AMD susceptibility with dysregulation of the complement cascade. Typically, complement factor H (CFH), complement factor B (CFB), complement component 2 (C2), and complement component 3 (C3) are associated with AMD. In this paper, we investigated the association between complement factor D (CFD), another factor of the complement system, and advanced AMD in a Caucasian population. Six single nucleotide polymorphisms (SNPs), rs1683564, rs35186399, rs1683563, rs3826945, rs34337649, and rs1651896, across the region covering CFD, were chosen for this study. One hundred and seventy-eight patients with advanced AMD and 161 age-matched normal controls were genotyped. Potential positive signals were further tested in another independent 445 advanced AMD patients and 190 controls. χ2 tests were performed to compare the allele frequencies between case and control groups. None of the six SNPs of CFD was found to be significantly associated with advanced AMD in our study. Our findings suggest that CFD may not play a major role in the genetic susceptibility to AMD because no association was found between the six SNPs analyzed in the CFD region and advanced AMD.

Sevelamer reduces endothelial inflammatory response to advanced glycation end products

PubMed Central

Gregório, Paulo C; Favretto, Giane; Sassaki, Guilherme L; Cunha, Regiane S; Becker-Finco, Alessandra; Pecoits-Filho, Roberto; Souza, Wesley M; Barreto, Fellype C

2018-01-01

Abstract Background Advanced glycation end products (AGEs) have been related to the pathogenesis of cardiovascular diseases (CVD), chronic kidney disease (CKD) and diabetes mellitus. We sought to investigate the binding capacity of sevelamer to both AGEs and uremic serum in vitro and then test this pharmaceutical effect as a potential vascular anti-inflammatory strategy. Methods AGEs were prepared by albumin glycation and characterized by absorbance and electrophoresis. Human endothelial cells were incubated in culture media containing AGEs and uremic serum with or without sevelamer. Receptor for advanced glycation end product (RAGE) expression was evaluated through immunocytochemistry and western blot to explore the interactions between AGEs and the endothelium. Inflammatory and endothelial dysfunction biomarkers, such as interleukin 6 (IL-6) and IL-8, monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1) and serum amyloid A (SAA) were also measured in cell supernatant. The chemotactic property of the supernatant was evaluated. Results AGEs significantly induced the expression of RAGE, inflammatory and endothelial activation biomarkers [IL-6, (P < 0.005); IL-8, MCP-1, PAI-1 and SAA (P < 0.001)] and monocyte chemotaxis as compared with controls. In addition, AGEs increased the levels of inflammatory biomarkers, which were observed after 6 h of endothelial cell incubation with uremic serum [IL-6 (P < 0.001) IL-8, MCP-1 and PAI-1 (P < 0.05)]. On the other hand, after 6 h of endothelial cell treatment with sevelamer, RAGE expression (P < 0.05) and levels of inflammatory biomarkers [IL-6 and IL-8 (P < 0.001), MCP-1 (P < 0.01), PAI-1 and SAA (P < 0.005)] significantly decreased compared with the AGEs/uremic serum treatment alone. Conclusions Sevelamer decreased both endothelial expression of RAGE and endothelial dysfunction biomarkers, induced by AGEs, and uremic serum. Further studies are necessary for a better understanding of the potential protective role of sevelamer on uremic serum and AGEs-mediated endothelial dysfunction. PMID:29423208

Engagement and recruitment of Māori and non-Māori people of advanced age to LiLACS NZ.

PubMed

Dyall, Lorna; Kepa, Mere; Hayman, Karen; Teh, Ruth; Moyes, Simon; Broad, Joanna B; Kerse, Ngaire

2013-04-01

Life and Living in Advanced Age: A Cohort Study in New Zealand (LiLACS NZ) aims to determine the predictors of successful advanced ageing and understand the trajectories of wellbeing in advanced age. This paper reports recruitment strategies used to enrol 600 Māori aged 80-90 years and 600 non-Māori aged 85 years living within a defined geographic boundary. Electoral roll and primary health lists of older people were used as a base for identification and recruitment, supplemented by word of mouth, community awareness raising and publicity. A Kaupapa Māori method was used to recruit Māori with: dual Māori and non-Māori research leadership; the formation of a support group; local tribal organisations and health providers recruiting participants; and use of the Māori language in interviews. Non-Māori were recruited through local health and community networks. Six organisations used differing strategies to invite older people to participate in several ways: complete full or partial interviews; complete physical assessments; provide a blood sample and provide access to medical records. During 14 months in 2010-2011, 421 of 766 (56%) eligible Māori and 516 of 870 (59%) eligible non-Māori were enrolled. Participation and contribution of information varied across the recruitment sites. Attention to appropriate recruitment techniques resulted in an acceptable engagement and recruitment for both Māori and non-Māori of advanced age in a longitudinal cohort study. There is high potential for meaningful results useful for participants, their whānau and families, health agencies, planners and policy. © 2013 The Authors. ANZJPH © 2013 Public Health Association of Australia.

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.

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

Altered serum glyceraldehyde-derived advanced glycation end product (AGE) and soluble AGE receptor levels indicate carbonyl stress in patients with schizophrenia.

PubMed

Takeda, Mayu; Ohnuma, Tohru; Takeuchi, Masayoshi; Katsuta, Narimasa; Maeshima, Hitoshi; Takebayashi, Yuto; Higa, Motoyuki; Nakamura, Toru; Nishimon, Shohei; Sannohe, Takahiro; Hotta, Yuri; Hanzawa, Ryo; Higashiyama, Ryoko; Shibata, Nobuto; Gohda, Tomohito; Suzuki, Yusuke; Yamagishi, Sho-ichi; Tomino, Yasuhiko; Arai, Heii

2015-04-23

Recent cross-sectional and longitudinal studies indicate that measurements of peripheral blood carbonyl stress markers such as the advanced glycation end product (AGE) pentosidine and the reactive carbonyl-detoxifying B6 vitamin pyridoxal could be used as therapeutic biological markers in subpopulations of schizophrenia patients. Glyceraldehyde-derived AGEs (Glycer-AGE) have strong neurotoxicity, and soluble receptors for AGEs (sRAGE) may ameliorate the effects of AGEs. In the present study, we measured Glycer-AGEs and sRAGE levels to determine their potential as diagnostic, therapeutic, or clinical biological markers in patients with schizophrenia. After enrollment of 61 admitted Japanese patients with acute schizophrenia and 39 healthy volunteers, 54 patients were followed up from the acute stage to remission. Serum biomarkers were measured in blood samples taken before breakfast using competitive enzyme-linked immunosorbent assays, and Glycer-AGEs were significantly higher and sRAGE levels were significantly lower in patients with acute schizophrenia than in healthy controls. Glycer-AGEs/sRAGE ratios were also higher in schizophrenia patients and were stable during the clinical course. Furthermore, discriminant analyses confirmed that Glycer-AGEs and Glycer-AGEs/sRAGE ratios are significant diagnostic markers for schizophrenia, and distinguished between patients and healthy controls in 70.0% of cases. However, these markers of carbonyl stress were not correlated with clinical features, including disease severity, or with daily chlorpromazine doses. These data indicate the potential of Glycer-AGEs, RAGEs, and their relative ratios as diagnostic markers for patients with schizophrenia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Accumulation of methylglyoxal increases the advanced glycation end-product levels in DRG and contributes to lumbar disk herniation-induced persistent pain.

PubMed

Liu, Cui-Cui; Zhang, Xin-Sheng; Ruan, Yu-Ting; Huang, Zhu-Xi; Zhang, Su-Bo; Liu, Meng; Luo, Hai-Jie; Wu, Shao-Ling; Ma, Chao

2017-08-01

Lumbar disk herniation (LDH) with discogenic low back pain and sciatica is a common and complicated musculoskeletal disorder. The underlying mechanisms are poorly understood, and there are no effective therapies for LDH-induced pain. In the present study, we found that the patients who suffered from LDH-induced pain had elevated plasma methylglyoxal (MG) levels. In rats, implantation of autologous nucleus pulposus (NP) to the left lumbar 5 spinal nerve root, which mimicked LDH, induced mechanical allodynia, increased MG level in plasma and dorsal root ganglion (DRG), and enhanced the excitability of small DRG neurons (<30 μm in diameter). Intrathecal injection of MG also induced mechanical allodynia, and its application to DRG neurons ex vivo increased the number of action potentials evoked by depolarizing current pulses. Furthermore, inhibition of MG accumulation by aminoguanidine attenuated the enhanced excitability of small DRG neurons and the mechanical allodynia induced by NP implantation. In addition, NP implantation increased levels of advanced glycation end products (AGEs) in DRG, and intrathecal injection of MG-derived AGEs induced the mechanical allodynia and DRG neuronal hyperactivity. Intrathecal injection of MG also significantly increased the expression of AGEs in DRG. Importantly, scavenging of MG by aminoguanidine also attenuated the increase in AGEs induced by NP implantation. These results suggested that LDH-induced MG accumulation contributed to persistent pain by increasing AGE levels. Thus generation of AGEs from MG may represent a target for treatment of LDH-induced pain. NEW & NOTEWORTHY Our study demonstrates that methylglyoxal accumulation via increasing advanced glycation end-product levels in dorsal root ganglion contributes to the persistent pain induced by lumbar disk herniation, which proposed potential targets for the treatment of lumbar disk herniation-induced persistent pain. Copyright © 2017 the American Physiological Society.

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.

How have changes in air bag designs affected frontal crash mortality?

PubMed

Braver, Elisa R; Shardell, Michelle; Teoh, Eric R

2010-07-01

To determine whether front air bag changes have affected occupant protection, frontal crash mortality rates were compared among front outboard occupants in vehicles having certified-advanced air bags (latest generation of air bags) or sled-certified air bags with and without advanced features. Poisson marginal structural models were used to calculate standardized mortality rate ratios (MRRs) for front occupants per registered vehicle. Vehicle age-corrected mortality rates were lower for drivers of vehicles having sled-certified air bags with advanced features than for drivers having sled-certified air bags without advanced features (MRR = 0.88; 95% confidence interval [CI]: 0.81-0.95), including unbelted men and drivers younger than 60. The mortality rate was higher, though not statistically significant, for drivers having certified-advanced air bags compared with sled-certified air bags with advanced features (vehicle age-corrected MRR = 1.13; 95% CI: 0.97-1.32) and significantly higher for belted drivers (MRR = 1.21; 95% CI: 1.04-1.39). Advanced air bag features appeared protective for some occupants. However, increased mortality rates among belted drivers of vehicles having certified-advanced air bags relative to those having sled-certified air bags with advanced features suggest that further study is needed to identify any potential problems with requirements for certification. 2010 Elsevier Inc. All rights reserved.

The health concerns and behaviours of primigravida: comparing advanced age pregnant women with their younger counterparts.

PubMed

Loke, Alice Yuen; Poon, Chung Fan

2011-04-01

This study was to describe and compare the health concerns, behaviours and anxiety of advanced age pregnant women (35 years and older) with their younger counterparts. Women have specific health concerns and behaviours during pregnancy. Delayed childbearing has an increased risk of adverse pregnancy outcomes and advanced age pregnant women may have more health concerns than younger ones. A cross-sectional study. Primigravidae Chinese women aged 35 or older (n = 47) and 188 younger than aged 35 were recruited in February and March of 2005 by convenient sampling from the antenatal clinic of a regional hospital in Hong Kong to complete a questionnaire. Advanced age pregnant women when compared with their counterparts were more likely to have tertiary education (42·6% vs. 28·7%) and a higher family monthly income of Hong Kong $40,001 or more (40·5% vs. 15·4%). They were more likely to be concerned the possibility of miscarriage (63·8% vs. 45·9%) and the physical demands of caring for the newborn (61·7% vs. 45·4%) but were more likely to take up healthy behaviours such as 'eating nutritious food' (100%) and avoiding 'wearing tight clothing and high-heel shoes'(100%). Advanced age women were more likely to be concerned about their 'recovery after childbirth' (63·8% vs. 42·7%), Down's syndrome (70·2% vs. 37·8%) and structural defects of their foetus (78·7% vs. 54·1%). The results of this study provide a background for improving prenatal care catering for the specific health concerns of the advanced aged and promotion of health behaviours among younger pregnant women. Antenatal, obstetric and community health nurses have the responsibility to provide education and support services catering to the special concerns of pregnant women at different ages. Health professionals should promote the prime time for childbearing and deliver messages regarding the potential problems associated with later childbearing at premarital counselling. © 2011 Blackwell Publishing Ltd.

Maternal educational status at birth, maternal educational advancement, and neurocognitive outcomes at age 10 years among children born extremely preterm.

PubMed

Joseph, Robert M; O'Shea, Thomas M; Allred, Elizabeth N; Heeren, Tim; Kuban, Karl K

2018-04-01

BackgroundTo determine if a key marker of socioeconomic status, maternal education, is associated with later neurocognitive and academic outcomes among children born extremely preterm (EP).MethodEight hundred and seventy-three children born at 23 to 27 weeks of gestation were assessed for cognitive and academic ability at age 10 years. With adjustments for gestational age (GA) and potential confounders, outcomes of children whose mothers had fewer years of education at the time of delivery and children whose mother advanced in education between birth and 10 years were examined.ResultsChildren of mothers in the lowest education stratum at birth were significantly more likely to score ≥2 SDs below normative expectation on 17 of 18 tests administered. Children of mothers who advanced in education (n=199) were at reduced risk for scoring ≥2 SDs on 15 of 18 measures, but this reduction was statistically significant on only 2 of 18 measures.ConclusionAmong EP children, socioeconomic disadvantage at birth, indexed by maternal education, is associated with significantly poorer neurocognitive and academic outcomes at 10 years of age, independently of GA. Maternal educational advancement during the child's first 10 years of life is associated with modestly improved neurocognitive outcomes.

Is there an association between advanced paternal age and endophenotype deficit levels in schizophrenia?

PubMed

Tsuang, Debby; Esterberg, Michelle; Braff, David; Calkins, Monica; Cadenhead, Kristin; Dobie, Dorcas; Freedman, Robert; Green, Michael F; Greenwood, Tiffany; Gur, Raquel; Gur, Ruben; Horan, William; Lazzeroni, Laura C; Light, Gregory A; Millard, Steven P; Olincy, Ann; Nuechterlein, Keith; Seidman, Larry; Siever, Larry; Silverman, Jeremy; Stone, William; Sprock, Joyce; Sugar, Catherine; Swerdlow, Neal; Tsuang, Ming; Turetsky, Bruce; Radant, Allen

2014-01-01

The children of older fathers have increased risks of developing schizophrenia spectrum disorders, and among those who develop these disorders, those with older fathers present with more severe clinical symptoms. However, the influence of advanced paternal age on other important domains related to schizophrenia, such as quantitative endophenotype deficit levels, remains unknown. This study investigated the associations between paternal age and level of endophenotypic impairment in a well-characterized family-based sample from the Consortium on the Genetics of Schizophrenia (COGS). All families included at least one affected subject and one unaffected sibling. Subjects met criteria for schizophrenia (probands; n = 293) or were unaffected first-degree siblings of those probands (n = 382). Paternal age at the time of subjects' birth was documented. Subjects completed a comprehensive clinical assessment and a battery of tests that measured 16 endophenotypes. After controlling for covariates, potential paternal age-endophenotype associations were analyzed using one model that included probands alone and a second model that included both probands and unaffected siblings. Endophenotype deficits in the Identical Pairs version of the 4-digit Continuous Performance Test and in the Penn Computerized Neurocognitive Battery verbal memory test showed significant associations with paternal age. However, after correcting for multiple comparisons, no endophenotype was significantly associated with paternal age. These findings suggest that factors other than advanced paternal age at birth may account for endophenotypic deficit levels in schizophrenia.

Extent, timing, and climatic significance of latest Pleistocene and Holocene glaciation in the Sierra Nevada, California

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

Clark, Douglas Howe

Despite more than a century of study, scant attention has been paid to the glacial record in the northern end of the Sierra Nevada, and to the smaller moraines deposited after the retreat of the Tioga (last glacial maximum) glaciers. Equilibrium-line altitude (ELA) estimates of the ice fields indicate that the Tioga ELA gradients there are consistent with similar estimates for the southern half of the range, and with an intensification of the modern temperature/precipitation pattern in the region. The Recess Peak advance has traditionally been considered to be mid-Neoglacial age, about 2--3,000 yr B.P., on the basis of relativemore » weathering estimates. Sediment cores of lakes dammed behind moraines correlative with Recess Peak in four widely spaced sites yields a series of high-resolution AMS radiocarbon dates which demonstrate that Recess Peak glaciers retreated before ~13,100 cal yr B.P.. This minimum limiting age indicates that the advance predates the North Atlantic Younger Dryas cooling. It also implies that there have been no advances larger than the Matthes in the roughly 12,000 year interval between it and the Recess Peak advance. This finding casts doubt on several recent studies that claim Younger Dryas glacier advances in western North America. The 13,100 cal yr B.P. date is also a minimum age for deglaciation of the sample sites used to calibrate the in situ production rates of cosmogenic 10Be and 26Al. The discrepancy between this age and the 11,000 cal yr B.P. exposure age assumed in the original calibration introduces a large (> 19%) potential error in late-Pleistocene exposure ages calculated using these production rates.« less

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.

Towards a better monitoring of seed ageing under ex situ seed conservation

PubMed Central

Fu, Yong-Bi; Ahmed, Zaheer; Diederichsen, Axel

2015-01-01

Long-term conservation of 7.4 million ex situ seed accessions held in agricultural genebanks and botanic gardens worldwide is a challenging mission for human food security and ecosystem services. Recent advances in seed biology and genomics may have opened new opportunities for effective management of seed germplasm under long-term storage. Here, we review the current development of tools for assessing seed ageing and research advances in seed biology and genomics, with a focus on exploring their potential as better tools for monitoring of seed ageing. Seed ageing is found to be associated with the changes reflected in reactive oxygen species and mitochondria-triggered programmed cell deaths, expression of antioxidative genes and DNA and protein repair genes, chromosome telomere lengths, epigenetic regulation of related genes (microRNA and methylation) and altered organelle and nuclear genomes. Among these changes, the signals from mitochondrial and nuclear genomes may show the most promise for use in the development of tools to predict seed ageing. Non-destructive and non-invasive analyses of stored seeds through calorimetry or imaging techniques are also promising. It is clear that research into developing advanced tools for monitoring seed ageing to supplement traditional germination tests will be fruitful for effective conservation of ex situ seed germplasm. PMID:27293711

Neuropsychological Performance in Advanced Age- Influences of Demographic Factors and Apolipoprotein E: Findings from the Cache County Memory Study

PubMed Central

Welsh-Bohmer, Katheen A.; Østbye, Truls; Sanders, Linda; Pieper, Carl F.; Hayden, Kathleen M.; Tschanz, JoAnn T.; Norton, Maria C.

2009-01-01

The Cache County Study of Memory in Aging (CCMS) is an epidemiological study of Alzheimer’s disease (AD), mild cognitive disorders, and aging in a population of exceptionally long-lived individuals (7th to 11th decade). Observation of population members without dementia provides an opportunity for establishing the range of normal neurocognitive performance in a representative sample of the very old. We examined neurocognitive performance of the normal participants undergoing full clinical evaluations (n=507) and we tested the potential modifying effects of APOE genotype, a known genetic risk factor for the later development of AD. The results indicate that advanced age and low education are related to lower test scores across nearly all of the neurocognitive measures. Gender and APOE ε4 both had negligible and inconsistent influences, affecting only isolated measures of memory and expressive speech (in case of gender). The gender and APOE effects disappeared once age and education were controlled. The study of this exceptionally long-lived population provides useful normative information regarding the broad range of “normal” cognition seen in advanced age. Among elderly without dementia or other cognitive impairment, APOE does not appear to exert any major effects on cognition once other demographic influences are controlled. PMID:18609337

Neuropsychological performance in advanced age: influences of demographic factors and Apolipoprotein E: findings from the Cache County Memory Study.

PubMed

Welsh-Bohmer, Katheen A; Ostbye, Truls; Sanders, Linda; Pieper, Carl F; Hayden, Kathleen M; Tschanz, JoAnn T; Norton, Maria C

2009-01-01

The Cache County Study of Memory in Aging (CCMS) is an epidemiological study of Alzheimer's disease (AD), mild cognitive disorders, and aging in a population of exceptionally long-lived individuals (7th to 11th decade). Observation of population members without dementia provides an opportunity for establishing the range of normal neurocognitive performance in a representative sample of the very old. We examined neurocognitive performance of the normal participants undergoing full clinical evaluations (n = 507) and we tested the potential modifying effects of apolipoprotein E (APOE) genotype, a known genetic risk factor for the later development of AD. The results indicate that advanced age and low education are related to lower test scores across nearly all of the neurocognitive measures. Gender and APOE epsilon4 both had negligible and inconsistent influences, affecting only isolated measures of memory and expressive speech (in case of gender). The gender and APOE effects disappeared once age and education were controlled. The study of this exceptionally long-lived population provides useful normative information regarding the broad range of "normal" cognition seen in advanced age. Among elderly without dementia or other cognitive impairment, APOE does not appear to exert any major effects on cognition once other demographic influences are controlled.

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.

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.

How Low Can You Go? Determining a Size Threshold for Implantation of a New Acoustic Transmitter in Age-0 White Sturgeon

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

Ashton, Neil K.; Liss, Stephanie A.; Walker, Ricardo W.

Telemetry studies are often used to investigate sturgeon habitat use and movement patterns; however, existing acoustic transmitters are generally too large to implant into age-0 sturgeon without harming the fish. Recent development of a miniaturized acoustic transmitter (cylindrical, 0.7 g in air, 24.2 mm long, 5.0 mm diameter) with up to 365 d battery life has the potential to advance our understanding of age-0 sturgeon ecology in rivers and lakes. Prior to use in field studies, it is essential to conduct experiments evaluating potential adverse transmitter effects on fish. We tested transmitter retention, fish survival, and growth of a broadmore » size range of age-0 white sturgeon (Acipenser transmontanus; 158–277 mm fork length; 26–126 g; 0.6–2.6% transmitter burden) in an 84 d laboratory study, with an ultimate goal of determining a minimum size threshold of sturgeon that can be implanted with this acoustic transmitter. At 84 d post-implantation, transmitter retention and fish survival were 100%. Specific growth rates were reduced at 7 and 14 d post-implantation, resulting in minimum fork length thresholds of 250 and 171 mm, respectively. Juveniles implanted with transmitters regained their growth potential by 28 d post-implantation and no size differences were detected in comparisons with unmarked control fish. This study demonstrates the ability to implant small age-0 sturgeon with high transmitter retention and fish survival, and only minor growth effects. Use of new miniaturized acoustic transmitters may give researchers a means to address questions about young-of-the-year fish recruitment, ecological patterns, and potentially advance conservation management of sturgeon populations.« less

Clinical application prospect of umbilical cord-derived mesenchymal stem cells on clearance of advanced glycation end products through autophagy on diabetic wound.

PubMed

Han, Yanfu; Sun, Tianjun; Tao, Ran; Han, Yanqing; Liu, Jing

2017-03-24

Nowadays, wound healing delay due to diabetes is considered to be closely related to the accumulation of advanced glycation end products (AGEs). Although mesenchymal stem cells (MSCs) exhibit positive effects on diabetic wound healing, related mechanisms are still not fully elucidated. It has been reported that MSCs can improve the activity of autophagy in injured tissues, thereby playing an important role in wound healing. The autophagy induced by MSCs may be beneficial to diabetic wound healing via removing AGEs, which provide new ideas for clinical treatment of diabetic wounds with the potential of broad application prospects. In this study, the current research situation and application prospect of umbilical cord-derived MSCs on the clearance of AGEs in diabetic wound were reviewed.

Advanced paternal age effects in neurodevelopmental disorders-review of potential underlying mechanisms.

PubMed

Janecka, M; Mill, J; Basson, M A; Goriely, A; Spiers, H; Reichenberg, A; Schalkwyk, L; Fernandes, C

2017-01-31

Multiple epidemiological studies suggest a relationship between advanced paternal age (APA) at conception and adverse neurodevelopmental outcomes in offspring, particularly with regard to increased risk for autism and schizophrenia. Conclusive evidence about how age-related changes in paternal gametes, or age-independent behavioral traits affect neural development is still lacking. Recent evidence suggests that the origins of APA effects are likely to be multidimensional, involving both inherited predisposition and de novo events. Here we provide a review of the epidemiological and molecular findings to date. Focusing on the latter, we present the evidence for genetic and epigenetic mechanisms underpinning the association between late fatherhood and disorder in offspring. We also discuss the limitations of the APA literature. We propose that different hypotheses relating to the origins of the APA effects are not mutually exclusive. Instead, multiple mechanisms likely contribute, reflecting the etiological complexity of neurodevelopmental disorders.

Domains and Determinants of Well-Being of Older Adults in India.

PubMed

Ladusingh, Laishram; Ngangbam, Sapana

2016-03-01

This study proposes a well-being index of older adults which integrates five domains, namely, activities of daily living, health status, psychological strength, life accomplishment and social ties, and examines potential socio-demographic, living arrangement, lifestyle and religiosity determinants of well-being. The present study uses micro data of 1255 older adults from the recent pilot survey for the Longitudinal Aging Study in India (LASI) conducted in 2010. The results suggest that normal activities of daily life, health, and social ties decline with advancing age, while life accomplishment remains stable over age. However, when all domains are integrated, well-being tends to fade out with advancing age. While smoking has a deterrent effect on well-being, better economic status, literacy, living in a joint family with spouse, religiosity, and regular physical exercise have a statistically significant positive effect on the well-being of older adults in India.

Advanced paternal age effects in neurodevelopmental disorders—review of potential underlying mechanisms

PubMed Central

Janecka, M; Mill, J; Basson, M A; Goriely, A; Spiers, H; Reichenberg, A; Schalkwyk, L; Fernandes, C

2017-01-01

Multiple epidemiological studies suggest a relationship between advanced paternal age (APA) at conception and adverse neurodevelopmental outcomes in offspring, particularly with regard to increased risk for autism and schizophrenia. Conclusive evidence about how age-related changes in paternal gametes, or age-independent behavioral traits affect neural development is still lacking. Recent evidence suggests that the origins of APA effects are likely to be multidimensional, involving both inherited predisposition and de novo events. Here we provide a review of the epidemiological and molecular findings to date. Focusing on the latter, we present the evidence for genetic and epigenetic mechanisms underpinning the association between late fatherhood and disorder in offspring. We also discuss the limitations of the APA literature. We propose that different hypotheses relating to the origins of the APA effects are not mutually exclusive. Instead, multiple mechanisms likely contribute, reflecting the etiological complexity of neurodevelopmental disorders. PMID:28140401

Goals and potential career advancement of licensed practical nurses in Japan.

PubMed

Ikeda, Mari; Inoue, Katsuya; Kamibeppu, Kiyoko

2008-10-01

To investigate the effects of personal and professional variables on career advancement intentions of working Licensed Practical Nurses (LPNs). In Japan, two levels of professional nursing licensures, the LPN and the registered nurse (RN), are likely to be integrated in the future. Therefore, it is important to know the career advancement intentions of LPNs. Questionnaires were sent to a sample of 356 LPNs. Analysis of variance (anova) and discriminative analysis were used. We found that those who had a positive image of LPNs along with a positive image of RNs were identified as showing interest in career advancement. The results of anova showed that age had a negative effect; however, discriminative analysis suggested that age is not as significant compared with other variables. Our results indicate that the 'image of RNs', and 'role-acceptance factors' have an effect on career advancement intentions of LPNs. Our results suggest that Nursing Managers should create a supportive working environment where the LPN would feel encouraged to carry out the nursing role, thereby creating a positive image of nursing in general which would lead to career motivation and pursuing RN status.

Characterizing harmful advanced glycation end-products (AGEs) and ribosylated aggregates of yellow mustard seed phytocystatin: Effects of different monosaccharides

NASA Astrophysics Data System (ADS)

Ahmed, Azaj; Shamsi, Anas; Bano, Bilqees

2017-01-01

Advanced glycation end products (AGEs) are at the core of variety of diseases ranging from diabetes to renal failure and hence gaining wide consideration. This study was aimed at characterizing the AGEs of phytocystatin isolated from mustard seeds (YMP) when incubated with different monosaccharides (glucose, ribose and mannose) using fluorescence, ultraviolet, circular dichroism (CD) spectroscopy and microscopy. Ribose was found to be the most potent glycating agent as evident by AGEs specific fluorescence and absorbance. YMP exists as a molten globule like structure on day 24 as depicted by high ANS fluorescence and altered intrinsic fluorescence. Glycated YMP as AGEs and ribose induced aggregates were observed at day 28 and 32 respectively. In our study we have also examined the anti-aggregative potential of polyphenol, resveratrol. Our results suggested the anti-aggregative behavior of resveratrol as it prevented the in vitro aggregation of YMP, although further studies are required to decode the mechanism by which resveratrol prevents the aggregation.

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

Development of Advanced 9Cr Ferritic-Martensitic Steels and Austenitic Stainless Steels for Sodium-Cooled Fast Reactor

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

Sham, Sam; Tan, Lizhen; Yamamoto, Yukinori

2013-01-01

Ferritic-martensitic (FM) steel Grade 92, with or without thermomechanical treatment (TMT), and austenitic stainless steels HT-UPS (high-temperature ultrafine precipitate strengthening) and NF709 were selected as potential candidate structural materials in the U.S. Sodium-cooled Fast Reactor (SFR) program. The objective is to develop advanced steels with improved properties as compared with reference materials such as Grade 91 and Type 316H steels that are currently in nuclear design codes. Composition modification and/or processing optimization (e.g., TMT and cold-work) were performed to improve properties such as resistance to thermal aging, creep, creep-fatigue, fracture, and sodium corrosion. Testings to characterize these properties for themore » advanced steels were conducted by the Idaho National Laboratory, the Argonne National Laboratory and the Oak Ridge National Laboratory under the U.S. SFR program. This paper focuses on the resistance to thermal aging and creep of the advanced steels. The advanced steels exhibited up to two orders of magnitude increase in creep life compared to the reference materials. Preliminary results on the weldment performance of the advanced steels are also presented. The superior performance of the advanced steels would improve reactor design flexibility, safety margins and economics.« less

Relationship of Advanced Glycation End Products With Cardiovascular Disease in Menopausal Women

PubMed Central

Pertynska-Marczewska, Magdalena

2015-01-01

Cardiovascular disease (CVD) represents the most significant cause of death in postmenopausal women. Advanced glycation end products (AGEs) are formed by nonenzymatic modification of proteins, lipids, and nucleic acids by glucose. This review focuses on the contribution of AGEs and their receptors to the development of CVD in menopause. Advanced glycation end products circulate and activate the proinflammatory endothelial cell surface receptor called RAGE, bind to the extracellular matrix of the cardiovascular system, or bind to the circulating anti-inflammatory soluble form of RAGE (sRAGE). Data emerging from human and animal studies suggest that AGEs and both receptors (RAGE and sRAGE) are implicated in the pathophysiology of CVD. Particular emphasis has been given to the role of AGE–RAGE axis in oxidative stress, inflammation, endothelial cell toxicity, and progression of atherosclerosis in menopause. Data accruing from human and animal studies suggest that RAGE expression level and circulating sRAGE level are associated with estradiol and are correlated with CVD risk factors, such as adiposity, dyslipidemia, insulin resistance, diabetes, and metabolic syndrome. By recognizing the impact of AGEs on atherosclerosis, pharmacological strategies targeting the AGE–RAGE pathway hold therapeutic potential for CVD in menopausal women. PMID:25228634

Three dimensional ultrasonography for advanced neurosonography (Neurosofe-3d). Analysis of acquisition-related factors influencing the quality of the brain volumes.

PubMed

Maiz, Nerea; Alonso, Ignacio; Belar, María; Burgos, Jorge; Irasarri, Ana; Molina, Francisca S; de Paco, Catalina; Pijoan, José I; Plasencia, Walter; Rodó, Carlota; Rodríguez, M Angeles; Tajada, Mauricio; Tubau, Albert

2016-11-01

To evaluate the acquisition-related factors influencing the quality of the brain volumes for further study of advanced neurosonography. This was a prospective multicentre study. Five centres were asked to include five cases each, acquiring two volumes per case, at different gestational ages. Ten operators performed an advanced neurosonography per case. The potential influence of the following factors on the number of evaluable structures was assessed: vaginal/ abdominal acquisition, position of the head, gestational age, subjective quality of the volume and the acquiring operator itself. Four hundred and thirty-two evaluations were included in the study. A total of 80% of the structures were evaluated satisfactorily in the axial plane, 67.1% and 55.1% in the coronal and sagittal plane, respectively. Sagittal volumes acquired transvaginally had a better quality than those acquired transabdominally. Gestational age affected the quality of axial and sagittal volumes (p < 0.001), and the best quality was obtained between 20 and 27 weeks. In axial and sagittal volumes, the head position influenced the percentage of structures visualized (p < 0.001, p < 0.001). Factors affecting the quality of the volume for advanced neurosonography are gestational age, fetal head position, transvaginal acquisition in sagittal volumes, the acquiring operator and the subjective quality of the volume. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.

[Age-related characteristics of the surface bioelectrical potential of human, canine and rat teeth and features of its distribution over the surface of the crown].

PubMed

Donskiĭ, G I; Pavliuchenko, O N; Palamarchuk, Iu N; Makarova, N Ia

1989-01-01

Using a digital electron voltmeter, bioelectrical potentials (BEPs) of dental crowns have been recorded in 180 patients, 36 dogs, and 93 white non-inbred rats. It has been established that the surface BEP is a marker of dental enamel maturation and does not depend on the species of mammals. On the other hand maturation processes differ in their rate on the cutting edge, equator, and neck: with advancing age algebraic difference between the magnitudes of surface BEPs decreases in humans and increases in dogs and rats.

Potential Dual Role of Eugenol in Inhibiting Advanced Glycation End Products in Diabetes: Proteomic and Mechanistic Insights

PubMed Central

Singh, Priyanka; Jayaramaiah, Ramesha H.; Agawane, Sachin B.; Vannuruswamy, Garikapati; Korwar, Arvind M.; Anand, Atul; Dhaygude, Vitthal S.; Shaikh, Mahemud L.; Joshi, Rakesh S.; Boppana, Ramanamurthy; Kulkarni, Mahesh J.; Thulasiram, Hirekodathakallu V.; Giri, Ashok P.

2016-01-01

Medicinally important genus Ocimum harbors a vast pool of chemically diverse metabolites. Current study aims at identifying anti-diabetic candidate compounds from Ocimum species. Major metabolites in O. kilimandscharicum, O. tenuiflorum, O. gratissimum were purified, characterized and evaluated for anti-glycation activity. In vitro inhibition of advanced glycation end products (AGEs) by eugenol was found to be highest. Preliminary biophysical analysis and blind docking studies to understand eugenol-albumin interaction indicated eugenol to possess strong binding affinity for surface exposed lysines. However, binding of eugenol to bovine serum albumin (BSA) did not result in significant change in secondary structure of protein. In vivo diabetic mice model studies with eugenol showed reduction in blood glucose levels by 38% likely due to inhibition of α-glucosidase while insulin and glycated hemoglobin levels remain unchanged. Western blotting using anti-AGE antibody and mass spectrometry detected notably fewer AGE modified peptides upon eugenol treatment both in vivo and in vitro. Histopathological examination revealed comparatively lesser lesions in eugenol-treated mice. Thus, we propose eugenol has dual mode of action in combating diabetes; it lowers blood glucose by inhibiting α-glucosidase and prevents AGE formation by binding to ε-amine group on lysine, protecting it from glycation, offering potential use in diabetic management. PMID:26739611

Potential Dual Role of Eugenol in Inhibiting Advanced Glycation End Products in Diabetes: Proteomic and Mechanistic Insights.

PubMed

Singh, Priyanka; Jayaramaiah, Ramesha H; Agawane, Sachin B; Vannuruswamy, Garikapati; Korwar, Arvind M; Anand, Atul; Dhaygude, Vitthal S; Shaikh, Mahemud L; Joshi, Rakesh S; Boppana, Ramanamurthy; Kulkarni, Mahesh J; Thulasiram, Hirekodathakallu V; Giri, Ashok P

2016-01-07

Medicinally important genus Ocimum harbors a vast pool of chemically diverse metabolites. Current study aims at identifying anti-diabetic candidate compounds from Ocimum species. Major metabolites in O. kilimandscharicum, O. tenuiflorum, O. gratissimum were purified, characterized and evaluated for anti-glycation activity. In vitro inhibition of advanced glycation end products (AGEs) by eugenol was found to be highest. Preliminary biophysical analysis and blind docking studies to understand eugenol-albumin interaction indicated eugenol to possess strong binding affinity for surface exposed lysines. However, binding of eugenol to bovine serum albumin (BSA) did not result in significant change in secondary structure of protein. In vivo diabetic mice model studies with eugenol showed reduction in blood glucose levels by 38% likely due to inhibition of α-glucosidase while insulin and glycated hemoglobin levels remain unchanged. Western blotting using anti-AGE antibody and mass spectrometry detected notably fewer AGE modified peptides upon eugenol treatment both in vivo and in vitro. Histopathological examination revealed comparatively lesser lesions in eugenol-treated mice. Thus, we propose eugenol has dual mode of action in combating diabetes; it lowers blood glucose by inhibiting α-glucosidase and prevents AGE formation by binding to ε-amine group on lysine, protecting it from glycation, offering potential use in diabetic management.

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.

Influence of age on androgen deprivation therapy-associated Alzheimer’s disease

NASA Astrophysics Data System (ADS)

Nead, Kevin T.; Gaskin, Greg; Chester, Cariad; Swisher-McClure, Samuel; Dudley, Joel T.; Leeper, Nicholas J.; Shah, Nigam H.

2016-10-01

We recently found an association between androgen deprivation therapy (ADT) and Alzheimer’s disease. As Alzheimer’s disease is a disease of advanced age, we hypothesize that older individuals on ADT may be at greatest risk. We conducted a retrospective multi-institutional analysis among 16,888 individuals with prostate cancer using an informatics approach. We tested the effect of ADT on Alzheimer’s disease using Kaplan-Meier age stratified analyses in a propensity score matched cohort. We found a lower cumulative probability of remaining Alzheimer’s disease-free between non-ADT users age ≥70 versus those age <70 years (p < 0.001) and between ADT versus non-ADT users ≥70 years (p = 0.034). The 5-year probability of developing Alzheimer’s disease was 2.9%, 1.9% and 0.5% among ADT users ≥70, non-ADT users ≥70 and individuals <70 years, respectively. Compared to younger individuals older men on ADT may have the greatest absolute Alzheimer’s disease risk. Future work should investigate the ADT Alzheimer’s disease association in advanced age populations given the greater potential clinical impact.

Pitavastatin attenuates AGEs-induced mitophagy via inhibition of ROS generation in the mitochondria of cardiomyocytes.

PubMed

Zha, Zhimin; Wang, Junhong; Li, Shiling; Guo, Yan

2017-11-01

This study aimed to investigate whether pitavastatin protected against injury induced by advanced glycation end products products (AGEs) in neonatal rat cardiomyocytes, and to examine the underlying mechanisms. Cardiomyocytes of neonatal rats were incubated for 48 hours with AGEs (100mg/mL), receptor for advanced glycation end products (RAGE), antibody (1 mg/mL) and pitavastatin (600 ng/mL). The levels of p62 and beclin1 were determined by Western blotting. Mitochondrial membrane potential (DYm) and the generation of reactive oxygen species (ROS) were measured through the JC-1 and DCFH-DA. In the AGEs group, the expression of beclin1 was remarkably increased compared to the control group, while the expression of p62 was significantly decreased. AGEs also markedly decreasedDYm and significantly increased ROS compared with the control group. After treatment with RAGE antibody or pitavastatin, the level of beclin1 was markedly decreased compared with the AGEs group, but the level of p62 was remarkably increased. In the AGEs+ RAGE antibody group and AGEs+ pitavastatin group,DYm was significantly increased and ROS was remarkably decreased compared with the AGEs group. In conclusion, AGEs-RAGE may induce autophagy of cardiomyocytes by generation of ROS and pitavastatin could protect against AGEs-induced injury against cardiomyocytes.

Is There an Association between Advanced Paternal Age and Endophenotype Deficit Levels in Schizophrenia?

PubMed Central

Tsuang, Debby; Esterberg, Michelle; Braff, David; Calkins, Monica; Cadenhead, Kristin; Dobie, Dorcas; Freedman, Robert; Green, Michael F.; Greenwood, Tiffany; Gur, Raquel; Gur, Ruben; Horan, William; Lazzeroni, Laura C.; Light, Gregory A.; Millard, Steven P.; Olincy, Ann; Nuechterlein, Keith; Seidman, Larry; Siever, Larry; Silverman, Jeremy; Stone, William; Sprock, Joyce; Sugar, Catherine; Swerdlow, Neal; Tsuang, Ming; Turetsky, Bruce; Radant, Allen

2014-01-01

The children of older fathers have increased risks of developing schizophrenia spectrum disorders, and among those who develop these disorders, those with older fathers present with more severe clinical symptoms. However, the influence of advanced paternal age on other important domains related to schizophrenia, such as quantitative endophenotype deficit levels, remains unknown. This study investigated the associations between paternal age and level of endophenotypic impairment in a well-characterized family-based sample from the Consortium on the Genetics of Schizophrenia (COGS). All families included at least one affected subject and one unaffected sibling. Subjects met criteria for schizophrenia (probands; n = 293) or were unaffected first-degree siblings of those probands (n = 382). Paternal age at the time of subjects’ birth was documented. Subjects completed a comprehensive clinical assessment and a battery of tests that measured 16 endophenotypes. After controlling for covariates, potential paternal age–endophenotype associations were analyzed using one model that included probands alone and a second model that included both probands and unaffected siblings. Endophenotype deficits in the Identical Pairs version of the 4-digit Continuous Performance Test and in the Penn Computerized Neurocognitive Battery verbal memory test showed significant associations with paternal age. However, after correcting for multiple comparisons, no endophenotype was significantly associated with paternal age. These findings suggest that factors other than advanced paternal age at birth may account for endophenotypic deficit levels in schizophrenia. PMID:24523888

The role of the Australasian Journal on Ageing in the Asia-Oceania region.

PubMed

Howe, Anna L

2013-10-01

The role of the Australasian Journal on Ageing (AJA) in the Asia-Oceania region has been developing over the 30 years of the journal's publication, and review of its current and potential future roles is timely in the context of a number of developments in the region. This review describes the regional reach of the AJA, presents an analysis of regional content published over the 5 years to 2012, discusses the regional context with reference to other journals published in the region, and proposes several strategies for advancing the AJA's regional role. Pursuing these strategies would realise the AJA's potential as a vehicle for promoting the exchange of multidisciplinary knowledge on ageing. © 2013 ACOTA.

A Chronology of Late-Glacial and Holocene Advances of Quelccaya Ice Cap, Peru, Based on 10Be and Radiocarbon Dating

NASA Astrophysics Data System (ADS)

Kelly, M. A.; Lowell, T. V.; Schaefer, J. M.

2007-12-01

The Quelccaya Ice Cap region in the southeastern Peruvian Andes (~13-14°S latitude) is a key location for the development of late-glacial and Holocene terrestrial paleoclimate records in the tropics. We present a chronology of past extents of Quelccaya Ice Cap based on ~thirty internally consistent 10Be dates of boulders on moraines and bedrock as well as twenty radiocarbon dates of organic material associated with moraines. Based on results from both dating methods, we suggest that significant advances of Quelccaya Ice Cap occurred during late-glacial time, at ~12,700-11,400 yr BP, and during Late Holocene time ~400-300 yr BP. Radiocarbon dating of organic material associated with moraines provides maximum and minimum ages for ice advances and recessions, respectively, thus providing an independent check on 10Be dates of boulders on moraines. The opportunity to use both 10Be and radiocarbon dating makes the Quelccaya Ice Cap region a potentially important low-latitude calibration site for production rates of cosmogenic nuclides. Our radiocarbon chronology provides a tighter constraint on maximum ages of late-glacial and Late Holocene ice advances. Upcoming field research will obtain organic material for radiocarbon dating to improve minimum age constrains for late-glacial and Late Holocene ice recessions.

A portable system for noninvasive assessment of advanced glycation end-products using skin fluorescence and reflectance spectrum

NASA Astrophysics Data System (ADS)

Wang, Y. K.; Zhu, L.; Zhang, L.; Zhang, G.; Liu, Y.; Wang, A.

2012-07-01

An optical system has been developed for noninvasive assessment of skin advanced glycation end-products (AGEs). The system comprises mainly a high-power ultraviolet light emitting diode (LED) as an excitation source, an LED array for the reflectance measurement, a trifurcated fiber-optic probe for light transmitting and receiving, and a compact spectrometer for light detecting. Both skin fluorescence of a subject and the reflectance spectrum of the same site can be obtained in a single measurement with the system. Demonstrative measurements with the system have been conducted. Results indicate that the measured reflectance spectrum can be used to compensate for the distortion of AGEs fluorescence, which is caused by skin absorption and scattering. The system is noninvasive, portable, easy to operate, and has potential applications for clinical diagnosis of AGE-related diseases, especially diabetes mellitus.

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

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.

OASIS 2: online application for survival analysis 2 with features for the analysis of maximal lifespan and healthspan in aging research.

PubMed

Han, Seong Kyu; Lee, Dongyeop; Lee, Heetak; Kim, Donghyo; Son, Heehwa G; Yang, Jae-Seong; Lee, Seung-Jae V; Kim, Sanguk

2016-08-30

Online application for survival analysis (OASIS) has served as a popular and convenient platform for the statistical analysis of various survival data, particularly in the field of aging research. With the recent advances in the fields of aging research that deal with complex survival data, we noticed a need for updates to the current version of OASIS. Here, we report OASIS 2 (http://sbi.postech.ac.kr/oasis2), which provides extended statistical tools for survival data and an enhanced user interface. In particular, OASIS 2 enables the statistical comparison of maximal lifespans, which is potentially useful for determining key factors that limit the lifespan of a population. Furthermore, OASIS 2 provides statistical and graphical tools that compare values in different conditions and times. That feature is useful for comparing age-associated changes in physiological activities, which can be used as indicators of "healthspan." We believe that OASIS 2 will serve as a standard platform for survival analysis with advanced and user-friendly statistical tools for experimental biologists in the field of aging research.

Characterizing harmful advanced glycation end-products (AGEs) and ribosylated aggregates of yellow mustard seed phytocystatin: Effects of different monosaccharides.

PubMed

Ahmed, Azaj; Shamsi, Anas; Bano, Bilqees

2017-01-15

Advanced glycation end products (AGEs) are at the core of variety of diseases ranging from diabetes to renal failure and hence gaining wide consideration. This study was aimed at characterizing the AGEs of phytocystatin isolated from mustard seeds (YMP) when incubated with different monosaccharides (glucose, ribose and mannose) using fluorescence, ultraviolet, circular dichroism (CD) spectroscopy and microscopy. Ribose was found to be the most potent glycating agent as evident by AGEs specific fluorescence and absorbance. YMP exists as a molten globule like structure on day 24 as depicted by high ANS fluorescence and altered intrinsic fluorescence. Glycated YMP as AGEs and ribose induced aggregates were observed at day 28 and 32 respectively. In our study we have also examined the anti-aggregative potential of polyphenol, resveratrol. Our results suggested the anti-aggregative behavior of resveratrol as it prevented the in vitro aggregation of YMP, although further studies are required to decode the mechanism by which resveratrol prevents the aggregation. Copyright © 2016 Elsevier B.V. All rights reserved.

Angiopoietin-1 protects the endothelial cells against advanced glycation end product injury by strengthening cell junctions and inhibiting cell apoptosis.

PubMed

Zhao, Jingling; Chen, Lei; Shu, Bin; Tang, Jinming; Zhang, Lijun; Xie, Julin; Liu, Xusheng; Xu, Yingbin; Qi, Shaohai

2015-08-01

Endothelial dysfunction is a major characteristic of diabetic vasculopathy. Protection of the vascular endothelium is an essential aspect of preventing and treating diabetic vascular complications. Although Angiopoietin-1 (Ang-1) is an important endothelial-specific protective factor, whether Ang-1 protects vascular cells undergoing advanced glycation end product (AGE) injury has not been investigated. The aim of the present study was to determine the potential effects of Ang-1 on endothelial cells after exposure to AGE. We show here that Ang-1 prevented AGE-induced vascular leakage by enhancing the adherens junctions between endothelial cells, and this process was mediated by the phosphorylation and membrane localization of VE-cadherin. Furthermore, Ang-1 also protected endothelial cells from AGE-induced death by regulating phosphatidylinositol 3-kinase (PI3K)/Akt-dependent Bad phosphorylation. Our findings suggest that the novel protective mechanisms of Ang-1 on endothelium are achieved by strengthening endothelial cell junctions and reducing endothelial cell death after AGE injury. © 2014 Wiley Periodicals, Inc.

Oxidation products are increased in patients affected by non-segmental generalized vitiligo.

PubMed

Vaccaro, Mario; Bagnato, Gianluca; Cristani, Mariateresa; Borgia, Francesco; Spatari, Giovanna; Tigano, Valeria; Saja, Antonina; Guarneri, Fabrizio; Cannavò, Serafinella P; Gangemi, Sebastiano

2017-08-01

Several lines of evidence support the relevance of reactive oxygen species (ROS) in vitiligo, but the exact role of glycation and oxidation of macromolecules needs to be better addressed. To investigate the involvement of advanced oxidation protein products (AOPPs) and advanced glycation end-products (AGEs), we performed a case-control association study by spectrofluorimetry and spectrophotometry, in 47 patients with non-segmental generalized vitiligo and 47 age- and sex-matched controls. Significantly higher levels of both AOPPs (p < 0.0001) and AGEs (p < 0.0001) were observed in vitiligo patients compared to healthy controls. In vitiligo patients, AGEs and AOPPs serum levels were directly associated with extension, duration of vitiligo, and disease activity. ROS, and in particular AGEs and AOPPs, could represent one of the main biomarkers to assess the onset and progression of vitiligo, due to the potential role as direct inducers of cell damage and also as autoimmunity triggers. Further longitudinal studies involving larger cohorts of patients are required to elucidate the role of oxidation products in the pathogenesis of vitiligo.

Memantine inhibits degradation of the articular cartilage extracellular matrix induced by advanced glycation end products (AGEs).

PubMed

Zhao, Jijun; Yu, Yinghao; Wu, Zhaofeng; Wang, Ling; Li, Wei

2017-07-01

The accumulation of inflammation and cartilage damage induced by advanced glycation end products (AGEs) are important hallmarks of osteoarthritis (OA). Memantine is a clinically licensed drug used for the treatment of moderate and severe Alzheimer's disease. To date, little information has been reported regarding the effects of memantine on cartilage destruction. In this study, we investigated the protective effects of memantine on AGE-induced degradation of collagen II and aggrecans in human SW1353 chondrocytes. Our results indicate that memantine ameliorated AGE-induced degradation of collagen II and aggrecan at the post-translational level in SW1353 cells, which were mediated by matrix metalloproteinase-13 (MMP-13) and A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), respectively. Mechanistically, memantine was found to attenuate the upregulation of the transcriptional factor interferon response factor-1 (IRF-1) induced by AGEs, as well as activation of the JAK2/STAT1 pathway. Our findings suggest that memantine may have a potential therapeutic effect in OA. Copyright © 2017. Published by Elsevier Masson SAS.

Neuroimaging of Cerebrovascular Disease in the Aging Brain

PubMed Central

Gupta, Ajay; Nair, Sreejit; Schweitzer, Andrew D.; Kishore, Sirish; Johnson, Carl E.; Comunale, Joseph P.; Tsiouris, Apostolos J.; Sanelli, Pina C.

2012-01-01

Cerebrovascular disease remains a significant public health burden with its greatest impact on the elderly population. Advances in neuroimaging techniques allow detailed and sophisticated evaluation of many manifestations of cerebrovascular disease in the brain parenchyma as well as in the intracranial and extracranial vasculature. These tools continue to contribute to our understanding of the multifactorial processes that occur in the age-dependent development of cerebrovascular disease. Structural abnormalities related to vascular disease in the brain and vessels have been well characterized with CT and MRI based techniques. We review some of the pathophysiologic mechanisms in the aging brain and cerebral vasculature and the related structural abnormalities detectable on neuroimaging, including evaluation of age-related white matter changes, atherosclerosis of the cerebral vasculature, and cerebral infarction. In addition, newer neuroimaging techniques, such as diffusion tensor imaging, perfusion techniques, and assessment of cerebrovascular reserve, are also reviewed, as these techniques can detect physiologic alterations which complement the morphologic changes that cause cerebrovascular disease in the aging brain.Further investigation of these advanced imaging techniques has potential application to the understanding and diagnosis of cerebrovascular disease in the elderly. PMID:23185721

Growth and maturity status of elite British junior tennis players.

PubMed

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

2016-10-01

Growth and maturation impact the selection, development and progression of youth athletes. Individual differences in the growth and maturity may afford a performance advantage, clouding coaches and practitioners' perceptions regarding current ability and future potential. This may result in the exclusion of talented, yet less physically gifted athletes. Participants were 91 male (n = 47) and female (n = 44) elite British Junior tennis players, 8-17 years of age (12.5 ± 1.9 years). Height and body mass were measured and compared to growth charts; hand-wrist radiographs were taken. Skeletal age (SA) was estimated with the Fels method and contrasted to chronological age (CA). Mean height and body mass of individual players ranged between the 50th and 90th centiles for age and sex. Females were advanced in SA relative to CA (0.3-0.89 years.) from 8 years. Males were average to delayed in maturation from 8 to 12 years, but advanced in SA from 14 to 16 years (0.75-1.23 years). Individual differences in growth and maturation appear to contribute towards the selection of elite junior tennis players, with a bias towards males and females who are advanced in maturation and comparatively tall and heavy for their age. This has important implications for talent identification and development.

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.

Contribution of maternal age to preterm birth rates in Denmark and Quebec, 1981-2008.

PubMed

Auger, Nathalie; Hansen, Anne V; Mortensen, Laust

2013-10-01

We sought evidence to support the hypothesis that advancing maternal age is potentially causing a rise in preterm birth (PTB) rates in high-income countries. We assessed maternal age-specific trends in PTB using all singleton live births in Denmark (n = 1 674 308) and Quebec (n = 2 291 253) from 1981 to 2008. We decomposed the country-specific contributions of age-specific PTB rates and maternal age distribution to overall PTB rates over time. PTB rates increased from 4.4% to 5.0% in Denmark and from 5.1% to 6.0% in Quebec. Rates increased the most in women aged 20 to 29 years, whereas rates decreased or remained stable in women aged 35 years and older. The overall increase over time was driven by age-specific PTB rates, although the contribution of younger women was countered by fewer births at this age in both Denmark and Quebec. PTB rates increased among women aged 20 to 29 years, but their contribution to the overall PTB rates was offset by older maternal age over time. Women aged 20 to 29 years should be targeted to reduce PTB rates, as potential for prevention may be greater in this age group.

Calculus in Elementary School: An Example of ICT-Based Curriculum Transformation

ERIC Educational Resources Information Center

Fluck, Andrew; Ranmuthugala, Dev; Chin, Chris; Penesis, Irene

2012-01-01

Integral calculus is generally regarded as a fundamental but advanced aspect of mathematics, and it is not generally studied until students are aged about fifteen or older. Understanding the transformative potential of information and communication technology, this project undertook an investigation in four Australian schools to train students…

Older Women's Career Development and Social Inclusion

ERIC Educational Resources Information Center

McMahon, Mary; Bimrose, Jenny; Watson, Mark

2010-01-01

This paper considers women's career development and the potential contribution of career development theory, research, practice and policy in advancing a social inclusion agenda. In particular, the paper focuses on older women in the contexts of an ageing population, labour market shortages and Australia's social inclusion agenda. Supporting young…

Much aMOOC about Nothing: Is Real Research Coming?

ERIC Educational Resources Information Center

Williams, Vicki; Su, Nai-Fen

2015-01-01

In this age of continual technology advances, educators have become somewhat used to rapid innovation and change brought on by new learning technologies. Higher education institutions are constantly researching new forms of educational delivery, but academe in general has had some difficulty understanding the potential of MOOCs. To date, serious…

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.

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.

Current role challenges in New Zealand aged residential care: the potential consequences for healthcare assistant role expansion.

PubMed

Shannon, Kay; McKenzie-Green, Barbara

2016-01-01

Challenges facing healthcare assistants in aged residential care are a focus of global debate. These challenges involve remuneration, education, skill mix, work conditions and organisational structures. We enter the discussion by acknowledging current work, education and remuneration for healthcare assistants. We then consider the supervisory relationships between registered nurses (RNs), enrolled nurses (ENs) and healthcare assistants, educational levels for RNs, ENs and healthcare assistants, and the interplay between organisation and practice in aged residential care. We suggest that improving work for the healthcare assistant has the potential to lead change in all role levels. Discussion paper. We argue that adjustments to work structures, education and skill advancement of RNs, ENs and healthcare assistants could improve staff working conditions and clarify practice boundaries. The ultimate result is likely to be an improvement to quality of care and the life of residents in aged residential care.

Magnetic resonance imaging of aging, accommodating, phakic, and pseudophakic ciliary muscle diameters

PubMed Central

Strenk, Susan A.; Strenk, Lawrence M.; Guo, Suqin

2012-01-01

PURPOSE To quantify in vivo accommodative changes in the aging human ciliary muscle diameter in phakic and pseudophakic eyes. SETTING Department of Surgery/Bioengineering, UMDNJ–Robert Wood Johnson Medical School, Piscataway, and the Institute of Ophthalmology and Visual Science UMDNJ–New Jersey Medical School, Newark, New Jersey, USA. METHODS Images were acquired from 48 eyes of 40 people between the ages of 22 and 91 years, 1 eye of 32 phakic volunteers and both eyes of 8 patients who had monocular implantation of a single-piece AcrySof intraocular lens (IOL) (Alcon Laboratories). Images were acquired during physiological accommodation and with accommodation at rest, and the diameter of the ciliary muscle ring was measured. RESULTS Results show the ciliary muscle remains active throughout life. The accommodative change in its diameter (mean 0.64 mm) (P<.00001) was undiminished by age or IOL implantation. Preliminary data showed that the accommodative decrease in muscle diameter in phakic and pseudophakic eyes was statistically identical. The phakic eyes had a marked decrease in ciliary muscle diameter with advancing age for both accommodative states (P<.000001 and P<.000001), which did not appear to be altered by IOL implantation. The lens equator was constant with age in the unaccommodated human eye, resulting in decreased circumlental space with advancing age in the phakic eyes. CONCLUSION Although the undiminished ability of the ciliary muscle to decrease its diameter with accommodation can be relied on in strategies for presbyopia correction, even in advanced presbyopia, the decreasing circumlental space and its potential effects on zonular tension must also be considered. PMID:17081859

Dietary Epigenetics in Cancer and Aging

PubMed Central

Tollefsbol, Trygve O.

2013-01-01

Although epigenetic aberrations frequently occur in aging and cancer and form a core component of these conditions, perhaps the most useful aspect of epigenetic processes is that they are readily reversible. Unlike genetic effects that also play a role in cancer and aging, epigenetic aberrations can be relatively easily corrected. One of the most widespread approaches to the epigenetic alterations in cancer and aging is dietary control. This can be achieved not only through the quality of the diet, but also through the quantity of calories that are consumed. Many phytochemicals such as sulforaphane from cruciferous vegetables and green tea have anticancer epigenetic effects and are also efficacious for preventing or treating the epigenetic aberrations of other age-associated diseases besides cancer. Likewise, the quantity of calories that are consumed have proven to be advantageous in preventing cancer and extending the lifespan through control of epigenetic mediators. The purpose of this chapter is to review some of the most recent advances in the epigenetics of cancer and aging and to provide insights into advances being made with respect to dietary intervention into these biological processes that have vast health implications and high translational potential. PMID:24114485

Aging alters mRNA expression of amyloid transporter genes at the blood-brain barrier.

PubMed

Osgood, Doreen; Miller, Miles C; Messier, Arthur A; Gonzalez, Liliana; Silverberg, Gerald D

2017-09-01

Decreased clearance of potentially toxic metabolites, due to aging changes, likely plays a significant role in the accumulation of amyloid-beta (Aβ) peptides and other macromolecules in the brain of the elderly and in the patients with Alzheimer's disease (AD). Aging is the single most important risk factor for AD development. Aβ transport receptor proteins expressed at the blood-brain barrier are significantly altered with age: the efflux transporters lipoprotein receptor-related protein 1 and P-glycoprotein are reduced, whereas the influx transporter receptor for advanced glycation end products is increased. These receptors play an important role in maintaining brain biochemical homeostasis. We now report that, in a rat model of aging, gene transcription is altered in aging, as measured by Aβ receptor gene messenger RNA (mRNA) at 3, 6, 9, 12, 15, 20, 30, and 36 months. Gene mRNA expression from isolated cerebral microvessels was measured by quantitative polymerase chain reaction. Lipoprotein receptor-related protein 1 and P-glycoprotein mRNA were significantly reduced in aging, and receptor for advanced glycation end products was increased, in parallel with the changes seen in receptor protein expression. Transcriptional changes appear to play a role in aging alterations in blood-brain barrier receptor expression and Aβ accumulation. Copyright © 2017 Elsevier Inc. All rights reserved.

Advanced glycation end products induce cell cycle arrest and proinflammatory changes in osteoarthritic fibroblast-like synovial cells

PubMed Central

2009-01-01

Introduction Advanced glycation end products (AGEs) have been introduced to be involved in the pathogenesis of osteoarthritis (OA). The influence of AGEs on osteoarthritic fibroblast-like synovial cells (FLS) has been incompletely understood as yet. The present study investigates a potential influence of AGE-modified bovine serum albumin (AGE-BSA) on cell growth, and on the expression of proinflammatory and osteoclastogenic markers in cultured FLS. Methods FLS were established from OA joints and stimulated with AGE-BSA. The mRNA expression of p27Kip1, RAGE (receptor for AGEs), nuclear factor kappa B subunit p65 (NFκB p65), tumor necrosis factor alpha (TNF-α, interleukin-6 (IL-6), receptor activator of NFκB ligand (RANKL) and osteoprotegerin was measured by real-time PCR. The respective protein expression was evaluated by western blot analysis or ELISA. NFκB activation was investigated by luciferase assay and electrophoretic mobility shift assay (EMSA). Cell cycle analysis, cell proliferation and markers of necrosis and early apoptosis were assessed. The specificity of the response was tested in the presence of an anti-RAGE antibody. Results AGE-BSA was actively taken up into the cells as determined by immunohistochemistry and western blots. AGE-induced p27Kip1 mRNA and protein expression was associated with cell cycle arrest and an increase in necrotic, but not apoptotic cells. NFκB activation was confirmed by EMSAs including supershift experiments. Anti-RAGE antibodies attenuated all AGE-BSA induced responses. The increased expression of RAGE, IL-6 and TNF-α together with NFκB activation indicates AGE-mediated inflammation. The decreased expression of RANKL and osteoprotegerin may reflect a diminished osteoclastogenic potential. Conclusions The present study demonstrates that AGEs modulate growth and expression of genes involved in the pathophysiological process of OA. This may lead to functional and structural impairment of the joints. PMID:19735566

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.

[Cardiac rehabilitation. Recent advances].

PubMed

Lellamo, Ferdinando; Volterrani, Maurizio

2010-03-01

Evidence derived from studies which support the relevance of exercise as a core component of cardiac rehabilitation programs are presented, along with the beneficial effects of exercise training in counteracting the mechanisms sustaining the atherosclerotic process and cardiovascular risk factors in the context of secundary, as well as primary, cardiovascular prevention. Practical guides to plan exercise training programs are also provided with suggestions for specific pathological conditions and advanced age. Recent advances on the benefits of exercise training in patients with heart failure are reported along with the potential of telemedicine for home rehabilitation aiming to a widespread diffusion of exercise as a cardiovascular therapy. Finally, the possible risks of exercise and practical open questions in cardiac rehabilitation are discussed.

Advanced glycation end products promote the proliferation and migration of primary rat vascular smooth muscle cells via the upregulation of BAG3

PubMed Central

Li, Cunshu; Chang, Ye; Li, Yuan; Chen, Shuang; Chen, Yintao; Ye, Ning; Dai, Dongxue; Sun, Yingxian

2017-01-01

The present study was aimed to investigate the role of reactive oxygen species (ROS) on advanced glycation end product (AGE)-induced proliferation and migration of vascular smooth muscle cells (VSMCs) and whether Bcl-2-associated athanogene 3 (BAG3) is involved in the process. Primary rat VSMCs were extracted and cultured in vitro. Cell viability was detected by MTT assay and cell proliferation was detected by EdU incorporation assay. Cell migration was detected by wound healing and Transwell assays. BAG3 was detected using qPCR and western blot analysis. Transcriptional and translational inhibitors (actinomycin D and cycloheximide, respectively) were used to study the effect of AGEs on the expression of BAG3 in VSMCs. Lentiviral plasmids containing short hairpin RNA (shRNA) against rat BAG3 or control shRNA were transduced into VSMCs. Cellular ROS were detected by 2′,7′-dichlorofluorescein diacetate (DCFH-DA) staining. Mitochondrial membrane potential was detected by tetramethylrhodamine methyl ester (TMRE) staining. AGEs significantly increased the expression of BAG3 in a dose-and time-dependent manner. Furthermore, AGEs mainly increased the expression of BAG3 mRNA by increasing the RNA synthesis rather than inhibiting the RNA translation. BAG3 knockdown reduced the proliferation and migration of VSMCs induced by AGEs. BAG3 knockdown reduced the generation of ROS and sustained the mitochondrial membrane potential of VSMCs. Reduction of ROS production by N-acetylcysteine (NAC), a potent antioxidant, also reduced the proliferation and migration of VSMCs. On the whole, the present study demonstrated for the first time that AGEs could increase ROS production and promote the proliferation and migration of VSMCs by upregulating BAG3 expression. This study indicated that BAG3 should be considered as a potential target for the prevention and/or treatment of vascular complications of diabetes. PMID:28350077

Advanced glycation end products promote the proliferation and migration of primary rat vascular smooth muscle cells via the upregulation of BAG3.

PubMed

Li, Cunshu; Chang, Ye; Li, Yuan; Chen, Shuang; Chen, Yintao; Ye, Ning; Dai, Dongxue; Sun, Yingxian

2017-05-01

The present study was aimed to investigate the role of reactive oxygen species (ROS) on advanced glycation end product (AGE)-induced proliferation and migration of vascular smooth muscle cells (VSMCs) and whether Bcl-2‑associated athanogene 3 (BAG3) is involved in the process. Primary rat VSMCs were extracted and cultured in vitro. Cell viability was detected by MTT assay and cell proliferation was detected by EdU incorporation assay. Cell migration was detected by wound healing and Transwell assays. BAG3 was detected using qPCR and western blot analysis. Transcriptional and translational inhibitors (actinomycin D and cycloheximide, respectively) were used to study the effect of AGEs on the expression of BAG3 in VSMCs. Lentiviral plasmids containing short hairpin RNA (shRNA) against rat BAG3 or control shRNA were transduced into VSMCs. Cellular ROS were detected by 2',7'-dichlorofluorescein diacetate (DCFH-DA) staining. Mitochondrial membrane potential was detected by tetramethylrhodamine methyl ester (TMRE) staining. AGEs significantly increased the expression of BAG3 in a dose-and time-dependent manner. Furthermore, AGEs mainly increased the expression of BAG3 mRNA by increasing the RNA synthesis rather than inhibiting the RNA translation. BAG3 knockdown reduced the proliferation and migration of VSMCs induced by AGEs. BAG3 knockdown reduced the generation of ROS and sustained the mitochondrial membrane potential of VSMCs. Reduction of ROS production by N-acetylcysteine (NAC), a potent antioxidant, also reduced the proliferation and migration of VSMCs. On the whole, the present study demonstrated for the first time that AGEs could increase ROS production and promote the proliferation and migration of VSMCs by upregulating BAG3 expression. This study indicated that BAG3 should be considered as a potential target for the prevention and/or treatment of vascular complications of diabetes.

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

National Trends and Predictors of Locally Advanced Penile Cancer in the United States (1998-2012).

PubMed

Chipollini, Juan; Chaing, Sharon; Peyton, Charles C; Sharma, Pranav; Kidd, Laura C; Giuliano, Anna R; Johnstone, Peter A; Spiess, Philippe E

2017-08-12

We analyzed the trends in presentation of squamous cell carcinoma (SCC) of the penis and determined the socioeconomic predictors for locally advanced (cT3-cT4) disease in the United States. The National Cancer Database was queried for patients with clinically nonmetastatic penile SCC and staging available from 1998 to 2012. Temporal trends per tumor stage were evaluated, and a multivariable logistic regression model was used to identify predictors for advanced presentation during the study period. A total of 5767 patients with stage ≤ T1-T2 (n = 5423) and T3-T4 (n = 344) disease were identified. Increasing trends were noted in all stages of penile SCC with a greater proportion of advanced cases over time (P = .001). Significant predictors of advanced presentation were age > 55 years, the presence of comorbidities, and Medicaid or no insurance (P < .05 for all). More penile SCC is being detected in the United States. Our results have demonstrated older age, presence of comorbidities, and Medicaid or no insurance as potential barriers to early access of care in the male population. Understanding the current socioeconomic gaps could help guide targeted interventions in vulnerable populations. Copyright © 2017 Elsevier Inc. All rights reserved.

[Find your 1%: prevalence and mortality of a community cohort of people with advanced chronic disease and palliative needs].

PubMed

Blay, Carles; Martori, Joan Carles; Limón, Esther; Oller, Ramon; Vila, Laura; Gómez-Batiste, Xavier

2017-11-17

To determine the prevalence and profiles of people with advanced chronic diseases in Primary Care and to analyse the elements related to their mortality in order to orient strategies for improvement in this level of care. An observational, analytical and prospective study during 3 years conducted on a cohort of patients with palliative needs. Three Primary Care teams of Osona (Catalonia). A total of 251 people identified as advanced patients using a systematic population-based strategy that included the NECPAL tool. Basic demographic and clinical profile (age, gender, type of residence, health stratification level and main disease); date, place, and cause of eventual deaths. 1% of the adult Primary Care population suffer from advanced diseases, of which 56.6% are women, and with a median age of 85 years. Dementia or advanced frailty is observed in 49.3%, and only 13.7% have cancer. Just under one-quarter (24.3%) live in nursing homes. The accumulated mortality at 3 years is 62.1%, with a median survival of 23 months. Factors significantly associated with the likelihood of dying are cancer, female gender, and over-aging. Patients died at their home (47.3%), in an intermediate care hospital (37.2%), or in an acute care hospital (15.5%), depending on certain explanatory factors. The prevalence and characteristics of advanced community-based disease coincide with that reported in the literature. Potentially, Primary Care is the reference level of care for these patients, especially if it incorporates nursing homes as a usual field of practice. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

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.

Next Steps for "Big Data" in Education: Utilizing Data-Intensive Research

ERIC Educational Resources Information Center

Dede, Chris

2016-01-01

Data-informed instructional methods offer tremendous promise for increasing the effectiveness of teaching, learning, and schooling. Yet-to-be-developed data science approaches have the potential to dramatically advance instruction for every student and to enhance learning for people of all ages. Next steps that emerged from a recent National…

Curcumin against advanced glycation end products (AGEs) and AGEs-induced detrimental agents.

PubMed

Alizadeh, Mohammad; Kheirouri, Sorayya

2017-11-29

This study was aimed to review and collate effects of curcumin on generation of advanced glycation end products (AGEs) and AGEs induced detrimental agents. Pubmed, Googlescholar, ScienceDirect, and Scopus databases were searched. Searching was not limited to specific publication period. Only English language original articles (in vitro, experimental and human) which had examined the effect of curcumin on AGEs formation and AGEs induced apoptosis, oxidative stress or inflammatory responses were included. To review effect of curcumin on AGEs formation, search terms were as following: ''curcumin" (title) and AGEs or pentosidine or methylglyoxal or carboxymethyllysine or glucosylation (title/abstract). Totally 104 articles were searched which 19 were selected for review. To review effect of curcumin on AGEs induced harmful agents, key words were as following: "curcumin" (title) and AGEs (title/abstract) and apoptosis or oxidative stress or DNA damage or cell injury or inflammatory or cell death or cell proliferation (title/abstract). Totally 126 articles were searched which 18 were found appropriate for review. Regarding curcumin and AGEs formation, ten eligible articles (1 human trial, 5 animal models and 4 in vitro) and with regarding curcumin and AGEs-induced complications, 17 articles (5 on apoptosis, 9 on oxidative stress, and 3 on inflammatory responses) were selected. Except one, all studies indicated that curcumin is able to prevent AGEs formation and AGEs-induced disturbances with different potential mechanisms. Curcumin can inhibit AGEs formation and AGEs-induced disturbances. More RCT researches are suggested to evaluate beneficial effect of curcumin regarding AGEs in different age-related chronic diseases, with specific attention to AGEs memberships.

Insulin-like Growth Factor 1 (IGF-1) as a marker of cognitive decline in normal ageing: A review.

PubMed

Frater, Julanne; Lie, David; Bartlett, Perry; McGrath, John J

2018-03-01

Insulin-like Growth Factor 1 (IGF-1) and its signaling pathway play a primary role in normal growth and ageing, however serum IGF-1 is known to reduce with advancing age. Recent findings suggest IGF-1 is essential for neurogenesis in the adult brain, and this reduction of IGF-1 with ageing may contribute to age-related cognitive decline. Experimental studies have shown manipulation of the GH/GF-1 axis can slow rates of cognitive decline in animals, making IGF-1 a potential biomarker of cognition, and/or its signaling pathway a possible therapeutic target to prevent or slow age-related cognitive decline. A systematic literature review and qualitative narrative summary of current evidence for IGF-1 as a biomarker of cognitive decline in the ageing brain was undertaken. Results indicate IGF-1 concentrations do not confer additional diagnostic information for those with cognitive decline, and routine clinical measurement of IGF-1 is not currently justified. In cases of established cognitive impairment, it remains unclear whether increasing circulating or brain IGF-1 may reverse or slow down the rate of further decline. Advances in neuroimaging, genetics, neuroscience and the availability of large well characterized biobanks will facilitate research exploring the role of IGF-1 in both normal ageing and age-related cognitive decline. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Associations Between Gross Motor and Communicative Development in At-Risk Infants

PubMed Central

LeBarton, Eve Sauer; Iverson, Jana M.

2016-01-01

Infants' advances in locomotion relate to advances in communicative development. However, little is known about these relations in infants at risk for delays in these domains and whether they may extend to earlier achievements in gross motor development in infancy. We examined whether advances in sitting and prone locomotion are related to communicative development in infants who have an older sibling with autism spectrum disorder (ASD) and are at risk for motor and communication delays (heightened-risk; HR). We conducted a longitudinal study with 37 HR infants who did not receive an ASD diagnosis at 36 months. Infants were observed monthly between the ages of 5 and 14 months. We assessed gross motor development using the Alberta Infant Motor Scales (AIMS) and recorded ages of onset of verbal and nonverbal communicative behaviors. Results indicated increased presence of early gross motor delay from 5 to 10 months. In addition, there were positive relations between sitting and gesture and babble onset and between prone development and gesture onset. Thus, links between gross motor development and communication extend to at-risk development and provide a starting point for future research on potential cascading consequences of motor advances on communication development. PMID:27314943

Retaining the nursing workforce: factors contributing to the reduction of nurses' turnover intention in Japan.

PubMed

Takase, Miyuki; Teraoka, Sachiko; Yabase, Kousuke

2016-01-01

The aim of this study was to investigate the effects of psychological contract fulfilment, perceived advancement opportunities and age on reducing the turnover intention of nurses in Japan. The factors that contribute to and mitigate the intentions of nurses to leave their organisations need to be investigated to understand the determinants of nurse turnover better. However, there is a paucity of studies identifying these mitigating factors. Potential participants were 1337 registered nurses and midwives, of whom 766 participated in the study (a return rate of 57%). The data were analysed using a moderated regression analysis. Fulfilment of the psychological contract and perceived advancement opportunities independently and jointly contributed to a reduction in nurses' turnover intentions. The results also showed that nurses' ages were negatively correlated with their turnover intentions. Fulfilment of the psychological contract and advancement opportunities are important for reducing nurses' turnover intentions, especially among younger nurses. Clear guidelines/evaluations of contributions made by nurses and their organisations are needed to enhance the experience of nurses in terms of psychological contract fulfilment. Moreover, a structured advancement support system needs to be implemented to reduce nurses' turnover intentions. © 2014 John Wiley & Sons Ltd.

Specific bioactive compounds in ginger and apple alleviate hyperglycemia in mice with high fat diet-induced obesity via Nrf2 mediated pathway.

PubMed

Sampath, Chethan; Rashid, Muhammed Raihan; Sang, Shengmin; Ahmedna, Mohamed

2017-07-01

Prolonged hyperglycemia activates the formation of advanced glycation end-products (AGEs). Major dicarbonyl compounds such as methylglyoxal or glyoxal are found to be the main precursors of AGEs and N(ε)-(carboxymethyl)lysine (CML) found to be predominantly higher in the diabetic population. We hypothesized that phloretin from apple and [6]-gingerol from ginger inhibit formation of AGEs and suppress the receptor for advanced glycation end products (RAGE) via nuclear factor erythroid-2-related-factor-2 (Nrf2)-dependent pathway. Phloretin and [6]-gingerol were supplemented at two different doses to C57BL/6 mice on high fat diet or standard diet for a period of 17weeks. Phloretin or [6]-gingerol supplementation significantly reduced plasma glucose, alanine aminotransferase, aspartate aminotransferase, AGEs and insulin levels. Phloretin and [6]-gingerol also decreased the levels of AGEs and CML levels, via Nrf2 pathway, enhancing GSH/GSSG ratio, heme oxygenase-1 and glyoxalase 1 in liver tissue. These results suggest that phloretin and [6]-gingerol are potential dietary compounds that can alleviate diabetes-induced complications. Copyright © 2017 Elsevier Ltd. All rights reserved.

The in vitro protective effects of curcumin and demethoxycurcumin in Curcuma longa extract on advanced glycation end products-induced mesangial cell apoptosis and oxidative stress.

PubMed

Liu, Ji-ping; Feng, Liang; Zhu, Mao-mao; Wang, Ru-Shang; Zhang, Ming-hua; Hu, Shao-ying; Jia, Xiao-bin; Wu, Jin-Jie

2012-11-01

Curcuma longa L. (CLL), a traditional herbal medicine, has been widely used for the prevention of diabetic vascular complications in recent years. However, the protective effects of curcuminoids in CLL on the AGEs-induced damage to mesangial cell are not fully understood. In this present study, dihydroethidium, superoxide dismutase kit, malondialdehyde kit, and acridine orange/ethidium bromide staining methods were used to evaluate the activities of curcumin and demethoxycurcumin (10(-11)-10(-9) M) on AGEs-induced oxidative stress and apoptosis, which were associated with the damage to mesangial cell. The results showed that these two compounds could significantly restore advanced glycation end products (AGEs)-induced apoptosis to normal levels (IC50 = 3.874 × 10(-11) M for curcumin and IC50 = 6.085 × 10(-11) M for demethoxycurcumin) and reduce remarkably reactive oxygen species generation in mesangial cell. Furthermore, curcumin and demethoxycurcumin dramatically elevated AGEs-decreased superoxide dismutase activity while significantly reducing AGEs-increased malondialdehyde content in cell culture supernatant. Our results suggest that both curcumin and demethoxycurcumin have a significant protective potential to the prevention of diabetic nephropathy. Georg Thieme Verlag KG Stuttgart · New York.

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.

Two new prenylflavonoids from Epimedii Herba and their inhibitory effects on advanced glycation end-products.

PubMed

Nakashima, Keisuke; Miyashita, Hiroyuki; Yoshimitsu, Hitoshi; Fujiwara, Yukio; Nagai, Ryoji; Ikeda, Tsuyoshi

2016-04-01

Because inhibitors of advanced glycation end-products (AGEs), for example pyridoxamine, significantly inhibit the development of retinopathy and neuropathy in rats with streptozotocin-induced diabetes, treatment with AGE inhibitors is believed to be a potential strategy for the prevention of lifestyle-related diseases such as diabetic complications. In the present study, the MeOH extract of Epimedii Herba (EH; aerial parts of Epimedium spp.) was found to inhibit the formation of N (ε) -(carboxymethyl)lysine (CML) and N (ω) -(carboxymethyl)arginine (CMA) during incubation of collagen-derived gelatin with ribose. Furthermore, compounds with inhibitory effects against CML and CMA formation were isolated from EH. Two new prenylflavonoids (compounds 1 and 2) and two known compounds (3 and 4) were found to significantly inhibit the formation of both CML and CMA; compound 4 (epimedokoreanin B) had the strongest inhibitory effect of the isolated compounds. These data suggest that epimedokoreanin B could prevent clinical complications of diabetes by inhibiting AGEs.

Effect of Embryo Banking on U.S. National Assisted Reproductive Technology Live Birth Rates.

PubMed

Kushnir, Vitaly A; Barad, David H; Albertini, David F; Darmon, Sarah K; Gleicher, Norbert

2016-01-01

Assisted Reproductive Technology (ART) reports generated by the Centers for Disease Control and Prevention (CDC) exclude embryo banking cycles from outcome calculations. We examined data reported to the CDC in 2013 for the impact of embryo banking exclusion on national ART outcomes by recalculating autologous oocyte ART live birth rates. Inflation of reported fresh ART cycle live birth rates was assessed for all age groups of infertile women as the difference between fresh cycle live births with reference to number of initiated fresh cycles (excluding embryo banking cycles), as typically reported by the CDC, and fresh cycle live births with reference to total initiated fresh ART cycles (including embryo banking cycles). During 2013, out of 121,351 fresh non-donor ART cycles 27,564 (22.7%) involved embryo banking. The proportion of banking cycles increased with female age from 15.5% in women <35 years to 56.5% in women >44 years. Concomitantly, the proportion of thawed cycles decreased with advancing female age (P <0.0001). Exclusion of embryo banking cycles led to inflation of live birth rates in fresh ART cycles, increasing in size in parallel to advancing female age and utilization of embryo banking, reaching 56.3% in women age >44. The inflation of live birth rates in thawed cycles could not be calculated from the publically available CDC data but appears to be even greater. Utilization of embryo banking increased during 2013 with advancing female age, suggesting a potential age selection bias. Exclusion of embryo banking cycles from national ART outcome reports significantly inflated national ART success rates, especially among older women. Exclusion of embryo banking cycles from US National Assisted Reproductive Technology outcome reports significantly inflates reported success rates especially in older women.

Effect of Embryo Banking on U.S. National Assisted Reproductive Technology Live Birth Rates

PubMed Central

Kushnir, Vitaly A.; Barad, David H.; Albertini, David F.; Darmon, Sarah K.; Gleicher, Norbert

2016-01-01

Background Assisted Reproductive Technology (ART) reports generated by the Centers for Disease Control and Prevention (CDC) exclude embryo banking cycles from outcome calculations. Methods We examined data reported to the CDC in 2013 for the impact of embryo banking exclusion on national ART outcomes by recalculating autologous oocyte ART live birth rates. Inflation of reported fresh ART cycle live birth rates was assessed for all age groups of infertile women as the difference between fresh cycle live births with reference to number of initiated fresh cycles (excluding embryo banking cycles), as typically reported by the CDC, and fresh cycle live births with reference to total initiated fresh ART cycles (including embryo banking cycles). Results During 2013, out of 121,351 fresh non-donor ART cycles 27,564 (22.7%) involved embryo banking. The proportion of banking cycles increased with female age from 15.5% in women <35 years to 56.5% in women >44 years. Concomitantly, the proportion of thawed cycles decreased with advancing female age (P <0.0001). Exclusion of embryo banking cycles led to inflation of live birth rates in fresh ART cycles, increasing in size in parallel to advancing female age and utilization of embryo banking, reaching 56.3% in women age >44. The inflation of live birth rates in thawed cycles could not be calculated from the publically available CDC data but appears to be even greater. Conclusions Utilization of embryo banking increased during 2013 with advancing female age, suggesting a potential age selection bias. Exclusion of embryo banking cycles from national ART outcome reports significantly inflated national ART success rates, especially among older women. Précis Exclusion of embryo banking cycles from US National Assisted Reproductive Technology outcome reports significantly inflates reported success rates especially in older women. PMID:27159215

Risk of Advanced Neoplasia in First-Degree Relatives with Colorectal Cancer: A Large Multicenter Cross-Sectional Study

PubMed Central

Quintero, Enrique; Gargallo, Carla; Lanas, Angel; Bujanda, Luis; Gimeno-García, Antonio Z.; Hernández-Guerra, Manuel; Nicolás-Pérez, David; Alonso-Abreu, Inmaculada; Morillas, Juan Diego; Balaguer, Francesc; Muriel, Alfonso

2016-01-01

Background First-degree relatives (FDR) of patients with colorectal cancer have a higher risk of developing colorectal cancer than the general population. For this reason, screening guidelines recommend colonoscopy every 5 or 10 y, starting at the age of 40, depending on whether colorectal cancer in the index-case is diagnosed at <60 or ≥60 y, respectively. However, studies on the risk of neoplastic lesions are inconclusive. The aim of this study was to determine the risk of advanced neoplasia (three or more non-advanced adenomas, advanced adenoma, or invasive cancer) in FDR of patients with colorectal cancer compared to average-risk individuals (i.e., asymptomatic adults 50 to 69 y of age with no family history of colorectal cancer). Methods and Findings This cross-sectional analysis includes data from 8,498 individuals undergoing their first lifetime screening colonoscopy between 2006 and 2012 at six Spanish tertiary hospitals. Of these individuals, 3,015 were defined as asymptomatic FDR of patients with colorectal cancer (“familial-risk group”) and 3,038 as asymptomatic with average-risk for colorectal cancer (“average-risk group”). The familial-risk group was stratified as one FDR, with one family member diagnosed with colorectal cancer at ≥60 y (n = 1,884) or at <60 y (n = 831), and as two FDR, with two family members diagnosed with colorectal cancer at any age (n = 300). Multiple logistic regression analysis was used for between-group comparisons after adjusting for potential confounders (age, gender, and center). Compared with the average-risk group, advanced neoplasia was significantly more prevalent in individuals having two FDR with colorectal cancer (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.36–2.66, p < 0.001), but not in those having one FDR with colorectal cancer diagnosed at ≥60 y (OR 1.03; 95% CI 0.83–1.27, p = 0.77) and <60 y (OR 1.19; 95% CI 0.90–1.58, p = 0.20). After the age of 50 y, men developed advanced neoplasia over two times more frequently than women and advanced neoplasia appeared at least ten y earlier. Fewer colonoscopies by 2-fold were required to detect one advanced neoplasia in men than in women. Major limitations of this study were first that although average-risk individuals were consecutively included in a randomized control trial, this was not the case for all individuals in the familial-risk cohort; and second, the difference in age between the average-risk and familial-risk cohorts. Conclusions Individuals having two FDR with colorectal cancer showed an increased risk of advanced neoplasia compared to those with average-risk for colorectal cancer. Men had over 2-fold higher risk of advanced neoplasia than women, independent of family history. These data suggest that screening colonoscopy guidelines should be revised in the familial-risk population. PMID:27138769

Biomarkers of aging in Drosophila.

PubMed

Jacobson, Jake; Lambert, Adrian J; Portero-Otín, Manuel; Pamplona, Reinald; Magwere, Tapiwanashe; Miwa, Satomi; Driege, Yasmine; Brand, Martin D; Partridge, Linda

2010-08-01

Low environmental temperature and dietary restriction (DR) extend lifespan in diverse organisms. In the fruit fly Drosophila, switching flies between temperatures alters the rate at which mortality subsequently increases with age but does not reverse mortality rate. In contrast, DR acts acutely to lower mortality risk; flies switched between control feeding and DR show a rapid reversal of mortality rate. Dietary restriction thus does not slow accumulation of aging-related damage. Molecular species that track the effects of temperatures on mortality but are unaltered with switches in diet are therefore potential biomarkers of aging-related damage. However, molecular species that switch upon instigation or withdrawal of DR are thus potential biomarkers of mechanisms underlying risk of mortality, but not of aging-related damage. Using this approach, we assessed several commonly used biomarkers of aging-related damage. Accumulation of fluorescent advanced glycation end products (AGEs) correlated strongly with mortality rate of flies at different temperatures but was independent of diet. Hence, fluorescent AGEs are biomarkers of aging-related damage in flies. In contrast, five oxidized and glycated protein adducts accumulated with age, but were reversible with both temperature and diet, and are therefore not markers either of acute risk of dying or of aging-related damage. Our approach provides a powerful method for identification of biomarkers of aging.

Biomarkers of ageing in Drosophila

PubMed Central

Jacobson, Jake; Portero-Otín, Manuel; Pamplona, Reinald; Magwere, Tapiwanashe; Miwa, Satomi; Driege, Yasmine; Brand, Martin D.; Partridge, Linda

2015-01-01

Summary Low environmental temperature and dietary restriction (DR) extend lifespan in diverse organisms. In the fruit fly Drosophila, switching flies between temperatures alters the rate at which mortality subsequently increases with age but does not reverse mortality rate. In contrast, DR acts acutely to lower mortality risk; flies switched between control feeding and DR show a rapid reversal of mortality rate. DR thus does not slow accumulation of ageing-related damage. Molecular species that track the effects of temperatures on mortality but are unaltered with switches in diet are therefore potential biomarkers of ageing-related damage. However, molecular species that switch upon instigation or withdrawal of DR are thus potential biomarkers of mechanisms underlying risk of mortality, but not of ageing-related damage. Using this approach, we assessed several commonly used biomarkers of ageing-related damage. Accumulation of fluorescent advanced glycation end products (AGEs) correlated strongly with mortality rate of flies at different temperatures but was independent of diet. Hence fluorescent AGEs are biomarkers of ageing-related damage in flies. In contrast, five oxidised and glycated protein adducts accumulated with age, but were reversible with both temperature and diet, and are therefore not markers either of acute risk of dying or of ageing-related damage. Our approach provides a powerful method for identification of biomarkers of ageing. PMID:20367621

Anorexia of Aging: Risk Factors, Consequences, and Potential Treatments.

PubMed

Landi, Francesco; Calvani, Riccardo; Tosato, Matteo; Martone, Anna Maria; Ortolani, Elena; Savera, Giulia; Sisto, Alex; Marzetti, Emanuele

2016-01-27

Older people frequently fail to ingest adequate amount of food to meet their essential energy and nutrient requirements. Anorexia of aging, defined by decrease in appetite and/or food intake in old age, is a major contributing factor to under-nutrition and adverse health outcomes in the geriatric population. This disorder is indeed highly prevalent and is recognized as an independent predictor of morbidity and mortality in different clinical settings. Even though anorexia is not an unavoidable consequence of aging, advancing age often promotes its development through various mechanisms. Age-related changes in life-style, disease conditions, as well as social and environmental factors have the potential to directly affect dietary behaviors and nutritional status. In spite of their importance, problems related to food intake and, more generally, nutritional status are seldom attended to in clinical practice. While this may be the result of an "ageist" approach, it should be acknowledged that simple interventions, such as oral nutritional supplementation or modified diets, could meaningfully improve the health status and quality of life of older persons.

Plasma Protein Oxidation and Its Correlation with Antioxidant Potential During Human Aging

PubMed Central

Pandey, Kanti Bhooshan; Mehdi, Mohd Murtaza; Maurya, Pawan Kumar; Rizvi, Syed Ibrahim

2010-01-01

Previous studies have indicated that the main molecular characteristic of aging is the progressive accumulation of oxidative damages in cellular macromolecules. Proteins are one of the main molecular targets of age-related oxidative stress, which have been observed during aging process in cellular systems. Reactive oxygen species (ROS) can lead to oxidation of amino acid side chains, formation of protein-protein cross-linkages, and oxidation of the peptide backbones. In the present study, we report the age-dependent oxidative alterations in biomarkers of plasma protein oxidation: protein carbonyls (PCO), advanced oxidation protein products (AOPPs) and plasma total thiol groups (T-SH) in the Indian population and also correlate these parameters with total plasma antioxidant potential. We show an age dependent decrease in T-SH levels and increase in PCO and AOPPs level. The alterations in the levels of these parameters correlated significantly with the total antioxidant capacity of the plasma. The levels of oxidized proteins in plasma provide an excellent biomarker of oxidative stress due to the relative long half-life of such oxidized proteins. PMID:20826915

Anorexia of Aging: Risk Factors, Consequences, and Potential Treatments

PubMed Central

Landi, Francesco; Calvani, Riccardo; Tosato, Matteo; Martone, Anna Maria; Ortolani, Elena; Savera, Giulia; Sisto, Alex; Marzetti, Emanuele

2016-01-01

Older people frequently fail to ingest adequate amount of food to meet their essential energy and nutrient requirements. Anorexia of aging, defined by decrease in appetite and/or food intake in old age, is a major contributing factor to under-nutrition and adverse health outcomes in the geriatric population. This disorder is indeed highly prevalent and is recognized as an independent predictor of morbidity and mortality in different clinical settings. Even though anorexia is not an unavoidable consequence of aging, advancing age often promotes its development through various mechanisms. Age-related changes in life-style, disease conditions, as well as social and environmental factors have the potential to directly affect dietary behaviors and nutritional status. In spite of their importance, problems related to food intake and, more generally, nutritional status are seldom attended to in clinical practice. While this may be the result of an “ageist” approach, it should be acknowledged that simple interventions, such as oral nutritional supplementation or modified diets, could meaningfully improve the health status and quality of life of older persons. PMID:26828516

Advanced glycation end-products and insulin signaling in granulosa cells

PubMed Central

Chatzigeorgiou, Antonios; Papageorgiou, Efstathia; Koundouras, Dimitrios; Koutsilieris, Michael

2016-01-01

Advanced glycation end-products (AGEs) may interfere with insulin intracellular signaling and glucose transport in human granulosa cells, potentially affecting ovarian function, follicular growth, linked with diminished fertility. The potential interaction of AGEs with insulin signaling pathways and glucose transport was investigated in human granulosa KGN cells. KGN cells were cultured with variable concentrations of human glycated albumin (HGA, 50–200 µg/mL) or insulin (100 ng/mL). Combined treatments of KGN cells with insulin (100 ng/mL) and HGA (200 µg/mL) were also performed. p-AKT levels and glucose transporter type 4 (Glut-4) translocation analysis were performed by Western blot. Phosphatidylinositol-3-kinase (PI3K)-specific signaling was checked by using the PI3K-inhibitor, LY294002. p-AKT levels were significantly increased following insulin treatment compared to basal levels or HGA exposure. This insulin-mediated AKT-phosphorylation was PI3K-specific and it was inhibited after combined treatment of insulin and HGA. Furthermore, Glut-4 translocation from the cytoplasm to the membrane compartments of KGN cells was remarkably reduced after the combined treatment of insulin and HGA. The present findings support that AGEs interfere with insulin signaling in granulosa cells and prevent Glut-4 membrane translocation suggesting that intra ovarian AGEs accumulation, from endogenous or exogenous sources, may contribute to the pathophysiology of states characterized with anovulation and insulin resistance such as polycystic ovary syndrome. PMID:25956684

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.

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.

Where Are All the Real Women in Higher Education?

ERIC Educational Resources Information Center

Pippins, Shirley

2008-01-01

As organizations like the American Council on Education are seeking to advance women in higher education, and many of them are approaching (or avoiding) retirement age, many women with great potential are questioning whether a leadership opportunity in higher education is for them. As a new generation of women leaders prepares to enter the higher…

Altered Expression of NF- κ B and SP1 after Exposure to Advanced Glycation End-Products and Effects of Neurotrophic Factors in AGEs Exposed Rat Retinas.

PubMed

Bikbova, Guzel; Oshitari, Toshiyuki; Baba, Takayuki; Yamamoto, Shuichi

2015-01-01

To determine the effect of advanced glycation end-products (AGEs) on neurite regeneration, and also to determine the regenerative effects of different neurotrophic factors (NTFs) on rat retinal explants, the retinas of SD rats were cultured in three-dimensional collagen gels and incubated in 6 types of media: (1) serum-free control culture media; (2) 100 μg/mL AGEs-BSA media; (3) AGEs-BSA + 100 ng/mL neurotrophin-4 (NT-4) media; (4) AGEs-BSA + 100 ng/mL hepatocyte growth factor media; (5) AGEs-BSA + 100 ng/mL glial cell line-derived neurotrophic factor media; or (6) AGEs-BSA + 100 µM tauroursodeoxycholic acid media. After 7 days, the number of regenerating neurites was counted. The explants were immunostained for nuclear factor-κB (NF-κB) and specificity protein 1 (SP1). Statistical analyses were performed by one-way ANOVA. In retinas incubated with AGEs, the numbers of neurites were fewer than in control. All of the NTFs increased the number of neurites, and the increase was more significant in the NT-4 group. The number of NF-κB and SP1 immunopositive cells was higher in retinas exposed to AGEs than in control. All of the NTFs decreased the number of NF-κB immunopositive cells but did not significantly affect SP1 expression. These results demonstrate the potential of the NTFs as axoprotectants in AGEs exposed retinal neurons.

Mesenchymal Stem Cells in Chronic Wounds: The Spectrum from Basic to Advanced Therapy

PubMed Central

Otero-Viñas, Marta; Falanga, Vincent

2016-01-01

Significance: Almost 7 million Americans have chronic cutaneous wounds and billions of dollars are spent on their treatment. The number of patients with nonhealing wounds keeps increasing worldwide due to an ever-aging population, increasing number of obese and diabetic patients, and cardiovascular disease. Recent Advances: Advanced treatments for difficult wounds are needed. Therapy with mesenchymal stem cells (MSCs) is attractive due to their differentiating potential, their immunomodulating properties, and their paracrine effects. Critical Issues: New technologies (including growth factors and skin substitutes) are now widely used for stimulating wound healing. However, in spite of these advances, the percentage of complete wound closure in most clinical situations is around 50–60%. Moreover, there is a high rate of wound recurrence. Future Directions: Recently, it has been demonstrated that MSCs speed up wound healing by decreasing inflammation, by promoting angiogenesis, and by decreasing scarring. However, there are some potential limitations to successful MSC therapy. These limitations include the need to improve cell delivery methods, cell viability, heterogeneity in MSC preparations, and suboptimal wound bed preparation. Further large, controlled clinical trials are needed to establish the safety of MSCs before widespread clinical application. PMID:27076993

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.

Veterans' informal caregivers in the "sandwich generation": a systematic review toward a resilience model.

PubMed

Smith-Osborne, Alexa; Felderhoff, Brandi

2014-01-01

Social work theory advanced the formulation of the construct of the sandwich generation to apply to the emerging generational cohort of caregivers, most often middle-aged women, who were caring for maturing children and aging parents simultaneously. This systematic review extends that focus by synthesizing the literature on sandwich generation caregivers for the general aging population with dementia and for veterans with dementia and polytrauma. It develops potential protective mechanisms based on empirical literature to support an intervention resilience model for social work practitioners. This theoretical model addresses adaptive coping of sandwich- generation families facing ongoing challenges related to caregiving demands.

The role of bluespaces in experiencing place, aging and wellbeing: Insights from Waiheke Island, New Zealand.

PubMed

Coleman, Tara; Kearns, Robin

2015-09-01

This paper examines how bluespaces inform experiences of place, being aged, and wellbeing among seniors on Waiheke, an island within the greater Auckland area in northern New Zealand. We draw on photo-elicitation interviews with seniors aged 65-94 to argue that bluespaces shape metaphors of 'islandness' that, in turn, help maintain wellbeing. We conclude that, although island settings pose unique challenges for seniors, (e.g. potential isolation, and a lack of advanced care), drawing on the qualities of bluespaces helps maintain a secure sense of self anchored in strong affective ties to place. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

Follicular fluid soluble receptor for advanced glycation end-products (sRAGE): a potential indicator of ovarian reserve.

PubMed

Merhi, Zaher; Irani, Mohamad; Doswell, Angela D; Ambroggio, Jennifer

2014-02-01

The interaction of advanced glycation end-products (AGEs) with their cellular receptor (RAGE) is implicated in the pathogenesis of abnormal ovarian follicular growth. RAGE has a circulating secretory receptor form, soluble RAGE (sRAGE), which neutralizes the action of AGEs and might exert a protective role on the follicular environment. The objective of the study was to investigate whether serum or follicular fluid (FF) sRAGE levels are associated with markers of ovarian reserve. Serum anti-Mullerian hormone (AMH) and sRAGE protein levels were correlated in 31 reproductive-aged women. An additional 33 women who underwent oocyte retrieval for in vitro fertilization were enrolled. AMH and its receptor (AMHR-II) mRNA levels were quantified in cumulus granulosa cells and FF sRAGE and AMH protein levels were measured. Granulosa cell AMH and AMHR-II gene expression, serum and FF AMH and sRAGE protein concentration, and number of oocytes retrieved were measured. In the serum, sRAGE levels were negatively correlated with body mass index (BMI) (r = -0.5, P < .001) but not with age or serum AMH. The higher the FF sRAGE, the lower the number of international units of gonadotropin needed per cycle independent of age, BMI, or day 3 FSH level (r = -0.4, P = .04). After adjusting for age, BMI, day 3 FSH, and the total dose of gonadotropins, FF sRAGE predicted the number of oocytes retrieved (R(2) = 0.27, P = .045). FF sRAGE positively correlated with FF AMH levels (r = 0.5, P = .0085). RT-PCR results showed no correlation between the FF sRAGE and AMH or AMHR-II mRNA levels. These data support a relationship between FF sRAGE and measures of ovarian reserve. The pathological significance of the harmful inflammatory AGEs in follicular health clearly requires further investigation. Targeting AGEs might offer potential therapeutic options for the treatment of diminished ovarian response.

Anti-glycation and anti-oxidation properties of Capsicum frutescens and Curcuma longa fruits: possible role in prevention of diabetic complication.

PubMed

Khan, Ibrar; Ahmad, Haroon; Ahmad, Bashir

2014-09-01

The accumulation of advanced glycationend products (AGE's) in the body, due to the non-enzymatic glycation of proteins is associated with several pathological conditions like aging and diabetes mellitus. Hence a plant having anti-glycation and anti-oxidation potentials may serve as therapeutic agent for diabetic complications and aging. In this study the anti-glycation and anti-oxidation properties of crude methanolic extracts of fruits of Capsicum frutescens and Curcuma longa were investigated. Among the two C. frutescens had more anti-glycation ability with a minimum inhibitory concentration (MIC50) of 90βg/mLas compared to 324βg/mL MIC50 of C. longa. Curcuma longa had the more anti-oxidation potential i.e. 35.01, 30.83 and 28.08% at 0.5mg, 0.25mg and 0.125mg respectively.

Screening colonoscopy for the detection of neoplastic lesions in asymptomatic HIV-infected subjects.

PubMed

Bini, E J; Green, B; Poles, M A

2009-08-01

Although non-AIDS defining malignancies are rapidly increasing as HIV-infected subjects live longer, little is know about the results of screening for colonic neoplasms (adenomatous polyps and adenocarcinomas) in this population. We conducted a screening colonoscopy study to determine the prevalence of colonic neoplasms in 136 asymptomatic HIV-infected subjects >or=50 years of age and 272 asymptomatic uninfected control subjects matched for age, sex, and family history of colorectal cancer. Advanced neoplasms were defined as adenomas >or=10 mm or any adenoma, regardless of size, with villous histology, high-grade dysplasia, or adenocarcinoma. The prevalence of neoplastic lesions was significantly higher in HIV-infected subjects than in control subjects (62.5% vs 41.2%, p<0.001), and remained highly significant after adjustment for potential confounding variables (odds ratio = 3.00; 95% confidence interval, 1.83 to 4.93). Among patients with colorectal adenocarcinoma, HIV-infected subjects were significantly younger (52.4 (SD 1.3) vs 60.3 (SD 4.0) years, p = 0.002) and were more likely to have advanced cancers (stage III or IV) than control subjects (60.0% vs 16.7%, p = 0.24). Of HIV-infected subjects with advanced neoplasms proximal to the splenic flexure, distal neoplastic lesions were absent in 88.9% of individuals and these would have been missed by flexible sigmoidoscopy. HIV-infected subjects have a higher prevalence of colonic neoplasms, and adenocarcinomas develop at a younger age and are more advanced than in uninfected subjects. Our findings suggest that screening colonoscopy should be offered to HIV-infected subjects, but the age of initiation and the optimal frequency of screening require further study.

Imaging Redox State in Mouse Muscles of Different Ages.

PubMed

Moon, Lily; Frederick, David W; Baur, Joseph A; Li, Lin Z

2017-01-01

Aging is the greatest risk factor for many diseases. Intracellular concentrations of nicotinamide adenine dinucleotide (NAD + ) and the NAD + -coupled redox state have been proposed to moderate many aging-related processes, yet the specific mechanisms remain unclear. The concentration of NAD + falls with age in skeletal muscle, yet there is no consensus on whether aging will increase or decrease the redox potential of NAD + /NADH. Oxidized flavin groups (Fp) (e.g. FAD, i.e., flavin adenine dinucleotide, contained in flavoproteins) and NADH are intrinsic fluorescent indicators of oxidation and reduction status of tissue, respectively. The redox ratio, i.e., the ratio of Fp to NADH, may be a surrogate indicator of the NAD + /NADH redox potential. In this study we used the Chance redox scanner (NADH/Fp fluorescence imaging at low temperature) to investigate the effect of aging on the redox state of mitochondria in skeletal muscles. The results showed that there are borderline significant differences in nominal concentrations of Fp and NADH, but not in the redox ratio s when comparing 3.5-month and 13-month old muscles of mice (n = 6). It may be necessary to increase the number of muscle samples and study mice of more advanced age.

High-Fat Diet and Voluntary Chronic Aerobic Exercise Recover Altered Levels of Aging-Related Tryptophan Metabolites along the Kynurenine Pathway

PubMed Central

Lee, Keon-Joo; Cho, Joo-Youn; Lee, Soon-Tae; Kim, Hwa Suk; Shim, Jun Hwa; Lee, Sang Kun; Kim, Manho

2017-01-01

Tryptophan metabolites regulate a variety of physiological processes, and their downstream metabolites enter the kynurenine pathway. Age-related changes of metabolites and activities of associated enzymes in this pathway are suggestable and would be potential intervention targets. Blood levels of serum tryptophan metabolites in C57BL/6 mice of different ages, ranging from 6 weeks to 10 months, were assessed using high-performance liquid chromatography, and the enzyme activities for each metabolic step were estimated using the ratio of appropriate metabolite levels. Mice were subjected to voluntary chronic aerobic exercise or high-fat diet to assess their ability to rescue age-related alterations in the kynurenine pathway. The ratio of serum kynurenic acid (KYNA) to 3-hydroxylkynurenine (3-HK) decreased with advancing age. Voluntary chronic aerobic exercise and high-fat diet rescued the decreased KYNA/3-HK ratio in the 6-month-old and 8-month-old mice groups. Tryptophan metabolites and their associated enzyme activities were significantly altered during aging, and the KYNA/3-HK ratio was a meaningful indicator of aging. Exercise and high-fat diet could potentially recover the reduction of the KYNA/3-HK ratio in the elderly. PMID:28680298

Oxidative stress and adipocyte biology: focus on the role of AGEs.

PubMed

Boyer, Florence; Vidot, Jennifer Baraka; Dubourg, Alexis Guerin; Rondeau, Philippe; Essop, M Faadiel; Bourdon, Emmanuel

2015-01-01

Diabetes is a major health problem that is usually associated with obesity, together with hyperglycemia and increased advanced glycation endproducts (AGEs) formation. Elevated AGEs elicit severe downstream consequences via their binding to receptors of AGEs (RAGE). This includes oxidative stress and oxidative modifications of biological compounds together with heightened inflammation. For example, albumin (major circulating protein) undergoes increased glycoxidation with diabetes and may represent an important biomarker for monitoring diabetic pathophysiology. Despite the central role of adipose tissue in many physiologic/pathologic processes, recognition of the effects of greater AGEs formation in this tissue is quite recent within the obesity/diabetes context. This review provides a brief background of AGEs formation and adipose tissue biology and thereafter discusses the impact of AGEs-adipocyte interactions in pathology progression. Novel data are included showing how AGEs (especially glycated albumin) may be involved in hyperglycemia-induced oxidative damage in adipocytes and its potential links to diabetes progression.

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

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.

Paternal age and intelligence: implications for age-related genomic changes in male germ cells.

PubMed

Malaspina, Dolores; Reichenberg, Avi; Weiser, Mark; Fennig, Shmuel; Davidson, Michael; Harlap, Susan; Wolitzky, Rachel; Rabinowitz, Jonathan; Susser, Ezra; Knobler, Haim Y

2005-06-01

A robust association between advancing paternal age and schizophrenia risk is reported, and genetic changes in the germ cells of older men are presumed to underlie the effect. If that is so, then the pathway may include effects on cognition, as those with premorbid schizophrenia are reported to have lower intelligence. There are also substantial genetic influences on intelligence, so de novo genetic events in male germ cells, which accompany advancing paternal age, may plausibly influence offspring intelligence. An association of paternal age with IQ in healthy adolescents may illuminate the mechanisms that link it to schizophrenia. We examined the association of paternal age and IQ scores using the Israeli Army Board data on 44 175 individuals from a richly described birth cohort, along with maternal age and other potential modifiers. A significant inverted U-shaped relationship was observed between paternal age and IQ scores, which was independent from a similar association of IQ scores with maternal age. These relationships were not significantly attenuated by controlling for multiple possible confounding factors, including the other parent's age, parental education, social class, sex and birth order, birth weight and birth complications. Overall, parental age accounted for approximately 2% of the total variance in IQ scores, with later paternal age lowering non-verbal IQ scores more than verbal IQ scores. We found independent effects of maternal and paternal age on offspring IQ scores. The paternal age effect may be explained by de novo mutations or abnormal methylation of paternally imprinted genes, whereas maternal age may affect fetal neurodevelopment through age-related alterations in the in-utero environment. The influence of late paternal age to modify non-verbal IQ may be related to the pathways that increase the risk for schizophrenia in the offspring of older fathers.

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.

Chemotherapy Toxicity Risk Score for Treatment Decisions in Older Adults with Advanced Solid Tumors.

PubMed

Nishijima, Tomohiro F; Deal, Allison M; Williams, Grant R; Sanoff, Hanna K; Nyrop, Kirsten A; Muss, Hyman B

2018-05-01

The decision whether to treat older adults with advanced cancer with standard therapy (ST) or reduced therapy (RT) is complicated by heterogeneity in aging. We assessed the potential utility of the chemotherapy toxicity risk score (CTRS) [J Clin Oncol 2011;29:3457-3465] for treatment decisions in older adults. This was a prospective observational study of patients aged ≥65 years receiving first-line chemotherapy for advanced cancer for which combination chemotherapy is the standard of care. Patients were categorized as high risk (CTRS ≥10), for whom RT (dose-reduced combination or single-agent chemotherapy) is deemed appropriate, or nonhigh risk (CTRS <10), for whom ST is deemed appropriate for toxicity. The primary objective was to estimate the agreement in chemotherapy choice (ST vs. RT) between the treating physician and the CTRS using a κ statistic. Fifty-eight patients (median age, 71 years) were enrolled. Thirty-eight patients received ST (21 had CTRS <10, and 17 had CTRS ≥10), and 20 patients received RT (12 had CTRS ≥10, and 8 had CTRS <10), with minimal agreement in chemotherapy choice (κ = 0.14; 95% CI, -0.10 to 0.38). Grade 3-4 toxicity and hospitalization occurred in 60% and 27% of 55 patients with follow-up data, respectively. Among patients receiving ST, patients with CTRS ≥10 had a higher incidence of toxicity (88% vs. 40%, p  = .006) and hospitalization (50% vs. 15%, p  = .03) than those with CTRS <10. Older patients with cancer with a high CTRS who receive combination chemotherapy have an exceedingly high rate of severe toxicity and hospitalization. The potential utility of the chemotherapy toxicity risk score (CTRS) in old adults with advanced solid tumors receiving first-line chemotherapy was assessed. Little agreement was found between chemotherapy treatment decisions based on the clinical impression versus what was recommended based on the CTRS. Among patients treated with standard-dose combination chemotherapy, patients with CTRS ≥10 had a very high incidence of grade 3-4 toxicities and hospitalization, which was significantly greater than that of patients with a low CTRS (<10). These findings suggest that the addition of CTRS to the clinical impression has a potential to improve treatment decisions. © AlphaMed Press 2018.

Effect of taurine on advanced glycation end products-induced hypertrophy in renal tubular epithelial cells

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

Huang, J.-S.; Chuang, L.-Y.; Guh, J.-Y.

2008-12-01

Mounting evidence indicates that advanced glycation end products (AGE) play a major role in the development of diabetic nephropathy (DN). Taurine is a well documented antioxidant agent. To explore whether taurine was linked to altered AGE-mediated renal tubulointerstitial fibrosis in DN, we examined the molecular mechanisms of taurine responsible for inhibition of AGE-induced hypertrophy in renal tubular epithelial cells. We found that AGE (but not non-glycated BSA) caused inhibition of cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, bcl-2 protein expression, and mitochondrial cytochrome c release in BSA, AGE,more » or the antioxidant taurine treatments in these cells. AGE-induced the Raf-1/extracellular signal-regulated kinase (ERK) activation was markedly blocked by taurine. Furthermore, taurine, the Raf-1 kinase inhibitor GW5074, and the ERK kinase inhibitor PD98059 may have the ability to induce cellular proliferation and cell cycle progression from AGE-treated cells. The ability of taurine, GW5074, or PD98059 to inhibit AGE-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of RAGE, p27{sup Kip1}, collagen IV, and fibronectin. The results obtained in this study suggest that taurine may serve as the potential anti-fibrotic activity in DN through mechanism dependent of its Raf-1/ERK inactivation in AGE-induced hypertrophy in renal tubular epithelial cells.« less

Strategies for Investigating Early Mars Using Returned Samples

NASA Technical Reports Server (NTRS)

Carrier, B. L.; Beaty, D. W.; McSween, H. Y.; Czaja, A. D.; Goreva, Y. S.; Hausrath, E. M.; Herd, C. D. K.; Humayun, M.; McCubbin, F. M.; McLennan, S. M.;

Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases.

PubMed

Franceschi, Claudio; Campisi, Judith

2014-06-01

Human aging is characterized by a chronic, low-grade inflammation, and this phenomenon has been termed as "inflammaging." Inflammaging is a highly significant risk factor for both morbidity and mortality in the elderly people, as most if not all age-related diseases share an inflammatory pathogenesis. Nevertheless, the precise etiology of inflammaging and its potential causal role in contributing to adverse health outcomes remain largely unknown. The identification of pathways that control age-related inflammation across multiple systems is therefore important in order to understand whether treatments that modulate inflammaging may be beneficial in old people. The session on inflammation of the Advances in Gerosciences meeting held at the National Institutes of Health/National Institute on Aging in Bethesda on October 30 and 31, 2013 was aimed at defining these important unanswered questions about inflammaging. This article reports the main outcomes of this session. © 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.

Inhibition of protein glycation by procyanidin-B2 enriched fraction of cinnamon: delay of diabetic cataract in rats.

PubMed

Muthenna, Puppala; Raghu, Ganugula; Akileshwari, Chandrasekhar; Sinha, Sukesh Narayana; Suryanarayana, Palla; Reddy, Geereddy Bhanuprakash

2013-11-01

Accumulation of advanced glycation endproducts (AGE) from nonenzymatic glycation of proteins has been implicated in several diabetic complications including diabetic cataract. Previously, we have reported that extracts of dietary agents such as cinnamon have the potential to inhibit AGE formation. In this study, we have shown procyanidin-B2 as the active component of cinnamon that is involved in AGE inhibition using bioassay-guided fractionation of eye lens proteins under in vitro conditions. The data indicate that procyanidin-B2 enriched fraction scavenges dicarbonyls. Further, procyanidin-B2 fraction of cinnamon inhibited the formation of glycosylated hemoglobin in human blood under ex vivo conditions. We have also demonstrated the physiological significance of procyanidin-B2 fraction in terms of delay of diabetic cataract through inhibition of AGE in diabetic rats. These findings establish the antiglycating potential of procyanidin-B2 fraction of cinnamon which suggests a scope for controlling AGE-mediated diabetic complications by food sources that are rich in proanthocyanidins like procyanidin-B2. © 2013 International Union of Biochemistry and Molecular Biology.

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.

Driving safety in elderly individuals.

PubMed

Marottoli, R A

1993-05-01

Driving safety in elderly individuals is becoming an increasingly important issue in geriatrics and in medical practice. The number of elderly drivers is increasing as the population ages, and especially as current generations of female drivers age. Concern is raised about their safe operation of motor vehicles because of the increasing likelihood with advancing age of developing conditions that may adversely affect the visual, cognitive, and motor abilities integral to driving. But this issue is not only a medical one, since there are social and political components as well. This discussion will describe the background of this issue, focus on the changes that may occur with aging and their potential relationship to driving ability, and, finally, will outline an approach that physicians may employ in their practice.

Demographic Analysis from Biometric Data: Achievements, Challenges, and New Frontiers.

PubMed

Sun, Yunlian; Zhang, Man; Sun, Zhenan; Tan, Tieniu

2018-02-01

Biometrics is the technique of automatically recognizing individuals based on their biological or behavioral characteristics. Various biometric traits have been introduced and widely investigated, including fingerprint, iris, face, voice, palmprint, gait and so forth. Apart from identity, biometric data may convey various other personal information, covering affect, age, gender, race, accent, handedness, height, weight, etc. Among these, analysis of demographics (age, gender, and race) has received tremendous attention owing to its wide real-world applications, with significant efforts devoted and great progress achieved. This survey first presents biometric demographic analysis from the standpoint of human perception, then provides a comprehensive overview of state-of-the-art advances in automated estimation from both academia and industry. Despite these advances, a number of challenging issues continue to inhibit its full potential. We second discuss these open problems, and finally provide an outlook into the future of this very active field of research by sharing some promising opportunities.

Pursuing Humanistic Medicine in a Technological Age.

PubMed

Bertman, Stephen

2017-06-01

The humanistic practice of medicine requires that the practitioner have sufficient time and appropriate focus. Both elements, however, are under assault by the high-speed, distraction-filled environment within which primary care is delivered today. Despite or perhaps because of modern medicine's technological advances, the potentially healing bond between doctor and patient is being frayed and the quality of care consequently degraded.

Fluorescence from the maillard reaction and its potential applications in food science.

PubMed

Matiacevich, Silvia B; Santagapita, Patricio R; Buera, M Pilar

2005-01-01

The chemistry of the Maillard reaction involves a complex set of steps, and its interpretation represents a challenge in basic and applied aspects of Food Science. Fluorescent compounds have been recognized as important early markers of the reaction in food products since 1942. However, the recent advances in the characterization of fluorophores' development were observed in biological and biomedical areas. The in vivo non-enzymatic glycosylation of proteins produces biological effects, promoting health deterioration. The characteristic fluorescence of advanced glycosylation end products (AGEs) is similar to that of Maillard food products and represents an indicator of the level of AGE-modified proteins, but the structure of the fluorescent groups is, typically, unknown. Application of fluorescence measurement is considered a potential tool for addressing key problems of food deterioration as an early marker or index of the damage of biomolecules. Fluorophores may be precursors of the brown pigments and/or end products. A general scheme of the Maillard reaction is proposed in this article, incorporating the pool concept. A correct interpretation of the effect of environmental and compositional conditions and their influences on the reaction kinetics may help to define the meaning of fluorescence development for each particular system.

Associations between gross motor and communicative development in at-risk infants.

PubMed

LeBarton, Eve Sauer; Iverson, Jana M

2016-08-01

Infants' advances in locomotion relate to advances in communicative development. However, little is known about these relations in infants at risk for delays in these domains and whether they may extend to earlier achievements in gross motor development in infancy. We examined whether advances in sitting and prone locomotion are related to communicative development in infants who have an older sibling with autism spectrum disorder (ASD) and are at risk for motor and communication delays (heightened-risk; HR). We conducted a longitudinal study with 37 HR infants who did not receive an ASD diagnosis at 36 months. Infants were observed monthly between the ages of 5 and 14 months. We assessed gross motor development using the Alberta Infant Motor Scales (AIMS) and recorded ages of onset of verbal and nonverbal communicative behaviors. Results indicated increased presence of early gross motor delay from 5 to 10 months. In addition, there were positive relations between sitting and gesture and babble onset and between prone development and gesture onset. Thus, links between gross motor development and communication extend to at-risk development and provide a starting point for future research on potential cascading consequences of motor advances on communication development. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

The role of musical aptitude and language skills in preattentive duration processing in school-aged children.

PubMed

Milovanov, Riia; Huotilainen, Minna; Esquef, Paulo A A; Alku, Paavo; Välimäki, Vesa; Tervaniemi, Mari

2009-08-28

We examined 10-12-year old elementary school children's ability to preattentively process sound durations in music and speech stimuli. In total, 40 children had either advanced foreign language production skills and higher musical aptitude or less advanced results in both musicality and linguistic tests. Event-related potential (ERP) recordings of the mismatch negativity (MMN) show that the duration changes in musical sounds are more prominently and accurately processed than changes in speech sounds. Moreover, children with advanced pronunciation and musicality skills displayed enhanced MMNs to duration changes in both speech and musical sounds. Thus, our study provides further evidence for the claim that musical aptitude and linguistic skills are interconnected and the musical features of the stimuli could have a preponderant role in preattentive duration processing.

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.

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

What do we know about the nutritional status of the very old? Insights from three cohorts of advanced age from the UK and New Zealand.

PubMed

Hill, Tom R; Mendonça, Nuno; Granic, Antoneta; Siervo, Mario; Jagger, Carol; Seal, Chris J; Kerse, Ngaire; Wham, Carol; Adamson, Ashley J; Mathers, John C

2016-08-01

Very old people (referred to as those aged 85 years and over) are the fastest growing age segment of many Western societies owing to the steady rise of life expectancy and decrease in later life mortality. In the UK, there are now more than 1·5 million very old people (2·5 % of total population) and the number is projected to rise to 3·3 million or 5 % over the next 20 years. Reduced mobility and independence, financial constraints, higher rates of hospitalisation, chronic diseases and disabilities, changes in body composition, taste perception, digestion and absorption of food all potentially influence either nutrient intake or needs at this stage of life. The nutritional needs of the very old have been identified as a research priority by the British Nutrition Foundation's Task Force report, Healthy Ageing: The Role of Nutrition and Lifestyle. However, very little is known about the dietary habits and nutritional status of the very old. The Newcastle 85+ study, a cohort of more than 1000 85-year olds from the North East of England and the Life and Living in Advanced Age study (New Zealand), a bicultural cohort study of advanced ageing of more than 900 participants from the Bay of Plenty and Rotorua regions of New Zealand are two unique cohort studies of ageing, which aim to assess the spectrum of health in the very old as well as examine the associations of health trajectories and outcomes with biological, clinical and social factors as each cohort ages. The nutrition domain included in both studies will help to fill the evidence gap by identifying eating patterns, and measures of nutritional status associated with better, or worse, health and wellbeing. This review will explore some of this ongoing work.

Tremor severity and age: a cross-sectional, population-based study of 2,524 young and midlife normal adults.

PubMed

Louis, Elan D; Hafeman, Danella; Parvez, Faruque; Liu, Xinhua; Alcalay, Roy N; Islam, Tariqul; Ahmed, Alauddin; Siddique, Abu Bakar; Patwary, Tazul Islam; Melkonian, Stephanie; Argos, Maria; Levy, Diane; Ahsan, Habibul

2011-07-01

Mild action tremor occurs in most normal people. Yet this tremor mainly has been studied within the context of advanced age rather than among the vast bulk of adults who are not elderly. Whether this tremor worsens during young and middle age is unknown. Using cross-sectional data from a large population-based study of young and midlife normal adults (age range, 18-60 years), we assessed whether increasing age is associated with more severe action tremor. Two thousand five hundred and twenty-four adults in Araihazar, Bangladesh, drew an Archimedes spiral with each hand. Tremor in spirals was rated (0-3) by a blinded neurologist, and a spiral score (range, 0-6) was assigned. Spiral score was correlated with age (r = 0.06, P = .004). With each advancing decade, the spiral score increased (P = .002) so that the spiral score in participants in the highest age group (age 60) was approximately twice that of participants in the youngest age group (age 18-19); P = .003. In the regression model that adjusted for potential confounders (sex, cigarettes, medications, asthma inhalers, and tea and betel nut use), spiral score was associated with age (P = .0045). In this cross-sectional, population-based study of more than 2500 young and midlife normal adults, there was a clear association between age and tremor severity. Although the magnitude of the correlation coefficient was modest, tremor severity was higher with each passing decade. These data suggest that age-dependent increase in tremor amplitude is not restricted to older people but occurs in all adult age groups. Copyright © 2011 Movement Disorder Society.

Validation of a Novel Electronic Health Record Patient Portal Advance Care Planning Delivery System.

PubMed

Bose-Brill, Seuli; Feeney, Michelle; Prater, Laura; Miles, Laura; Corbett, Angela; Koesters, Stephen

2018-06-26

Advance care planning allows patients to articulate their future care preferences should they no longer be able to make decisions on their own. Early advance care planning in outpatient settings provides benefits such as less aggressive care and fewer hospitalizations, yet it is underutilized due to barriers such as provider time constraints and communication complexity. Novel methods, such as patient portals, provide a unique opportunity to conduct advance care planning previsit planning for outpatient care. This follow-up to our pilot study aimed to conduct pragmatic testing of a novel electronic health record-tethered framework and its effects on advance care planning delivery in a real-world primary care setting. Our intervention tested a previsit advance care planning workflow centered around a framework sent via secure electronic health record-linked patient portal in a real-world clinical setting. The primary objective of this study was to determine its impact on frequency and quality of advance care planning documentation. We conducted a pragmatic trial including 2 sister clinical sites, one site implementing the intervention and the other continuing standard care. A total of 419 patients aged between 50 and 93 years with active portal accounts received intervention (n=200) or standard care (n=219). Chart review analyzed the presence of advance care planning and its quality and was graded with previously established scoring criteria based on advance care planning best practice guidelines from multiple nations. A total of 19.5% (39/200) of patients who received previsit planning responded to the framework. We found that the intervention site had statistically significant improvement in new advance care planning documentation rates (P<.01) and quality (P<.01) among all eligible patients. Advance care planning documentation rates increased by 105% (19/39 to 39/39) and quality improved among all patients who engaged in the previsit planning framework (n=39). Among eligible patients aged between 50 and 60 years at the intervention site, advance care planning documentation rates increased by 37% (27/96 to 37/96). Advance care planning documentation rates increased 34% among high users (27/67 to 36/67). Advance care planning previsit planning using a secure electronic health record-supported patient portal framework yielded improvement in the presence of advance care planning documentation, with highest improvement in active patient portal users and patients aged between 50 and 60 years. Targeted previsit patient portal advance care planning delivery in these populations can potentially improve the quality of care in these populations. ©Seuli Bose-Brill, Michelle Feeney, Laura Prater, Laura Miles, Angela Corbett, Stephen Koesters. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 26.06.2018.

Concurrent hippocampal induction of MHC II pathway components and glial activation with advanced aging is not correlated with cognitive impairment

PubMed Central

2011-01-01

Background Age-related cognitive dysfunction, including impairment of hippocampus-dependent spatial learning and memory, affects approximately half of the aged population. Induction of a variety of neuroinflammatory measures has been reported with brain aging but the relationship between neuroinflammation and cognitive decline with non-neurodegenerative, normative aging remains largely unexplored. This study sought to comprehensively investigate expression of the MHC II immune response pathway and glial activation in the hippocampus in the context of both aging and age-related cognitive decline. Methods Three independent cohorts of adult (12-13 months) and aged (26-28 months) F344xBN rats were behaviorally characterized by Morris water maze testing. Expression of MHC II pathway-associated genes identified by transcriptomic analysis as upregulated with advanced aging was quantified by qPCR in synaptosomal fractions derived from whole hippocampus and in hippocampal subregion dissections (CA1, CA3, and DG). Activation of astrocytes and microglia was assessed by GFAP and Iba1 protein expression, and by immunohistochemical visualization of GFAP and both CD74 (Ox6) and Iba1. Results We report a marked age-related induction of neuroinflammatory signaling transcripts (i.e., MHC II components, toll-like receptors, complement, and downstream signaling factors) throughout the hippocampus in all aged rats regardless of cognitive status. Astrocyte and microglial activation was evident in CA1, CA3 and DG of intact and impaired aged rat groups, in the absence of differences in total numbers of GFAP+ astrocytes or Iba1+ microglia. Both mild and moderate microglial activation was significantly increased in all three hippocampal subregions in aged cognitively intact and cognitively impaired rats compared to adults. Neither induction of MHCII pathway gene expression nor glial activation correlated to cognitive performance. Conclusions These data demonstrate a novel, coordinated age-related induction of the MHC II immune response pathway and glial activation in the hippocampus, indicating an allostatic shift toward a para-inflammatory phenotype with advancing age. Our findings demonstrate that age-related induction of these aspects of hippocampal neuroinflammation, while a potential contributing factor, is not sufficient by itself to elicit impairment of spatial learning and memory in models of normative aging. Future efforts are needed to understand how neuroinflammation may act synergistically with cognitive-decline specific alterations to cause cognitive impairment. PMID:21989322

Concurrent hippocampal induction of MHC II pathway components and glial activation with advanced aging is not correlated with cognitive impairment.

PubMed

VanGuilder, Heather D; Bixler, Georgina V; Brucklacher, Robert M; Farley, Julie A; Yan, Han; Warrington, Junie P; Sonntag, William E; Freeman, Willard M

2011-10-11

Age-related cognitive dysfunction, including impairment of hippocampus-dependent spatial learning and memory, affects approximately half of the aged population. Induction of a variety of neuroinflammatory measures has been reported with brain aging but the relationship between neuroinflammation and cognitive decline with non-neurodegenerative, normative aging remains largely unexplored. This study sought to comprehensively investigate expression of the MHC II immune response pathway and glial activation in the hippocampus in the context of both aging and age-related cognitive decline. Three independent cohorts of adult (12-13 months) and aged (26-28 months) F344xBN rats were behaviorally characterized by Morris water maze testing. Expression of MHC II pathway-associated genes identified by transcriptomic analysis as upregulated with advanced aging was quantified by qPCR in synaptosomal fractions derived from whole hippocampus and in hippocampal subregion dissections (CA1, CA3, and DG). Activation of astrocytes and microglia was assessed by GFAP and Iba1 protein expression, and by immunohistochemical visualization of GFAP and both CD74 (Ox6) and Iba1. We report a marked age-related induction of neuroinflammatory signaling transcripts (i.e., MHC II components, toll-like receptors, complement, and downstream signaling factors) throughout the hippocampus in all aged rats regardless of cognitive status. Astrocyte and microglial activation was evident in CA1, CA3 and DG of intact and impaired aged rat groups, in the absence of differences in total numbers of GFAP+ astrocytes or Iba1+ microglia. Both mild and moderate microglial activation was significantly increased in all three hippocampal subregions in aged cognitively intact and cognitively impaired rats compared to adults. Neither induction of MHCII pathway gene expression nor glial activation correlated to cognitive performance. These data demonstrate a novel, coordinated age-related induction of the MHC II immune response pathway and glial activation in the hippocampus, indicating an allostatic shift toward a para-inflammatory phenotype with advancing age. Our findings demonstrate that age-related induction of these aspects of hippocampal neuroinflammation, while a potential contributing factor, is not sufficient by itself to elicit impairment of spatial learning and memory in models of normative aging. Future efforts are needed to understand how neuroinflammation may act synergistically with cognitive-decline specific alterations to cause cognitive impairment.

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.

Ability of resveratrol to inhibit advanced glycation end product formation and carbohydrate-hydrolyzing enzyme activity, and to conjugate methylglyoxal.

PubMed

Shen, Yixiao; Xu, Zhimin; Sheng, Zhanwu

2017-02-01

Glycation can generate advanced glycation end products (AGE) and its intermediates methylglyoxal (MGO) and glyoxal in foods, which increase the risk of developing diabetes diseases. In this study, the effect of resveratrol against AGE formation, carbohydrate-hydrolyzing enzyme activity and trapping MGO capability were evaluated. Resveratrol showed a significant inhibition capability against AGE formation in bovine serum albumin (BSA)-fructose, BSA-MGO and arginine-MGO models with inhibition percentages of 57.94, 85.95 and 99.35%, respectively. Furthermore, resveratrol acted as a competitive inhibitor for α-amylase with IC50 3.62μg/ml, while it behaved in an uncompetitive manner for α-glucosidase with an IC50 of 17.54μg/l. A prevention of BSA protein glycation was observed in the BSA-fructose model with addition of resveratrol. Three types of resveratrol-MGO adducts were identified in the model consisting of MGO and resveratrol. The results demonstrated that resveratrol has potential in reducing glycation in foods and retarding carbohydrate-hydrolyzing enzyme activities. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identification of C1q as a Binding Protein for Advanced Glycation End Products.

PubMed

Chikazawa, Miho; Shibata, Takahiro; Hatasa, Yukinori; Hirose, Sayumi; Otaki, Natsuki; Nakashima, Fumie; Ito, Mika; Machida, Sachiko; Maruyama, Shoichi; Uchida, Koji

2016-01-26

Advanced glycation end products (AGEs) make up a heterogeneous group of molecules formed from the nonenzymatic reaction of reducing sugars with the free amino groups of proteins. The abundance of AGEs in a variety of age-related diseases, including diabetic complications and atherosclerosis, and their pathophysiological effects suggest the existence of innate defense mechanisms. Here we examined the presence of serum proteins that are capable of binding glycated bovine serum albumin (AGEs-BSA), prepared upon incubation of BSA with dehydroascorbate, and identified complement component C1q subcomponent subunit A as a novel AGE-binding protein in human serum. A molecular interaction analysis showed the specific binding of C1q to the AGEs-BSA. In addition, we identified DNA-binding regions of C1q, including a collagen-like domain, as the AGE-binding site and established that the amount of positive charge on the binding site was the determining factor. C1q indeed recognized several other modified proteins, including acylated proteins, suggesting that the binding specificity of C1q might be ascribed, at least in part, to the electronegative potential of the ligand proteins. We also observed that C1q was involved in the AGEs-BSA-activated deposition of complement proteins, C3b and C4b. In addition, the AGEs-BSA mediated the proteolytic cleavage of complement protein 5 to release C5a. These findings provide the first evidence of AGEs as a new ligand recognized by C1q, stimulating the C1q-dependent classical complement pathway.

Ameliorating Effect of Akebia quinata Fruit Extracts on Skin Aging Induced by Advanced Glycation End Products

PubMed Central

Shin, Seoungwoo; Son, Dahee; Kim, Minkyung; Lee, Seungjun; Roh, Kyung-Baeg; Ryu, Dehun; Lee, Jongsung; Jung, Eunsun; Park, Deokhoon

2015-01-01

The accumulation of free radicals and advanced glycation end products (AGEs) in the skin plays a very important role in skin aging. Both are known to interact with each other. Therefore, natural compounds or extracts that possess both antioxidant and antiglycation activities might have great antiageing potential. Akebia quinata fruit extract (AQFE) has been used to treat urinary tract inflammatory disease in traditional Korean and Chinese medicines. In the present study, AQFE was demonstrated to possess antioxidant and antiglycation activity. AQFE protects human dermal fibroblasts (HDFs) from oxidative stress and inhibits cellular senescence induced by oxidative stress. We also found that AQFE inhibits glycation reaction between BSA and glucose. The antiglycation activity of AQFE was dose-dependent. In addition, the antiglycation activity of AQFE was confirmed in a human skin explant model. AQFE reduced CML expression and stimulated fibrillin-1 expression in comparison to the methyglyoxal treatment. In addition, the possibility of the extract as an anti-skin aging agent has also been clinically validated. Our analysis of the crow’s feet wrinkle showed that there was a decrease in the depth of deep furrows in RI treated with AQFE cream over an eight-week period. The overall results suggest that AQFE may work as an anti-skin aging agent by preventing oxidative stress and other complications associated with AGEs formation. PMID:26569300

Advanced reproductive age and fertility.

PubMed

Liu, Kimberly; Case, Allison

2011-11-01

To improve awareness of the natural age-related decline in female and male fertility with respect to natural fertility and assisted reproductive technologies (ART) and provide recommendations for their management, and to review investigations in the assessment of ovarian aging. This guideline reviews options for the assessment of ovarian reserve and fertility treatments using ART with women of advanced reproductive age presenting with infertility. The outcomes measured are the predictive value of ovarian reserve testing and pregnancy rates with natural and assisted fertility. Published literature was retrieved through searches of PubMed or Medline, CINAHL, and The Cochrane Library in June 2010, using appropriate key words (ovarian aging, ovarian reserve, advanced maternal age, advanced paternal age, ART). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated into the guideline to December 2010. The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table). Primary and specialist health care providers and women will be better informed about ovarian aging and the age-related decline in natural fertility and about options for assisted reproductive technology. 1. Women in their 20s and 30s should be counselled about the age-related risk of infertility when other reproductive health issues, such as sexual health or contraception, are addressed as part of their primary well-woman care. Reproductive-age women should be aware that natural fertility and assisted reproductive technology success (except with egg donation) is significantly lower for women in their late 30s and 40s. (II-2A) 2. Because of the decline in fertility and the increased time to conception that occurs after the age of 35, women > 35 years of age should be referred for infertility work-up after 6 months of trying to conceive. (III-B) 3. Ovarian reserve testing may be considered for women ≥ 35 years of age or for women < 35 years of age with risk factors for decreased ovarian reserve, such as a single ovary, previous ovarian surgery, poor response to follicle-stimulating hormone, previous exposure to chemotherapy or radiation, or unexplained infertility. (III-B) 4. Ovarian reserve testing prior to assisted reproductive technology treatment may be used for counselling but has a poor predictive value for non-pregnancy and should be used to exclude women from treatment only if levels are significantly abnormal. (II-2A) 5. Pregnancy rates for controlled ovarian hyperstimulation are low for women > 40 years of age. Women > 40 years should consider IVF if they do not conceive within 1 to 2 cycles of controlled ovarian hyperstimulation. (II-2B) 6. The only effective treatment for ovarian aging is oocyte donation. A woman with decreased ovarian reserve should be offered oocyte donation as an option, as pregnancy rates associated with this treatment are significantly higher than those associated with controlled ovarian hyperstimulation or in vitro fertilization with a woman's own eggs. (II-2B) 7. Women should be informed that the risk of spontaneous pregnancy loss and chromosomal abnormalities increases with age. Women should be counselled about and offered appropriate prenatal screening once pregnancy is established. (II-2A) 8. Pre-conception counselling regarding the risks of pregnancy with advanced maternal age, promotion of optimal health and weight, and screening for concurrent medical conditions such as hypertension and diabetes should be considered for women > age 40. (III-B) 9. Advanced paternal age appears to be associated with an increased risk of spontaneous abortion and increased frequency of some autosomal dominant conditions, autism spectrum disorders, and schizophrenia. Men > age 40 and their partners should be counselled about these potential risks when they are seeking pregnancy, although the risks remain small. (II-2C).

Associations Between Vitamin D Intake and Progression to Incident Advanced Age-Related Macular Degeneration.

PubMed

Merle, Bénédicte M J; Silver, Rachel E; Rosner, Bernard; Seddon, Johanna M

2017-09-01

There is growing evidence of the importance of nutrition in age-related macular degeneration (AMD), but no prospective studies have explored the impact of vitamin D. We evaluated the association between vitamin D intake and progression to advanced AMD. Among 2146 participants (3965 eyes), 541 (777 eyes) progressed from early or intermediate AMD to advanced disease (mean follow-up: 9.4 years) based on ocular imaging. Nutrients were log transformed and calorie adjusted. Survival analysis was used to assess associations between incident advanced disease and vitamin D intake. Neovascular disease (NV) and geographic atrophy (GA) were evaluated separately. Combined effects of dietary vitamin D and calcium were assessed based on high or low consumption of each nutrient. There was a lower risk of progression to advanced AMD in the highest versus lowest quintile of dietary vitamin D intake after adjustment for demographic, behavioral, ocular, and nutritional factors (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.43-0.83; P trend = 0.0007). Similar results were observed for NV (HR: 0.59; 95% CI: 0.39-0.89; P trend = 0.005) but not GA (HR: 0.83; 95% CI: 0.53-1.30; P trend = 0.35). A protective effect was observed for advanced AMD among participants with high vitamin D and low calcium compared to the group with low levels for each nutrient (HR: 0.67; 95% CI: 0.50-0.88; P = 0.005). When supplement use was considered, the effect was in the protective direction but was not significant. A diet rich in vitamin D may prevent or delay progression to advanced AMD, especially NV. Additional exploration is needed to elucidate the potential protective role of vitamin D and its contribution to reducing visual loss.

Forensic DNA methylation profiling from evidence material for investigative leads

PubMed Central

Lee, Hwan Young; Lee, Soong Deok; Shin, Kyoung-Jin

2016-01-01

DNA methylation is emerging as an attractive marker providing investigative leads to solve crimes in forensic genetics. The identification of body fluids that utilizes tissue-specific DNA methylation can contribute to solving crimes by predicting activity related to the evidence material. The age estimation based on DNA methylation is expected to reduce the number of potential suspects, when the DNA profile from the evidence does not match with any known person, including those stored in the forensic database. Moreover, the variation in DNA implicates environmental exposure, such as cigarette smoking and alcohol consumption, thereby suggesting the possibility to be used as a marker for predicting the lifestyle of potential suspect. In this review, we describe recent advances in our understanding of DNA methylation variations and the utility of DNA methylation as a forensic marker for advanced investigative leads from evidence materials. [BMB Reports 2016; 49(7): 359-369] PMID:27099236

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

Pursuing Humanistic Medicine in a Technological Age

PubMed Central

2017-01-01

The humanistic practice of medicine requires that the practitioner have sufficient time and appropriate focus. Both elements, however, are under assault by the high-speed, distraction-filled environment within which primary care is delivered today. Despite or perhaps because of modern medicine’s technological advances, the potentially healing bond between doctor and patient is being frayed and the quality of care consequently degraded. PMID:28725861

"When You're a Baby You Don't Have Puberty": Understanding of Puberty and Human Reproduction in Late Childhood and Early Adolescence

ERIC Educational Resources Information Center

Hurwitz, Lisa B.; Lauricella, Alexis R.; Hightower, Brianna; Sroka, Iris; Woodruff, Teresa K.; Wartella, Ellen

2017-01-01

Basic knowledge of human reproduction can help youth prepare for puberty and make later classes focused on advanced reproductive health topics manageable. With the intention of potentially informing the creation of learning materials, we conducted a needs assessment among children ages 7 to 12 in our suburban Chicago community to ascertain their…

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

Rapid aneuploidy testing (knowing less) versus traditional karyotyping (knowing more) for advanced maternal age: what would be missed, who should decide?

PubMed

Leung, W C; Lau, E T; Lau, W L; Tang, Rebecca; Wong, Shell Fean; Lau, T K; Tse, K T; Wong, S F; To, W K; Ng, Lucy K L; Lao, T T; Tang, Mary H Y

2008-02-01

The application of rapid aneuploidy testing as a stand-alone approach in prenatal diagnosis is much debated. The major criticism of this targeted approach is that it will not detect other chromosomal abnormalities that will be picked up by traditional karyotyping. This study aimed to study the nature of such chromosomal abnormalities and whether parents would choose to terminate affected pregnancies. Retrospective study on a cytogenetic database. Eight public hospitals in Hong Kong. The karyotype results of 19 517 amniotic fluid cultures performed for advanced maternal age (>or=35 years) from 1997 to 2002 were classified according to whether they were detectable by rapid aneuploidy testing. The outcomes of pregnancies with abnormal karyotypes were reviewed from patient records. In all, 333 (1.7%) amniotic fluid cultures yielded abnormal karyotypes; 175 (52.6%) of these were detected by rapid aneuploidy testing, and included trisomy 21 (n=94, 28.2%), trisomy 18 or 13 (n=21, 6.3%), and sex chromosome abnormalities (n=60, 18.0%). The other 158 (47.4%) chromosomal abnormalities were not detectable by rapid aneuploidy testing, of which 63 (18.9%) were regarded to be of potential clinical significance and 95 (28.5%) of no clinical significance. Pregnancy outcomes in 327/333 (98.2%) of these patients were retrieved. In total, 143 (42.9%) of these pregnancies were terminated: 93/94 (98.9%) for trisomy 21, 20/21 (95.2%) for trisomy 18 or 13, 19/60 (31.7%) for sex chromosome abnormalities, and 11/63 (17.5%) for other chromosomal abnormalities with potential clinical significance. There were no terminations in the 95 pregnancies in which karyotyping results were regarded to be of no clinical significance. 'Knowing less' by the rapid aneuploidy stand-alone testing could miss about half of all chromosomal abnormalities detectable by amniocentesis performed for advanced maternal age. Findings from two fifths of the latter were of potential clinical significance, and the parents chose to terminate one out of six of the corresponding pregnancies. If both techniques are available, parents could have enhanced autonomy to choose.

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.

Advance Care Planning for Older Homeless-Experienced Adults: Results from the Health Outcomes of People Experiencing Homelessness in Older Middle Age Study.

PubMed

Sudore, Rebecca L; Cuervo, Isabel Arellano; Tieu, Lina; Guzman, David; Kaplan, Lauren M; Kushel, Margot

2018-05-09

Older homeless-experienced adults have low engagement in advance care planning (ACP) despite high morbidity and mortality. We conducted a cross-sectional analysis of a cohort of 350 homeless-experienced adults aged 50 and older in Oakland, California. We assessed the prevalence of potential surrogate decision-makers, ACP contemplation, discussions, and ACP documentation (surrogate designation, advance directives). We used multivariable logistic regression to examine factors associated with ACP discussions and documentation. The median age of the cohort was 59 (range 52-82), 75.2% were male, and 82.1% were black. Sixty-one percent reported a potential surrogate, 21.5% had discussed ACP, and 19.0% reported ACP documentation. In multivariable models, having 1 to 5 confidants versus none (adjusted odds ratio (aOR)=5.8, 95% confidence interval (CI)=1.7-20.0), 3 or more chronic conditions versus none (aOR=2.3, 95% CI=0.9-5.6), and a recent primary care visit (aOR=2.1, 95% CI=1.0-4.4) were associated with higher odds of ACP discussions and each additional 5 years of homelessness (aOR=0.7, 95% CI=0.5-0.9) with lower odds. Having 1 to 5 confidants (aOR=5.0, 95% CI=1.4-17.5), being black (aOR=5.5, 95% CI=1.5-19.5), and having adequate versus limited literacy (aOR=7.0, 95% CI=1.5-32.4) were associated with higher odds of ACP documentation and illicit drug use (aOR=0.3, 95% CI=0.1-0.9) with lower odds. Although the majority of older homeless-experienced adults have a potential surrogate, few have discussed or documented their ACP wishes; the odds of both were greater with larger social networks. Future interventions must be customized for individuals with limited social networks and address the instability of homelessness, health literacy, and the constraints of safety-net healthcare settings. © 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.

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.

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

Antiglycation and antioxidation properties of Juglans regia and Calendula officinalis: possible role in reducing diabetic complications and slowing down ageing.

PubMed

Ahmad, Haroon; Khan, Ibrar; Wahid, Abdul

2012-09-01

Accumulation of advanced glycation end products (AGEs) in the body due to the non-enzymatic glycation of proteins and oxidation is associated with aging and diabetes mellitus. In this study we wanted to investigate the antiglycation and antioxidation potential of two medicinal plants: Juglans regia and Calendula officinalis. In-vitro investigation was carried out to discover the antiglycation and antioxidation potential of J. regia and C. officinalis. Using an Ultraviolet Double-beam Spectrophotometer, we evaluated the antiglycation property of the crude methanolic extracts of J. regia and C. officinalis by assessing their ability to inhibit the Maillard reaction. Employing the same instrument we also measured the antioxidation potential of these plant extracts using the nitric oxide (NO) free radical-scavenging assay. J. regia had greater antiglycation ability, with a minimum inhibitory concentration (MIC50) of 28 microg/mL as compared with that of C. officinalis (270 microg/mL). C. officinalis had greater antioxidation potential (26.10, 22.07 and 16.06% at 0.5 mg, 0.25 mg and 0.125 mg, respectively, as compared with 18.15, 16.50 and 16.06% of J. regia, respectively). J. regia and C. officinalis inhibited the Maillard reaction and prevented oxidation in-vitro. Hence, the extracts of these plants could have therapeutic uses in curbing chronic diabetic complications and slowing down aging.

Deductive reasoning, brain maturation, and science concept acquisition: Are they linked?

NASA Astrophysics Data System (ADS)

Lawson, Anton E.

The present study tested the alternative hypotheses that the poor performance of the intuitive and transitional students on the concept acquisition tasks employed in the Lawson et al. (1991) study was due either to their failure (a) to use deductive reasoning to test potentially relevant task features, as suggested by Lawson et al. (1991); (b) to identify potentially relevant features; or (c) to derive and test a successful problem-solving strategy. To test these hypotheses a training session, which consisted of a series of seven concept acquisition tasks, was designed to reveal to students key task features and the deductive reasoning pattern necessary to solve the tasks. The training was individually administered to students (ages 5-14 years). Results revealed that none of the five- and six-year-olds, approximately half of the seven-year-olds, and virtually all of the students eight years and older responded successfully to the training. These results are viewed as contradictory to the hypothesis that the intuitive and transitional students in the Lawson et al. (1991) study lacked the reasoning skills necessary to identify and test potentially relevant task features. Instead, the results support the hypothesis that their poor performance was due to their failure to use hypothetico-deductive reasoning to derive an effective strategy. Previous research is cited that indicates that the brain's frontal lobes undergo a pronounced growth spurt from about four years of age to about seven years of age. In fact, the performance of normal six-year-olds and adults with frontal lobe damage on tasks such as the Wisconsin Card Sorting Task (WCST), a task similar in many ways to the present concept acquisition tasks, has been found to be identical. Consequently, the hypothesis is advanced that maturation of the frontal lobes can explain the striking improvement in performance at age seven. A neural network of the role of the frontal lobes in task performance based upon the work of Levine and Prueitt (1989) is presented. The advance in reasoning that presumably results from effective operation of the frontal lobes is seen as a fundamental advance in intellectual development because it enables children to employ an inductive-deductive reasoning pattern to change their minds when confronted with contradictory evidence regarding features of perceptible objects, a skill necessary for descriptive concept acquisition. It is suggested that a further qualitative advance in intellectual development occurs when an analogous pattern of abductive-deductive reasoning is applied to hypothetical objects and/or processes to allow for alternative hypothesis testing and theoretical concept acquisition. Apparently this is the reasoning pattern needed to derive an effective problem-solving strategy to solve the concept acquisition tasks of Lawson et al. (1991) when direct instruction is not provided. Implications for the science classroom are suggested.

Plan of Action for Real-World Translation of LGBTQ Health and Aging Research.

PubMed

Fredriksen-Goldsen, Karen I; Kim, Hyun-Jun; McKenzie, Glenise L; Krinsky, Lisa; Emlet, Charles A

2017-12-01

Despite accumulating evidence of health disparities, there exists limited translational research to enhance optimal health and aging of lesbian, gay, bisexual, transgender, and queer-identified * (LGBTQ) older adults. Based on the Health Equity Promotion Model that addresses the distinct needs and strengths of LGBTQ older adults, we underscore the important role of collaborations among researchers, practitioners, and communities to build community capacity. Given the rapidly shifting context, we advance principles to guide future work that will enhance translational research and the development of evidence-based practice so that LGBTQ older adults can reach their full health potential.

Amadorins: novel post-Amadori inhibitors of advanced glycation reactions.

PubMed

Khalifah, R G; Baynes, J W; Hudson, B G

1999-04-13

The present review focuses on the background and progress that led to discovery of specific inhibition of post-Amadori formation of advanced glycation end products, or AGEs. The "classic" or Hodge pathway begins with glucose condensation with amino groups to form a Schiff base aldimine adduct that undergoes rearrangement to a ketoamine Amadori product. This pathway is considered an important route to AGE formation that has been implicated in glucose-mediated damage in vivo (3-5). We recently described a facile procedure for isolation of proteins rich in Amadori adducts but free of AGEs, thus permitting study of pathways of conversion of Amadori compounds to AGEs. This in turn led to a unique and rapid post-Amadori screening assay for putative "Amadorins," which we define here as inhibitors of the conversion of Amadori intermediates to AGEs in the absence of excess free or reversibly bound (Schiff base) sugar. Our screening assay then led to the identification of pyridoxamine (Pyridorin) as the first member of this class of Amadorin compounds. Rather unexpectedly, the assay also led to the clear demonstration that the well-known AGE inhibitor aminoguanidine, currently in Phase 3 clinical trials for treatment of diabetic nephropathy, has negligible Amadorin activity. In view of the importance of Amadori compounds as intermediates in AGE formation in vivo, the therapeutic potential of Pyridorin is currently being investigated and is now showing highly promising results in different animal models. Copyright 1999 Academic Press.

Mindful Sustainable Aging: Advancing a Comprehensive Approach to the Challenges and Opportunities of Old Age

PubMed Central

Nilsson, Håkan; Bülow, Pia H.; Kazemi, Ali

2015-01-01

The primary aim of this article is to present a new concept called mindful sustainable aging (MSA), which is informed by mindfulness practices that support the physical, the mental, and especially, the social and the existential dimensions of old life. The concept of MSA is discussed and compared with four influential psychosocial theories in the field of gerontology, i.e., activity theory, disengagement theory, successful aging theory and gerotranscendence theory. The article ends with reviewing research on how mindfulness practice can help to manage, diminish and/or improve a number of serious physical conditions that are common among older people. The potential of mindfulness when it comes to facilitating for older adults in their quest for spiritual and existential meaning is discussed extensively throughout the article. PMID:27247673

Systematic literature review of the risk factors, comorbidities, and consequences of hypogonadism in men.

PubMed

Zarotsky, V; Huang, M-Y; Carman, W; Morgentaler, A; Singhal, P K; Coffin, D; Jones, T H

2014-11-01

The objective of this review was to summarize the literature on the risk factors, comorbidities, and consequences of male hypogonadism, which is defined as a syndrome complex that includes biochemical confirmation of low testosterone (T) and the consistent symptoms and signs associated with low T. A systematic literature search was performed in PubMed/MEDLINE, EMBASE, Cochrane Library for articles published in the last 10 years on risk factors, comorbidities, and consequences of male hypogonadism. Of the 53 relevant studies identified, nine examined potential risk factors, 14 examined potential comorbidities, and 30 examined potential consequences of male hypogonadism. Based on studies conducted in Asia, Australia, Europe, and North & South America, the important factors that predicted and correlated with hypogonadism were advanced age, obesity, a diagnosis of metabolic syndrome (MetS), and a poor general health status. Diabetes mellitus was correlated with hypogonadism in most studies, but was not established as a risk factor. Although diseases, such as coronary heart disease, hypertension, stroke, and peripheral arterial disease did not predict hypogonadism, they did correlate with incident low T. The data reviewed on potential consequences suggest that low T levels may be linked to earlier all-cause and cardiovascular related mortality among men. This literature review suggests that men with certain factors, such as advanced age, obesity, MetS, and poor general health, are more likely to have and develop hypogonadism. Low levels of T may have important long-term negative health consequences. © 2014 American Society of Andrology and European Academy of Andrology.

Vitamin E in Sarcopenia: Current Evidences on Its Role in Prevention and Treatment

PubMed Central

Abdul Karim, Norwahidah; Wan Ngah, Wan Zurinah

2014-01-01

Sarcopenia is a geriatric syndrome that is characterized by gradual loss of muscle mass and strength with increasing age. Although the underlying mechanism is still unknown, the contribution of increased oxidative stress in advanced age has been recognized as one of the risk factors of sarcopenia. Thus, eliminating reactive oxygen species (ROS) can be a strategy to combat sarcopenia. In this review, we discuss the potential role of vitamin E in the prevention and treatment of sarcopenia. Vitamin E is a lipid soluble vitamin, with potent antioxidant properties and current evidence suggesting a role in the modulation of signaling pathways. Previous studies have shown its possible beneficial effects on aging and age-related diseases. Although there are evidences suggesting an association between vitamin E and muscle health, they are still inconclusive compared to other more extensively studied chronic diseases such as neurodegenerative diseases and cardiovascular diseases. Therefore, we reviewed the role of vitamin E and its potential protective mechanisms on muscle health based on previous and current in vitro and in vivo studies. PMID:25097722

A capture method based on the VC1 domain reveals new binding properties of the human receptor for advanced glycation end products (RAGE).

PubMed

Degani, Genny; Altomare, Alessandra A; Colzani, Mara; Martino, Caterina; Mazzolari, Angelica; Fritz, Guenter; Vistoli, Giulio; Popolo, Laura; Aldini, Giancarlo

2017-04-01

The Advanced Glycation and Lipoxidation End products (AGEs and ALEs) are a heterogeneous class of compounds derived from the non-enzymatic glycation or protein adduction by lipoxidation break-down products. The receptor for AGEs (RAGE) is involved in the progression of chronic diseases based on persistent inflammatory state and oxidative stress. RAGE is a pattern recognition receptor (PRR) and the inhibition of the interaction with its ligands or of the ligand accumulation have a potential therapeutic effect. The N-terminal domain of RAGE, the V domain, is the major site of AGEs binding and is stabilized by the adjacent C1 domain. In this study, we set up an affinity assay relying on the extremely specific biological interaction AGEs ligands have for the VC1 domain. A glycosylated form of VC1, produced in the yeast Pichia pastoris, was attached to magnetic beads and used as insoluble affinity matrix (VC1-resin). The VC1 interaction assay was employed to isolate specific VC1 binding partners from in vitro generated AGE-albumins and modifications were identified/localized by mass spectrometry analysis. Interestingly, this method also led to the isolation of ALEs produced by malondialdehyde treatment of albumins. Computational studies provided a rational-based interpretation of the contacts established by specific modified residues and amino acids of the V domain. The validation of VC1-resin in capturing AGE-albumins from complex biological mixtures such as plasma and milk, may lead to the identification of new RAGE ligands potentially involved in pro-inflammatory and pro-fibrotic responses, independently of their structures or physical properties, and without the use of any covalent derivatization process. In addition, the method can be applied to the identification of antagonists of RAGE-ligand interaction. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Anti-Advanced Glycation End-product and Free Radical Scavenging Activity of Plants from the Yucatecan Flora

PubMed Central

Dzib-Guerra, Wendy del C.; Escalante-Erosa, Fabiola; García-Sosa, Karlina; Derbré, Séverine; Blanchard, Patricia; Richomme, Pascal; Peña-Rodríguez, Luis M.

2016-01-01

Background: Formation and accumulation of advanced glycation end-products (AGE) is recognized as a major pathogenic process in diabetic complications, atherosclerosis and cardiovascular diseases. In addition, reactive oxygen species and free radicals have also been reported to participate in AGE formation and in cell damage. Natural products with antioxidant and antiAGE activity have great therapeutic potential in the treatment of diabetes, hypertension and related complications. Objective: to test ethanolic extracts and aqueous-traditional preparations of plants used to treat diabetes, hypertension and obesity in Yucatecan traditional medicine for their anti-AGE and free radical scavenging activities. Materials and Methods: ethanolic extracts of leaves, stems and roots of nine medicinal plants, together with their traditional preparations, were prepared and tested for their anti-AGE and antioxidant activities using the inhibition of advanced glycation end products and DPPH radical scavenging assays, respectively. Results: the root extract of C. fistula (IC50= 0.1 mg/mL) and the leaf extract of P. auritum (IC50= 0.35 mg/mL) presented significant activity against vesperlysine and pentosidine-like AGE. Although none of the aqueous traditional preparations showed significant activity in the anti-AGE assay, both the traditional preparations and the ethanolic extracts of E. tinifolia, M. zapota, O. campechianum and P. auritum showed significant activity in the DPPH reduction assay. Conclusions: the results suggest that the metabolites responsible for the detected radical-scavenging activity are different to those involved in inhibiting AGE formation; however, the extracts with antioxidant activity may contain other metabolites which are able to prevent AGE formation through a different mechanism. SUMMARY Ethanolic extracts from nine plants used to treat diabetes, hypertension and obesity in Yucatecan traditional medicine were tested for their anti-AGE and free radical scavenging activities.Significant activity against vesperlysine and pentosidine-like AGE was detected in the root extract of Cassia fistula and the leaf extract of Piper auritum.Traditional preparations and the ethanolic extracts of Ehretia tinifolia, Manilkara zapota, Ocimum campechianum and Piper auritum showed significant activity in the DPPH reduction assay.Results suggest that the metabolites responsible for the detected radical-scavenging activity are different to those involved in inhibiting AGE formation. Abbreviations Used: AGE: Advanced glycation end-product; DPPH: 2,2-Diphenyl-1-picrylhydrazyl; DM: Diabetes mellitus; ROS: Reactive oxygen species; BSA: Bovine serum albumin; EtOH: Ethanol; EtOAc: Ethyl acetate; ANOVA: Analysis of variance; BA: Brosimum alicastrum; BS: Bunchosia swartziana; CF: Cassia fistula; CN: Cocos nucifera; ET: Ehretia tinifolia; MZ: Manilkara zapota; OC: Ocimum campechianum; PA: Piper auritum; RM: Rhizophora mangle; L: Leaves; S: Stems; R: Roots; T: traditional preparation; I: Inflorescences; W: Water PMID:27695268

Anti-Advanced Glycation End-product and Free Radical Scavenging Activity of Plants from the Yucatecan Flora.

PubMed

Dzib-Guerra, Wendy Del C; Escalante-Erosa, Fabiola; García-Sosa, Karlina; Derbré, Séverine; Blanchard, Patricia; Richomme, Pascal; Peña-Rodríguez, Luis M

2016-01-01

Formation and accumulation of advanced glycation end-products (AGE) is recognized as a major pathogenic process in diabetic complications, atherosclerosis and cardiovascular diseases. In addition, reactive oxygen species and free radicals have also been reported to participate in AGE formation and in cell damage. Natural products with antioxidant and antiAGE activity have great therapeutic potential in the treatment of diabetes, hypertension and related complications. Objective: to test ethanolic extracts and aqueous-traditional preparations of plants used to treat diabetes, hypertension and obesity in Yucatecan traditional medicine for their anti-AGE and free radical scavenging activities. ethanolic extracts of leaves, stems and roots of nine medicinal plants, together with their traditional preparations, were prepared and tested for their anti-AGE and antioxidant activities using the inhibition of advanced glycation end products and DPPH radical scavenging assays, respectively. the root extract of C. fistula (IC 50 = 0.1 mg/mL) and the leaf extract of P. auritum (IC 50 = 0.35 mg/mL) presented significant activity against vesperlysine and pentosidine-like AGE. Although none of the aqueous traditional preparations showed significant activity in the anti-AGE assay, both the traditional preparations and the ethanolic extracts of E. tinifolia, M. zapota, O. campechianum and P. auritum showed significant activity in the DPPH reduction assay. the results suggest that the metabolites responsible for the detected radical-scavenging activity are different to those involved in inhibiting AGE formation; however, the extracts with antioxidant activity may contain other metabolites which are able to prevent AGE formation through a different mechanism. Ethanolic extracts from nine plants used to treat diabetes, hypertension and obesity in Yucatecan traditional medicine were tested for their anti-AGE and free radical scavenging activities.Significant activity against vesperlysine and pentosidine-like AGE was detected in the root extract of Cassia fistula and the leaf extract of Piper auritum .Traditional preparations and the ethanolic extracts of Ehretia tinifolia, Manilkara zapota, Ocimum campechianum and Piper auritum showed significant activity in the DPPH reduction assay.Results suggest that the metabolites responsible for the detected radical-scavenging activity are different to those involved in inhibiting AGE formation. Abbreviations Used : AGE: Advanced glycation end-product; DPPH: 2,2-Diphenyl-1-picrylhydrazyl; DM: Diabetes mellitus; ROS: Reactive oxygen species; BSA: Bovine serum albumin; EtOH: Ethanol; EtOAc: Ethyl acetate; ANOVA: Analysis of variance; BA: Brosimum alicastrum ; BS: Bunchosia swartziana ; CF: Cassia fistula ; CN: Cocos nucifera ; ET: Ehretia tinifolia ; MZ: Manilkara zapota ; OC: Ocimum campechianum ; PA: Piper auritum ; RM: Rhizophora mangle ; L: Leaves; S: Stems; R: Roots; T: traditional preparation; I: Inflorescences; W: Water.

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

[Small Area Variation in Demographic Aging - Informal and Formal Nursing Care Ratios and Care Preferences of Senior Citizens Inform Health Care Planners].

PubMed

Alltag, Sophie; Nowossadeck, Sonja; Stein, Janine; Hajek, André; König, Hans-Helmut; Riedel-Heller, Steffi G; Nowossadeck, Enno

2017-10-01

Objective Demographic aging affects the number of older individuals potentially in need of care and age groups of younger individuals potentially providing formal and informal care. This study examines the current and future demographic aging and care preferences on a county level in Saxony. Methods To analyze demographic aging, formal (FISR) and informal intergenerational support ratios (IISR) based on population data from the Federal Institute for Research on Building, Urban Affairs and Spatial Development (BBSR) were used. Ratios were calculated for every county in Saxony from 2012 to 2035. Care preferences for care settings of senior German citizens in Saxony were determined by a representative telephone survey (n = 101; 65+). Results FISR and IISR tend to progress in similar ways and are reduced by 50 % by 2035. Regarding nursing care preferences, the majority preferred being cared for at home. Implications Upcoming care ratios may inform community health care planners and decision makers on critical constellations in advance. Strategies to ensure the future elderly care are to be developed and implemented. © Georg Thieme Verlag KG Stuttgart · New York.

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

Variation in polyphenolic profiles, antioxidant and antimicrobial activity of different Achillea species as natural sources of antiglycative compounds.

PubMed

Afshari, Mahvash; Rahimmalek, Mehdi; Miroliaei, Mehran

2018-05-19

A comparative study was carried out on the methanolic extracts from six Achillea species and the examined polyphenols from these plants on the formation of advanced glycation end-products (AGE) in vitro. A. pachycephala which was richer in flavonoids (15 mg quercetin/g W) and phenolics (111.10 mg tannic acid/g DW) with substantial antioxidant activity (IC 50 = 365.5 μg/ml) presented strong anti-AGE properties. Chlorogenic acid, luteolin, quercetin and caffeic acid were identified as the major polyphenols in the extracts by HPLC. In general, polyphenolic content follows the order A. pachycephalla > A. nobilis > A. filipendulina > A. santolina > A. aucheri > A. millefolium. Most extracts exhibited marked anti-AGE ability in the bovine serum albumin (BSA)/methylglyoxal (MG) system, though A. pachycephala showed the highest potential. The formation of AGEs was assessed by monitoring the production of fluorescent products and Circular dichroism (CD) spectroscopy. Diminution in free radical production (assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays) is discussed as potential mechanism for delay or reduced AGE. The results demonstrate the antiglycative, antioxidant and antimicrobial potential of Achillea species which can be attribute to polyphenols content and the effectiveness on generation of AGEs, thus Achillea species can be considered as natural sources for slowing down glycation related diseases. This article is protected by copyright. All rights reserved. This article is protected by copyright. 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.

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.

Trichomonas vaginalis infection and risk of advanced prostate cancer.

PubMed

Shui, Irene M; Kolb, Suzanne; Hanson, Christi; Sutcliffe, Siobhan; Rider, Jennifer R; Stanford, Janet L

2016-05-01

The epidemiologic evidence for an association of Trichomonas vaginalis (Tv) with overall prostate cancer is mixed, but some studies suggest Tv may increase risk of more aggressive disease. The aim of this study was to assess whether Tv serostatus is associated with advanced or fatal prostate cancer. A total of 146 men with advanced (metastatic or fatal) prostate cancer and 181 age-matched controls were selected from two prior population-based, case-control studies. Tv serostatus was determined with the same laboratory methods used in previous epidemiologic studies. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression to compare Tv serostatus in prostate cancer cases and controls adjusted for potential confounders. The seroprevalence of Tv in controls was 23%. Tv serostatus was not associated with an increased risk of metastatic or fatal prostate cancer (ORs < 1). Our study does not support an increased risk of advanced or fatal prostate cancer in men seropositive for Tv. © 2016 Wiley Periodicals, Inc.

The relationship between demographic characteristics and motivational factors in the employees of social security hospitals in Mazandaran.

PubMed

Heidarian, Ali Reza; Jafari Kelarijani, Seyed Ebrahim; Jamshidi, Reza; Khorshidi, Mohamad

2015-01-01

Health worker motivation has the potential to have a large impact on health system performance, and this depends on some factors. The purpose of this study was to determine the factors affecting this motivation. From Winter 2013 to Spring 2014, 1046 employees and physicians (439 males and 607 females) with a mean age of 36 and 37.2 years in men and women, respectively were chosen in selected hospitals of Social Security Organization (SSO). They were randomly categorized into six different classes of service record, age education class of hiring (permanent and contractual), marital status, and gender. The variables assessed via the classification groups were as follows: interpersonal relations, working conditions, equity, pay, job security, supervision, advancement, recognition, responsibility, and attractiveness of job, educational and organizational policies. Bachelor's degree (65%) or higher were the education degrees of most participants. Significant relations were observed regarding age, marital status, hiring, gender and years of service with promotion, recognition, responsibility, attractiveness of job, education, relations, working condition, equity, salary, job security, supervision and organizational policies. There were significant relations with hire status and degree with advancement and other variables. There were significant relations between marital status, gender, years of service and age with the above variables. The results show that the important variables that influence motivational factors are academic degree, hire status, marital status, gender, age and years of service.

Advanced glycation end product-induced astrocytic differentiation of cultured neurospheres through inhibition of Notch-Hes1 pathway-mediated neurogenesis.

PubMed

Guo, Yijing; Wang, Pin; Sun, Haixia; Cai, Rongrong; Xia, Wenqing; Wang, Shaohua

2013-12-23

This study aims to investigate the roles of the Notch-Hes1 pathway in the advanced glycation end product (AGE)-mediated differentiation of neural stem cells (NSCs). We prepared pLentiLox3.7 lentiviral vectors that express short hairpin RNA (shRNA) against Notch1 and transfected it into NSCs. Cell differentiation was analyzed under confocal laser-scanning microscopy. The percentage of neurons and astrocytes was quantified by normalizing the total number of TUJ1+ (Neuron-specific class III β-tubulin) and GFAP+ (Glial fibrillary acidic protein) cells to the total number of Hoechst 33342-labeled cell nuclei. The protein and gene expression of Notch-Hes1 pathway components was examined via western blot analysis and real-time PCR. After 1 week of incubation, we found that AGE-bovine serum albumin (BSA) (400 μg/mL) induced the astrocytic differentiation of cultured neurospheres and inhibited neuronal formation. The expression of Notch-Hes1 pathway components was upregulated in the cells in the AGE-BSA culture medium. Immunoblot analysis indicated that shRNA silencing of Notch1 expression in NSCs significantly increases neurogenesis and suppresses astrocytic differentiation in NSCs incubated with AGE-BSA. AGEs promote the astrocytic differentiation of cultured neurospheres by inhibiting neurogenesis through the Notch-Hes1 pathway, providing a potential therapeutic target for hyperglycemia-related cognitive deficits.

Advanced glycosylation end product promotes forkhead box O1 and inhibits Wnt pathway to suppress capacities of epidermal stem cells.

PubMed

Zhu, Jie; Wang, Peng; Yu, Zhimin; Lai, Wei; Cao, Yi; Huang, Pinbo; Xu, Qiaodong; Yu, Menglei; Xu, Junyao; Huang, Zitong; Zeng, Bing

2016-01-01

Diabetes mellitus is frequently accompanied by chronic complications like delayed wound healing, which is consider to be attributed to the accumulation of advanced glycosylation end product (AGE). However, the impacts of AGE on epidermal stem cells (ESCs) are largely unknown. This study aims to address the influence and mechanism of AGE on ESCs. ESCs isolated from rats were cultured in AGE-modified bovine serum albumin and transfected with small interfering RNA to knock down AGE-specific receptor (AGER). Expression of stem cell markers integrin β1 (ITGB1) and keratin 19 (KRT19), cell viability, apoptosis and reactive oxygen species (ROS) were examined. Wnt pathway-related factors Wnt family member 1 (WNT1), WNT3A, β-catenin, v-myc avian myelocytomatosis viral oncogene homolog (MYC), cyclin D1 (CCND1) and matrix metallopeptidase 7 (MMP7) were quantified. The interaction between forkhead box O1 (FOXO1) and β-catenin was assessed by co-immunoprecipitation. Results indicated that AGE down-regulated ITGB1 and KRT19 expression, suppressed ESC viability and promoted apoptosis, and ROS level ( P < 0.01), implying decreased capacities of ESCs. AGE also promoted AGER and FOXO1, while AGER knockdown had the opposite effects. Moreover, AGER knockdown elevated the level of WNT1, WNT3A, MYC, CCND1 and MMP7 that were suppressed by AGE ( P < 0.01). Immunoprecipitation analysis showed that FOXO1 could compete with lymphoid enhancer binding factor 1 to interact with β-catenin, which might help to elucidate the mechanism of AGE repressing ESCs. This study helps to understand the mechanism of accumulated AGE in affecting ESC capacities, and provides potential therapeutic targets to meliorate diabetic wound healing.

Repairing the Aged Parkinsonian Striatum: Lessons from the Lab and Clinic.

PubMed

Mercado, Natosha M; Collier, Timothy J; Freeman, Thomas; Steece-Collier, Kathy

2016-12-01

The primary risk factor associated with Parkinson's disease (PD) is advanced age. While there are symptomatic therapies for PD, efficacy of these eventually wane and/or side-effects develop over time. An alternative experimental therapy that has received a great deal of attention over the past several decades has been neural transplantation aimed at replacing nigral dopamine (DA) neurons that degenerate in PD. However, in PD patients and parkinsonian rats, advanced age is associated with inferior benefit following intrastriatal grafting of embryonic DA neurons. Traditionally it has been thought that decreased therapeutic benefit results from the decreased survival of grafted DA neurons and the accompanying poor reinnervation observed in the aged host. However, recent clinical and preclinical data suggest that factors inherent to the aged striatum per se limit successful brain repair. In this short communication, we focus discussion on the implications of our recent grafting study in aged parkinsonian rats, with additional emphasis on a recent clinical report of the outcome of cell therapy in an aged PD patient with long-term (24 years) survival of DA neuron grafts. To address aging as a limiting factor in successful brain repair, we use the example of cell transplantation as a means to interrogate the environment of the aged striatum and identify factors that may, or may not, respond to interventions aimed at improving the prospects for adequate repair of the aged brain. We offer discussion of how these recent reports, in the context of other historical grafting studies, might provide new insight into specific risk factors that have potential to negatively impact all DA cell or terminal replacement strategies for clinical use in PD.

Adult Degenerative Scoliosis with Spinal Stenosis Treated with Stand-Alone Cage via an Extreme Lateral Transpsoas Approach; a Case Report and Literature Review

PubMed Central

von Keudell, Arvind; Alimi, Marjan; Gebhard, Harry; Härtl, Roger

2015-01-01

We report the case of a 73-year-old female with severe degenerative scoliosis and back and leg pain that was successfully treated with stand- alone cages via an extreme lateral transpsoas approach. This patient had declined open surgery and instrumentation due to her advanced age concerns about potential side effects. PMID:26110180

Aging and involuntary attention capture: electrophysiological evidence for preserved attentional control with advanced age.

PubMed

Lien, Mei-Ching; Gemperle, Alison; Ruthruff, Eric

2011-03-01

The present study examined whether people become more susceptible to capture by salient objects as they age. Participants searched a target display for a letter in a specific color and indicated its identity. In Experiment 1, this target display was preceded by a non-informative cue display containing one target-color box, one ignored-color box, and two white boxes. On half of the trials, this cue display also contained a salient-but-irrelevant abrupt onset. To assess capture by the target-color cue, we used the N2pc component of the event-related potential, thought to reflect attentional allocation to the left or right visual field. The target-color box in the cue display produced a substantial N2pc effect for younger adults and, most importantly, this effect was not diminished by the presence of an abrupt onset. Therefore, the abrupt onset was unable to capture attention away from the target-color cue. Critically, older adults demonstrated the same resistance to capture by the abrupt onset. Experiment 2 extended these findings to irrelevant color singleton cues. Thus, we argue that the ability to attend to relevant stimuli and resist capture by salient-but-irrelevant stimuli is preserved with advancing age. (c) 2011 APA, all rights reserved.

Developing vaccines for an aging population.

PubMed

Black, Steven; De Gregorio, Ennio; Rappuoli, Rino

2015-04-01

The demographics of the world's population are changing, with many adults now surviving into their 80s. With this change comes the need to protect the aging and other underserved populations not only against infectious diseases but also against cancer and other chronic conditions. New technologies derived from recent advances in the fields of immunology, structural biology, synthetic biology, and genomics have brought a revolution in the vaccine field. Among them, vaccine adjuvants have the potential to harness the immune system to provide protection against new types of diseases, improve protection in young children, and expand this protection to adults and the elderly. However, in order to do so we need also to overcome the nontechnical challenges that could limit the implementation of innovative vaccines, including controversies regarding the safety of adjuvants, increasing regulatory complexity, the inadequate methods used to assess the value of novel vaccines, and the resulting industry alienation from future investment. This Perspective summarizes the outcome of a recent multidisciplinary symposium entitled "Enhancing Vaccine Immunity and Value," held in Siena, Italy, in July 2014, that addressed two related questions: how to improve vaccine efficacy by using breakthrough technologies and how to capture the full potential of novel vaccines. Copyright © 2015, American Association for the Advancement of Science.

Black males' self-perceptions of academic ability and gifted potential in advanced science classes

NASA Astrophysics Data System (ADS)

Rascoe, Barbara Jean

The purpose of this study was to examine gifted Black males' self-perceptions of academic ability and gifted potential in science. Major concerns were to determine how these self-perceptions of academic ability and gifted potential influenced gifted Black males' capacity to compete in advanced science classes and to determine how science teachers may have influenced participants' self-perceptions of academic ability and gifted potential. This study required an approach that would allow an interpretive aspect for the experiences of gifted Black males in advanced science classes. An intrinsic qualitative case study design with a critical theory framework was used. Data were collected using semi-structured interviews, which were audiotaped and transcribed. Each participant was interviewed twice and each interview averaged 45 minutes. The purposeful sample consisted of nine gifted high school Black males between the ages of fourteen and eighteen. The constant comparative method was used to analyze the data. The categories of gifted Black males' self-perceptions of academic ability and gifted potential included gifted high achievers, gifted 'could do better' high achievers, gifted 'could do better' situational nonachievers, and gifted 'could do better' underachievers. Gifted Black male participants' perceptions regarding their science teachers' influence on their self-perceptions of academic ability and gifted potential included validation, reinforcement, and enhancement. These participants' perceptions regarding how science teachers' influenced their academic performance in science included science teachers' content knowledge, science teachers' skills to make science challenging and engaging, and a safe learning environment. The conclusions of this study described competing power dynamics of science teachers and gifted Black males' interactions in the science learning environment. The discussion also included a summary of relationships among the emergent themes. Implications are posited for science teaching education programs and future research.

Blast transformation and fibrotic progression in polycythemia vera and essential thrombocythemia: a literature review of incidence and risk factors

PubMed Central

Cerquozzi, S; Tefferi, A

2015-01-01

Polycythemia vera (PV) and essential thrombocythemia (ET) constitute two of the three BCR-ABL1-negative myeloproliferative neoplasms and are characterized by relatively long median survivals (approximately 14 and 20 years, respectively). Potentially fatal disease complications in PV and ET include disease transformation into myelofibrosis (MF) or acute myeloid leukemia (AML). The range of reported frequencies for post-PV MF were 4.9–6% at 10 years and 6–14% at 15 years and for post-ET MF were 0.8–4.9% at 10 years and 4–11% at 15 years. The corresponding figures for post-PV AML were 2.3–14.4% at 10 years and 5.5–18.7% at 15 years and for post-ET AML were 0.7–3% at 10 years and 2.1–5.3% at 15 years. Risk factors cited for post-PV MF include advanced age, leukocytosis, reticulin fibrosis, splenomegaly and JAK2V617F allele burden and for post-ET MF include advanced age, leukocytosis, anemia, reticulin fibrosis, absence of JAK2V617F, use of anagrelide and presence of ASXL1 mutation. Risk factors for post-PV AML include advanced age, leukocytosis, reticulin fibrosis, splenomegaly, abnormal karyotype, TP53 or RUNX1 mutations as well as use of pipobroman, radiophosphorus (P32) and busulfan and for post-ET AML include advanced age, leukocytosis, anemia, extreme thrombocytosis, thrombosis, reticulin fibrosis, TP53 or RUNX1 mutations. It is important to note that some of the aforementioned incidence figures and risk factor determinations are probably inaccurate and at times conflicting because of the retrospective nature of studies and the inadvertent labeling, in some studies, of patients with prefibrotic primary MF or ‘masked' PV, as ET. Ultimately, transformation of MPN leads to poor outcomes and management remains challenging. Further understanding of the molecular events leading to disease transformation is being investigated. PMID:26565403

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.

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.

[Advance directives in patients with kidney disease or other general medical diagnoses].

PubMed

Driehorst, F; Keller, F

2014-03-01

After the law on living will was released in 2009 in Germany, an increased use of advance directives was observed. Since patients with kidney diseases are facing the potential or real need for expensive and invasive renal replacement therapy, one could speculate that they will either less or even more frequently state an advance directive than patients with other diseases. A structured interviewing was performed of all patients on a nephrology ward where also patients with other general medical conditions are treated. The study was approved by our local ethics committee (protocol # 303/08). All admitted patients were successively included who could give signed consent. The investigation was performed between July 2009 and April 2010 by a single interviewer (FD). Among 505 admitted patients, 211 were included but 11 patients did not consent to the investigation. Of the 200 investigated patients, 121 had a renal diagnosis and 79 other medical diseases. Compared to other European studies, the frequency of advance directives was high (26 %), underlining its clinical relevance. Upon multivariate logistic regression analysis the odds ratio (95 % confidence interval, CI) for the presence of an advance directive was significantly increased only by the age (1.06; CI 1.03-1.09; p = 0.001), but not by the underlying diagnosis (1.47; CI 0.72-2.97; p = 0.287). Significantly more patients did forego resuscitation than did dialysis in their living will (16 vs. 4) while the majority was undecided (36 vs. 47; p = 0.01). Age was found the more impacting variable than the renal diagnosis on the prevalence of advance directives. Patients with a renal diagnosis should be encouraged to make a statement on dialysis in their living will. © Georg Thieme Verlag KG Stuttgart · New York.

An evidence-based review on the influence of aging with a spinal cord injury on subjective quality of life

PubMed Central

Sakakibara, Brodie M.; Hitzig, Sander L.; Miller, William C.; Eng, Janice J.

2012-01-01

Study Design Systematic review. Objectives To identify changes in subjective quality of life (QoL) as one ages with a spinal cord injury (SCI). Setting Vancouver, Canada. Methods Electronic databases were searched for studies reporting on age-related QoL changes over time. Data from relevant studies were transcribed into data extraction forms and analyzed by years post-injury (YPI) and chronologic age. Each study was assigned a level of evidence based on a modified Sackett scale. Results Twenty-one studies, each with a low level of evidence, were included for review. The results indicated that regardless of chronologic age, individuals with relatively new SCI have the potential to improve their QoL. Among individuals with advanced YPI, overall QoL is consistently reported as good or excellent over time, however, with variations in different QoL domains. Conclusion The QoL of individuals aging with a SCI has the potential to improve, and remain high and stable over time. Since the identified studies provide low levels of evidence, more longitudinal research with greater methodological and measurement rigour is needed to corroborate the findings and conclusions of this review. Sponsorship The Rick Hansen Institute and the Ontario Neurotrauma Foundation. PMID:22450883

Potential Therapeutic Effects of Lipoic Acid on Memory Deficits Related to Aging and Neurodegeneration.

PubMed

Molz, Patrícia; Schröder, Nadja

2017-01-01

The aging process comprises a series of organic alterations, affecting multiple systems, including the nervous system. Aging has been considered the main risk factor for the advance of neurodegenerative diseases, many of which are accompanied by cognitive impairment. Aged individuals show cognitive decline, which has been associated with oxidative stress, as well as mitochondrial, and consequently energetic failure. Lipoic acid (LA), a natural compound present in food and used as a dietary supplement, has been considered a promising agent for the treatment and/or prevention of neurodegenerative disorders. In spite of a number of preclinical studies showing beneficial effects of LA in memory functioning, and pointing to its neuroprotective potential effect, to date only a few studies have examined its effects in humans. Investigations performed in animal models of memory loss associated to aging and neurodegenerative disorders have shown that LA improves memory in a variety of behavioral paradigms. Moreover, cell and molecular mechanisms underlying LA effects have also been investigated. Accordingly, LA displays antioxidant, antiapoptotic, and anti-inflammatory properties in both in vivo and in vitro studies. In addition, it has been shown that LA reverses age-associated loss of neurotransmitters and their receptors, which can underlie its effects on cognitive functions. The present review article aimed at summarizing and discussing the main studies investigating the effects of LA on cognition as well as its cell and molecular effects, in order to improve the understanding of the therapeutic potential of LA on memory loss during aging and in patients suffering from neurodegenerative disorders, supporting the development of clinical trials with LA.

Potential Therapeutic Effects of Lipoic Acid on Memory Deficits Related to Aging and Neurodegeneration

PubMed Central

Molz, Patrícia; Schröder, Nadja

2017-01-01

The aging process comprises a series of organic alterations, affecting multiple systems, including the nervous system. Aging has been considered the main risk factor for the advance of neurodegenerative diseases, many of which are accompanied by cognitive impairment. Aged individuals show cognitive decline, which has been associated with oxidative stress, as well as mitochondrial, and consequently energetic failure. Lipoic acid (LA), a natural compound present in food and used as a dietary supplement, has been considered a promising agent for the treatment and/or prevention of neurodegenerative disorders. In spite of a number of preclinical studies showing beneficial effects of LA in memory functioning, and pointing to its neuroprotective potential effect, to date only a few studies have examined its effects in humans. Investigations performed in animal models of memory loss associated to aging and neurodegenerative disorders have shown that LA improves memory in a variety of behavioral paradigms. Moreover, cell and molecular mechanisms underlying LA effects have also been investigated. Accordingly, LA displays antioxidant, antiapoptotic, and anti-inflammatory properties in both in vivo and in vitro studies. In addition, it has been shown that LA reverses age-associated loss of neurotransmitters and their receptors, which can underlie its effects on cognitive functions. The present review article aimed at summarizing and discussing the main studies investigating the effects of LA on cognition as well as its cell and molecular effects, in order to improve the understanding of the therapeutic potential of LA on memory loss during aging and in patients suffering from neurodegenerative disorders, supporting the development of clinical trials with LA. PMID:29311912

Parental age and offspring mortality: Negative effects of reproductive ageing may be counterbalanced by secular increases in longevity.

PubMed

Barclay, Kieron; Myrskylä, Mikko

2018-07-01

As parental ages at birth continue to rise, concerns about the effects of fertility postponement on offspring are increasing. Due to reproductive ageing, advanced parental ages have been associated with negative health outcomes for offspring, including decreased longevity. The literature, however, has neglected to examine the potential benefits of being born at a later date. Secular declines in mortality mean that later birth cohorts are living longer. We analyse mortality over ages 30-74 among 1.9 million Swedish men and women born 1938-60, and use a sibling comparison design that accounts for all time-invariant factors shared by the siblings. When incorporating cohort improvements in mortality, we find that those born to older mothers do not suffer any significant mortality disadvantage, and that those born to older fathers have lower mortality. These findings are likely to be explained by secular declines in mortality counterbalancing the negative effects of reproductive ageing.

Basic science and pathogenesis of ageing with HIV: potential mechanisms and biomarkers.

PubMed

Lagathu, Claire; Cossarizza, Andrea; Béréziat, Véronique; Nasi, Milena; Capeau, Jacqueline; Pinti, Marcello

2017-06-01

: The increased prevalence of age-related comorbidities and mortality is worrisome in ageing HIV-infected patients. Here, we aim to analyse the different ageing mechanisms with regard to HIV infection. Ageing results from the time-dependent accumulation of random cellular damage. Epigenetic modifications and mitochondrial DNA haplogroups modulate ageing. In antiretroviral treatment-controlled patients, epigenetic clock appears to be advanced, and some haplogroups are associated with HIV infection severity. Telomere shortening is enhanced in HIV-infected patients because of HIV and some nucleoside analogue reverse transcriptase inhibitors. Mitochondria-related oxidative stress and mitochondrial DNA mutations are increased during ageing and also by some nucleoside analogue reverse transcriptase inhibitors. Overall, increased inflammation or 'inflammageing' is a major driver of ageing and could result from cell senescence with secreted proinflammatory mediators, altered gut microbiota, and coinfections. In HIV-infected patients, the level of inflammation and innate immunity activation is enhanced and related to most comorbidities and to mortality. This status could result, in addition to age, from the virus itself or viral protein released from reservoirs, from HIV-enhanced gut permeability and dysbiosis, from antiretroviral treatment, from frequent cytomegalovirus and hepatitis C virus coinfections, and also from personal and environmental factors, as central fat accumulation or smoking. Adaptive immune activation and immunosenescence are associated with comorbidities and mortality in the general population but are less predictive in HIV-infected patients. Biomarkers to evaluate ageing in HIV-infected patients are required. Numerous systemic or cellular inflammatory, immune activation, oxidative stress, or senescence markers can be tested in serum or peripheral blood mononuclear cells. The novel European Study to Establish Biomarkers of Human Ageing MARK-AGE algorithm, evaluating the biological age, is currently assessed in HIV-infected patients and reveals an advanced biological age. Some enhanced inflammatory or innate immune activation markers are interesting but still not validated for the patient's follow-up. To be able to assess patients' biological age is an important objective to improve their healthspan.

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.

Parental age and the risk of attention-deficit/hyperactivity disorder: a nationwide, population-based cohort study.

PubMed

Chudal, Roshan; Joelsson, Petteri; Gyllenberg, David; Lehti, Venla; Leivonen, Susanna; Hinkka-Yli-Salomäki, Susanna; Gissler, Mika; Sourander, Andre

2015-06-01

An increasing number of studies has shown an association between parental age and psychiatric disorders. However, there are inconsistent results regarding whether age at parenthood is associated with attention-deficit/hyperactivity disorder (ADHD). The aim of this study is to examine whether low or advanced parental age is associated with ADHD. In this nested case-control study, we identified 10,409 individuals with ADHD born in Finland during 1991 to 2005 and diagnosed with ADHD between 1995 and 2011, along with 39,125 controls matched on sex, date, and place of birth, from nationwide population-based registers. Conditional logistic regression was used to examine the association between parental age and ADHD in offspring, adjusting for potential confounding due to parental psychiatric history, maternal socioeconomic status, marital status, maternal smoking during pregnancy, number of previous births, and birth weight for gestational age. Fathers younger than 20 years had a 1.5-fold (odds ratio [OR] = 1.55, 95% CI = 1.11-2.18, p = .01) increased risk of having offspring with ADHD as compared to fathers aged 25 to 29 years. Mothers of the same age group had a 1.4-fold (OR = 1.41, 95% CI = 1.15-1.72, p =.0009) increased risk. Advanced maternal age was inversely associated with ADHD (OR = 0.79, 95% CI = 0.64-0.97, p = .02). ADHD was associated with young fathers or mothers at the time of birth. Health professionals working with young parents should be aware of the increased risk of ADHD in offspring. This will improve early detection; however, for the development of preventive measures and appropriate interventions, more information on the developmental pathways is needed. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Circulating Concentrations of Advanced Glycation end Products, its Association With the Development of Diabetes Mellitus.

PubMed

Jiménez, Itzel Uribe; Díaz-Díaz, Eulises; Castro, Jorge Salmerón; Ramos, Julia Pérez; León, Mario Cárdenas; Alvarado Ríos, José Antonio; Auriostigue Bautista, Juan Carlos; Correa-Rotter, Ricardo; Aguilar Salinas, Carlos Alberto; Larrea, Fernando

2017-05-01

Diabetes Mellitus (DM) is characterized by the production and accumulation of advanced glycation end products (AGEs), which are one of the key mechanisms in the development of its chronic complications. To assess the serum AGEs concentration by a radioimmunoassay (RIA) developed in our laboratory, to establish reference values in healthy population and to evaluate the diagnostic potential of measuring longitudinal changes in circulating AGEs concentrations to predict the development of DM. Clinical and metabolic parameters were obtained from a cohort of 781 Mexican people, initially and then seven years later. AGEs were quantified by a specific RIA. Associations of the changes in circulating levels of AGEs with the appearance of impaired fasting glucose (IFG), and the development of DM were evaluated. Diabetic subjects had higher circulating levels of AGEs than normoglycemic subjects or individuals with IFG in both samples studied (471 vs. 246 and 342 μU/mL, p <0.001; and 912 vs. 428 and 519 μU/mL, p <0.001; respectively). A multinomial logistic regression analysis showed that subjects who had AGEs concentration ≥400 μU/mL in the baseline sample had a relative risk ratio of 1.98 to develop IFG seven years later (p = 0.003). While the subjects who had AGEs concentration ≥450 μU/mL in the baseline sample had a relative risk ratio of 10.7 to develop DM seven years later (p <0.001). Circulating AGEs concentration is a good early marker to predict risk of developing DM. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

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

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.

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.

Decision Making Processes and Outcomes

PubMed Central

Hicks Patrick, Julie; Steele, Jenessa C.; Spencer, S. Melinda

2013-01-01

The primary aim of this study was to examine the contributions of individual characteristics and strategic processing to the prediction of decision quality. Data were provided by 176 adults, ages 18 to 93 years, who completed computerized decision-making vignettes and a battery of demographic and cognitive measures. We examined the relations among age, domain-specific experience, working memory, and three measures of strategic information search to the prediction of solution quality using a 4-step hierarchical linear regression analysis. Working memory and two measures of strategic processing uniquely contributed to the variance explained. Results are discussed in terms of potential advances to both theory and intervention efforts. PMID:24282638

Plan of Action for Real-World Translation of LGBTQ Health and Aging Research

PubMed Central

Kim, Hyun-Jun; McKenzie, Glenise L.; Krinsky, Lisa; Emlet, Charles A.

2017-01-01

Abstract Despite accumulating evidence of health disparities, there exists limited translational research to enhance optimal health and aging of lesbian, gay, bisexual, transgender, and queer-identified* (LGBTQ) older adults. Based on the Health Equity Promotion Model that addresses the distinct needs and strengths of LGBTQ older adults, we underscore the important role of collaborations among researchers, practitioners, and communities to build community capacity. Given the rapidly shifting context, we advance principles to guide future work that will enhance translational research and the development of evidence-based practice so that LGBTQ older adults can reach their full health potential. PMID:29099666

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

Grey-matter network disintegration as predictor of cognitive and motor function with aging.

PubMed

Koini, Marisa; Duering, Marco; Gesierich, Benno G; Rombouts, Serge A R B; Ropele, Stefan; Wagner, Fabian; Enzinger, Christian; Schmidt, Reinhold

2018-06-01

Loss of grey-matter volume with advancing age affects the entire cortex. It has been suggested that atrophy occurs in a network-dependent manner with advancing age rather than in independent brain areas. The relationship between networks of structural covariance (SCN) disintegration and cognitive functioning during normal aging is not fully explored. We, therefore, aimed to (1) identify networks that lose GM integrity with advancing age, (2) investigate if age-related impairment of integrity in GM networks associates with cognitive function and decreasing fine motor skills (FMS), and (3) examine if GM disintegration is a mediator between age and cognition and FMS. T1-weighted scans of n = 257 participants (age range: 20-87) were used to identify GM networks using independent component analysis. Random forest analysis was implemented to examine the importance of network integrity as predictors of memory, executive functions, and FMS. The associations between GM disintegration, age and cognitive performance, and FMS were assessed using mediation analyses. Advancing age was associated with decreasing cognitive performance and FMS. Fourteen of 20 GM networks showed integrity changes with advancing age. Next to age and education, eight networks (fronto-parietal, fronto-occipital, temporal, limbic, secondary somatosensory, cuneal, sensorimotor network, and a cerebellar network) showed an association with cognition and FMS (up to 15.08%). GM networks partially mediated the effect between age and cognition and age and FMS. We confirm an age-related decline in cognitive functioning and FMS in non-demented community-dwelling subjects and showed that aging selectively affects the integrity of GM networks. The negative effect of age on cognition and FMS is associated with distinct GM networks and is partly mediated by their disintegration.

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.

The Third Nuclear Age: How I Learned to Start Worrying about the Clean Bomb

DTIC Science & Technology

2013-02-14

Fourth generation fusion nuclear weapons (FGNW) represent a significant improvement in nuclear weapons technology and suggest the potential for...future challenges that the United States and its Air Force may face twenty-five years from now. This paper does not answer whether the fusion technology...is possible and assumes it as an inevitable technological advancement. Instead, this study predicts a world in which low yield, clean fusion

Tobacco control advocacy in the age of social media: using Facebook, Twitter and change.

PubMed

Hefler, Marita; Freeman, Becky; Chapman, Simon

2013-05-01

The tobacco industry's use of social media sites, such as Facebook, is an emerging area of research; however, this is the first study of the potential for social media to advance tobacco control. This paper presents three case studies of using social media for tobacco control advocacy, demonstrates how social media can facilitate direct and effective action, and provides tools and lessons learned for future campaigns.

Characterization of bone marrow-derived mesenchymal stem cells in aging.

PubMed

Baker, Natasha; Boyette, Lisa B; Tuan, Rocky S

2015-01-01

Adult mesenchymal stem cells are a resource for autologous and allogeneic cell therapies for immune-modulation and regenerative medicine. However, patients most in need of such therapies are often of advanced age. Therefore, the effects of the aged milieu on these cells and their intrinsic aging in vivo are important considerations. Furthermore, these cells may require expansion in vitro before use as well as for future research. Their aging in vitro is thus also an important consideration. Here, we focus on bone marrow mesenchymal stem cells (BMSCs), which are unique compared to other stem cells due to their support of hematopoietic cells in addition to contributing to bone formation. BMSCs may be sensitive to age-related diseases and could perpetuate degenerative diseases in which bone remodeling is a contributory factor. Here, we review (1) the characterization of BMSCs, (2) the characterization of in vivo-aged BMSCs, (3) the characterization of in vitro-aged BMSCs, and (4) potential approaches to optimize the performance of aged BMSCs. This article is part of a Special Issue entitled "Stem Cells and Bone". Copyright © 2014 Elsevier Inc. All rights reserved.

The African Turquoise Killifish: A Model for Exploring Vertebrate Aging and Diseases in the Fast Lane.

PubMed

Harel, Itamar; Brunet, Anne

2015-01-01

Why and how organisms age remains a mystery, and it defines one of the biggest challenges in biology. Aging is also the primary risk factor for many human pathologies, such as cancer, diabetes, cardiovascular diseases, and neurodegenerative diseases. Thus, manipulating the aging rate and potentially postponing the onset of these devastating diseases could have a tremendous impact on human health. Recent studies, relying primarily on nonvertebrate short-lived model systems, have shown the importance of both genetic and environmental factors in modulating the aging rate. However, relatively little is known about aging in vertebrates or what processes may be unique and specific to these complex organisms. Here we discuss how advances in genomics and genome editing have significantly expanded our ability to probe the aging process in a vertebrate system. We highlight recent findings from a naturally short-lived vertebrate, the African turquoise killifish, which provides an attractive platform for exploring mechanisms underlying vertebrate aging and age-related diseases. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

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.

Physical Activity in Advanced Age: Physical Activity, Function, and Mortality in Advanced Age: A Longitudinal Follow Up (LiLACS NZ).

PubMed

Mace Firebaugh, Casey; Moyes, Simon; Jatrana, Santosh; Rolleston, Anna; Kerse, Ngaire

2018-01-18

The relationship between physical activity, function, and mortality is not established in advanced age. Physical activity, function, and mortality were followed in a cohort of Māori and non-Māori adults living in advanced age for a period of six years. Generalised Linear regression models were used to analyse the association between physical activity and NEADL while Kaplan-Meier survival analysis, and Cox-proportional hazard models were used to assess the association between the physical activity and mortality. The Hazard Ratio for mortality for those in the least active physical activity quartile was 4.1 for Māori and 1.8 for non- Māori compared to the most active physical activity quartile. There was an inverse relationship between physical activity and mortality, with lower hazard ratios for mortality at all levels of physical activity. Higher levels of physical activity were associated with lower mortality and higher functional status in advanced aged adults.

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.

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

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.

Maximising the Opportunity for Healthy Ageing: Online Mental Health Measurement and Targeted Interventions.

PubMed

Iasiello, Matthew; Bartholomaeus, Jonathan; Jarden, Aaron; van Agteren, Joseph

2018-01-01

Longevity is a valuable resource for society, as older people are increasingly looking for new ways to contribute after retirement. Their contribution is however dependent upon their physical health, mental health and wellbeing. The potential role that mental health and wellbeing, two separate but interrelated constructs, play often are both under-recognised and insufficiently targeted. Positive ageing is a positive and constructive view of ageing, where older people actively work on maintaining a positive attitude, work towards keeping fit and healthy, and strive to maximize their wellbeing. Interventions stimulating positive ageing show promising results for both mental health and wellbeing, and telehealth can play an important role in improving the reach and effectiveness of positive ageing interventions. Telehealth solutions can also help researchers reliably measure and better understand the drivers of wellbeing at individual and population levels; results that can both form the basis for advancing the field of positive ageing and help inform public policy.

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.

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.

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.

Pregnancy and Birth Outcomes Among Primiparae at Very Advanced Maternal Age: At What Price?

PubMed

Ben-David, Alon; Glasser, Saralee; Schiff, Eyal; Zahav, Aliza Segev; Boyko, Valentina; Lerner-Geva, Liat

2016-04-01

In light of the potential physical and emotional costs to both woman and child, this study was conducted to assess pregnancy complications and birth outcomes in primiparae at very advanced maternal age (VAMA, aged ≥45) compared to younger primiparae. Retrospective cohort study comparing 222 VAMA primiparae and a reference group of 222 primiparae aged 30-35, delivering at Sheba Medical Center from 2008 through 2013. VAMA primiparae were more likely than younger primiparae to be single, to have chronic health conditions, and higher rates of gestational diabetes mellitus (GDM), gestational-hypertension (GHTN) and preeclampsia-eclampsia. VAMA primiparae conceived mostly by oocyte donation. They were more likely to be hospitalized during pregnancy, to deliver preterm and by cesarean birth. Infants of VAMA primiparae were at greater risk for low birthweight and Neonatal Intensive Care Unit admission. There were no differences in outcomes between VAMA primiparae with or without preexisting chronic conditions, or between those aged 45-49 and ≥50. In multivariable analysis VAMA was an independent risk factor for GDM, GHTN and preeclamsia-eclampsia, with adjusted odds ratio of 2.38 (95 % CI 1.32, 4.29), 5.80 (95 % CI 2.66, 12.64) and 2.45 (95 % CI 1.03, 5.85); respectively. The effect of age disappeared in multiple pregnancies. Primiparity at VAMA holds a significant risk for adverse pregnancy and birth outcomes. The absence of chronic medical conditions or the use of a young oocyte donor does not improve these outcomes. Multiple pregnancies hold additional risk and may diminish the effect of age. Primiparity at an earlier age should be encouraged.

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.

Associations Between Vitamin D Intake and Progression to Incident Advanced Age-Related Macular Degeneration

PubMed Central

Merle, Bénédicte M. J.; Silver, Rachel E.; Rosner, Bernard; Seddon, Johanna M.

2017-01-01

Purpose There is growing evidence of the importance of nutrition in age-related macular degeneration (AMD), but no prospective studies have explored the impact of vitamin D. We evaluated the association between vitamin D intake and progression to advanced AMD. Methods Among 2146 participants (3965 eyes), 541 (777 eyes) progressed from early or intermediate AMD to advanced disease (mean follow-up: 9.4 years) based on ocular imaging. Nutrients were log transformed and calorie adjusted. Survival analysis was used to assess associations between incident advanced disease and vitamin D intake. Neovascular disease (NV) and geographic atrophy (GA) were evaluated separately. Combined effects of dietary vitamin D and calcium were assessed based on high or low consumption of each nutrient. Results There was a lower risk of progression to advanced AMD in the highest versus lowest quintile of dietary vitamin D intake after adjustment for demographic, behavioral, ocular, and nutritional factors (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.43–0.83; P trend = 0.0007). Similar results were observed for NV (HR: 0.59; 95% CI: 0.39–0.89; P trend = 0.005) but not GA (HR: 0.83; 95% CI: 0.53–1.30; P trend = 0.35). A protective effect was observed for advanced AMD among participants with high vitamin D and low calcium compared to the group with low levels for each nutrient (HR: 0.67; 95% CI: 0.50–0.88; P = 0.005). When supplement use was considered, the effect was in the protective direction but was not significant. Conclusions A diet rich in vitamin D may prevent or delay progression to advanced AMD, especially NV. Additional exploration is needed to elucidate the potential protective role of vitamin D and its contribution to reducing visual loss. PMID:28892825

Health implications of new age technologies for adolescents: a review of the research.

PubMed

Bailin, Alexandra; Milanaik, Ruth; Adesman, Andrew

2014-10-01

Within the past 20 years, there have been profound advances in personal technology. Although adolescents have embraced the Internet, video games and smart phones, with their extraordinary potential for education, entertainment and connecting with peers, respectively, there is a 'dark side' to these new age technologies. This article identifies many of the adverse physical, psychological, developmental and emotional consequences of our new age technologies. As Internet access has become easier, faster and more ubiquitous, there is increased evidence of its potential for direct and indirect harm to teens. Sexually explicit material is now indiscriminately available to youth, and studies have linked pornography with a number of negative health effects. Internet addiction is a problem even among teenagers who do not view pornography online. The rise of the Internet and social media sites now makes it easier for a student to bully a peer, and adolescents represent the majority of cyberbullying victims These technologies not only carry increased morbidity but also mortality, with increased suicides due to cyberbullying and motor vehicle deaths due to texting while driving. Paediatricians play a critical role in educating adolescents and their parents about the risks associated with new age technologies.

Life and living in advanced age: a cohort study in New Zealand--e Puāwaitanga o Nga Tapuwae Kia Ora Tonu, LiLACS NZ: study protocol.

PubMed

Hayman, Karen J; Kerse, Ngaire; Dyall, Lorna; Kepa, Mere; Teh, Ruth; Wham, Carol; Clair, Valerie Wright-St; Wiles, Janine; Keeling, Sally; Connolly, Martin J; Wilkinson, Tim J; Moyes, Simon; Broad, Joanna B; Jatrana, Santosh

2012-06-29

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. 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. 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.

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

Higher cardiovascular disease prevalence and mortality among younger blacks compared to whites.

PubMed

Jolly, Stacey; Vittinghoff, Eric; Chattopadhyay, Arpita; Bibbins-Domingo, Kirsten

2010-09-01

Blacks have higher rates of cardiovascular disease than whites. The age at which these differential rates emerge has not been fully examined. We examined cardiovascular disease prevalence and mortality among black and white adults across the adult age spectrum and explored potential mediators of these differential disease prevalence rates. We conducted a cross-sectional analysis of National Health and Nutrition Examination Survey data from 1999-2006. We estimated age-adjusted and age-specific prevalence ratios (PR) for cardiovascular disease (heart failure, stroke, or myocardial infarction) for blacks versus whites in adults aged 35 years and older and examined potential explanatory factors. From the National Compressed Mortality File 5-year aggregate file of 1999-2003, we determined age-specific cardiovascular disease mortality rates. In young adulthood, cardiovascular disease prevalence was higher in blacks than whites (35-44 years PR 1.9; 95% confidence interval [CI], 1.1-3.4). The black-white PR decreased with each decade of advancing age (P for trend=.04), leading to a narrowing of the racial gap at older ages (65-74 years PR 1.2; 95% CI, 0.8-1.6; > or =75 years PR 1.0; 95% CI, 0.7-1.4). Clinical and socioeconomic factors mediated some, but not all, of the excess cardiovascular disease prevalence among young to middle-aged blacks. Over a quarter (28%) of all cardiovascular disease deaths among blacks occurred in those aged <65 years, compared with 13% among whites. Reducing black/white disparities in cardiovascular disease will require a focus on young and middle-aged blacks.

Emerging perspectives in social neuroscience and neuroeconomics of aging

PubMed Central

Mather, Mara

2011-01-01

This article introduces the special issue of ‘Social Cognitive and Affective Neuroscience’ on Aging Research, and offers a broad conceptual and methodological framework for considering advances in life course research in social neuroscience and neuroeconomics. The authors highlight key areas of inquiry where aging research is raising new insights about how to conceptualize and examine critical questions about the links between cognition, emotion and motivation in social and economic behavior, as well as challenges that need to be addressed when taking a life course perspective in these fields. They also point to several emerging approaches that hold the potential for addressing these challenges, through bridging approaches from laboratory and population-based science, bridging inquiry across life stages and expanding measurement of core psychological phenotypes. PMID:21482573

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

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

Prevalence and risk factors of advanced colorectal neoplasms in asymptomatic Korean people between 40 and 49 years of age.

PubMed

Koo, Ja Eun; Kim, Kyung-Jo; Park, Hye Won; Kim, Hong-Kyu; Choe, Jae Won; Chang, Hye-Sook; Lee, Ji Young; Myung, Seung-Jae; Yang, Suk-Kyun; Kim, Jin-Ho

2017-01-01

Current guidelines recommend colon cancer screening for persons aged over 50 years. However, there are few data on colorectal cancer screening in 40- to 49-year-olds. This study assessed the prevalence and risk factors of colorectal neoplasms in 40- to 49-year-old Koreans. We analyzed the results of screening colonoscopies of 6680 persons 40-59 years of age (2206 aged 40-49 and 4474 aged 50-59 years). The prevalence of overall and advanced neoplasms in the 40- to 49-year age group was lower than in the 50- to 59-year age group (26.7% and 2.4% vs 37.8% and 3.5%, respectively). However, the prevalence of overall and advanced neoplasms increased to 39.1% and 5.4%, respectively, in 45- to 49-year-old individuals with metabolic syndrome. In the 40- to 49-year age group, age, current smoking, and metabolic syndrome were associated with an increased risk of advanced neoplasms (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.04-1.30; OR 3.12, 95% CI 1.20-8.12; and OR 2.00, 95% CI 1.09-3.67, respectively). Individuals aged 40-49 years had a lower prevalence of colorectal neoplasms than those aged 50-59 years, but some 40- to 49-year-olds showed a similar prevalence to those aged 50-59 years. Age, current smoking habits, and metabolic syndrome are associated with an increased risk of advanced neoplasms in subjects aged 40-49 years. Further studies are needed to stratify the risks of colon cancer and guide targeted screening in persons younger than 50 years old. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

The Under-Utilization and Problems Associated with the Advanced Placement Program of Adult High School Students

ERIC Educational Resources Information Center

Barham, Mary Ann

2009-01-01

The purpose of this study was to investigate the low participation rate among high school students 18 years of age or older in Advanced Placement courses. The subjects in this study were 129 Advanced Placement Students and 129 non-Advanced Placement high school students 18 years of age or older in five high schools in two Louisiana parishes.…

The potential role of advanced glycation end products (AGEs) and soluble receptors for AGEs (sRAGE) in the pathogenesis of adult-onset still's disease.

PubMed

Chen, Der-Yuan; Chen, Yi-Ming; Lin, Chi-Chen; Hsieh, Chia-Wei; Wu, Yen-Ching; Hung, Wei-Ting; Chen, Hsin-Hua; Lan, Joung-Liang

2015-05-09

Accumulating evidence has demonstrated a pathogenic role of advanced glycation end products (AGEs) and receptors for AGEs (RAGE) in inflammation. Soluble RAGE (sRAGE), with the same ligands-binding capacity as full-length RAGE, acts as a "decoy" receptor. However, there has been scanty data regarding AGEs and sRAGE in adult-onset Still's disease (AOSD). This study aimed to investigate AGEs and sRAGE levels in AOSD patients and examine their association with clinical characteristics. Using ELISA, plasma levels of AGEs and sRAGE were determined in 52 AOSD patients, 36 systemic lupus erythematosus(SLE) patients and 16 healthy controls(HC). Their associations with activity parameters and disease courses were evaluated. Significantly higher median levels of AGEs were observed in active AOSD patients (16.75 pg/ml) and active SLE patients (14.80 pg/ml) than those in HC (9.80 pg/ml, both p < 0.001). AGEs levels were positively correlated with activity scores (r = 0.836, p < 0.001), ferritin levels (r = 0.372, p < 0.05) and CRP levels (r = 0.396, p < 0.005) in AOSD patients. Conversely, significantly lower median levels of sRAGE were observed in active AOSD patients (632.2 pg/ml) and active SLE patients (771.6 pg/ml) compared with HC (1051.7 pg/ml, both p < 0.001). Plasma sRAGE levels were negatively correlated with AOSD activity scores (r = -0.320, p < 0.05). In comparison to AOSD patients with monocyclic pattern, significantly higher AGEs levels were observed in those with polycyclic or chronic articular pattern. With treatment, AGEs levels declined while sRAGE levels increased in parallel with the decrease in disease activity. The elevation of AGEs levels with concomitant decreased sRAGE levels in active AOSD patients, suggests their pathogenic role in AOSD.

Generation of glyceraldehyde-derived advanced glycation end-products in pancreatic cancer cells and the potential of tumor promotion

PubMed Central

Takata, Takanobu; Ueda, Tadashi; Sakasai-Sakai, Akiko; Takeuchi, Masayoshi

2017-01-01

AIM To determine the possibility that diabetes mellitus promotes pancreatic ductal adenocarcinoma via glyceraldehyde (GA)-derived advanced glycation-end products (GA-AGEs). METHODS PANC-1, a human pancreatic cancer cell line, was treated with 1-4 mmol/L GA for 24 h. The cell viability and intracellular GA-AGEs were measured by WST-8 assay and slot blotting. Moreover, immunostaining of PANC-1 cells with an anti-GA-AGE antibody was performed. Western blotting (WB) was used to analyze the molecular weight of GA-AGEs. Heat shock proteins 90α, 90β, 70, 27 and cleaved caspase-3 were analyzed by WB. In addition, PANC-1 cells were treated with GA-AGEs-bovine serum albumin (GA-AGEs-BSA), as a model of extracellular GA-AGEs, and proliferation of PANC-1 cells was measured. RESULTS In PANC-1 cells, GA induced the production of GA-AGEs and cell death in a dose-dependent manner. PANC-1 cell viability was approximately 40% with a 2 mmol/L GA treatment and decreased to almost 0% with a 4 mmol/L GA treatment (each significant difference was P < 0.01). Cells treated with 2 and 4 mmol/L GA produced 6.4 and 21.2 μg/mg protein of GA-AGEs, respectively (P < 0.05 and P < 0.01). The dose-dependent production of some high-molecular-weight (HMW) complexes of HSP90β, HSP70, and HSP27 was observed following administration of GA. We considered HMW complexes to be dimers and trimers with GA-AGEs-mediated aggregation. Cleaved caspase-3 could not be detected with WB. Furthermore, 10 and 20 μg/mL GA-AGEs-BSA was 27% and 34% greater than that of control cells, respectively (P < 0.05 and P < 0.01). CONCLUSION Although intracellular GA-AGEs induce pancreatic cancer cell death, their secretion and release may promote the proliferation of other pancreatic cancer cells. PMID:28785145

The relationship between demographic characteristics and motivational factors in the employees of social security hospitals in Mazandaran

PubMed Central

Heidarian, Ali Reza; Jafari Kelarijani, Seyed Ebrahim; Jamshidi, Reza; Khorshidi, Mohamad

2015-01-01

Background: Health worker motivation has the potential to have a large impact on health system performance, and this depends on some factors. The purpose of this study was to determine the factors affecting this motivation. Methods: From Winter 2013 to Spring 2014, 1046 employees and physicians (439 males and 607 females) with a mean age of 36 and 37.2 years in men and women, respectively were chosen in selected hospitals of Social Security Organization (SSO). They were randomly categorized into six different classes of service record, age education class of hiring (permanent and contractual), marital status, and gender. The variables assessed via the classification groups were as follows: interpersonal relations, working conditions, equity, pay, job security, supervision, advancement, recognition, responsibility, and attractiveness of job, educational and organizational policies. Results: Bachelor’s degree (65%) or higher were the education degrees of most participants. Significant relations were observed regarding age, marital status, hiring, gender and years of service with promotion, recognition, responsibility, attractiveness of job, education, relations, working condition, equity, salary, job security, supervision and organizational policies. There were significant relations with hire status and degree with advancement and other variables. There were significant relations between marital status, gender, years of service and age with the above variables. Conclusion: The results show that the important variables that influence motivational factors are academic degree, hire status, marital status, gender, age and years of service. PMID:26644886

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.

As naturalistic as it gets: subtitles in the English classroom in Norway

PubMed Central

Vulchanova, Mila; Aurstad, Lisa M. G.; Kvitnes, Ingrid E. N.; Eshuis, Hendrik

2015-01-01

This study aimed to investigate the effects of subtitles in the context of authentic material on second language comprehension and potentially, second language acquisition for Norwegian learners of English. Participants in the study were 49 17-year-old students and 65 16-year-old students, who were all native speakers of Norwegian learning English as an L2 in high school. Both age groups were divided into three Conditions, where one group watched an episode of the American animated cartoon Family Guy with Norwegian subtitles, one group with English subtitles, and one group watched the episode with no subtitles. On a comprehension questionnaire conducted immediately after watching the episode positive short-term effects of both native language (L1) and target language (L2) subtitles were found for both age groups. However, no differences in terms of the language of the subtitles were found in the older and more advanced group. Four weeks later the participants responded to a word definition task and a word recall task to investigate potential long-term effects of the subtitles. The only long-term effect was found in the word definition task and was modulated by age. We found, however, that native language subtitles impact negatively on performance on the comprehension task. The results from this study suggest that the mere presence of subtitles as an additional source of information enhances learners' comprehension of the plot and content in animated audio-visual material in their L2. The absence of differences in terms of the language of the subtitles in the more advanced group suggests that both intralanguage and interlanguage subtitles can aid target language comprehension in very advanced learners, most probably due to better consolidated vocabulary knowledge in that group. The two groups differed also on predictors of performance on the two lexical tasks. While in the less proficient younger group, vocabulary status best predicted performance on both tasks (vocabulary predicts vocabulary), for the very advanced older group, grammar was a stronger predictor, highlighting the importance of generic language competence and skills in L2 tasks for highly proficient L2 users. We also found an effect of written L2 skills on performance on both lexical tasks indicative of the role of orthography in vocabulary consolidation. PMID:25620938

Thioredoxin reverses age-related hypertension by chronically improving vascular redox and restoring eNOS function

PubMed Central

Hilgers, Rob H. P.; Kundumani-Sridharan, Venkatesh; Subramani, Jaganathan; Chen, Leon C.; Cuello, Luis G.; Rusch, Nancy J.; Das, Kumuda C.

2017-01-01

The incidence of high blood pressure with advancing age is notably high, and it is an independent prognostic factor for the onset or progression of a variety of cardiovascular disorders. Although age-related hypertension is an established phenomenon, current treatments are only palliative but not curative. Thus, there is a critical need for a curative therapy against age-related hypertension, which could greatly decrease the incidence of cardiovascular disorders. We show that overexpression of human thioredoxin (TRX), a redox protein, in mice prevents age-related hypertension. Further, injection of recombinant human TRX (rhTRX) for three consecutive days reversed hypertension in aged wild-type mice, and this effect lasted for at least 20 days. Arteries of wild-type mice injected with rhTRX or mice with TRX overexpression exhibited decreased arterial stiffness, greater endothelium-dependent relaxation, increased nitric oxide production, and decreased superoxide anion (O2•−) generation compared to either saline-injected aged wild-type mice or mice with TRX deficiency. Our study demonstrates a potential translational role of rhTRX in reversing age-related hypertension with long-lasting efficacy. PMID:28179506

Age dependence of plasma phospholipid fatty acid levels: potential role of linoleic acid in the age-associated increase in docosahexaenoic acid and eicosapentaenoic acid concentrations.

PubMed

de Groot, Renate H M; van Boxtel, Martin P J; Schiepers, Olga J G; Hornstra, Gerard; Jolles, Jelle

2009-10-01

Limited information is available with respect to the association between age and the plasma phospholipid fatty acid profile. Therefore we investigated the association between plasma phospholipid fatty acid status and age after correction for sex, smoking, alcohol use, BMI and fish intake. Plasma phospholipid fatty acid composition was measured and information on fish intake and other potential covariates was collected in 234 participants of the Maastricht Aging Study. The participants were healthy individuals of both sexes with an age range between 36 and 88 years. Hierarchical linear regression analyses were applied to study the relationship between age and fatty acid concentrations. After correction for fish consumption and other relevant covariates, a significant positive relationship was observed between age of the subjects and their plasma phospholipid concentrations of DHA (22 : 6n-3, P = 0.006) and EPA (20 : 5n-3; P = 0.001). Age contributed 2.3 and 3.9 % to the amount of explained variance, respectively. The higher n-3 long-chain PUFA status at advanced age was confirmed by lower concentrations of their putative 'shortage marker' Osbond acid (ObA, 22 : 5n-6; P = 0.022 for the relationship with age after correction for covariates and fish intake, R2 0.022). Concentrations of linoleic acid (LA; 18 : 2n-6) were negatively associated with age (P < 0.001; R2 0.061). In conclusion, DHA and EPA concentrations appeared to be higher in older age groups, partly because of a higher fish intake and partly because of another age-associated mechanism, possibly involving the well-known competition with LA.

Sensory Perception and Aging in Model Systems: From the Outside In

PubMed Central

Linford, Nancy J.; Kuo, Tsung-Han; Chan, Tammy P.; Pletcher, Scott D.

2014-01-01

Sensory systems provide organisms from bacteria to human with the ability to interact with the world. Numerous senses have evolved that allow animals to detect and decode cues from sources in both their external and internal environments. Recent advances in understanding the central mechanisms by which the brains of simple organisms evaluate different cues and initiate behavioral decisions, coupled with observations that sensory manipulations are capable of altering organism lifespan, have opened the door for powerful new research into aging. While direct links between sensory perception and aging have been established only recently, here we discuss these initial discoveries and evaluate the potential for different forms of sensory processing to modulate lifespan across taxa. Harnessing the neurobiology of simple model systems to study the biological impact of sensory experiences will yield insights into the broad influence of sensory perception in mammals and may help uncover new mechanisms of healthy aging. PMID:21756108

Sensory perception and aging in model systems: from the outside in.

PubMed

Linford, Nancy J; Kuo, Tsung-Han; Chan, Tammy P; Pletcher, Scott D

2011-01-01

Sensory systems provide organisms from bacteria to humans with the ability to interact with the world. Numerous senses have evolved that allow animals to detect and decode cues from sources in both their external and internal environments. Recent advances in understanding the central mechanisms by which the brains of simple organisms evaluate different cues and initiate behavioral decisions, coupled with observations that sensory manipulations are capable of altering organismal lifespan, have opened the door for powerful new research into aging. Although direct links between sensory perception and aging have been established only recently, here we discuss these initial discoveries and evaluate the potential for different forms of sensory processing to modulate lifespan across taxa. Harnessing the neurobiology of simple model systems to study the biological impact of sensory experiences will yield insights into the broad influence of sensory perception in mammals and may help uncover new mechanisms of healthy aging.

Facilitating interdisciplinary design specification of "smart" homes for aging in place.

PubMed

Demiris, George; Skubic, Marjorie; Rantz, Marilyn J; Courtney, Karen L; Aud, Myra A; Tyrer, Harry W; He, Zhihai; Lee, Jia

2006-01-01

"Smart homes" are defined as residences equipped with sensors and other advanced technology applications that enhance residents' independence and can be used for aging in place. The objective of this study is to determine design specifications for smart residences as defined by professional groups involved both in care delivery to senior citizens and development of devices and technologies to support aging. We assessed the importance of specific devices and sensors and their advantages and disadvantages as perceived by the interdisciplinary expert team. This work lays the ground for the implementation of smart home residencies and confirms that only an interdisciplinary design approach can address all the technical, clinical and human factors related challenges associated with home-based technologies that support aging. Our findings indicate that the use of adaptive technology that can be installed in the home environment has the potential to not only support but also empower individual senior users.

Building for the future: essential infrastructure for rodent ageing studies.

PubMed

Wells, Sara E; Bellantuono, Ilaria

2016-08-01

When planning ageing research using rodent models, the logistics of supply, long term housing and infrastructure provision are important factors to take into consideration. These issues need to be prioritised to ensure they meet the requirements of experiments which potentially will not be completed for several years. Although these issues are not unique to this discipline, the longevity of experiments and indeed the animals, requires a high level of consistency and sustainability to be maintained throughout lengthy periods of time. Moreover, the need to access aged stock or material for more immediate experiments poses many issues for the completion of pilot studies and/or short term intervention studies on older models. In this article, we highlight the increasing demand for ageing research, the resources and infrastructure involved, and the need for large-scale collaborative programmes to advance studies in both a timely and a cost-effective way.

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.

DKK1 rescues osteogenic differentiation of mesenchymal stem cells isolated from periodontal ligaments of patients with diabetes mellitus induced periodontitis

PubMed Central

Liu, Qi; Hu, Cheng-Hu; Zhou, Cui-Hong; Cui, Xiao-Xia; Yang, Kun; Deng, Chao; Xia, Jia-Jia; Wu, Yan; Liu, Lu-Chuan; Jin, Yan

2015-01-01

Multiple studies have shown that diabetes mellitus is an established risk factor for periodontitis. Recently mesenchymal stem cells derived from periodontal ligament (PDLSCs) have been utilized to reconstruct tissues destroyed by chronic inflammation. However, impact of periodontitis with diabetes mellitus on PDLSCs and mechanisms mediating effects of complex microenvironments remain poorly understood. In this study, we found multiple differentiation potential of PDLSCs from chronic periodontitis with diabetes mellitus donors (D-PDLSCs) was damaged significantly. Inhibition of NF-κB signaling could rescue osteogenic potential of PDLSCs from simple chronic periodontitis patients (P-PDLSCs), whereas did not promote D-PDLSCs osteogenesis. In addition, we found expression of DKK1 in D-PDLSCs did not respond to osteogenic signal and decreased osteogenic potential of D-PDLSCs treated with DKK1 could be reversed. To further elucidate different character between P-PDLSCs and D-PDLSCs, we treated PDLSCs with TNF-α and advanced glycation end products (AGEs), and find out AGEs which enhance effect of TNF-α in PDLSCs might mediate special personality of D-PDLSCs. The adverse effect of AGEs in PDLSCs could be reversed when PDLSCs were treated with DKK1. These results suggested DKK1 mediating WNT signaling might be a therapy target to rescue potential of PDLSCs in periodontitis with diabetes mellitus. PMID:26278788

Molecular inflammation: underpinnings of aging and age-related diseases.

PubMed

Chung, Hae Young; Cesari, Matteo; Anton, Stephen; Marzetti, Emanuele; Giovannini, Silvia; Seo, Arnold Young; Carter, Christy; Yu, Byung Pal; Leeuwenburgh, Christiaan

2009-01-01

Recent scientific studies have advanced the notion of chronic inflammation as a major risk factor underlying aging and age-related diseases. In this review, low-grade, unresolved, molecular inflammation is described as an underlying mechanism of aging and age-related diseases, which may serve as a bridge between normal aging and age-related pathological processes. Accumulated data strongly suggest that continuous (chronic) upregulation of pro-inflammatory mediators (e.g., TNF-alpha, IL-1beta, IL-6, COX-2, iNOS) are induced during the aging process due to an age-related redox imbalance that activates many pro-inflammatory signaling pathways, including the NF-kappaB signaling pathway. These pro-inflammatory molecular events are discussed in relation to their role as basic mechanisms underlying aging and age-related diseases. Further, the anti-inflammatory actions of aging-retarding caloric restriction and exercise are reviewed. Thus, the purpose of this review is to describe the molecular roles of age-related physiological functional declines and the accompanying chronic diseases associated with aging. This new view on the role of molecular inflammation as a mechanism of aging and age-related pathogenesis can provide insights into potential interventions that may affect the aging process and reduce age-related diseases, thereby promoting healthy longevity.

Molecular Inflammation: Underpinnings of Aging and Age-related Diseases

PubMed Central

Chung, Hae Young; Cesari, Matteo; Anton, Stephen; Marzetti, Emanuele; Giovannini, Silvia; Seo, Arnold Young; Carter, Christy; Yu, Byung Pal; Leeuwenburgh, Christiaan

2013-01-01

Recent scientific studies have advanced the notion of chronic inflammation as a major risk factor underlying aging and age-related diseases. In this review, low-grade, unresolved, molecular inflammation is described as an underlying mechanism of aging and age-related diseases, which may serve as a bridge between normal aging and age-related pathological processes. Accumulated data strongly suggest that continuous (chronic) up-regulation of pro-inflammatory mediators (e.g., TNF-α, IL-1β, 6, COX-2, iNOS) are induced during the aging process due to an age-related redox imbalance that activates many pro-inflammatory signaling pathways, including the NF-κB signaling pathway. These pro-inflammatory molecular events are discussed in relation to their role as basic mechanisms underlying aging and age-related diseases. Further, the anti-inflammatory actions of aging-retarding caloric restriction and exercise are reviewed. Thus, the purpose of this review is to describe the molecular roles of age-related physiological functional declines and the accompanying chronic diseases associated with aging. This new view on the role of molecular inflammation as a mechanism of aging and age-related pathogenesis can provide insights into potential interventions that may affect the aging process and reduce age-related diseases, thereby promoting healthy longevity. PMID:18692159

Maternal and early life factors of tooth emergence patterns and number of teeth at one and two years of age

PubMed Central

Ntani, Georgia; Day, Peter F; Baird, Janis; Godfrey, Keith M; Robinson, Sian M; Cooper, Cyrus; Inskip, Hazel M

2015-01-01

Various environmental factors have been associated with the timing of eruption of primary dentition, but the evidence to date comes from small studies with limited information on potential risk factors. We aimed to investigate associations between tooth emergence patterns and pre-conception, pregnancy and post-natal influences. Dentition patterns were recorded at ages one and two years in 2,915 children born to women in the Southampton Women’s Survey from whom information had been collected on maternal factors before conception and during pregnancy. In mutually adjusted regression models we found that: children were more dentally advanced at ages one and two years if their mothers had smoked during pregnancy or they were longer at birth; mothers of children whose dental development was advanced at age two years tended to have poorer socioeconomic circumstances, and to have reported a slower walking speed pre-pregnancy; and children of mothers of Asian ethnicity had later tooth development than those of white mothers. The findings add to the evidence of environmental impacts on the timing of the eruption of primary dentition in indicating that maternal smoking during pregnancy, socio-economic status and physical activity (assessed by reported walking speed) may influence the child’s primary dentition. Early life factors, including size at birth are also associated with dentition patterns, as is maternal ethnicity. PMID:25936832

Default mode network as a potential biomarker of chemotherapy-related brain injury

PubMed Central

Kesler, Shelli R.

2014-01-01

Chronic medical conditions and/or their treatments may interact with aging to alter or even accelerate brain senescence. Adult onset cancer, for example, is a disease associated with advanced aging and emerging evidence suggests a profile of subtle but diffuse brain injury following cancer chemotherapy. Breast cancer is currently the primary model for studying these “chemobrain” effects. Given the widespread changes to brain structure and function as well as the common impairment of integrated cognitive skills observed following breast cancer chemotherapy, it is likely that large-scale brain networks are involved. Default mode network (DMN) is a strong candidate considering its preferential vulnerability to aging and sensitivity to toxicity and disease states. Additionally, chemotherapy is associated with several physiologic effects including increased inflammation and oxidative stress that are believed to elevate toxicity in the DMN. Biomarkers of DMN connectivity could aid in the development of treatments for chemotherapy-related cognitive decline. For example, certain nutritional interventions could potentially reduce the metabolic changes (e.g. amyloid beta toxicity) associated with DMN disruption. PMID:24913897

Growing old, yet staying young: The role of telomeres in bats' exceptional longevity.

PubMed

Foley, Nicole M; Hughes, Graham M; Huang, Zixia; Clarke, Michael; Jebb, David; Whelan, Conor V; Petit, Eric J; Touzalin, Frédéric; Farcy, Olivier; Jones, Gareth; Ransome, Roger D; Kacprzyk, Joanna; O'Connell, Mary J; Kerth, Gerald; Rebelo, Hugo; Rodrigues, Luísa; Puechmaille, Sébastien J; Teeling, Emma C

2018-02-01

Understanding aging is a grand challenge in biology. Exceptionally long-lived animals have mechanisms that underpin extreme longevity. Telomeres are protective nucleotide repeats on chromosome tips that shorten with cell division, potentially limiting life span. Bats are the longest-lived mammals for their size, but it is unknown whether their telomeres shorten. Using >60 years of cumulative mark-recapture field data, we show that telomeres shorten with age in Rhinolophus ferrumequinum and Miniopterus schreibersii , but not in the bat genus with greatest longevity, Myotis . As in humans, telomerase is not expressed in Myotis myotis blood or fibroblasts. Selection tests on telomere maintenance genes show that ATM and SETX , which repair and prevent DNA damage, potentially mediate telomere dynamics in Myotis bats. Twenty-one telomere maintenance genes are differentially expressed in Myotis , of which 14 are enriched for DNA repair, and 5 for alternative telomere-lengthening mechanisms. We demonstrate how telomeres, telomerase, and DNA repair genes have contributed to the evolution of exceptional longevity in Myotis bats, advancing our understanding of healthy aging.

Bimolecular interaction of argpyrimidine (a Maillard reaction product) in in vitro non-enzymatic protein glycation model and its potential role as an antiglycating agent.

PubMed

Bhattacherjee, Abhishek; Dhara, Kaliprasanna; Chakraborti, Abhay Sankar

2017-09-01

Non- enzymatic glycation, also known as Maillard reaction, is one of the most important and investigated reactions in biochemistry. Maillard reaction products (MRPs) like protein-derived advanced glycation end products (AGEs) are often referred to cause pathophysiological complications in human systems. On contrary, several MRPs are exogenously used as antioxidant, antimicrobial and flavouring agents. In the preset study, we have shown that argpyrimidine, a well-established AGE, interacts with bovine serum albumin (BSA) and glucose individually in standard BSA-glucose model system and successfully inhibits glycation of the protein. Bimolecular interaction of argpyrimidine with glucose or BSA has been studied independently. Chromatographic purification, different spectroscopic studies and molecular modeling have been used to evaluate the nature and pattern of interactions. Binding of argpyrimidine with BSA prevents incorporation of glucose inside the native protein. Argpyrimidine can also directly entrap glucose. Both these interactions may be associated with the antiglycation potential of argpyrimidine, indicating a beneficial function of an AGE. Copyright © 2017 Elsevier B.V. All rights reserved.

Genome-Environment Interactions That Modulate Aging: Powerful Targets for Drug Discovery

PubMed Central

Wuttke, Daniel; Wood, Shona H.; Plank, Michael; Vora, Chintan

2012-01-01

Aging is the major biomedical challenge of this century. The percentage of elderly people, and consequently the incidence of age-related diseases such as heart disease, cancer, and neurodegenerative diseases, is projected to increase considerably in the coming decades. Findings from model organisms have revealed that aging is a surprisingly plastic process that can be manipulated by both genetic and environmental factors. Here we review a broad range of findings in model organisms, from environmental to genetic manipulations of aging, with a focus on those with underlying gene-environment interactions with potential for drug discovery and development. One well-studied dietary manipulation of aging is caloric restriction, which consists of restricting the food intake of organisms without triggering malnutrition and has been shown to retard aging in model organisms. Caloric restriction is already being used as a paradigm for developing compounds that mimic its life-extension effects and might therefore have therapeutic value. The potential for further advances in this field is immense; hundreds of genes in several pathways have recently emerged as regulators of aging and caloric restriction in model organisms. Some of these genes, such as IGF1R and FOXO3, have also been associated with human longevity in genetic association studies. The parallel emergence of network approaches offers prospects to develop multitarget drugs and combinatorial therapies. Understanding how the environment modulates aging-related genes may lead to human applications and disease therapies through diet, lifestyle, or pharmacological interventions. Unlocking the capacity to manipulate human aging would result in unprecedented health benefits. PMID:22090473

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.

Structural Imaging Measures of Brain Aging

PubMed Central

Lockhart, Samuel N.

2014-01-01

During the course of normal aging, biological changes occur in the brain that are associated with changes in cognitive ability. This review presents data from neuroimaging studies of primarily “normal” or healthy brain aging. As such, we focus on research in unimpaired or nondemented older adults, but also include findings from lifespan studies that include younger and middle aged individuals as well as from populations with prodromal or clinically symptomatic disease such as cerebrovascular or Alzheimer’s disease. This review predominantly addresses structural MRI biomarkers, such as volumetric or thickness measures from anatomical images, and measures of white matter injury and integrity respectively from FLAIR or DTI, and includes complementary data from PET and cognitive or clinical testing as appropriate. The findings reveal highly consistent age-related differences in brain structure, particularly frontal lobe and medial temporal regions that are also accompanied by age-related differences in frontal and medial temporal lobe mediated cognitive abilities. Newer findings also suggest that degeneration of specific white matter tracts such as those passing through the genu and splenium of the corpus callosum may also be related to age-related differences in cognitive performance. Interpretation of these findings, however, must be tempered by the fact that comorbid diseases such as cerebrovascular and Alzheimer’s disease also increase in prevalence with advancing age. As such, this review discusses challenges related to interpretation of current theories of cognitive aging in light of the common occurrence of these later-life diseases. Understanding the differences between “Normal” and “Healthy” brain aging and identifying potential modifiable risk factors for brain aging is critical to inform potential treatments to stall or reverse the effects of brain aging and possibly extend cognitive health for our aging society. PMID:25146995

Structural imaging measures of brain aging.

PubMed

Lockhart, Samuel N; DeCarli, Charles

2014-09-01

During the course of normal aging, biological changes occur in the brain that are associated with changes in cognitive ability. This review presents data from neuroimaging studies of primarily "normal" or healthy brain aging. As such, we focus on research in unimpaired or nondemented older adults, but also include findings from lifespan studies that include younger and middle aged individuals as well as from populations with prodromal or clinically symptomatic disease such as cerebrovascular or Alzheimer's disease. This review predominantly addresses structural MRI biomarkers, such as volumetric or thickness measures from anatomical images, and measures of white matter injury and integrity respectively from FLAIR or DTI, and includes complementary data from PET and cognitive or clinical testing as appropriate. The findings reveal highly consistent age-related differences in brain structure, particularly frontal lobe and medial temporal regions that are also accompanied by age-related differences in frontal and medial temporal lobe mediated cognitive abilities. Newer findings also suggest that degeneration of specific white matter tracts such as those passing through the genu and splenium of the corpus callosum may also be related to age-related differences in cognitive performance. Interpretation of these findings, however, must be tempered by the fact that comorbid diseases such as cerebrovascular and Alzheimer's disease also increase in prevalence with advancing age. As such, this review discusses challenges related to interpretation of current theories of cognitive aging in light of the common occurrence of these later-life diseases. Understanding the differences between "Normal" and "Healthy" brain aging and identifying potential modifiable risk factors for brain aging is critical to inform potential treatments to stall or reverse the effects of brain aging and possibly extend cognitive health for our aging society.

Development and evaluation of an aged care specific Advance Care Plan.

PubMed

Silvester, William; Parslow, Ruth A; Lewis, Virginia J; Fullam, Rachael S; Sjanta, Rebekah; Jackson, Lynne; White, Vanessa; Hudson, Rosalie

2013-06-01

To report on the quality of advance care planning (ACP) documents in use in residential aged care facilities (RACF) in areas of Victoria Australia prior to a systematic intervention; to report on the development and performance of an aged care specific Advance Care Plan template used during the intervention. An audit of the quality of pre-existing documentation used to record resident treatment preferences and end-of-life wishes at participating RACFs; development and pilot of an aged care specific Advance Care Plan template; an audit of the completeness and quality of Advance Care Plans completed on the new template during a systematic ACP intervention. 19 selected RACFs (managed by 12 aged care organisations) in metropolitan and regional areas of Victoria. Documentation in use at facilities prior to the ACP intervention most commonly recorded preferences regarding hospital transfer, life prolonging treatment and personal/cultural/religious wishes. However, 7 of 12 document sets failed to adequately and clearly specify the resident's preferences as regards life prolonging medical treatment. The newly developed aged care specific Advance Care Plan template was met with approval by participating RACFs. Of 203 Advance Care Plans completed on the template throughout the project period, 49% included the appointment of a Medical Enduring Power of Attorney. Requests concerning medical treatment were specified in almost all completed documents (97%), with 73% nominating the option of refusal of life-prolonging treatment. Over 90% of plans included information concerning residents' values and beliefs, and future health situations that the resident would find to be unacceptable were specified in 78% of completed plans. Standardised procedures and documentation are needed to improve the quality of processes, documents and outcomes of ACP in the residential aged care sector.

Age, Sex, and Racial Differences in Neuroimaging Use in Acute Stroke: A Population-Based Study.

PubMed

Vagal, A; Sanelli, P; Sucharew, H; Alwell, K A; Khoury, J C; Khatri, P; Woo, D; Flaherty, M; Kissela, B M; Adeoye, O; Ferioli, S; De Los Rios La Rosa, F; Martini, S; Mackey, J; Kleindorfer, D

2017-10-01

Limited information is available regarding differences in neuroimaging use for acute stroke work-up. Our objective was to assess whether race, sex, or age differences exist in neuroimaging use and whether these differences depend on the care center type in a population-based study. Patients with stroke (ischemic and hemorrhagic) and transient ischemic attack were identified in a metropolitan, biracial population using the Greater Cincinnati/Northern Kentucky Stroke Study in 2005 and 2010. Multivariable regression was used to determine the odds of advanced imaging use (CT angiography/MR imaging/MR angiography) for race, sex, and age. In 2005 and 2010, there were 3471 and 3431 stroke/TIA events, respectively. If one adjusted for covariates, the odds of advanced imaging were higher for younger (55 years or younger) compared with older patients, blacks compared with whites, and patients presenting to an academic center and those seen by a stroke team or neurologist. The observed association between race and advanced imaging depended on age; in the older age group, blacks had higher odds of advanced imaging compared with whites (odds ratio, 1.34; 95% CI, 1.12-1.61; P < .01), and in the younger group, the association between race and advanced imaging was not statistically significant. Age by race interaction persisted in the academic center subgroup ( P < .01), but not in the nonacademic center subgroup ( P = .58). No significant association was found between sex and advanced imaging. Within a large, biracial stroke/TIA population, there is variation in the use of advanced neuroimaging by age and race, depending on the care center type. © 2017 by American Journal of Neuroradiology.

Advanced Glycation End Products and Oxidative Stress in Type 2 Diabetes Mellitus

PubMed Central

Nowotny, Kerstin; Jung, Tobias; Höhn, Annika; Weber, Daniela; Grune, Tilman

2015-01-01

Type 2 diabetes mellitus (T2DM) is a very complex and multifactorial metabolic disease characterized by insulin resistance and β cell failure leading to elevated blood glucose levels. Hyperglycemia is suggested to be the main cause of diabetic complications, which not only decrease life quality and expectancy, but are also becoming a problem regarding the financial burden for health care systems. Therefore, and to counteract the continually increasing prevalence of diabetes, understanding the pathogenesis, the main risk factors, and the underlying molecular mechanisms may establish a basis for prevention and therapy. In this regard, research was performed revealing further evidence that oxidative stress has an important role in hyperglycemia-induced tissue injury as well as in early events relevant for the development of T2DM. The formation of advanced glycation end products (AGEs), a group of modified proteins and/or lipids with damaging potential, is one contributing factor. On the one hand it has been reported that AGEs increase reactive oxygen species formation and impair antioxidant systems, on the other hand the formation of some AGEs is induced per se under oxidative conditions. Thus, AGEs contribute at least partly to chronic stress conditions in diabetes. As AGEs are not only formed endogenously, but also derive from exogenous sources, i.e., food, they have been assumed as risk factors for T2DM. However, the role of AGEs in the pathogenesis of T2DM and diabetic complications—if they are causal or simply an effect—is only partly understood. This review will highlight the involvement of AGEs in the development and progression of T2DM and their role in diabetic complications. PMID:25786107

Advanced Maternal Age and the Risk of Low Birth Weight and Preterm Delivery: a Within-Family Analysis Using Finnish Population Registers

PubMed Central

Goisis, Alice; Remes, Hanna; Barclay, Kieron; Martikainen, Pekka; Myrskylä, Mikko

2017-01-01

Abstract Advanced maternal age at birth is considered a major risk factor for birth outcomes. It is unclear to what extent this association is confounded by maternal characteristics. To test whether advanced maternal age at birth independently increases the risk of low birth weight (<2,500 g) and preterm birth (<37 weeks’ gestation), we compared between-family models (children born to different mothers at different ages) with within-family models (children born to the same mother at different ages). The latter procedure reduces confounding by unobserved parental characteristics that are shared by siblings. We used Finnish population registers, including 124,098 children born during 1987–2000. When compared with maternal ages 25–29 years in between-family models, maternal ages of 35–39 years and ≥40 years were associated with percentage increases of 1.1 points (95% confidence intervals: 0.8, 1.4) and 2.2 points (95% confidence intervals: 1.4, 2.9), respectively, in the probability of low birth weight. The associations are similar for the risk of preterm delivery. In within-family models, the relationship between advanced maternal age and low birth weight or preterm birth is statistically and substantively negligible. In Finland, advanced maternal age is not independently associated with the risk of low birth weight or preterm delivery among mothers who have had at least 2 live births. PMID:29206985

Muscle Stem Cells: A Model System for Adult Stem Cell Biology.

PubMed

Cornelison, Ddw; Perdiguero, Eusebio

2017-01-01

Skeletal muscle stem cells, originally termed satellite cells for their position adjacent to differentiated muscle fibers, are absolutely required for the process of skeletal muscle repair and regeneration. In the last decade, satellite cells have become one of the most studied adult stem cell systems and have emerged as a standard model not only in the field of stem cell-driven tissue regeneration but also in stem cell dysfunction and aging. Here, we provide background in the field and discuss recent advances in our understanding of muscle stem cell function and dysfunction, particularly in the case of aging, and the potential involvement of muscle stem cells in genetic diseases such as the muscular dystrophies.

Aging stem cells. A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging.

PubMed

Zhang, Weiqi; Li, Jingyi; Suzuki, Keiichiro; Qu, Jing; Wang, Ping; Zhou, Junzhi; Liu, Xiaomeng; Ren, Ruotong; Xu, Xiuling; Ocampo, Alejandro; Yuan, Tingting; Yang, Jiping; Li, Ying; Shi, Liang; Guan, Dee; Pan, Huize; Duan, Shunlei; Ding, Zhichao; Li, Mo; Yi, Fei; Bai, Ruijun; Wang, Yayu; Chen, Chang; Yang, Fuquan; Li, Xiaoyu; Wang, Zimei; Aizawa, Emi; Goebl, April; Soligalla, Rupa Devi; Reddy, Pradeep; Esteban, Concepcion Rodriguez; Tang, Fuchou; Liu, Guang-Hui; Belmonte, Juan Carlos Izpisua

2015-06-05

Werner syndrome (WS) is a premature aging disorder caused by WRN protein deficiency. Here, we report on the generation of a human WS model in human embryonic stem cells (ESCs). Differentiation of WRN-null ESCs to mesenchymal stem cells (MSCs) recapitulates features of premature cellular aging, a global loss of H3K9me3, and changes in heterochromatin architecture. We show that WRN associates with heterochromatin proteins SUV39H1 and HP1α and nuclear lamina-heterochromatin anchoring protein LAP2β. Targeted knock-in of catalytically inactive SUV39H1 in wild-type MSCs recapitulates accelerated cellular senescence, resembling WRN-deficient MSCs. Moreover, decrease in WRN and heterochromatin marks are detected in MSCs from older individuals. Our observations uncover a role for WRN in maintaining heterochromatin stability and highlight heterochromatin disorganization as a potential determinant of human aging. Copyright © 2015, American Association for the Advancement of Science.

Effects of Normal Aging on Visuo-Motor Plasticity

NASA Technical Reports Server (NTRS)

Roller, Carrie A.; Cohen, Helen S.; Kimball, Kay T.; Bloomberg, Jacob J.

2001-01-01

Normal aging is associated with declines in neurologic function. Uncompensated visual and vestibular problems may have dire consequences including dangerous falls. Visuomotor plasticity is a form of behavioral neural plasticity which is important in the process of adapting to visual or vestibular alteration, including those changes due to pathology, pharmacotherapy, surgery or even entry into a microgravity or underwater environment. In order to determine the effects of aging on visuomotor plasticity, we chose the simple and easily measured paradigm of visual-motor re-arrangement created by using visual displacement prisms while throwing small balls at a target. Subjects threw balls before, during and after wearing a set of prisms which displace the visual scene by twenty degrees to the right. Data obtained during adaptation were modeled using multilevel analyses for 73 subjects aged 20 to 80 years. We found no statistically significant difference in measures of visuomotor plasticity with advancing age. Further studies are underway examining variable practice training as a potential mechanism for enhancing this form of behavioral neural plasticity.

Effects of normal aging on visuo-motor plasticity

NASA Technical Reports Server (NTRS)

Roller, Carrie A.; Cohen, Helen S.; Kimball, Kay T.; Bloomberg, Jacob J.

2002-01-01

Normal aging is associated with declines in neurologic function. Uncompensated visual and vestibular problems may have dire consequences including dangerous falls. Visuo-motor plasticity is a form of behavioral neural plasticity, which is important in the process of adapting to visual or vestibular alteration, including those changes due to pathology, pharmacotherapy, surgery or even entry into microgravity or an underwater environment. To determine the effects of aging on visuo-motor plasticity, we chose the simple and easily measured paradigm of visual-motor rearrangement created by using visual displacement prisms while throwing small balls at a target. Subjects threw balls before, during and after wearing a set of prisms which displace the visual scene by twenty degrees to the right. Data obtained during adaptation were modeled using multilevel modeling techniques for 73 subjects, aged 20 to 80 years. We found no statistically significant difference in measures of visuo-motor plasticity with advancing age. Further studies are underway examining variable practice training as a potential mechanism for enhancing this form of behavioral neural plasticity.

The microbiota and microbiome in aging: potential implications in health and age-related diseases.

PubMed

Zapata, Heidi J; Quagliarello, Vincent J

2015-04-01

Advances in bacterial deoxyribonucleic acid sequencing allow for characterization of the human commensal bacterial community (microbiota) and its corresponding genome (microbiome). Surveys of healthy adults reveal that a signature composite of bacteria characterizes each unique body habitat (e.g., gut, skin, oral cavity, vagina). A myriad of clinical changes, including a basal proinflammatory state (inflamm-aging), that directly interface with the microbiota of older adults and enhance susceptibility to disease accompany aging. Studies in older adults demonstrate that the gut microbiota correlates with diet, location of residence (e.g., community dwelling, long-term care settings), and basal level of inflammation. Links exist between the microbiota and a variety of clinical problems plaguing older adults, including physical frailty, Clostridium difficile colitis, vulvovaginal atrophy, colorectal carcinoma, and atherosclerotic disease. Manipulation of the microbiota and microbiome of older adults holds promise as an innovative strategy to influence the development of comorbidities associated with aging. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

Small molecule SIRT1 activators for the treatment of aging and age-related diseases

PubMed Central

Hubbard, Basil P.; Sinclair, David A.

2014-01-01

Recent studies in mice have identified single molecules that can delay multiple diseases of aging and extend lifespan. In theory, such molecules could prevent dozens of diseases simultaneously, significantly extending healthy years of life. In this review we discuss recent advances, controversies, opportunities, and challenges surrounding the development of SIRT1 activators, molecules with the potential to delay aging and age-related diseases. Sirtuins comprise a family of NAD+-dependent deacylases that are central to the body’s response to diet and exercise. New studies indicate that both natural and synthetic sirtuin activating compounds (STACs) work via a common allosteric mechanism to stimulate sirtuin activity, thereby conferring broad health benefits in rodents, primates, and possibly humans. The fact that the two-thirds of people in the USA who consume multiple dietary supplements consume resveratrol, a SIRT1 activator, underscores the importance of understanding the biochemical mechanism, physiological effects, and safety of STACs. PMID:24439680

GRC Supporting Technology for NASA's Advanced Stirling Radioisotope Generator (ASRG)

NASA Technical Reports Server (NTRS)

Schreiber, Jeffrey G.; Thieme, Lanny G.

2008-01-01

From 1999 to 2006, the NASA Glenn Research Center (GRC) supported a NASA project to develop a high-efficiency, nominal 110-We Stirling Radioisotope Generator (SRG110) for potential use on NASA missions. Lockheed Martin was selected as the System Integration Contractor for the SRG110, under contract to the Department of Energy (DOE). The potential applications included deep space missions, and Mars rovers. The project was redirected in 2006 to make use of the Advanced Stirling Convertor (ASC) that was being developed by Sunpower, Inc. under contract to GRC, which would reduce the mass of the generator and increase the power output. This change would approximately double the specific power and result in the Advanced Stirling Radioisotope Generator (ASRG). The SRG110 supporting technology effort at GRC was replanned to support the integration of the Sunpower convertor and the ASRG. This paper describes the ASRG supporting technology effort at GRC and provides details of the contributions in some of the key areas. The GRC tasks include convertor extended-operation testing in air and in thermal vacuum environments, heater head life assessment, materials studies, permanent magnet characterization and aging tests, structural dynamics testing, electromagnetic interference and electromagnetic compatibility characterization, evaluation of organic materials, reliability studies, and analysis to support controller development.

A decline in female baboon hypothalamo-pituitary-adrenal axis activity anticipates aging.

PubMed

Yang, Shanshan; Gerow, Kenneth G; Huber, Hillary F; Considine, McKenna M; Li, Cun; Mattern, Vicki; Comuzzie, Anthony G; Ford, Stephen P; Nathanielsz, Peter W

2017-05-09

Stressors that disrupt homeostasis advance aging. Glucocorticoids regulate multiple processes that determine the aging trajectory. Debate exists regarding life-course circulating glucocorticoid concentrations. Rodent and nonhuman primate studies indicate circulating glucocorticoids fall from early life. We measured fasting morning cortisol in 24 female baboons (6-21 years, human equivalent ~18-70). We also quantified hypothalamic paraventricular nuclear (PVN) arginine vasopressin (AVP), corticotropin-releasing hormone, steroid receptors, and pituitary proopiomelanocortin immunohistochemically in 14 of these females at 6-13 years. We identified significant age-related 1) linear fall in cortisol and PVN AVP from as early as 6 years; 2) increased PVN glucocorticoid and mineralocorticoid receptors; 3) increased PVN 11β-hydroxysteroid dehydrogenase 1 and 2, regulators of local cortisol production, and 4) decreased pituitary proopiomelanocortin. Our data identify increased age-related negative feedback and local PVN cortisol production as potential mechanisms decreasing PVN drive to hypothalamo-pituitary-adrenal axis activity that result in the age-related circulating cortisol fall. Further studies are needed to determine whether the cortisol fall 1) causes aging, 2) protects by slowing aging, or 3) is an epiphenomenon unrelated to aging processes. We conclude that aging processes are best studied by linear life-course analysis beginning early in life.

AGEs induce Alzheimer-like tau pathology and memory deficit via RAGE-mediated GSK-3 activation.

PubMed

Li, Xiao-Hong; Lv, Bing-Ling; Xie, Jia-Zhao; Liu, Jing; Zhou, Xin-Wen; Wang, Jian-Zhi

2012-07-01

Accumulation of β-amyloid and hyperphosphorylated tau with synapse damage and memory deterioration are hallmark lesions of Alzheimer disease (AD), but the upstream causative factors are elusive. The advanced glycation endproducts (AGEs) are elevated in AD brains and the AGEs can stimulate β-amyloid production. Whether and how AGEs may cause AD-like tau hyperphosphorylation and memory-related deficits is not known. Here we report that AGEs induce tau hyperphosphorylation, memory deterioration, decline of synaptic proteins, and impairment of long-term potentiation (LTP) in rats. In SK-NS-H cells, upregulation of AGEs receptor (RAGE), inhibition of Akt, and activation of glycogen synthase kinase-3 (GSK-3), Erk1/2, and p38 were observed after treatment with AGEs. In rats, blockage of RAGE attenuated the AGE-induced GSK-3 activation, tau hyperphosphorylation, and memory deficit with restoration of synaptic functions, and simultaneous inhibition of GSK-3 also antagonized the AGE-induced impairments. Our data reveal that AGEs can induce tau hyperphosphorylation and impair synapse and memory through RAGE-mediated GSK-3 activation and targeting RAGE/GSK-3 pathway can efficiently improve the AD-like histopathological changes and memory deterioration. Copyright © 2012 Elsevier Inc. All rights reserved.

Outpatient Prescribing Errors and the Impact of Computerized Prescribing

PubMed Central

Gandhi, Tejal K; Weingart, Saul N; Seger, Andrew C; Borus, Joshua; Burdick, Elisabeth; Poon, Eric G; Leape, Lucian L; Bates, David W

2005-01-01

Background Medication errors are common among inpatients and many are preventable with computerized prescribing. Relatively little is known about outpatient prescribing errors or the impact of computerized prescribing in this setting. Objective To assess the rates, types, and severity of outpatient prescribing errors and understand the potential impact of computerized prescribing. Design Prospective cohort study in 4 adult primary care practices in Boston using prescription review, patient survey, and chart review to identify medication errors, potential adverse drug events (ADEs) and preventable ADEs. Participants Outpatients over age 18 who received a prescription from 24 participating physicians. Results We screened 1879 prescriptions from 1202 patients, and completed 661 surveys (response rate 55%). Of the prescriptions, 143 (7.6%; 95% confidence interval (CI) 6.4% to 8.8%) contained a prescribing error. Three errors led to preventable ADEs and 62 (43%; 3% of all prescriptions) had potential for patient injury (potential ADEs); 1 was potentially life-threatening (2%) and 15 were serious (24%). Errors in frequency (n=77, 54%) and dose (n=26, 18%) were common. The rates of medication errors and potential ADEs were not significantly different at basic computerized prescribing sites (4.3% vs 11.0%, P=.31; 2.6% vs 4.0%, P=.16) compared to handwritten sites. Advanced checks (including dose and frequency checking) could have prevented 95% of potential ADEs. Conclusions Prescribing errors occurred in 7.6% of outpatient prescriptions and many could have harmed patients. Basic computerized prescribing systems may not be adequate to reduce errors. More advanced systems with dose and frequency checking are likely needed to prevent potentially harmful errors. PMID:16117752

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.

Placental Dysfunction Underlies Increased Risk of Fetal Growth Restriction and Stillbirth in Advanced Maternal Age Women.

PubMed

Lean, Samantha C; Heazell, Alexander E P; Dilworth, Mark R; Mills, Tracey A; Jones, Rebecca L

2017-08-29

Pregnancies in women of advanced maternal age (AMA) are susceptible to fetal growth restriction (FGR) and stillbirth. We hypothesised that maternal ageing is associated with utero-placental dysfunction, predisposing to adverse fetal outcomes. Women of AMA (≥35 years) and young controls (20-30 years) with uncomplicated pregnancies were studied. Placentas from AMA women exhibited increased syncytial nuclear aggregates and decreased proliferation, and had increased amino acid transporter activity. Chorionic plate and myometrial artery relaxation was increased compared to controls. AMA was associated with lower maternal serum PAPP-A and sFlt and a higher PlGF:sFlt ratio. AMA mice (38-41 weeks) at E17.5 had fewer pups, more late fetal deaths, reduced fetal weight, increased placental weight and reduced fetal:placental weight ratio compared to 8-12 week controls. Maternofetal clearance of 14 C-MeAIB and 3 H-taurine was reduced and uterine arteries showed increased relaxation. These studies identify reduced placental efficiency and altered placental function with AMA in women, with evidence of placental adaptations in normal pregnancies. The AMA mouse model complements the human studies, demonstrating high rates of adverse fetal outcomes and commonalities in placental phenotype. These findings highlight placental dysfunction as a potential mechanism for susceptibility to FGR and stillbirth with AMA.

Age-dependence of power spectral density and fractal dimension of bone mineralized matrix in atomic force microscope topography images: potential correlates of bone tissue age and bone fragility in female femoral neck trabeculae

PubMed Central

Milovanovic, Petar; Djuric, Marija; Rakocevic, Zlatko

2012-01-01

There is an increasing interest in bone nano-structure, the ultimate goal being to reveal the basis of age-related bone fragility. In this study, power spectral density (PSD) data and fractal dimensions of the mineralized bone matrix were extracted from atomic force microscope topography images of the femoral neck trabeculae. The aim was to evaluate age-dependent differences in the mineralized matrix of human bone and to consider whether these advanced nano-descriptors might be linked to decreased bone remodeling observed by some authors and age-related decline in bone mechanical competence. The investigated bone specimens belonged to a group of young adult women (n = 5, age: 20–40 years) and a group of elderly women (n = 5, age: 70–95 years) without bone diseases. PSD graphs showed the roughness density distribution in relation to spatial frequency. In all cases, there was a fairly linear decrease in magnitude of the power spectra with increasing spatial frequencies. The PSD slope was steeper in elderly individuals (−2.374 vs. −2.066), suggesting the dominance of larger surface morphological features. Fractal dimension of the mineralized bone matrix showed a significant negative trend with advanced age, declining from 2.467 in young individuals to 2.313 in the elderly (r = 0.65, P = 0.04). Higher fractal dimension in young women reflects domination of smaller mineral grains, which is compatible with the more freshly remodeled structure. In contrast, the surface patterns in elderly individuals were indicative of older tissue age. Lower roughness and reduced structural complexity (decreased fractal dimension) of the interfibrillar bone matrix in the elderly suggest a decline in bone toughness, which explains why aged bone is more brittle and prone to fractures. PMID:22946475

Age-dependence of power spectral density and fractal dimension of bone mineralized matrix in atomic force microscope topography images: potential correlates of bone tissue age and bone fragility in female femoral neck trabeculae.

PubMed

Milovanovic, Petar; Djuric, Marija; Rakocevic, Zlatko

2012-11-01

There is an increasing interest in bone nano-structure, the ultimate goal being to reveal the basis of age-related bone fragility. In this study, power spectral density (PSD) data and fractal dimensions of the mineralized bone matrix were extracted from atomic force microscope topography images of the femoral neck trabeculae. The aim was to evaluate age-dependent differences in the mineralized matrix of human bone and to consider whether these advanced nano-descriptors might be linked to decreased bone remodeling observed by some authors and age-related decline in bone mechanical competence. The investigated bone specimens belonged to a group of young adult women (n = 5, age: 20-40 years) and a group of elderly women (n = 5, age: 70-95 years) without bone diseases. PSD graphs showed the roughness density distribution in relation to spatial frequency. In all cases, there was a fairly linear decrease in magnitude of the power spectra with increasing spatial frequencies. The PSD slope was steeper in elderly individuals (-2.374 vs. -2.066), suggesting the dominance of larger surface morphological features. Fractal dimension of the mineralized bone matrix showed a significant negative trend with advanced age, declining from 2.467 in young individuals to 2.313 in the elderly (r = 0.65, P = 0.04). Higher fractal dimension in young women reflects domination of smaller mineral grains, which is compatible with the more freshly remodeled structure. In contrast, the surface patterns in elderly individuals were indicative of older tissue age. Lower roughness and reduced structural complexity (decreased fractal dimension) of the interfibrillar bone matrix in the elderly suggest a decline in bone toughness, which explains why aged bone is more brittle and prone to fractures. © 2012 The Authors Journal of Anatomy © 2012 Anatomical Society.

Playing the Long Game: Considering the Future of Augmentative and Alternative Communication Research and Service.

PubMed

Reichle, Joe; Drager, Kathryn; Caron, Jessica; Parker-McGowan, Quannah

2016-11-01

This article examines the growth of aided augmentative and alternative communication (AAC) in providing support to children and youth with significant communication needs. Addressing current trends and offering a discussion of needs and probable future advances is framed around five guiding principles initially introduced by Williams, Krezman, and McNaughton. These include: (1) communication is a basic right and the use of AAC, especially at a young age, can help individuals realize their communicative potential; (2) AAC, like traditional communication, requires it to be fluid with the ability to adapt to different environments and needs; (3) AAC must be individualized and appropriate for each user; (4) AAC must support full participation in society across all ages and interests; and (5) individuals who use AAC have the right to be involved in all aspects of research, development, and intervention. In each of these areas current advances, needs, and future predictions are offered and discussed in terms of researchers' and practitioners' efforts to a continued upward trajectory of research and translational service delivery. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Studies of advanced glycation end products and oxidation biomarkers for type 2 diabetes

USDA-ARS?s Scientific Manuscript database

Advanced glycation end products (AGEs) are formed upon nonenzymatic reactions of sugars or their metabolites with proteins and other cellular constituents. Many AGEs are long lived. Recent findings suggest that AGEs may predict diabetes and its complications and thus may warrant further study. The o...

Aged garlic extract and S-allyl cysteine prevent formation of advanced glycation endproducts.

PubMed

Ahmad, Muhammad Saeed; Pischetsrieder, Monika; Ahmed, Nessar

2007-04-30

Hyperglycaemia causes increased protein glycation and the formation of advanced glycation endproducts which underlie the complications of diabetes and ageing. Glycation is accompanied by metal-catalysed oxidation of glucose and Amadori products to form free radicals capable of protein fragmentation. Aged garlic extract is a potent antioxidant with established lipid-lowering effects attributed largely to a key ingredient called S-allyl cysteine. This study investigated the ability of aged garlic extract and S-allyl cysteine to inhibit advanced glycation in vitro. Bovine serum albumin (BSA) was glycated in the presence of Cu(2+) ions and different concentrations of aged garlic extract and protein fragmentation was examined by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Lysozyme was glycated by glucose or methylglyoxal in the presence of different concentrations of aged garlic extract or S-allyl cysteine with subsequent analysis of glycation-derived crosslinking using SDS-PAGE. Amadori-rich protein was prepared by dialysing lysozyme that had been glycated by ribose for 24 h. This ribated lysozyme was reincubated and the effects of aged garlic extract, S-allyl cysteine and pyridoxamine on glycation-induced crosslinking was monitored. Aged garlic extract inhibited metal-catalysed protein fragmentation. Both aged garlic extract and S-allyl cysteine inhibited formation of glucose and methylglyoxal derived advanced glycation endproducts and showed potent Amadorin activity when compared to pyridoxamine. S-allyl cysteine inhibited formation of carboxymethyllysine (CML), a non-crosslinked advanced glycation endproduct derived from oxidative processes. Further studies are required to assess whether aged garlic extract and S-allyl cysteine can protect against the harmful effects of glycation and free radicals in diabetes and ageing.

Compact modeling of total ionizing dose and aging effects in MOS technologies

DOE PAGES

Esqueda, Ivan S.; Barnaby, Hugh J.; King, Michael Patrick

2015-06-18

This paper presents a physics-based compact modeling approach that incorporates the impact of total ionizing dose (TID) and stress-induced defects into simulations of metal-oxide-semiconductor (MOS) devices and integrated circuits (ICs). This approach utilizes calculations of surface potential (ψs) to capture the charge contribution from oxide trapped charge and interface traps and to describe their impact on MOS electrostatics and device operating characteristics as a function of ionizing radiation exposure and aging effects. The modeling approach is demonstrated for bulk and silicon-on-insulator (SOI) MOS device. The formulation is verified using TCAD simulations and through the comparison of model calculations and experimentalmore » I-V characteristics from irradiated devices. The presented approach is suitable for modeling TID and aging effects in advanced MOS devices and ICs.« less

Analytical approaches to the diagnosis and treatment of aging and aging-related disease: redox status and proteomics.

PubMed

Calabrese, V; Dattilo, S; Petralia, A; Parenti, R; Pennisi, M; Koverech, G; Calabrese, V; Graziano, A; Monte, I; Maiolino, L; Ferreri, T; Calabrese, E J

2015-05-01

Basal levels of oxidants are indispensible for redox signaling to produce adaptive cellular responses such as vitagenes linked to cell survival; however, at higher levels, they are detrimental to cells, contributing to aging and to the pathogenesis of numerous age-related diseases. Aging is a complex systemic process and the major gap in aging research reminds the insufficient knowledge about pathways shifting from normal "healthy" aging to disease-associated pathological aging. The major complication of normal "healthy" aging is in fact the increasing risk of age-related diseases such as cardiovascular diseases, diabetes mellitus, and neurodegenerative pathologies that can adversely affect the quality of life in general, with enhanced incidences of comorbidities and mortality. In this context, global "omics" approaches may help to dissect and fully study the cellular and molecular mechanisms of aging and age-associated processes. The proteome, being more close to the phenotype than the transcriptome and more stable than the metabolome, represents the most promising "omics" field in aging research. In the present study, we exploit recent advances in the redox biology of aging and discuss the potential of proteomics approaches as innovative tools for monitoring at the proteome level the extent of protein oxidative insult and related modifications with the identification of targeted proteins.

Teaching in the Age of Electrons

NASA Astrophysics Data System (ADS)

Impey, C. D.

2002-12-01

Technology opens up a bewildering array of opportunities and options for faculty teaching courses to large groups of non-science majors. The trick is in understanding which modes of instruction increase the engagement and learning of students. Among the tools that show good potential for advancing learning in introductory astronomy classes are virtual worlds, exercises that use real astronomy data sets, expert systems, and content accessible by phone. Some of the capabilities of a new web site to assist astronomy instructors, www.astronomica.org, will be demonstrated.

Glucose-derived AGEs enhance human gastric cancer metastasis through RAGE/ERK/Sp1/MMP2 cascade.

PubMed

Deng, Ruyuan; Mo, Fengbo; Chang, Bowen; Zhang, Qi; Ran, Hui; Yang, Shuhua; Zhu, Zhiqiang; Hu, Lei; Su, Qing

2017-11-28

Advanced glycation end products (AGEs) have been reported to take part in many cancer processes. Whether AGEs contribute to gastric cancer (GC) course and the underlying mechanism are still unclear. Here, glucose-derived AGEs are detected to be accumulated in tumor tissues and blood of patients with GC. As the receptor for AGEs, RAGE is highly expressed in cancer tissues, and closely associated with the depth of cancer invasion, lymph node metastasis and TNM stage. Both in vivo and in vitro treatment of AGEs accelerate the tumor invasion and metastasis, with upregualtion of RAGE, Specificity Protein 1 (Sp1), and MMP2 protein expression, as well as enhancement of MMP2 activity. Either RAGE-blocking antibody or Sp1-knockdown can partially block the AGEs-induced effects. Moreover, AGEs increased the phosphorylation of ERK, and reducing the phosphorylation level of ERK by MEK1/2 inhibitor decreased the expression of Sp1. These results indicate that accumulation of glucose-derived AGEs may act as one of potential risk factors for GC progression and promote the invasion and metastasis of gastric cancer partially through the activation of RAGE/ERK/Sp1/MMP2 pathway.

Glucose-derived AGEs enhance human gastric cancer metastasis through RAGE/ERK/Sp1/MMP2 cascade

PubMed Central

Deng, Ruyuan; Mo, Fengbo; Chang, Bowen; Zhang, Qi; Ran, Hui; Yang, Shuhua; Zhu, Zhiqiang; Hu, Lei; Su, Qing

2017-01-01

Advanced glycation end products (AGEs) have been reported to take part in many cancer processes. Whether AGEs contribute to gastric cancer (GC) course and the underlying mechanism are still unclear. Here, glucose-derived AGEs are detected to be accumulated in tumor tissues and blood of patients with GC. As the receptor for AGEs, RAGE is highly expressed in cancer tissues, and closely associated with the depth of cancer invasion, lymph node metastasis and TNM stage. Both in vivo and in vitro treatment of AGEs accelerate the tumor invasion and metastasis, with upregualtion of RAGE, Specificity Protein 1 (Sp1), and MMP2 protein expression, as well as enhancement of MMP2 activity. Either RAGE-blocking antibody or Sp1-knockdown can partially block the AGEs-induced effects. Moreover, AGEs increased the phosphorylation of ERK, and reducing the phosphorylation level of ERK by MEK1/2 inhibitor decreased the expression of Sp1. These results indicate that accumulation of glucose-derived AGEs may act as one of potential risk factors for GC progression and promote the invasion and metastasis of gastric cancer partially through the activation of RAGE/ERK/Sp1/MMP2 pathway. PMID:29262634

Fertility effects of cancer treatment.

PubMed

Marsden, Donald E; Hacker, Neville

2003-01-01

Cancer sufferers are a subfertile group, and most treatments have the potential to adversely affect gonadal function. As cancer treatment becomes more effective and survival rates improve there are more cancer survivors in the reproductive age group for whom parenting is an important consideration. This article outlines the effects on fertility of cancer treatments and techniques to minimise the risk of infertility. The overall prospects for younger cancer sufferers to either retain their fertility or have genetic offspring is now better than ever before, due to advances in assisted reproductive technology, the appropriate use of fertility sparing surgery and other techniques to reduce the toxicity of therapy on the reproductive organs. These advances raise new moral and ethical concerns that must be considered before advising cancer sufferers of the options for preserving reproductive capacity.

Skeletal advance and arrest in giant non-metamorphosing African clawed frog tadpoles (Xenopus laevis: Daudin)

PubMed Central

Kerney, Ryan; Wassersug, Richard; Hall, Brian K

2010-01-01

This study examines the skeletons of giant non-metamorphosing (GNM) Xenopus laevis tadpoles, which arrest their development indefinitely before metamorphosis, and grow to excessively large sizes in the absence of detectable thyroid glands. Cartilage growth is isometric; however, chondrocyte size is smaller in GNM tadpoles than in controls. Most cartilages stain weakly with alcian blue, and several cartilages are calcified (unlike controls). However, cartilages subjacent to periosteum-derived bone retain strong affinities for alcian blue, indicating a role for periosteum-derived bone in the retention of glycosaminoglycans during protracted larval growth. Bone formation in the head, limb, and axial skeletons is advanced in comparison with stage-matched controls, but arrests at various mid-metamorphic states. Both dermal and periosteum-derived bones grow to disproportionately large sizes in comparison to controls. Additionally, mature monocuspid teeth form in several GNM tadpoles. Advances in skeletal development are attributable to the old ages and large sizes of these tadpoles, and reveal unexpected developmental potentials of the pre-metamorphic skeleton. PMID:20402828

Reproduction beyond menopause: how old is too old for assisted reproductive technology?

PubMed Central

Havemann, Dara L.; Phelps, John Y.

2010-01-01

Background Due to the recent media attention on postmenopausal women giving birth, there has been an increased scrutiny on the utility and safety of assisted reproductive technology in postmenopausal women. Objective The purpose of this commentary is to discuss the following: 1) the limitations and complications of ART in women of advanced reproductive age; 2) the balance between the welfare of the mother and that of the child; 3) the double standards of advanced reproductive age; and 4) the importance of financial and social support systems and preconception counseling with advanced reproductive age. Conclusion When providing in-vitro fertilization services to women of advanced reproductive age, special considerations must be given to ensure the welfare of mother and the child and that the principles of beneficence and nonmaleficence are guaranteed. PMID:20454846

Are microRNAs true sensors of ageing and cellular senescence?

PubMed

Williams, Justin; Smith, Flint; Kumar, Subodh; Vijayan, Murali; Reddy, P Hemachandra

2017-05-01

All living beings are programmed to death due to aging and age-related processes. Aging is a normal process of every living species. While all cells are inevitably progressing towards death, many disease processes accelerate the aging process, leading to senescence. Pathologies such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, cardiovascular disease, cancer, and skin diseases have been associated with deregulated aging. Healthy aging can delay onset of all age-related diseases. Genetics and epigenetics are reported to play large roles in accelerating and/or delaying the onset of age-related diseases. Cellular mechanisms of aging and age-related diseases are not completely understood. However, recent molecular biology discoveries have revealed that microRNAs (miRNAs) are potential sensors of aging and cellular senescence. Due to miRNAs capability to bind to the 3' untranslated region (UTR) of mRNA of specific genes, miRNAs can prevent the translation of specific genes. The purpose of our article is to highlight recent advancements in miRNAs and their involvement in cellular changes in aging and senescence. Our article discusses the current understanding of cellular senescence, its interplay with miRNAs regulation, and how they both contribute to disease processes. Copyright © 2016 Elsevier B.V. All rights reserved.

Advanced Maternal Age and the Risk of Low Birth Weight and Preterm Delivery: a Within-Family Analysis Using Finnish Population Registers.

PubMed

Goisis, Alice; Remes, Hanna; Barclay, Kieron; Martikainen, Pekka; Myrskylä, Mikko

2017-12-01

Advanced maternal age at birth is considered a major risk factor for birth outcomes. It is unclear to what extent this association is confounded by maternal characteristics. To test whether advanced maternal age at birth independently increases the risk of low birth weight (<2,500 g) and preterm birth (<37 weeks' gestation), we compared between-family models (children born to different mothers at different ages) with within-family models (children born to the same mother at different ages). The latter procedure reduces confounding by unobserved parental characteristics that are shared by siblings. We used Finnish population registers, including 124,098 children born during 1987-2000. When compared with maternal ages 25-29 years in between-family models, maternal ages of 35-39 years and ≥40 years were associated with percentage increases of 1.1 points (95% confidence intervals: 0.8, 1.4) and 2.2 points (95% confidence intervals: 1.4, 2.9), respectively, in the probability of low birth weight. The associations are similar for the risk of preterm delivery. In within-family models, the relationship between advanced maternal age and low birth weight or preterm birth is statistically and substantively negligible. In Finland, advanced maternal age is not independently associated with the risk of low birth weight or preterm delivery among mothers who have had at least 2 live births. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.

Assessment of competence to complete advance directives: validation of a patient centred approach

PubMed Central

Fazel, Seena; Hope, Tony; Jacoby, Robin

1999-01-01

Objective To develop a patient centred approach for the assessment of competence to complete advance directives (“living wills”) of elderly people with cognitive impairment. Design Semistructured interviews. Setting Oxfordshire. Subjects 50 elderly volunteers living in the community, and 50 patients with dementia on first referral from primary care. Main outcome measures Psychometric properties of competence assessment. Results This patient centred approach for assessing competence to complete advance directives can discriminate between elderly persons living in the community and elderly patients with dementia. The procedure has good interrater (r=0.95) and test-retest (r=0.97) reliability. Validity was examined by relating this approach with a global assessment of competence to complete an advance directive made by two of us (both specialising in old age psychiatry). The data were also used to determine the best threshold score for discriminating between those competent and those incompetent to complete an advance directive. Conclusion A patient centred approach to assess competence to complete advance directives can be reliably and validly used in routine clinical practice. Key messagesAdvance directives could potentially be useful for patients with dementia as a means of extending their autonomy when they become incompetentCompetence to complete an advance directive involves understanding possible future clinical situationsVignettes presenting hypothetical medical problems were tested in 100 elderly people, and were found to validly and reliably discriminate between volunteers living in the community and patients with dementiaWe suggest that two clinical vignettes, each followed by a semistructured interview comprising 10 points, can aid in the assessment of competence to complete advance directives PMID:10024254

Increased radial glia quiescence, decreased reactivation upon injury and unaltered neuroblast behavior underlie decreased neurogenesis in the aging zebrafish telencephalon.

PubMed

Edelmann, Kathrin; Glashauser, Lena; Sprungala, Susanne; Hesl, Birgit; Fritschle, Maike; Ninkovic, Jovica; Godinho, Leanne; Chapouton, Prisca

2013-09-01

The zebrafish has recently become a source of new data on the mechanisms of neural stem cell (NSC) maintenance and ongoing neurogenesis in adult brains. In this vertebrate, neurogenesis occurs at high levels in all ventricular regions of the brain, and brain injuries recover successfully, owing to the recruitment of radial glia, which function as NSCs. This new vertebrate model of adult neurogenesis is thus advancing our knowledge of the molecular cues in use for the activation of NSCs and fate of their progeny. Because the regenerative potential of somatic stem cells generally weakens with increasing age, it is important to assess the extent to which zebrafish NSC potential decreases or remains unaltered with age. We found that neurogenesis in the ventricular zone, in the olfactory bulb, and in a newly identified parenchymal zone of the telencephalon indeed declines as the fish ages and that oligodendrogenesis also declines. In the ventricular zone, the radial glial cell population remains largely unaltered morphologically but enters less frequently into the cell cycle and hence produces fewer neuroblasts. The neuroblasts themselves do not change their behavior with age and produce the same number of postmitotic neurons. Thus, decreased neurogenesis in the physiologically aging zebrafish brain is correlated with an increasing quiescence of radial glia. After injuries, radial glia in aged brains are reactivated, and the percentage of cell cycle entry is increased in the radial glia population. However, this reaction is far less pronounced than in younger animals, pointing to irreversible changes in aging zebrafish radial glia. Copyright © 2013 Wiley Periodicals, Inc.

The potential of space exploration for education

NASA Technical Reports Server (NTRS)

Shair, Fredrick H.

1993-01-01

Space exploration and observations from space offer unique opportunities with respect to education. Recent technical advances have significantly increased the width and sensitivity of the electromagnetic spectrum window through which we are able to 'see' the universe. Observations from space have forced a realization that the earth is a beautiful, complex, and interconnected system. Space astronomy and the remote sensing of objects throughout our solar system have the potential of providing unique educational opportunities. Modern technologies have significantly reduced the cost of collecting, transmitting and processing data. Consequently, we are entering an age where it is possible to open up the process of discovery to almost everyone - and especially to young people throughout the world.

Can Parasitic Worms Cure the Modern World's Ills?

PubMed

Harnett, Margaret M; Harnett, William

2017-09-01

There has been increasing recognition that the alarming surge in allergy and autoimmunity in the industrialised and developing worlds shadows the rapid eradication of pathogens, such as parasitic helminths. Appreciation of this has fuelled an explosion in research investigating the therapeutic potential of these worms. This review considers the current state-of-play with a particular focus on exciting recent advances in the identification of potential novel targets for immunomodulation that can be exploited therapeutically. Furthermore, we contemplate the prospects for designing worm-derived immunotherapies for an ever-widening range of inflammatory diseases, including, for example, obesity, cardiovascular disease, and ageing as well as neurodevelopmental disorders like autism. Copyright © 2017 Elsevier Ltd. All rights reserved.

Glutamine metabolism in advanced age

PubMed Central

2016-01-01

Glutamine, reviewed extensively in the last century, is a key substrate for the splanchnic bed in the whole body and is a nutrient of particular interest in gastrointestinal research. A marked decrease in the plasma glutamine concentration has recently been observed in neonates and adults during acute illness and stress. Although some studies in newborns have shown parenteral and enteral supplementation with glutamine to be of benefit (by decreasing proteolysis and activating the immune system), clinical trials have not demonstrated prolonged advantages such as reductions in mortality or risk of infections in adults. In addition, glutamine is not able to combat the muscle wasting associated with disease or age-related sarcopenia. Oral glutamine supplementation initiated before advanced age in rats increases gut mass and improves the villus height of mucosa, thereby preventing the gut atrophy encountered in advanced age. Enterocytes from very old rats continuously metabolize glutamine into citrulline, which allowed, for the first time, the use of citrulline as a noninvasive marker of intestinal atrophy induced by advanced age. PMID:26936258

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.

Advanced glycation end products and antioxidant status in type 2 diabetic patients with and without peripheral artery disease.

PubMed

Lapolla, Annunziata; Piarulli, Francesco; Sartore, Giovanni; Ceriello, Antonio; Ragazzi, Eugenio; Reitano, Rachele; Baccarin, Lorenzo; Laverda, Barbara; Fedele, Domenico

2007-03-01

Advanced glycation end products (AGEs), pentosidine and malondialdehyde (MDA), are elevated in type 2 diabetic subjects with coronary and carotid angiopathy. We investigated the relationship of AGEs, MDA, total reactive antioxidant potentials (TRAPs), and vitamin E in type 2 diabetic patients with and without peripheral artery disease (PAD). AGEs, pentosidine, MDA, TRAP, vitamin E, and ankle-brachial index (ABI) were measured in 99 consecutive type 2 diabetic subjects and 20 control subjects. AGEs, pentosidine, and MDA were higher and vitamin E and TRAP were lower in patients with PAD (ABI <0.9) than in patients without PAD (ABI >0.9) (P < 0.001). After multiple regression analysis, a correlation between AGEs and pentosidine, as independent variables, and ABI, as the dependent variable, was found in both patients with and without PAD (r = 0.9198, P < 0.001 and r = 0.5764, P < 0.001, respectively) but not in control subjects. When individual regression coefficients were evaluated, only that due to pentosidine was confirmed as significant. For patients with PAD, considering TRAP, vitamin E, and MDA as independent variables and ABI as the dependent variable produced an overall significant regression (r = 0.6913, P < 0.001). The regression coefficients for TRAP and vitamin E were not significant, indicating that the model is best explained by a single linear regression between MDA and ABI. These findings were also confirmed by principal component analysis. Results show that pentosidine and MDA are strongly associated with PAD in type 2 diabetic patients.

Concomitant use of analgesics and psychotropics in home-dwelling elderly people – Kuopio 75 + study

PubMed Central

Hartikainen, Sirpa; Mäntyselkä, Pekka; Louhivuori-Laako, Kirsti; Enlund, Hannes; Sulkava, Raimo

2005-01-01

Aims To investigate the extent of concomitant use of analgesic and psychotropic medicines among home-dwelling elderly people aged at least 75 years in Finland. Methods This was a population-based study in Finland, performed as part of Kuopio 75 + study focusing on the clinical epidemiology of diseases, medication and functional capacity. A random sample of 700 persons was drawn from the total population of the city of Kuopio, eastern Finland, aged 75 years on January 1, 1998 (n = 4518). Ninety-nine persons could not be examined and 78 were living in long-term institutions, so that the number of home-dwelling elderly persons amounted to 523. A trained nurse interviewed the participants about their use of medicines, and a geriatrician examined their overall physical and mental status. Dementia and depression were diagnosed according to the DSM IV criteria. Both regular and irregular prescribed and nonprescribed drug use was recorded. Results Every fourth elderly person (27.2%) used analgesics and psychotropics concomitantly, this use becoming twice as common with advancing age (19.6% in the age group 75–79 years, 38.2% among the oldest, aged 85 + years). Concomitant use of psychotropics and opioids also became more common with increasing age (2.8% in age group 75–79 years and 9.6% in the oldest group, aged 85 + years). The use of opioids was nearly twice as common among concomitant users (19.7%) than among those using only analgesics (11.3%). Concomitant users suffered from interfering daily pain and daily pain at rest more commonly than nonusers of analgesics. Depression, sleeping problems and polypharmacy were more common among the concomitant users, who had also had more hip fractures than the rest. Conclusions Concomitant use of analgesics and psychotropics becomes more common with advancing age and is a potential risk factor for adverse drug effects. PMID:16120070

The influence of age on perceptions of anticipated financial inadequacy by palliative radiation outpatients.

PubMed

Francoeur, Richard B

2007-12-01

A consistent body of knowledge suggests that with advancing age, adults tend to report lower financial strain from their current economic condition. But are more negative perceptions shifted onto their expectations about their future economic condition? This study of seriously ill outpatients investigates whether advancing age is related to more negative expectations of future health-related financial strain, in which illness progression would necessitate greater health care consumption. Ordinal probit multivariate regression was conducted on survey findings from 268 outpatients initiating palliative radiation for recurrent cancer. Half were retirees age>/=65. Age comparisons are reported when there was no recent work transition. As age advances (from 40 to 84), outpatients incurring low objective financial stress were more likely to reveal that their health insurance and finances would be less adequate to meet future health needs. Previously, these outpatients were reported to minimize perceptions of current financial strain as age advances. Therefore, older outpatients may cope with current circumstances by displacing perceptions of financial inadequacy onto plausible future situations of cancer progression demanding greater healthcare consumption. Financial strain may be hidden in older outpatients initiating palliative radiation. These outpatients appear at risk of foregoing appropriate healthcare. Targeted screening and advocacy are warranted.

Early Selection versus Late Correction: Age-Related Differences in Controlling Working Memory Contents

PubMed Central

Schwarzkopp, Tina; Mayr, Ulrich; Jost, Kerstin

2016-01-01

We examined whether a reduced ability to ignore irrelevant information is responsible for the age-related decline of working-memory (WM) functions. By means of event-related brain potentials we will show that filtering is not out of service in older adults but shifted to a later processing stage. Participants performed a visual short-term memory task (change-detection task) in which targets were presented along with distractors. To allow early selection, a cue was presented in advance of each display, indicating where the targets were to appear. Despite this relatively easy selection criterion, older adults’ filtering was delayed as indicated by the amplitude pattern of the contralateral delay activity. Importantly, WM-equated younger adults did not show a delay indicating that the delay is specific to older adults and not a general phenomenon that comes with low WM capacity. Moreover, the analysis of early visual potentials revealed qualitatively different perceptual/attentional processing between the age groups. Young adults exhibited stronger distractor sensitivity that in turn facilitated filtering. Older adults, in contrast, seemed to initially store distractors and to suppress them after the fact. These early-selection versus late-correction modes suggest an age-related shift in the strategy to control the contents of WM. PMID:27253867

Antiglycating potential of acesulfame potassium: an artificial sweetener.

PubMed

Ali, Ahmad; More, Tejashree Anil; Hoonjan, Amaritpal Kaur; Sivakami, Subramanian

2017-10-01

Sweeteners have replaced the natural sugars in the food and beverage industry because of many reasons, such as hyperglycemia and cost. Saccharin, sucralose, aspartame and acesulfame-K are the most commonly used sweeteners. In the present study, the abovementioned artificial sweeteners were used to assess their glycating properties by established methods such as browning, fructosamine assay, determination of carbonyl content, protein aggregation, and measurement of fluorescence. Amadori and advanced glycation end products (AGEs) are formed as a result of the interaction between carbonyl groups of reducing sugars and amino groups of proteins and other macromolecules during glycation. The objective of this study was to investigate the influence of artificial sweeteners on the formation of AGEs and protein oxidation in an in vitro model of glucose-mediated protein glycation. The results indicated that the abovementioned artificial sweeteners do not enhance the process of glycation. On the other hand, acesulfame-K was found to have antiglycating potential as it caused decreased formation of Amadori products and AGEs. Further studies are essential in the characterization of Amadori products and AGEs produced as a result of interaction between sweeteners and proteins, which are interfered with by sweeteners. This study is significant in understanding the probable role of artificial sweeteners in the process of glycation and the subsequent effect on macromolecular alteration.

Improvements in IVF in women of advanced age.

PubMed

Gleicher, Norbert; Kushnir, Vitaly A; Albertini, David F; Barad, David H

2016-07-01

Women above age 40 years in the US now represent the most rapidly growing age group having children. Patients undergoing in vitro fertilization (IVF) are rapidly aging in parallel. Especially where egg donations are legal, donation cycles, therefore, multiply more rapidly than autologous IVF cycles. The donor oocytes, however, are hardly ever a preferred patient choice. Since with use of own eggs, live birth rates decline with advancing age but remain stable (and higher) with donor eggs, older patients always face the difficult and very personal choice between poorer chances with own and better chances with donor oocytes. Physician contribution to this decision should in our opinion be restricted to accurate outcome information for both options. Achievable pregnancy and live birth rates in older women are, however, frequently underestimated, thereby mistakenly biasing fertility providers, private insurance companies and even regulatory government agencies. Restriction on access to IVF for older women is then often the consequence. In this review, we summarize the limited published data on best treatments of 'older' ovaries, while also addressing treatment approaches that should be avoided in older women. This focused review, therefore, to a degree is subjective. Research addressing aging ovaries in IVF has been disappointingly sparse, and has in our opinion too heavily concentrated on methods of embryo selection (ES), which, especially in older women, not only fail to improve IVF outcomes, but actually, negatively affect live birth chances. We conclude that, aside from breakthroughs in gamete creation, only pharmacological interventions into early (small growing follicle stages) follicle maturation will offer new potential to positively impact oocyte and embryo quality and, therefore, IVF outcomes. Research, therefore, should be accordingly redirected. © 2016 Society for Endocrinology.

Middle-Aged Independent-Living African Americans' Selections for Advance Directives: A Case Study

ERIC Educational Resources Information Center

McDaniel, Brenda J.

2013-01-01

The purpose of this collective embedded qualitative case study was to examine the perspectives of three middle-aged independent-living African Americans who had participated in the process of advance care planning (ACP) and completed at least two advance directives (ADs), a Durable Power of Attorney for Health Care (DPAHC) and a Living Will (LW).…

Adapted physical exercise enhances activation and differentiation potential of satellite cells in the skeletal muscle of old mice.

PubMed

Cisterna, Barbara; Giagnacovo, Marzia; Costanzo, Manuela; Fattoretti, Patrizia; Zancanaro, Carlo; Pellicciari, Carlo; Malatesta, Manuela

2016-05-01

During ageing, a progressive loss of skeletal muscle mass and a decrease in muscle strength and endurance take place, in the condition termed sarcopenia. The mechanisms of sarcopenia are complex and still unclear; however, it is known that muscle atrophy is associated with a decline in the number and/or efficiency of satellite cells, the main contributors to muscle regeneration. Physical exercise proved beneficial in sarcopenia; however, knowledge of the effect of adapted physical exercise on the myogenic properties of satellite cells in aged muscles is limited. In this study the amount and activation state of satellite cells as well as their proliferation and differentiation potential were assessed in situ by morphology, morphometry and immunocytochemistry at light and transmission electron microscopy on 28-month-old mice submitted to adapted aerobic physical exercise on a treadmill. Sedentary age-matched mice served as controls, and sedentary adult mice were used as a reference for an unperturbed control at an age when the capability of muscle regeneration is still high. The effect of physical exercise in aged muscles was further analysed by comparing the myogenic potential of satellite cells isolated from old running and old sedentary mice using an in vitro system that allows observation of the differentiation process under controlled experimental conditions. The results of this ex vivo and in vitro study demonstrated that adapted physical exercise increases the number and activation of satellite cells as well as their capability to differentiate into structurally and functionally correct myotubes (even though the age-related impairment in myotube formation is not fully reversed): this evidence further supports adapted physical exercise as a powerful, non-pharmacological approach to counteract sarcopenia and the age-related deterioration of satellite cell capabilities even at very advanced age. © 2016 Anatomical Society.

FY 2017 – Thermal Aging Effects on Advanced Structural Materials

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

Li, Meimei; Natesan, K; Chen, Wei-Ying

This report provides an update on the evaluation of the effect of thermal aging on tensile properties of existing laboratory-sized heats of Alloy 709 austenitic stainless steel and the completion of effort on the thermal aging effect on the tensile properties of optimized G92 ferritic-martensitic steel. The report is a Level 3 deliverable in FY17 (M3AT-17AN1602081), under the Work Package AT-17AN160208, “Advanced Alloy Testing - ANL” performed by the Argonne National Laboratory (ANL), as part of the Advanced Reactor Technologies Program.

Mortality Measurement at Advanced Ages: A Study of the Social Security Administration Death Master File

PubMed Central

Gavrilov, Leonid A.; Gavrilova, Natalia S.

2011-01-01

Accurate estimates of mortality at advanced ages are essential to improving forecasts of mortality and the population size of the oldest old age group. However, estimation of hazard rates at extremely old ages poses serious challenges to researchers: (1) The observed mortality deceleration may be at least partially an artifact of mixing different birth cohorts with different mortality (heterogeneity effect); (2) standard assumptions of hazard rate estimates may be invalid when risk of death is extremely high at old ages and (3) ages of very old people may be exaggerated. One way of obtaining estimates of mortality at extreme ages is to pool together international records of persons surviving to extreme ages with subsequent efforts of strict age validation. This approach helps researchers to resolve the third of the above-mentioned problems but does not resolve the first two problems because of inevitable data heterogeneity when data for people belonging to different birth cohorts and countries are pooled together. In this paper we propose an alternative approach, which gives an opportunity to resolve the first two problems by compiling data for more homogeneous single-year birth cohorts with hazard rates measured at narrow (monthly) age intervals. Possible ways of resolving the third problem of hazard rate estimation are elaborated. This approach is based on data from the Social Security Administration Death Master File (DMF). Some birth cohorts covered by DMF could be studied by the method of extinct generations. Availability of month of birth and month of death information provides a unique opportunity to obtain hazard rate estimates for every month of age. Study of several single-year extinct birth cohorts shows that mortality trajectory at advanced ages follows the Gompertz law up to the ages 102–105 years without a noticeable deceleration. Earlier reports of mortality deceleration (deviation of mortality from the Gompertz law) at ages below 100 appear to be artifacts of mixing together several birth cohorts with different mortality levels and using cross-sectional instead of cohort data. Age exaggeration and crude assumptions applied to mortality estimates at advanced ages may also contribute to mortality underestimation at very advanced ages. PMID:22308064

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.

Effects of RAGE-Specific Inhibitor FPS-ZM1 on Amyloid-β Metabolism and AGEs-Induced Inflammation and Oxidative Stress in Rat Hippocampus.

PubMed

Hong, Yan; Shen, Chao; Yin, Qingqing; Sun, Menghan; Ma, Yingjuan; Liu, Xueping

2016-05-01

An increased level of advanced glycation end products (AGEs) is observed in brains of patients with Alzheimer's disease (AD). AGEs and receptor for AGEs (RAGE) play important roles in the pathogenesis of AD. FPS-ZM1 is a high-affinity RAGE-specific blocker that inhibits amyloid-β binding to RAGE, neurological damage and inflammation in the APP(sw/0) transgenic mouse model of AD. FPS-ZM1 is not toxic to mice and can easily cross the blood-brain barrier. In this study, an AGEs-RAGE-activated rat model were established by intrahippocampal injection of AGEs, then these rats were treated with intraperitoneal administration of FPS-ZM1 and the possible neuroprotective effects were investigated. We found that AGEs administration induced an-regulation of Abeta production, inflammation, and oxidative stress, and an increased escape latency of rats in the Morris water maze test, all of these are significantly reduced by FPS-ZM1 treatment. Our results suggest that the AGEs-RAGE pathway is responsible for cognitive deficits, and therefore may be a potential treatment target. FPS-ZM1 might be a novel therapeutic agent to treat AD patients.

Anti-glycation activities of phenolic constituents from Silybum marianum (Milk Thistle) flower in vitro and on human explants.

PubMed

Shin, Seoungwoo; Lee, Jung-A; Kim, Minkyung; Kum, Hyunwoo; Jung, Eunsun; Park, Deokhoon

2015-02-19

Glycation is an ageing reaction of naturally occurring sugars with dermal proteins, with clinical signs appearing in vivo around age 30, and increasing steadily/regularly with age. The suppleness of the dermis is affected by the formation of bridges between proteins and sugars (Maillard's reaction). The accumulation of advanced glycation end products (AGEs) in skin plays a very important role in skin ageing. Therefore, natural compounds or extracts that possess antiglycation activities may have great anti-ageing potential. In the present study, Silybum marianum flower extract (SMFE) was demonstrated to possess antiglycation activity. We found that SMFE inhibits glycation reaction between BSA and glucose. In addition, antiglycation activity of SMFE was confirmed in a human skin explants model. SMFE reduced Nε-(carboxymethyl) lysine (CML) expression, whereas SMFE stimulated fibrillin-1 expression compared to treatment with methyglyoxal. An active ingredient contributing to the observed activities was identified as silibinin. The antiglycation activity of silibinin was dose-dependent. The beneficial effects of silibinin may be applied to prevention or management of AGE-mediated pathologies, targeting in a pleiotropic and complementary way the biochemical and cellular bases of skin aging.

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

Reducing age of autism diagnosis: developmental social neuroscience meets public health challenge

PubMed Central

Klin, Ami; Klaiman, Cheryl; Jones, Warren

2015-01-01

Summary Autism spectrum disorder (autism) is a highly prevalent and heterogeneous family of neurodevelopmental disorders of genetic origins with potentially devastating implications for child, family, health and educational systems. Despite advances in paper-and-pencil screening and in standardization of diagnostic procedures, diagnosis of autism in the US still hovers around the ages of four or five years, later still in disadvantaged communities, and several years after the age of two to three years when the condition can be reliably diagnosed by expert clinicians. As early detection and treatment are two of the most important factors optimizing outcome, and given that diagnosis is typically a necessary condition for families to have access to early treatment, reducing age of diagnosis has become one of the greatest priorities of the field. Recent advances in developmental social neuroscience promise the advent of cost-effective and community-viable, performance-based procedures, and suggest a complementary method for promoting universal screening and much greater access to the diagnosis process. Small but critical studies have already reported on experiments that differentiate groups of children at risk for autism from controls, and at least one study so far could predict diagnostic classification and level of disability on the basis of a brief experiment. Although the road to translating such procedures into effective devices for screening diagnosis is still a long one, and premature claims should be avoided, this effort could be critical in addressing this worldwide public health challenge. PMID:25726820

Regional mid-Pleistocene glaciation in central Patagonia

NASA Astrophysics Data System (ADS)

Hein, Andrew S.; Cogez, Antoine; Darvill, Christopher M.; Mendelova, Monika; Kaplan, Michael R.; Herman, Frédéric; Dunai, Tibor J.; Norton, Kevin; Xu, Sheng; Christl, Marcus; Rodés, Ángel

2017-05-01

Southern South America contains a glacial geomorphological record that spans the past million years and has the potential to provide palaeoclimate information for several glacial periods in Earth's history. In central Patagonia, two major outlet glaciers of the former Patagonian Ice Sheet carved deep basins ∼50 km wide and extending over 100 km into the Andean plain east of the mountain front. A succession of nested glacial moraines offers the possibility of determining when the ice lobes advanced and whether such advances occurred synchronously. The existing chronology, which was obtained using different methods in each valley, indicates the penultimate moraines differ in age by a full glacial cycle. Here, we test this hypothesis further using a uniform methodology that combines cosmogenic nuclide ages from moraine boulders, moraine cobbles and outwash cobbles. 10Be concentrations in eighteen outwash cobbles from the Moreno outwash terrace in the Lago Buenos Aires valley yield surface exposure ages of 169-269 ka. We find 10Be inheritance is low and therefore use the oldest surface cobbles to date the deposit at 260-270 ka, which is indistinguishable from the age obtained in the neighbouring Lago Pueyrredón valley. This suggests a regionally significant glaciation during Marine Isotope Stage 8, and broad interhemispheric synchrony of glacial maxima during the mid to late Pleistocene. Finally, we find the dated outwash terrace is 70-100 ka older than the associated moraines. On the basis of geomorphological observations, we suggest this difference can be explained by exhumation of moraine boulders.

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.

Cytomegalovirus (CMV) research in immune senescence comes of age: overview of the 6th International Workshop on CMV and Immunosenescence.

PubMed

Nikolich-Žugich, Janko; van Lier, René A W

2017-06-01

Cytomegalovirus (CMV) is one of the most complex and most ubiquitous latent persistent viruses, with a considerable ability to evade and manipulate the immune system. Following an early-life infection, most immunocompetent humans spend several decades living with CMV, and, because the virus in these hosts does not cause manifest disease, CMV can be considered part of normal aging for more than half of humanity. However, there is accumulating evidence that CMV carriage is not a null event and that both potentially harmful and potentially beneficial outcomes emanate from the interaction of CMV with its mammalian hosts. This article provides an overview of the 6th International Workshop on CMV and Immunosenescence, highlighting the advances in the field made in the past two years, as related to CMV epidemiology/geroscience, CMV virology with an accent on latency, and CMV immune evasion and immune recognition of the virus and its antigens.

Science and technology integration for increased human potential and societal outcomes.

PubMed

Roco, Mihail C

2004-05-01

Unifying science based on the material unity of nature at the nanoscale provides a new foundation for knowledge, innovation, and integration of technology. Revolutionary and synergistic advances at the interfaces between previously separated fields of science, engineering and areas of relevance are ready to create nano-bio-info-cogno (NBIC) transforming tools. Developments in systems approach, mathematics, and computation in conjunction with NBIC allow us to understand the natural world and scientific research as closely coupled, complex, hierarchical entities. At this unique moment of scientific and technical achievement, improvement of human performance at individual and group levels, as well as development of suitable revolutionary products, becomes possible and these are primary goals for converging new technologies. NBIC addresses long-term advances in key areas of human activity, including working, learning, aging, group interaction, organizations, and human evolution ((Roco and Bainbridge, 2003)). Fundamentally new tools, technologies, and products will be integrated into individual and social human architecture. This introductory chapter of the Annals outlines research and education trends, funding activities, and the potential of development of revolutionary products and services.

Complexity of Advanced Glycation End Products in Foods: Where Are We Now?

PubMed

Zhu, Yingdong; Snooks, Hunter; Sang, Shengmin

2018-02-14

Recent clinical trials indicate that consumption of dietary advanced glycation end products (AGEs) may promote the development of major chronic diseases. However, the outcomes of human studies have proven inconclusive as a result of estimates of the total AGE intake being taken with a single AGE in most of the studies. In this perspective, we summarized the major types of AGEs derived from proteins, nucleic acids, and phospholipids during food processing and suggested a panel of AGEs as markers to better measure the intake of total dietary AGEs in human studies.

Advanced glycation end products increase carbohydrate responsive element binding protein expression and promote cancer cell proliferation.

PubMed

Chen, Hanbei; Wu, Lifang; Li, Yakui; Meng, Jian; Lin, Ning; Yang, Dianqiang; Zhu, Yemin; Li, Xiaoyong; Li, Minle; Xu, Ye; Wu, Yuchen; Tong, Xuemei; Su, Qing

2014-09-01

Diabetic patients have increased levels of advanced glycation end products (AGEs) and the role of AGEs in regulating cancer cell proliferation is unclear. Here, we found that treating colorectal and liver cancer cells with AGEs promoted cell proliferation. AGEs stimulated both the expression and activation of a key transcription factor called carbohydrate responsive element binding protein (ChREBP) which had been shown to promote glycolytic and anabolic activity as well as proliferation of colorectal and liver cancer cells. Using siRNAs or the antagonistic antibody for the receptor for advanced glycation end-products (RAGE) blocked AGEs-induced ChREBP expression or cell proliferation in cancer cells. Suppressing ChREBP expression severely impaired AGEs-induced cancer cell proliferation. Taken together, these results demonstrate that AGEs-RAGE signaling enhances cancer cell proliferation in which AGEs-mediated ChREBP induction plays an important role. These findings may provide new explanation for increased cancer progression in diabetic patients. Copyright © 2014. Published by Elsevier Ireland Ltd.

Advanced glycation endproducts in diabetes and diabetic complications.

PubMed

Vlassara, Helen; Striker, Gary E

2013-12-01

This review presents insights from studies of advanced glycation end products (AGEs) in humans and mice. Although the emphasis is on the effects of exogenous AGEs and the suppression of specific host defense mechanisms, AGEs are also formed intracellularly, where they may contribute to several normal intracellular functions. It is only when the overall levels of AGEs in the extracellular and the intracellular spaces exceeds the ability of the native antioxidant (and AGE) defenses that they pose a problem. Copyright © 2013 Elsevier Inc. All rights reserved.

A revised method for calculation of life expectancy tables from individual death records which provides increased accuracy at advanced ages.

PubMed

Mathisen, R W; Mazess, R B

1981-02-01

The authors present a revised method for calculating life expectancy tables for populations where individual ages at death are known or can be estimated. The conventional and revised methods are compared using data for U.S. and Hungarian males in an attempt to determine the accuracy of each method in calculating life expectancy at advanced ages. Means of correcting errors caused by age rounding, age exaggeration, and infant mortality are presented

A novel monoclonal antibody targeting carboxymethyllysine, an advanced glycation end product in atherosclerosis and pancreatic cancer.

PubMed

Wendel, Ulrika; Persson, Nina; Risinger, Christian; Bengtsson, Eva; Nodin, Björn; Danielsson, Lena; Welinder, Charlotte; Nordin Fredrikson, Gunilla; Jansson, Bo; Blixt, Ola

2018-01-01

Advanced glycation end products are formed by non-enzymatic reactions between proteins and carbohydrates, causing irreversible lysine and arginine alterations that severely affect protein structure and function. The resulting modifications induce inflammation by binding to scavenger receptors. An increase in advanced glycation end products is observed in a number of diseases e.g. atherosclerosis and cancer. Since advanced glycation end products also are present in healthy individuals, their detection and quantification are of great importance for usage as potential biomarkers. Current methods for advanced glycation end product detection are though limited and solely measure total glycation. This study describes a new epitope-mapped single chain variable fragment, D1-B2, against carboxymethyllysine, produced from a phage library that was constructed from mouse immunizations. The phage library was selected against advanced glycation end product targets using a phage display platform. Characterization of its binding pattern was performed using large synthetic glycated peptide and protein libraries displayed on microarray slides. D1-B2 showed a preference for an aspartic acid, three positions N-terminally from a carboxymethyllysine residue and also bound to a broad collection of glycated proteins. Positive immunohistochemical staining of mouse atherosclerotic plaques and of a tissue microarray of human pancreatic tumors confirmed the usability of the new scFv for advanced glycation end product detection in tissues. This study demonstrates a promising methodology for high-throughput generation of epitope-mapped monoclonal antibodies against AGE.

A novel monoclonal antibody targeting carboxymethyllysine, an advanced glycation end product in atherosclerosis and pancreatic cancer

PubMed Central

Wendel, Ulrika; Persson, Nina; Risinger, Christian; Bengtsson, Eva; Nodin, Björn; Danielsson, Lena; Welinder, Charlotte; Nordin Fredrikson, Gunilla

2018-01-01

Advanced glycation end products are formed by non-enzymatic reactions between proteins and carbohydrates, causing irreversible lysine and arginine alterations that severely affect protein structure and function. The resulting modifications induce inflammation by binding to scavenger receptors. An increase in advanced glycation end products is observed in a number of diseases e.g. atherosclerosis and cancer. Since advanced glycation end products also are present in healthy individuals, their detection and quantification are of great importance for usage as potential biomarkers. Current methods for advanced glycation end product detection are though limited and solely measure total glycation. This study describes a new epitope-mapped single chain variable fragment, D1-B2, against carboxymethyllysine, produced from a phage library that was constructed from mouse immunizations. The phage library was selected against advanced glycation end product targets using a phage display platform. Characterization of its binding pattern was performed using large synthetic glycated peptide and protein libraries displayed on microarray slides. D1-B2 showed a preference for an aspartic acid, three positions N-terminally from a carboxymethyllysine residue and also bound to a broad collection of glycated proteins. Positive immunohistochemical staining of mouse atherosclerotic plaques and of a tissue microarray of human pancreatic tumors confirmed the usability of the new scFv for advanced glycation end product detection in tissues. This study demonstrates a promising methodology for high-throughput generation of epitope-mapped monoclonal antibodies against AGE. PMID:29420566

Leading in a Technological Age

ERIC Educational Resources Information Center

Yadgir, Sheri A.

2011-01-01

Technology is advancing more rapidly than at any time in history since the beginning of the Industrial Revolution. In fact, experts say that the world is leaving the Industrial Age of the 20th century and entering an Information Age that will lead into the future. These advances mean that important changes are being made in all areas of life--and…

A risk score for the prediction of advanced age-related macular degeneration: Development and validation in 2 prospective cohorts

USDA-ARS?s Scientific Manuscript database

We aimed to develop an eye specific model which used readily available information to predict risk for advanced age-related macular degeneration (AMD). We used the Age-Related Eye Disease Study (AREDS) as our training dataset, which consisted of the 4,507 participants (contributing 1,185 affected v...

Personalized plasma-based medicine to treat age-related diseases.

PubMed

Anitua, Eduardo; Troya, María; Zalduendo, Mar; Orive, Gorka

2017-05-01

As social and health needs are changing, new challenges to develop innovative alternatives arise to address unmet medical needs. Personalized medicine is emerging as a promising and appealing therapeutic option. The use of patient's own plasma and platelets as therapeutics is providing new avenues in the treatment of acute and chronic tissue injuries by promoting tissue repair and regeneration. Plasma and platelet-based therapies mimic the physiological repair process by releasing autologous growth factors and creating a natural, biodegradable and transient scaffold that acts as transient matrix. This review summarizes the recent advances and challenges in the field of personalized plasma-based medicine and its potential to treat age-related diseases. Copyright © 2016. Published by Elsevier B.V.

Evidence of prostate cancer "reverse stage migration" toward more advanced disease at diagnosis: Data from the Pennsylvania Cancer Registry.

PubMed

Reese, Adam C; Wessel, Sean R; Fisher, Susan G; Mydlo, Jack H

2016-08-01

The widespread adoption of prostate-specific antigen-based prostate cancer screening caused a stage migration toward earlier stage disease at diagnosis. We investigated whether this stage migration has persisted in a contemporary analysis of a population-based statewide cancer registry. We analyzed the Pennsylvania Cancer Registry, a statewide registry of all newly diagnosed cancers. Data were collected on prostate cancers diagnosed between 1992 and 2012. We determined age-adjusted prostate cancer incidence and mortality rates, as well as the distribution of tumor stage (localized, regional, or metastatic) at diagnosis, and assessed for changes in these variables over time using joinpoint analysis. Between 1992 and 2012, 210,831 new cases of prostate cancer were diagnosed in Pennsylvania, and 33,948 men died of disease. Age-adjusted prostate cancer incidence rates, and specifically the incidence of localized disease, have decreased dramatically since 2007 to 2008. Due to the decreased diagnosis of localized disease, regional and metastatic tumors have made up a greater percentage of all prostate cancer diagnoses in recent years, despite a relatively stable incidence of these advanced stage tumors. Over the past 2 decades, age-adjusted prostate cancer incidence rates in Pennsylvania have decreased, primarily because of the decreased detection of early-stage disease. There has been a corresponding shift toward more advanced disease at diagnosis. These findings may be explained by the decreased use of prostate-specific antigen-based screening, among other factors. The 2012 United States Preventative Services Task Force recommendations against prostate cancer screening may exacerbate this concerning trend, potentially resulting in an increase in prostate cancer-specific mortality. Copyright © 2016 Elsevier Inc. All rights reserved.

Sudden cardiac death in non-dialysis chronic kidney disease patients.

PubMed

Caravaca, Francisco; Chávez, Edgar; Alvarado, Raúl; García-Pino, Guadalupe; Luna, Enrique

2016-01-01

A relatively high proportion of deaths in dialysis patients occur suddenly and unexpectedly. The incidence of sudden cardiac death (SCD) in non-dialysis advanced chronic kidney disease (CKD) stages has been less well investigated. This study aims to determine the incidence and predictors of SCD in a cohort of 1078 patients with CKD not yet on dialysis. Prospective observational cohort study, which included patients with advanced CKD not yet on dialysis (stage 4-5). The association between baseline variables and SCD was assessed using Cox and competing-risk (Fine and Grey) regression models. Demographic, clinical information, medication use, and baseline biochemical parameters of potential interest were included as covariates. During the study period (median follow-up time 12 months), 210 patients died (19%), and SCD occurred in 34 cases (16% of total deaths). All-cause mortality and SCD incidence rates were 113 (95% CI: 99-128), and 18 (95% CI: 13-26) events per 1000 patients/year, respectively. By Cox regression analysis, covariates significantly associated with SCD were: Age, comorbidity index, and treatment with antiplatelet drugs. This latter covariate showed a beneficial effect over the development of SCD. By competing-risk regression, in which the competing event was non-sudden death from any cause, only age and comorbidity index remained significantly associated with SCD. SCD is relatively common in non-dialysis advanced CKD patients. SCD was closely related to age and comorbidity, and some indirect data from this study suggest that unrecognised or undertreated cardiovascular disease may predispose to a higher risk of SCD. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Republished review: Gene therapy for ocular diseases.

PubMed

Liu, Melissa M; Tuo, Jingsheng; Chan, Chi-Chao

2011-07-01

The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.

Gene therapy for ocular diseases.

PubMed

Liu, Melissa M; Tuo, Jingsheng; Chan, Chi-Chao

2011-05-01

The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.

Age-related differences in event-related potentials for early visual processing of emotional faces.

PubMed

Hilimire, Matthew R; Mienaltowski, Andrew; Blanchard-Fields, Fredda; Corballis, Paul M

2014-07-01

With advancing age, processing resources are shifted away from negative emotional stimuli and toward positive ones. Here, we explored this 'positivity effect' using event-related potentials (ERPs). Participants identified the presence or absence of a visual probe that appeared over photographs of emotional faces. The ERPs elicited by the onsets of angry, sad, happy and neutral faces were recorded. We examined the frontocentral emotional positivity (FcEP), which is defined as a positive deflection in the waveforms elicited by emotional expressions relative to neutral faces early on in the time course of the ERP. The FcEP is thought to reflect enhanced early processing of emotional expressions. The results show that within the first 130 ms young adults show an FcEP to negative emotional expressions, whereas older adults show an FcEP to positive emotional expressions. These findings provide additional evidence that the age-related positivity effect in emotion processing can be traced to automatic processes that are evident very early in the processing of emotional facial expressions. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

17β-estradiol regulates the RNA-binding protein Nova1, which then regulates the alternative splicing of estrogen receptor β in the aging female rat brain.

PubMed

Shults, Cody L; Dingwall, Caitlin B; Kim, Chun K; Pinceti, Elena; Rao, Yathindar S; Pak, Toni R

2018-01-01

Alternative RNA splicing results in the translation of diverse protein products arising from a common nucleotide sequence. These alternative protein products are often functional and can have widely divergent actions from the canonical protein. Studies in humans and other vertebrate animals have demonstrated that alternative splicing events increase with advanced age, sometimes resulting in pathological consequences. Menopause represents a critical transition for women, where the beneficial effects of estrogens are no longer evident; therefore, factors underlying increased pathological conditions in women are confounded by the dual factors of aging and declining estrogens. Estrogen receptors (ERs) are subject to alternative splicing, the spliced variants increase following menopause, and they fail to efficiently activate estrogen-dependent signaling pathways. However, the factors that regulate the alternative splicing of ERs remain unknown. We demonstrate novel evidence supporting a potential biological feedback loop where 17β-estradiol regulates the RNA-binding protein Nova1, which, in turn, regulates the alternative splicing of ERβ. These data increase our understanding of ER alternative splicing and could have potential implications for women taking hormone replacement therapy after menopause. Copyright © 2017 Elsevier Inc. All rights reserved.

Mesenchymal stem cell-derived inflammatory fibroblasts mediate interstitial fibrosis in the aging heart.

PubMed

Trial, JoAnn; Entman, Mark L; Cieslik, Katarzyna A

2016-02-01

Pathologic fibrosis in the aging mouse heart is associated with dysregulated resident mesenchymal stem cells (MSC) arising from reduced stemness and aberrant differentiation into dysfunctional inflammatory fibroblasts. Fibroblasts derived from aging MSC secrete higher levels of 1) collagen type 1 (Col1) that directly contributes to fibrosis, 2) monocyte chemoattractant protein-1 (MCP-1) that attracts leukocytes from the blood and 3) interleukin-6 (IL-6) that facilitates transition of monocytes into myeloid fibroblasts. The transcriptional activation of these proteins is controlled via the farnesyltransferase (FTase)-Ras-Erk pathway. The intrinsic change in the MSC phenotype acquired by advanced age is specific for the heart since MSC originating from bone wall (BW-MSC) or fibroblasts derived from them were free of these defects. The potential therapeutic interventions other than clinically approved strategies based on findings presented in this review are discussed as well. This article is a part of a Special Issue entitled "Fibrosis and Myocardial Remodeling". Copyright © 2015 Elsevier Ltd. All rights reserved.

Health and aging: development of the Irish Longitudinal Study on Ageing health assessment.

PubMed

Cronin, Hilary; O'Regan, Clare; Finucane, Ciaran; Kearney, Patricia; Kenny, Rose Anne

2013-05-01

To assist researchers planning studies similar to The Irish Longitudinal Study on Ageing (TILDA), concerning the development of the health assessment component, to promote use of the archived data set, to inform researchers of the methods employed, and to complement the accompanying article on normative values. Prospective, longitudinal study of older adults. Republic of Ireland. Eight thousand five hundred four community-dwelling adults who participated in wave 1 of the TILDA study. The main areas of focus for the TILDA health assessments are neurocardiovascular instability, locomotion, and vision. The article describes the scientific rationale for the choice of assessments and seeks to determine the potential advantages of incorporating novel biomeasures and technologies in population-based studies to advance understanding of aging-related disorders. The detailed description of the physical measures will facilitate cross-national comparative research and put into context the normative values outlined in the subsequent article. © 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.

Atrial fibrillation in the elderly: the potential contribution of reactive oxygen species

PubMed Central

Schillinger, Kurt J.; Patel, Vickas V.

2012-01-01

Atrial fibrillation (AF) is the most commonly encountered cardiac arrhythmia, and is a significant source of healthcare expenditures throughout the world. It is an arrhythmia with a very clearly defined predisposition for individuals of advanced age, and this fact has led to intense study of the mechanistic links between aging and AF. By promoting oxidative damage to multiple subcellular and cellular structures, reactive oxygen species (ROS) have been shown to induce the intra- and extra-cellular changes necessary to promote the pathogenesis of AF. In addition, the generation and accumulation of ROS have been intimately linked to the cellular processes which underlie aging. This review begins with an overview of AF pathophysiology, and introduces the critical structures which, when damaged, predispose an otherwise healthy atrium to AF. The available evidence that ROS can lead to damage of these critical structures is then reviewed. Finally, the evidence linking the process of aging to the pathogenesis of AF is discussed. PMID:23341843

Glycation inhibitors extend yeast chronological lifespan by reducing advanced glycation end products and by back regulation of proteins involved in mitochondrial respiration.

PubMed

Kazi, Rubina S; Banarjee, Reema M; Deshmukh, Arati B; Patil, Gouri V; Jagadeeshaprasad, Mashanipalya G; Kulkarni, Mahesh J

2017-03-06

Advanced Glycation End products (AGEs) are implicated in aging process. Thus, reducing AGEs by using glycation inhibitors may help in attenuating the aging process. In this study using Saccharomyces cerevisiae yeast system, we show that Aminoguanidine (AMG), a well-known glycation inhibitor, decreases the AGE modification of proteins in non-calorie restriction (NR) (2% glucose) and extends chronological lifespan (CLS) similar to that of calorie restriction (CR) condition (0.5% glucose). Proteomic analysis revealed that AMG back regulates the expression of differentially expressed proteins especially those involved in mitochondrial respiration in NR condition, suggesting that it switches metabolism from fermentation to respiration, mimicking CR. AMG induced back regulation of differentially expressed proteins could be possibly due to its chemical effect or indirectly by glycation inhibition. To delineate this, Metformin (MET), a structural analog of AMG and a mild glycation inhibitor and Hydralazine (HYD), another potent glycation inhibitor but not structural analog of AMG were used. HYD was more effective than MET in mimicking AMG suggesting that glycation inhibition was responsible for restoration of differentially expressed proteins. Thus glycation inhibitors particularly AMG, HYD and MET extend yeast CLS by reducing AGEs, modulating the expression of proteins involved in mitochondrial respiration and possibly by scavenging glucose. This study reports the role of glycation in aging process. In the non-caloric restriction condition, carbohydrates such as glucose promote protein glycation and reduce CLS. While, the inhibitors of glycation such as AMG, HYD, MET mimic the caloric restriction condition by back regulating deregulated proteins involved in mitochondrial respiration which could facilitate shift of metabolism from fermentation to respiration and extend yeast CLS. These findings suggest that glycation inhibitors can be potential molecules that can be used in management of aging. Copyright © 2017 Elsevier B.V. All rights reserved.

Managing Breast Cancer in the Older Patient

PubMed Central

O’Connor, Tracey; Shinde, Arvind; Doan, Caroline; Katheria, Vani; Hurria, Arti

2013-01-01

Breast cancer is a disease associated with aging, with almost one-half of all new breast cancer cases diagnosed annually in the United States occurring in women age 65 and older. Recent data suggest that although breast cancer outcomes in younger women have shown substantial improvement as a result of advances in treatment and screening, the benefits in older women have been less pronounced. Although older adults have been under-represented on cancer clinical trials there is an emerging body of literature to help guide treatment decisions. For early stage breast cancer, the discussion regarding treatment options involves balancing the reduction in risk of recurrence gained by specific therapies with the potential for increased treatment-related toxicity potentially exacerbated by physiological decline or comorbidities that often co-exist in the older population. A key component of care of the older adult is the recognition that chronologic age alone cannot guide the management of an older individual with breast cancer; rather, treatment decisions must also take into account an individual’s functional status, estimated life expectancy, the risks and benefits of the therapy, potential barriers to treatment, and patient preference. This article reviews the available evidence for therapeutic management of early-stage breast cancer in older adults, and highlights data from geriatric oncology literature that provides a basis on which to facilitate evidence-based treatment. PMID:24472802

State of Health and Quality of Life of Women at Advanced Age

PubMed Central

Pinkas, Jarosław; Gujski, Mariusz; Humeniuk, Ewa; Raczkiewicz, Dorota; Bejga, Przemysław; Owoc, Alfred; Bojar, Iwona

2016-01-01

Background Evaluation of the state of health, quality of life, and the relationship between the level of the quality of life and health status in a group of women at an advanced age (90 years of age and older) in Poland. Material/Methods The study was conducted in 2014 in an all-Polish sample of 870 women aged 90 years and older. The research instruments were: the authors’ questionnaire and several standardized tests: Katz Index of Independence in Activities of Daily Living (Katz ADL), Abbreviated Mental Test Score (AMTS), and the World Health Organization Quality of Life (WHOQOL)-BREF. The results of the study were statistically analyzed using significant t-test for mean and regression analysis. Results The majority of women at an advanced age suffered from chronic pain (76%) and major geriatric problems such as hypoacusis (81%), visual disturbances (69%) and urinary incontinence (60%); the minority of women at an advanced age suffered from falls and fainting (39%), stool incontinence (17%), severe functional impairment (24%), and cognitive impairment (10%). On a scale of 1 to 5, women at an advanced age assessed positively for overall quality of life (mean 3.3), social relationships (3.5), and environment (3.2), but negatively for general health, physical health, and psychological health (2.7, 2.7, and 2.8, respectively). The presence of chronic pain and geriatric problems, including urinary and stool incontinences, falls and faint ing, visual disturbances and hypoacusis, significantly decreased overall quality of life; general health, physical health, psychological health, social relationships, and environment. Overall quality of life, general health, physical health, psychological health, social relationships, and environment was correlated with functional and cognitive impairments. Conclusions Quality of life of women at an advanced age decreased if chronic pain, major geriatric problems, or functional or cognitive impairments occurred. PMID:27580565

Influence of aging on the activity of mice Sca-1+CD31- cardiac stem cells.

PubMed

Wu, Qiong; Zhan, Jinxi; Pu, Shiming; Qin, Liu; Li, Yun; Zhou, Zuping

2017-01-03

Therapeutic application of cardiac resident stem/progenitor cells (CSC/CPCs) is limited due to decline of their regenerative potential with donor age. A variety of studies have shown that the cardiac aging was the problem of the stem cells, but little is known about the impact of age on the subgroups CSC/CPCs, the relationship between subgroups CSC/CPCs ageing and age-related dysfunction. Here, we studied Sca-1+CD31- subgroups of CSCs from younger(2~3months) and older(22~24months) age mice, biological differentiation was realized using specific mediums for 14 days to induce cardiomyocyte, smooth muscle cells or endothelial cells and immunostain analysis of differentiated cell resulting were done. Proliferation and cell cycle were measured by flow cytometry assay, then used microarray to dissect variability from younger and older mice. Although the number of CSCs was higher in older mice, the advanced age significantly reduced the differentiation ability into cardiac cell lineages and the proliferation ability. Transcriptional changes in Sca-1+CD31- subgroups of CSCs during aging are related to Vitamin B6 metabolism, circadian rhythm, Tyrosine metabolism, Complement and coagulation cascades. Taking together these results indicate that Cardiac resident stem/progenitor cells have significant differences in their proliferative, pluripotency and gene profiles and those differences are age depending.

Serum Levels of Toxic AGEs (TAGE) May Be a Promising Novel Biomarker for the Onset/Progression of Lifestyle-Related Diseases.

PubMed

Takeuchi, Masayoshi

2016-06-07

Advanced glycation end-products (AGEs) generated with aging or in the presence of diabetes mellitus, particularly AGEs derived from the glucose/fructose metabolism intermediate glyceraldehyde (Glycer-AGEs; termed toxic AGEs (TAGE)), were recently shown to be closely involved in the onset/progression of diabetic vascular complications via the receptor for AGEs (RAGE). TAGE also contribute to various diseases, such as cardiovascular disease; nonalcoholic steatohepatitis; cancer; Alzheimer's disease, and; infertility. This suggests the necessity of minimizing the influence of the TAGE-RAGE axis in order to prevent the onset/progression of lifestyle-related diseases (LSRD) and establish therapeutic strategies. Changes in serum TAGE levels are closely associated with LSRD related to overeating, a lack of exercise, or excessive ingestion of sugars/dietary AGEs. We also showed that serum TAGE levels, but not those of hemoglobin A1c, glucose-derived AGEs, or Nε-(carboxymethyl)lysine, have potential as a biomarker for predicting the progression of atherosclerosis and future cardiovascular events. We herein introduce the usefulness of serum TAGE levels as a biomarker for the prevention/early diagnosis of LSRD and the evaluation of the efficacy of treatments; we discuss whether dietary AGE/sugar intake restrictions reduce the generation/accumulation of TAGE, thereby preventing the onset/progression of LSRD.

Serum Levels of Toxic AGEs (TAGE) May Be a Promising Novel Biomarker for the Onset/Progression of Lifestyle-Related Diseases

PubMed Central

Takeuchi, Masayoshi

2016-01-01

Advanced glycation end-products (AGEs) generated with aging or in the presence of diabetes mellitus, particularly AGEs derived from the glucose/fructose metabolism intermediate glyceraldehyde (Glycer-AGEs; termed toxic AGEs (TAGE)), were recently shown to be closely involved in the onset/progression of diabetic vascular complications via the receptor for AGEs (RAGE). TAGE also contribute to various diseases, such as cardiovascular disease; nonalcoholic steatohepatitis; cancer; Alzheimer’s disease, and; infertility. This suggests the necessity of minimizing the influence of the TAGE-RAGE axis in order to prevent the onset/progression of lifestyle-related diseases (LSRD) and establish therapeutic strategies. Changes in serum TAGE levels are closely associated with LSRD related to overeating, a lack of exercise, or excessive ingestion of sugars/dietary AGEs. We also showed that serum TAGE levels, but not those of hemoglobin A1c, glucose-derived AGEs, or Nε-(carboxymethyl)lysine, have potential as a biomarker for predicting the progression of atherosclerosis and future cardiovascular events. We herein introduce the usefulness of serum TAGE levels as a biomarker for the prevention/early diagnosis of LSRD and the evaluation of the efficacy of treatments; we discuss whether dietary AGE/sugar intake restrictions reduce the generation/accumulation of TAGE, thereby preventing the onset/progression of LSRD. PMID:27338481

Understanding the link between sexual selection, sexual conflict and aging using crickets as a model.

PubMed

Archer, C Ruth; Hunt, John

2015-11-01

Aging evolved because the strength of natural selection declines over the lifetime of most organisms. Weak natural selection late in life allows the accumulation of deleterious mutations and may favor alleles that have positive effects on fitness early in life, but costly pleiotropic effects expressed later on. While this decline in natural selection is central to longstanding evolutionary explanations for aging, a role for sexual selection and sexual conflict in the evolution of lifespan and aging has only been identified recently. Testing how sexual selection and sexual conflict affect lifespan and aging is challenging as it requires quantifying male age-dependent reproductive success. This is difficult in the invertebrate model organisms traditionally used in aging research. Research using crickets (Orthoptera: Gryllidae), where reproductive investment can be easily measured in both sexes, has offered exciting and novel insights into how sexual selection and sexual conflict affect the evolution of aging, both in the laboratory and in the wild. Here we discuss how sexual selection and sexual conflict can be integrated alongside evolutionary and mechanistic theories of aging using crickets as a model. We then highlight the potential for research using crickets to further advance our understanding of lifespan and aging. Copyright © 2015 Elsevier Inc. All rights reserved.

Bioactive natural products from novel microbial sources.

PubMed

Challinor, Victoria L; Bode, Helge B

2015-09-01

Despite the importance of microbial natural products for human health, only a few bacterial genera have been mined for the new natural products needed to overcome the urgent threat of antibiotic resistance. This is surprising, given that genome sequencing projects have revealed that the capability to produce natural products is not a rare feature among bacteria. Even the bacteria occurring in the human microbiome produce potent antibiotics, and thus potentially are an untapped resource for novel compounds, potentially with new activities. This review highlights examples of bacteria that should be considered new sources of natural products, including anaerobes, pathogens, and symbionts of humans, insects, and nematodes. Exploitation of these producer strains, combined with advances in modern natural product research methodology, has the potential to open the way for a new golden age of microbial therapeutics. © 2015 New York Academy of Sciences.

Sulforaphane inhibits advanced glycation end product-induced pericyte damage by reducing expression of receptor for advanced glycation end products.

PubMed

Maeda, Sayaka; Matsui, Takanori; Ojima, Ayako; Takeuchi, Masayoshi; Yamagishi, Sho-Ichi

2014-09-01

Advanced glycation end products (AGEs) not only inhibit DNA synthesis but also play a role in diabetic retinopathy by evoking apoptosis and inflammation in retinal pericytes via interaction with a receptor for AGE (RAGE). Similarly, sulforaphane, which is a naturally occurring isothiocyanate that is found in widely consumed cruciferous vegetables, protects against oxidative stress-induced tissue damage. Therefore, we hypothesized that sulforaphane could inhibit AGE-induced pericytes injury through its antioxidative properties. Advanced glycation end product stimulated superoxide generation as well as RAGE gene and protein expression in bovine-cultured retinal pericytes, and these effects were prevented by the treatment with sulforaphane. Antibodies directed against RAGE also blocked AGE-evoked reactive oxygen species generation in pericytes. Sulforaphane and antibodies directed against RAGE significantly inhibited the AGE-induced decrease in DNA synthesis, apoptotic cell death, and up-regulation of monocyte chemoattractant protein 1 messenger RNA levels in pericytes. For the first time, the present study demonstrates that sulforaphane could inhibit DNA synthesis, apoptotic cell death, and inflammatory reactions in AGE-exposed pericytes, partly by suppressing RAGE expression via its antioxidative properties. Blockade of the AGE-RAGE axis in pericytes by sulforaphane might be a novel therapeutic target for the treatment of diabetic retinopathy. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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

Embracing a Revolution - Telemedicine.

PubMed

Dheer, Ajay; Chaturvedi, R K

2005-01-01

The recent advances in information and communication technologies offer real and practical opportunities to health professionals to share expertise and resources in health care over distances. For a country like India with pockets of medical excellence surrounded by a vast number of badly equipped hospitals with limited specialists, telemedicine could revolutionize health care. The potential of telemedicine seem to be vital in avoiding the frame of travel, in timely getting specialist advise to remote areas, minimizing the cost and of course an opportunity to learn from each other. In developed countries the technological advancement and research aims primarily to satiate the needs of their armed forces and to ensure tactical and technical supremacy. The medical community in the Indian Armed Forces should harness the technologies and embrace this revolution of the information age to provide world class combat casualty care.

Advanced Glycation End-products and Bone Fractures.

PubMed

Vashishth, Deepak

2009-08-01

Bone does not turn over uniformly, and becomes susceptible to post-translational modification by non-enzymatic glycation (NEG). NEG of bone causes the formation of advanced glycation end-products (AGEs) and this process is accelerated with aging, diabetes and antiresorptive postmenopausal osteoporosis therapy. Due to the elevated incidence of fracture associated with aging and diabetes, several studies have attempted to measure and evaluate AGEs as biomarkers for fracture risk. Here current methods of estimating AGEs in bone by liquid chromatography and fluorometric assay are summarized and the relationships between AGEs and fracture properties at whole bone, apparent tissue and matrix levels are discussed.

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.

Age-dependent phenotypic characteristics of a triple transgenic mouse model of Alzheimer disease.

PubMed

Pietropaolo, Susanna; Feldon, Joram; Yee, Benjamin K

2008-08-01

The triple-transgenic mouse line (3 x Tg-AD) harboring PS1M146V, APPSwe, and taup301L transgenes represents the only transgenic model for Alzheimer's disease (AD) to date capturing both beta-amyloid and tau neuropathology. The present study provides an extensive behavioral characterization of the 3 x Tg-AD mouse line, evaluating the emergence of noncognitive and cognitive AD-like symptoms at two ages corresponding to the early (6-7 months) and advanced (12-13 months) stages of AD-pathology. Enhanced responsiveness to aversive stimulation was detected in mutant mice at both ages: the 3 x Tg-AD genotype enhanced acoustic startle response and facilitated performance in the cued-version of the water maze. These noncognitive phenotypes were accompanied by hyperactivity and reduced locomotor habituation in the open field at the older age. Signs of cognitive aberrations were also detected at both ages, but they were limited to associative learning. The present study suggests that this popular transgenic mouse model of AD has clear phenotypes beyond the cognitive domain, and their potential relationship to the cognitive phenotypes should be further explored.

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

Role of advanced glycation end products in cellular signaling☆

PubMed Central

Ott, Christiane; Jacobs, Kathleen; Haucke, Elisa; Navarrete Santos, Anne; Grune, Tilman; Simm, Andreas

2014-01-01

Improvements in health care and lifestyle have led to an elevated lifespan and increased focus on age-associated diseases, such as neurodegeneration, cardiovascular disease, frailty and arteriosclerosis. In all these chronic diseases protein, lipid or nucleic acid modifications are involved, including cross-linked and non-degradable aggregates, such as advanced glycation end products (AGEs). Formation of endogenous or uptake of dietary AGEs can lead to further protein modifications and activation of several inflammatory signaling pathways. This review will give an overview of the most prominent AGE-mediated signaling cascades, AGE receptor interactions, prevention of AGE formation and the impact of AGEs during pathophysiological processes. PMID:24624331

Drugs of abuse that mediate advanced glycation end product formation: a chemical link to disease pathology.

PubMed

Treweek, Jennifer B; Dickerson, Tobin J; Janda, Kim D

2009-05-19

Nicotine and methamphetamine are frequently abused in modern society, despite the increasing evidence of their addictive, neuropharmacological, and toxic effects. Tobacco, the most widely abused substance, is the leading cause of preventable death in the United States, killing nearly half a million Americans annually. A methamphetamine epidemic has also spread during the past decade; severe neurotoxicity and addictiveness contribute to the drug's notoriety. Although the majority of research on these two drugs is of pharmacological and neurobiological motivation, further study of these molecules from a chemical perspective may provide novel mechanistic insight into either their addictive potential or their pathological effects. For example, nicotine and methamphetamine share a common structural feature, a secondary amine, suggesting that these molecules could possess similar (or analogous) in vivo reactivity. Discoveries concerning the synthetic requirements for aqueous aldol catalysis and the feasibility of the enamine mechanism under physiological conditions have given rise to the hypothesis that ingested molecules, such as abused drugs, could participate in reactions utilizing an enamine intermediate in vivo. The chemical reactivity of exogenous drugs with amine functionalities was initially examined in the context of the Maillard reaction, or nonenzymatic browning. The heating of reducing sugars with amino acids yields a brown solution; studies of this reaction were originally applied to food chemistry for the production of distinct flavors and aromas. Further research has since revealed numerous instances in which the in vivo production of advanced glycation end products (AGEs) through the Maillard reaction contribute to the pathology of disease states. Specifically, the modification of long-lived proteins by glycation and glycoxidation and the accumulation of these AGEs compromise the original function of such proteins and change the mechanical properties of affected tissue. In this Account, we summarize our investigations into the capacity for exogenous compounds to initiate the Maillard reaction and the corresponding physiological and immunological impact of the drug-conjugated AGEs that form. Many of the pathological components of diabetes, atherosclerosis, cancer, macular degeneration, Alzheimer's disease, and even the normal aging process are attributable to AGEs and their potential for aggregate formation in the vasculature. A deeper understanding of AGEs, and particularly glycated proteins, will provide fundamental mechanistic insight into disease origins.

Higher Estimated Net Endogenous Acid Production May Be Associated with Increased Prevalence of Nonalcoholic Fatty Liver Disease in Chinese Adults in Hong Kong

PubMed Central

Chan, Ruth; Wong, Vincent Wai-Sun; Chu, Winnie Chiu-Wing; Wong, Grace Lai-Hung; Li, Liz Sin; Leung, Jason; Chim, Angel Mei-Ling; Yeung, David Ka-Wai; Sea, Mandy Man-Mei; Woo, Jean; Chan, Francis Ka-Leung; Chan, Henry Lik-Yuen

2015-01-01

Nonalcoholic fatty liver disease (NAFLD) has been associated with reduced growth hormone levels and signaling. Such hormonal changes also occur in metabolic acidosis. Since mild metabolic acidosis can be diet induced, diet-induced acid load may constitute a nutritional factor with possible influence on NAFLD development. This study explored whether a higher diet-induced acid load is associated with an increased likelihood of NAFLD. Apparently healthy Chinese adults (330 male, 463 female) aged 19-72 years were recruited through population screening between 2008 and 2010 in a cross-sectional population-based study in Hong Kong. Estimated net endogenous acid production (NEAP) was calculated using Frassetto’s method and potential renal acid load (PRAL) was calculated using Remer’s method based on dietary data from a food frequency questionnaire. NAFLD was defined as intrahepatic triglyceride content at >5% by proton-magnetic resonance spectroscopy. Possible advanced fibrosis was defined as liver stiffness at >7.9 kPa by transient elastography. Multivariate logistic regression models were used to examine the association between each measure of dietary acid load and prevalent NAFLD or possible advanced fibrosis with adjustment for potential anthropometric and lifestyle factors. 220 subjects (27.7%) were diagnosed with NAFLD. Estimated NEAP was positively associated with the likelihood of having NAFLD after adjustment for age, sex, body mass index, current drinker status and the presence of metabolic syndrome [OR (95% CI) = 1.25 (1.02-1.52), p = 0.022]. The association was slightly attenuated but remained significant when the model was further adjusted for other dietary variables. No association between PRAL and NAFLD prevalence was observed. Both estimated NEAP and PRAL were not associated with the presence of possible advance fibrosis. Our findings suggest that there may be a modest association between diet-induced acid load and NAFLD. More studies are needed to ascertain the link between diet-induced acid load and NAFLD and to investigate the underlying mechanisms. PMID:25905490

'Healthy Ageing' policies and anti-ageing ideologies and practices: on the exercise of responsibility.

PubMed

Cardona, Beatriz

2008-12-01

This paper explores how the exercise of the ethics of 'responsibility' for health care advanced through 'healthy ageing' and 'successful ageing' narratives in Western countries animates an array of 'authorities', including the 'anti-ageing medicine' movement as a strategy to address the anxieties of growing old in Western societies and as a tool to exercise the ethos of 'responsibility'. The choice of this type of authority as a source of guidance for self-constitution and the exercise of the 'responsible self', this paper will argue, enables the enactment of a type of late modernity notion of citizenship for ageing individuals based on principles of agelessness, health, independence and consumption power. Through interviews with anti-ageing consumers, however, it is also possible to argue the existence of tensions and contradictions that such a rigid model of self-constitution in later life produces, and the potential forms of resistance and contestations that may emerge as a result. In this way the current 'war on anti-ageing medicine' (Vincent 2003) becomes also symptomatic of bigger 'wars' taking place not only between institutions competing for control over knowledge and management of ageing, but between those in favour and against the homogenisation of life under the language of universal science, reason and market rationality.

Influence of paternal age on perinatal outcomes.

PubMed

Hurley, Emily G; DeFranco, Emily A

2017-11-01

There is an increasing trend to delay childbearing to advanced parental age. Increased risks of advanced maternal age and assisted reproductive technologies are widely accepted. There are limited data regarding advanced paternal age. To adequately counsel patients on risk, more research regarding advanced paternal age is necessary. We sought to determine the influence of paternal age on perinatal outcomes, and to assess whether this influence differs between pregnancies achieved spontaneously and those achieved with assisted reproductive technology. A population-based retrospective cohort study of all live births in Ohio from 2006 through 2012 was completed. Data were evaluated to determine if advanced paternal age is associated with an increased risk of adverse outcomes in pregnancies. The analysis was stratified by status of utilization of assisted reproductive technology. Generalized linear regression models assessed the association of paternal age on pregnancy complications in assisted reproductive technology and spontaneously conceived pregnancies, after adjusting for maternal age, race, multifetal gestation, and Medicaid status, using Stata software (Stata, Release 12; StataCorp, College Station, TX). Paternal age was documented in 82.2% of 1,034,552 live births in Ohio during the 7-year study period. Paternal age ranged from 12-87 years, with a median of 30 (interquartile range, 26-35) years. Maternal age ranged from 11-62 years, with a median of 27 (interquartile range, 22-31) years. The use of assisted reproductive technology in live births increased as paternal age increased: 0.1% <30 years vs 2.5% >60 years, P < .001. After accounting for maternal age and other confounding risk factors, increased paternal age was not associated with a significant increase in the rate of preeclampsia, preterm birth, fetal growth restriction, congenital anomaly, genetic disorder, or neonatal intensive care unit admission. The influence of paternal age on pregnancy outcomes was similar in pregnancies achieved with and without assisted reproductive technology. Older paternal age does not appear to pose an independent risk of adverse perinatal outcomes, in pregnancies achieved either with or without assisted reproductive technology. However, small effect sizes such as very small risk increases or decreases may not be detectable despite the large sample size in this study of >830,000 births. Copyright © 2017 Elsevier Inc. All rights reserved.

Epidemiology, Pathophysiology, and Natural History of Pulmonary Embolism.

PubMed

Turetz, Meredith; Sideris, Andrew T; Friedman, Oren A; Triphathi, Nidhi; Horowitz, James M

2018-06-01

Pulmonary embolism (PE) is a common and potentially deadly form of venous thromboembolic disease. It is the third most common cause of cardiovascular death and is associated with multiple inherited and acquired risk factors as well as advanced age. The prognosis from PE depends on the degree of obstruction and hemodynamic effects of PE and understanding the pathophysiology helps in risk-stratifying patients and determining treatment. Though the natural history of thrombus is resolution, a subset of patients have chronic residual thrombus, contributing to the post-PE syndrome.

Creating Age Asymmetry: Consequences of Inheriting Damaged Goods in Mammalian Cells.

PubMed

Moore, Darcie L; Jessberger, Sebastian

2017-01-01

Accumulating evidence suggests that mammalian cells asymmetrically segregate cellular components ranging from genomic DNA to organelles and damaged proteins during cell division. Asymmetric inheritance upon mammalian cell division may be specifically important to ensure cellular fitness and propagate cellular potency to individual progeny, for example in the context of somatic stem cell division. We review here recent advances in the field and discuss potential effects and underlying mechanisms that mediate asymmetric segregation of cellular components during mammalian cell division. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Nutrition, Aging, and Memory in Elders (NAME) study: design and methods for a study of micronutrients and cognitive function in a homebound elderly population.

PubMed

Scott, Tammy M; Peter, Inga; Tucker, Katherine L; Arsenault, Lisa; Bergethon, Peter; Bhadelia, Rafeeque; Buell, Jennifer; Collins, Lauren; Dashe, John F; Griffith, John; Hibberd, Patricia; Leins, Drew; Liu, Timothy; Ordovas, Jose M; Patz, Samuel; Price, Lori Lyn; Qiu, Wei Qiao; Sarnak, Mark; Selhub, Jacob; Smaldone, Lauren; Wagner, Carey; Wang, Lixia; Weiner, Daniel; Yee, Jacqueline; Rosenberg, Irwin; Folstein, Marshal

2006-06-01

Micronutrient status can affect cognitive function in the elderly; however, there is much to learn about the precise effects. Understanding mediating factors by which micronutrient status affects cognitive function would contribute to elders' quality of life and their ability to remain in the home. The Nutrition, Aging, and Memory in Elders (NAME) Study is designed to advance the current level of knowledge by investigating potential mediating factors by which micronutrient status contributes to cognitive impairment and central nervous system abnormalities in the elderly. NAME targets homebound elders because they are understudied and particularly at risk for poor nutritional status. Subjects are community-based elders aged 60 and older, recruited through area Aging Services Access Points. The NAME core data include demographics; neuropsychological testing and activities of daily living measures; food frequency, health and behavioral questionnaires; anthropometrics; gene status; plasma micronutrients, homocysteine, and other blood determinants. A neurological examination, psychiatric examination, and brain MRI and volumetric measurements are obtained from a sub-sample. Preliminary data from first 300 subjects are reported. These data show that the NAME protocol is feasible and that the enrolled subjects are racially diverse, at-risk, and had similar basic demographics to the population from which they were drawn. The goal of the NAME study is to evaluate novel relationships between nutritional factors and cognitive impairment. These data may provide important information on potential new therapeutic strategies and supplementation standards for the elderly to maintain cognitive function and potentially reduce the public health costs of dementia.

Acute myeloid leukemia targets for bispecific antibodies

PubMed Central

Hoseini, S S; Cheung, N K

2017-01-01

Despite substantial gains in our understanding of the genomics of acute myelogenous leukemia (AML), patient survival remains unsatisfactory especially among the older age group. T cell-based therapy of lymphoblastic leukemia is rapidly advancing; however, its application in AML is still lagging behind. Bispecific antibodies can redirect polyclonal effector cells to engage chosen targets on leukemia blasts. When the effector cells are natural-killer cells, both antibody-dependent and antibody-independent mechanisms could be exploited. When the effectors are T cells, direct tumor cytotoxicity can be engaged followed by a potential vaccination effect. In this review, we summarize the AML-associated tumor targets and the bispecific antibodies that have been studied. The potentials and limitations of each of these systems will be discussed. PMID:28157217

Advanced cogeneration research study: Executive summary

NASA Technical Reports Server (NTRS)

Bluhm, S. A.; Moore, N.; Rosenberg, L.; Slonski, M.

1983-01-01

This study provides a broad based overview of selected areas relevant to the development of a comprehensive Southern California Edison (SCE) advanced cogeneration project. The areas studied are: (1) Cogeneration potential in the SCE service territory; (2) Advanced cogeneration technologies; and (3) Existing cogeneration computer models. An estimated 3700 MW sub E could potentially be generated from existing industries in the Southern California Edison service territory using cogeneration technology. Of this total, current technology could provide 2600 MW sub E and advanced technology could provide 1100 MW sub E. The manufacturing sector (SIC Codes 20-39) was found to have the highest average potential for current cogeneration technology. The mining sector (SIC Codes 10-14) was found to have the highest potential for advanced technology.

Glacier advance during Marine Isotope Stage 11 in the McMurdo Dry Valleys of Antarctica

PubMed Central

Swanger, Kate M.; Lamp, Jennifer L.; Winckler, Gisela; Schaefer, Joerg M.; Marchant, David R.

2017-01-01

We mapped six distinct glacial moraines alongside Stocking Glacier in the McMurdo Dry Valleys, Antarctica. Stocking Glacier is one of several alpine glaciers in the Dry Valleys fringed by multiple cold-based drop moraines. To determine the age of the outermost moraine, we collected 10 boulders of Ferrar Dolerite along the crest of the moraine and analyzed mineral separates of pyroxene for cosmogenic 3He. On the basis of these measurements, the exposure age for the outermost moraine is 391 ± 35 ka. This represents the first documented advance of alpine glacier ice in the Dry Valleys during Marine Isotope Stage (MIS) 11. At this time, Stocking Glacier was ~20–30% larger than today. The cause of ice expansion is uncertain, but most likely it is related to increased atmospheric temperature and precipitation, associated with reduced ice extent in the nearby Ross Embayment. The data suggest complex local environmental response to warm climates in Antarctica and have implications for glacial response to Holocene warming. The study also demonstrates the potential for using alpine glacier chronologies in the Transantarctic Mountains as proxies for retreat of grounded glacier ice in the Ross Embayment. PMID:28139676

Risk assessment model for development of advanced age-related macular degeneration.

PubMed

Klein, Michael L; Francis, Peter J; Ferris, Frederick L; Hamon, Sara C; Clemons, Traci E

2011-12-01

To design a risk assessment model for development of advanced age-related macular degeneration (AMD) incorporating phenotypic, demographic, environmental, and genetic risk factors. We evaluated longitudinal data from 2846 participants in the Age-Related Eye Disease Study. At baseline, these individuals had all levels of AMD, ranging from none to unilateral advanced AMD (neovascular or geographic atrophy). Follow-up averaged 9.3 years. We performed a Cox proportional hazards analysis with demographic, environmental, phenotypic, and genetic covariates and constructed a risk assessment model for development of advanced AMD. Performance of the model was evaluated using the C statistic and the Brier score and externally validated in participants in the Complications of Age-Related Macular Degeneration Prevention Trial. The final model included the following independent variables: age, smoking history, family history of AMD (first-degree member), phenotype based on a modified Age-Related Eye Disease Study simple scale score, and genetic variants CFH Y402H and ARMS2 A69S. The model did well on performance measures, with very good discrimination (C statistic = 0.872) and excellent calibration and overall performance (Brier score at 5 years = 0.08). Successful external validation was performed, and a risk assessment tool was designed for use with or without the genetic component. We constructed a risk assessment model for development of advanced AMD. The model performed well on measures of discrimination, calibration, and overall performance and was successfully externally validated. This risk assessment tool is available for online use.

A population neuroscience approach to the study of cerebral small vessel disease in mid- and late-life: an Invited Review.

PubMed

Jorgensen, Dana R; Shaaban, C Elizabeth; Wiley, Clayton A; Gianaros, Peter J; Mettenburg, Joseph; Rosano, Caterina

2018-02-02

Aging in later life engenders numerous changes to the cerebral microvasculature. Such changes can remain clinically silent, but are associated with greater risk for negative health outcomes over time. Knowledge is limited about the pathogenesis, prevention, and treatment of potentially detrimental changes in the cerebral microvasculature that occur with advancing age. In this review, we summarize literature on aging of the cerebral microvasculature, and we propose a conceptual framework to fill existing research gaps and advance future work on this heterogeneous phenomenon. We propose that the major gaps in this area are attributable to an incomplete characterization of cerebrovascular pathology, the populations being studied, and the temporality of exposure to risk factors. Specifically, currently available measures of age-related cerebral microvasculature changes are indirect, primarily related to parenchymal damage rather than direct quantification of small vessel damage-limiting the understanding of cerebral small vessel disease (cSVD) itself. Moreover, studies seldom account for variability in the health-related conditions or interactions with risk factors, which are likely determinants of cSVD pathogenesis. Lastly, study designs are predominantly cross-sectional, and/or have relied on single time point measures, leaving no clear evidence of time trajectories of risk factors or of change in cerebral microvasculature. We argue that more resources should be invested in (1) developing methodological approaches and basic science models to better understand the pathogenic and etiological nature of age-related brain microvascular diseases, and (2) implementing state-of-the-science population study designs that account for the temporal evolution of cerebral microvascular changes in diverse populations across the life-span.

Impact of Oxidative Stress Biomarkers and Carboxymethyllysine (An Advanced Glycation End Product) on Prostate Cancer: A Prospective Study

PubMed Central

Yang, Shuman; Pinney, Susan M.; Mallick, Palash; Ho, Shuk-Mei; Bracken, Bruce; Wu, Tianying

2015-01-01

Introduction Biomarkers of oxidative stress and advanced glycation end products (AGE) have been linked to the development of prostate cancer, but evidence from human studies is either scarce or controversial. Materials and Methods We conducted a prospective nested case-control study among 48 men (24 prostate cancer cases and 24 controls) aged 48–76 years at baseline. The participants of our study were a part of the Fernald Community Cohort (FCC). Prostate cancer cases and controls were matched individually on age (± 3 years) with 1:1 ratio. Biomarkers included urine F2-isoprostanes (markers of lipid oxidation), plasma fluorescent oxidation products (FlOPs; markers of global oxidation) and carboxymethyllysine (CML; a major end-stage AGE). Results At baseline, cases had similar age, body mass index, proportion of family history of prostate cancer, history of benign prostatic hyperplasia, history of hypertension, history of diabetes, smokers and plasma glucose levels as compared to controls. Levels of plasma CML were significantly higher in cases than in controls (182 vs. 152 μg/ml, P < 0.05). In the conditional logistic regression model, an increase in CML equivalent to one standard deviation was associated with increased risk of incident prostate cancer (Relative risk = 1.79, 95% confidence interval = 1.00–3.21), and accounted for ~8% variance of prostate cancer liability. Urine F2-isoprostanes and plasma FlOPs were not associated with prostate cancer incidence. Conclusion Higher levels of plasma CML were associated with increased risk of prostate cancer. This suggests a potential new pathway for prostate cancer prediction and treatment. PMID:25972296

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.

Genetic polymorphisms and skin aging: the identification of population genotypic groups holds potential for personalized treatments.

PubMed

Naval, Jordi; Alonso, Vicente; Herranz, Miquel Angel

2014-01-01

Skin changes are among the most visible signs of aging. Skin properties such as hydration, elasticity, and antioxidant capacity play a key role in the skin aging process. Skin aging is a complex process influenced by heritable and environmental factors. Recent studies on twins have revealed that up to 60% of the skin aging variation between individuals can be attributed to genetic factors, while the remaining 40% is due to non-genetic factors. Recent advances in genomics and bioinformatics approaches have led to the association of certain single nucleotide polymorphisms (SNPs) to skin properties. Our aim was to classify individuals based on an ensemble of multiple polymorphisms associated with certain properties of the skin for providing personalized skin care and anti-aging therapies. We identified the key proteins and SNPs associated with certain properties of the skin that contribute to skin aging. We selected a set of 13 SNPs in gene coding for these proteins which are potentially associated with skin aging. Finally, we classified a sample of 120 female volunteers into ten clusters exhibiting different skin properties according to their genotypic signature. This is the first study that describes the actual frequency of genetic polymorphisms and their distribution in clusters involved in skin aging in a Caucasian population. Individuals can be divided into genetic clusters defined by genotypic variables. These genotypic variables are linked with polymorphisms in one or more genes associated with certain properties of the skin that contribute to a person's perceived age. Therefore, by using this classification, it is possible to characterize human skin care and anti-aging needs on the basis of an individual's genetic signature, thus opening the door to personalized treatments addressed at specific populations. This is part of an ongoing effort towards personalized anti-aging therapies combining genetic signatures with environmental and life style evaluations.

Genetic polymorphisms and skin aging: the identification of population genotypic groups holds potential for personalized treatments

PubMed Central

Naval, Jordi; Alonso, Vicente; Herranz, Miquel Angel

2014-01-01

Introduction Skin changes are among the most visible signs of aging. Skin properties such as hydration, elasticity, and antioxidant capacity play a key role in the skin aging process. Skin aging is a complex process influenced by heritable and environmental factors. Recent studies on twins have revealed that up to 60% of the skin aging variation between individuals can be attributed to genetic factors, while the remaining 40% is due to non-genetic factors. Recent advances in genomics and bioinformatics approaches have led to the association of certain single nucleotide polymorphisms (SNPs) to skin properties. Our aim was to classify individuals based on an ensemble of multiple polymorphisms associated with certain properties of the skin for providing personalized skin care and anti-aging therapies. Methods and results We identified the key proteins and SNPs associated with certain properties of the skin that contribute to skin aging. We selected a set of 13 SNPs in gene coding for these proteins which are potentially associated with skin aging. Finally, we classified a sample of 120 female volunteers into ten clusters exhibiting different skin properties according to their genotypic signature. Conclusion This is the first study that describes the actual frequency of genetic polymorphisms and their distribution in clusters involved in skin aging in a Caucasian population. Individuals can be divided into genetic clusters defined by genotypic variables. These genotypic variables are linked with polymorphisms in one or more genes associated with certain properties of the skin that contribute to a person’s perceived age. Therefore, by using this classification, it is possible to characterize human skin care and anti-aging needs on the basis of an individual’s genetic signature, thus opening the door to personalized treatments addressed at specific populations. This is part of an ongoing effort towards personalized anti-aging therapies combining genetic signatures with environmental and life style evaluations. PMID:25061327

Kinematics of Signature Writing in Healthy Aging*

PubMed Central

Caligiuri, Michael P.; Kim, Chi; Landy, Kelly M.

2014-01-01

Forensic document examiners (FDE) called upon to distinguish a genuine from a forged signature of an elderly person are often required to consider the question of age-related deterioration and whether the available exemplars reliably capture the natural effects of aging of the original writer. An understanding of the statistical relationship between advanced age and handwriting movements can reduce the uncertainty that may exist in an examiner’s approach to questioned signatures formed by elderly writers. The primary purpose of this study was to systematically examine age-related changes in signature kinematics in healthy writers. Forty-two healthy subjects between the ages of 60–91 years participated in this study. Signatures were recorded using a digitizing tablet and commercial software was used to examine the temporal and spatial stroke kinematics and pen pressure. Results indicated that vertical stroke duration and dysfluency increased with age, whereas vertical stroke amplitude and velocity decreased with age. Pen pressure decreased with age. We found that a linear model characterized the best-fit relationship between advanced age and handwriting movement parameters for signature formation. Male writers exhibited stronger age effects than female writers, especially for pen pressure and stroke dysfluency. The present study contributes to an understanding of how advanced age alters signature formation in otherwise healthy adults. PMID:24673648

New Advances in Re-Os Geochronology of Organic-rich Sedimentary Rocks.

NASA Astrophysics Data System (ADS)

Creaser, R. A.; Selby, D.; Kendall, B. S.

2003-12-01

Geochronology using 187Re-187Os is applicable to limited rock and mineral matrices, but one valuable application is the determination of depositional ages for organic-rich clastic sedimentary rocks like black shales. Clastic sedimentary rocks, in most cases, do not yield depositional ages using other radioactive isotope methods, but host much of Earth's fossil record upon which the relative geological timescale is based. As such, Re-Os dating of black shales has potentially wide application in timescale calibration studies and basin analysis, if sufficiently high precision and accuracy could be achieved. This goal requires detailed, systematic studies and evaluation of factors like standard compound stoichiometry, geologic effects, and the 187Re decay constant. Ongoing studies have resulted in an improved understanding of the abilities, limitations and systematics of the Re-Os geochronometer in black shales. First-order knowledge of the effects of processes like hydrocarbon maturation and low-grade metamorphism is now established. Hydrocarbon maturation does not impact the ability of the Re-Os geochronometer to determine depositional ages from black shales. The Re-Os age determined for the Exshaw Fm of western Canada is accurate within 2σ analytical uncertainty of the known age of the unit (U-Pb monazite from ash, conodont biostratigraphy). This suggests that the large improvement in precision attained for Re-Os dating of black shales by Cohen et al (ESPL 1999) over the pioneering work of Ravizza & Turekian (GCA 1989), relates to advances in analytical methodologies and sampling strategies, rather than a lack of disturbance by hydrocarbon maturation. We have found that a significant reduction in isochron scatter can be achieved by using an alternate dissolution medium, which preferentially attacks organic matter in which Re and Os are largely concentrated. This likely results from a more limited release of detrital Os and Re held in silicate materials during dissolution, compared with the inverse aqua regia medium used for Carius tube analysis. Using these "organic-selective" dissolution techniques, precise depositional ages have now been obtained from samples with very low TOC contents ( ˜0.5%), meaning that a greater range of clastic sedimentary rocks is amenable for Re-Os age dating. Well-fitted Re-Os isochrons of plausible geological age have also been determined from low-TOC shales subjected to chlorite-grade regional metamorphism. These results further illustrate the wide, but currently underutilized, potential of the Re-Os geochronometer in shales. The precision of age data attainable by the Re-Os system directly from black shales can be better than +/- 1% uncertainty (2σ , derived from isochron regression analysis), and the derived ages are demonstrably accurate.

Advanced Glycation End Products in Foods and a Practical Guide to Their Reduction in the Diet

PubMed Central

URIBARRI, JAIME; WOODRUFF, SANDRA; GOODMAN, SUSAN; CAI, WEIJING; CHEN, XUE; PYZIK, RENATA; YONG, ANGIE; STRIKER, GARY E.; VLASSARA, HELEN

2013-01-01

Modern diets are largely heat-processed and as a result contain high levels of advanced glycation end products (AGEs). Dietary advanced glycation end products (dAGEs) are known to contribute to increased oxidant stress and inflammation, which are linked to the recent epidemics of diabetes and cardiovascular disease. This report significantly expands the available dAGE database, validates the dAGE testing methodology, compares cooking procedures and inhibitory agents on new dAGE formation, and introduces practical approaches for reducing dAGE consumption in daily life. Based on the findings, dry heat promotes new dAGE formation by >10- to 100-fold above the uncooked state across food categories. Animal-derived foods that are high in fat and protein are generally AGE-rich and prone to new AGE formation during cooking. In contrast, carbohydrate-rich foods such as vegetables, fruits, whole grains, and milk contain relatively few AGEs, even after cooking. The formation of new dAGEs during cooking was prevented by the AGE inhibitory compound aminoguanidine and significantly reduced by cooking with moist heat, using shorter cooking times, cooking at lower temperatures, and by use of acidic ingredients such as lemon juice or vinegar. The new dAGE database provides a valuable instrument for estimating dAGE intake and for guiding food choices to reduce dAGE intake. PMID:20497781

Factors associated with non-participation and dropout among cancer patients in a cluster-randomised controlled trial.

PubMed

Roick, J; Danker, H; Kersting, A; Briest, S; Dietrich, A; Dietz, A; Einenkel, J; Papsdorf, K; Lordick, F; Meixensberger, J; Mössner, J; Niederwieser, D; Prietzel, T; Schiefke, F; Stolzenburg, J-U; Wirtz, H; Singer, S

2018-01-01

We investigated the impact of demographic and disease related factors on non-participation and dropout in a cluster-randomised behavioural trial in cancer patients with measurements taken between hospitalisation and 6 months thereafter. The percentages of non-participation and dropout were documented at each time point. Factors considered to be potentially related with non-participation and dropout were as follows: age, sex, marital status, education, income, employment status, tumour site and stage of disease. Of 1,338 eligible patients, 24% declined participation at baseline. Non-participation was higher in older patients (Odds Ratio [OR] 2.1, CI: 0.6-0.9) and those with advanced disease (OR 2.0, CI: 0.1-1.3). Dropout by 6 months was 25%. Dropout was more frequent with increased age (OR 2.8, CI: 0.8-1.2), advanced disease (OR 3.0, CI: 1.0-1.2), being married (OR 2.4, CI 0.7-1.1) and less frequent with university education (OR 0.4, CI -1.3 to -0.8) and middle income (OR 0.4, CI -0.9 to -0.7). When planning clinical trials, it is important to be aware of patient groups at high risk of non-participation or dropout, for example older patients or those with advanced disease. Trial designs should consider their special needs to increase their rate of participation. © 2017 John Wiley & Sons Ltd.

Osteoporosis treatment: recent developments and ongoing challenges

PubMed Central

Khosla, Sundeep; Hofbauer, Lorenz C

2018-01-01

Osteoporosis is an enormous and growing public health problem. Once considered an inevitable consequence of ageing, it is now eminently preventable and treatable. Ironically, despite tremendous therapeutic advances, there is an increasing treatment gap for patients at high fracture risk. In this Series paper, we trace the evolution of drug therapy for osteoporosis, which began in the 1940s with the demonstration by Fuller Albright that treatment with oestrogen could reverse the negative calcium balance that developed in women after menopause or oophorectomy. We note a watershed in osteoporosis drug discovery around the year 2000, when the approach to developing novel therapeutics shifted from one driven by discoveries in animal studies and clinical observations (eg, oestrogen, calcitonin, and teriparatide) or opportunistic repurposing of existing compounds (eg, bisphosphonates) to one driven by advances in fundamental bone biology (eg, denosumab) coupled with clues from patients with rare bone diseases (eg, romosozumab, odanacatib). Despite these remarkable advances, concerns about rare side-effects of anti-resorptive drugs, particularly bisphosphonates, and the absence of clear evidence in support of their long-term efficacy is leading many patients who could benefit from drug therapy to not take these drugs. As such, there remains an important clinical need to develop ways to enhance patient acceptance and compliance with these effective drugs, and to continue to develop new drugs that do not cause these side-effects and have prolonged anabolic effects on bone. Such changes could lead to a true reversal of this potentially devastating disease of ageing. PMID:28689769

‘Fine-tuning’ blood flow to the exercising muscle with advancing age: an update

PubMed Central

Wray, D. Walter; Richardson, Russell S.

2016-01-01

During dynamic exercise, oxygen demand from the exercising muscle is dramatically elevated, requiring a marked increase in skeletal muscle blood flow that is accomplished through a combination of systemic sympathoexcitation and local metabolic vasodilatation. With advancing age, the balance between these factors appears to be disrupted in favour of vasoconstriction, leading to an impairment in exercising skeletal muscle blood flow in the elderly. This ‘hot topic’ review aims to provide an update to our current knowledge of age-related changes in the neural and local mechanisms that contribute to this ‘fine-tuning’ of blood flow during exercise. The focus is on results from recent human studies that have adopted a reductionist approach to explore how age-related changes in both vasodilators (nitric oxide) and vasoconstrictors (endothelin-1, α-adrenergic agonists and angiotensin II) interact and how these changes impact blood flow to the exercising skeletal muscle with advancing age. PMID:25858164

The molecular responses of skeletal muscle satellite cells to continuous expression of IGF-1: implications for the rescue of induced muscular atrophy in aged rats

NASA Technical Reports Server (NTRS)

Chakravarthy, M. V.; Booth, F. W.; Spangenburg, E. E.

2001-01-01

Approximately 50% of humans older than 85 years have physical frailty due to weak skeletal muscles. This indicates a need for determining mechanisms to combat this problem. A critical cellular factor for postnatal muscle growth is a population of myogenic precursor cells called satellite cells. Given the complex process of sarcopenia, it has been postulated that, at some point in this process, a limited satellite cell proliferation potential could become rate-limiting to the regrowth of old muscles. It is conceivable that if satellite cell proliferative capacity can be maintained or enhanced with advanced age, sarcopenia could potentially be delayed or prevented. Therefore, the purposes of this paper are to describe whether IGF-I can prevent muscular atrophy induced by repeated cycles of hindlimb immobilization, increase the in vitro proliferation in satellite cells from these muscles and, if so, the molecular mechanisms by which IGF-I mediates this increased proliferation. Our results provide evidence that IGF-I can enhance aged muscle regrowth possibly through increased satellite cell proliferation. The results also suggest that IGF-I enhances satellite cell proliferation by decreasing the cell cycle inhibitor, p27Kip1, through the PI3'-K/Akt pathway. These data provide molecular evidence for IGF-I's rescue effect upon aging-associated skeletal muscle atrophy.

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.

[Inhibitory effects of extracts from Moutan Cortex on formation of advanced glycation end-products (AGEs) in vitro and specificity screening of its potential active components].

PubMed

Chen, Juan; Zhang, Li; Zhang, Ming-Hua; Zhao, Di; Yuan, Jia-Rui; Feng, Liang; Jia, Xiao-Bin

2016-03-01

In this study, bovine serum albumin (BSA)/methylglyoxal (MGO) non-enzymatic glycosylation reaction system was used for the evaluation of the inhibitory effects of Moutan Cortex extracts on the formation of AGEs. The HPLC-LC-ESI-MS/MS technology was adopted to test and indentify active components in Moutan Cortex against AGEs formation. The different concentrations of extracts (crude herb concentration 50, 100, 150, 200, 250 g•L⁻¹) from Moutan Cortexwas determined by fluorospectrophotometry, indicating an activity against AGEs formation in different concentrations of extracts, the inhibition ratio were (36.2±5.3)%, (43.5±6.2)%, (55.4±7.8)%, (68.6±6.7)%, (70.4±8.2)%, respectively after 6-day reaction in a dose dependent manner. Besides, the forming speed of AGEs tended to be steady after 24 h reaction. The HPLC technology was used to analyze chromatograms before and after the incubation of Moutan Cortex and methylglyoxal, identify changes in five chromatographic peaks and show decrease or increase in chromatographic peaks. These substances were trigalloyl glucose, tetragalloyl glucose, galloylpaeoniflorin, hexagalloyl glucose and benzoylpaeoniflorin after LC-ESI-MS/MS identification. Extracts from Moutan Cortex showed the remarkable inhibitory effects against formation of AGEs in BSA/glucose system. Furthermore, these potential active components might be associated with the efficacy of Moutan Cortex on treatment of diabetic nephropathy, which enriches basic studies for Moutan Cortex and provides ideas and reference basis for subsequent studies. Copyright© by the Chinese Pharmaceutical Association.

Radiocarbon dating of terrestrial carbonates

USGS Publications Warehouse

Pigati, Jeffrey S.; Rink, W. Jack; Thompson, Jeroen

2014-01-01

Terrestrial carbonates encompass a wide range of materials that potentially could be used for radiocarbon (14C) dating. Biogenic carbonates, including shells and tests of terrestrial and aquatic gastropods, bivalves, ostracodes, and foraminifera, are preserved in a variety of late Quaternary deposits and may be suitable for 14C dating. Primary calcareous deposits (marls, tufa, speleothems) and secondary carbonates (rhizoliths, fracture fill, soil carbonate) may also be targeted for dating when conditions are favorable. This chapter discusses issues that are commonly encountered in 14C dating of terrestrial carbonates, including isotopic disequilibrium and open-system behavior, as well as methods used to determine the reliability of ages derived from these materials. Recent methodological advancements that may improve the accuracy and precision of 14C ages of terrestrial carbonates are also highlighted.

Hormetic modulation of hepatic insulin sensitivity by advanced glycation end products.

PubMed

Fabre, Nelly T; Thieme, Karina; Silva, Karolline S; Catanozi, Sérgio; Cavaleiro, Ana Mercedes; Pinto, Danilo A C; Okamoto, Maristela M; Morais, Mychel Raony P T; Falquetto, Bárbara; Zorn, Telma M; Machado, Ubiratan F; Passarelli, Marisa; Correa-Giannella, Maria Lúcia

2017-05-15

Because of the paucity of information regarding metabolic effects of advanced glycation end products (AGEs) on liver, we evaluated effects of AGEs chronic administration in (1) insulin sensitivity; (2) hepatic expression of genes involved in AGEs, glucose and fat metabolism, oxidative stress and inflammation and; (3) hepatic morphology and glycogen content. Rats received intraperitoneally albumin modified (AlbAGE) or not by advanced glycation for 12 weeks. AlbAGE induced whole-body insulin resistance concomitantly with increased hepatic insulin sensitivity, evidenced by activation of AKT, inactivation of GSK3, increased hepatic glycogen content, and decreased expression of gluconeogenesis genes. Additionally there was reduction in hepatic fat content, in expression of lipogenic, pro-inflamatory and pro-oxidative genes and increase in reactive oxygen species and in nuclear expression of NRF2, a transcription factor essential to cytoprotective response. Although considered toxic, AGEs become protective when administered chronically, stimulating AKT signaling, which is involved in cellular defense and insulin sensitivity. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Liraglutide attenuates the migration of retinal pericytes induced by advanced glycation end products.

PubMed

Lin, Wen-Jian; Ma, Xue-Fei; Hao, Ming; Zhou, Huan-Ran; Yu, Xin-Yang; Shao, Ning; Gao, Xin-Yuan; Kuang, Hong-Yu

2018-07-01

Retinal pericyte migration represents a novel mechanism of pericyte loss in diabetic retinopathy (DR), which plays a crucial role in the early impairment of the blood-retinal barrier (BRB). Glucagon-like peptide-1 (GLP-1) has been shown to protect the diabetic retina in the early stage of DR; however, the relationship between GLP-1 and retinal pericytes has not been discussed. In this study, advanced glycation end products (AGEs) significantly increased the migration of primary bovine retinal pericytes without influencing cell viability. AGEs also significantly enhanced phosphatidylinositol 3-kinase (PI3K)/Akt activation, and changed the expressions of migration-related proteins, including phosphorylated focal adhesion kinase (p-FAK), matrix metalloproteinase (MMP)-2 and vinculin. PI3K inhibition significantly attenuated the AGEs-induced migration of retinal pericytes and reversed the overexpression of MMP-2. Glucagon-like peptide-1 receptor (Glp1r) was expressed in retinal pericytes, and liraglutide, a GLP-1 analog, significantly attenuated the migration of pericytes by Glp1r and reversed the changes in p-Akt/Akt, p-FAK/FAK, vinculin and MMP-2 levels induced by AGEs, indicating that the protective effect of liraglutide was associated with the PI3K/Akt pathway. These results provided new insights into the mechanism underlying retinal pericyte migration. The early use of liraglutide exerts a potential bebefical effect on regulating pericyte migration, which might contribute to mechanisms that maintain the integrity of vascular barrier and delay the development of DR. Copyright © 2018 Elsevier Inc. All rights reserved.

Nutritional supplements modulate fluorescent protein-bound advanced glycation endproducts and digestive enzymes related to type 2 diabetes mellitus.

PubMed

Koch, Emily R; Deo, Permal

2016-09-01

Chronic hyperglycemia enhances the formation of advanced glycation endproducts (AGEs) and reactive oxygen species (ROS), contributing to diabetic complications. Thus, controlling blood glucose levels, inhibiting the formation of AGEs and reducing ROS are key therapeutic targets in early stage type 2 diabetes. The inhibitory effects of seven commercial liquid nutritional supplements against carbohydrate hydrolysing enzymes, α-amylase and α-glucosidase, was determined by dinitrosalicylic (DNS) reagent and p-nitrophenyl-α-D-glucopyranoside solution, respectively. Antiglycation activity was determined using the formation of fluorescent protein-bound AGEs. Total phenolic and flavonoid content and antioxidant properties (1,1-diphenyl-2-picrylhydrazyl antioxidant activity (DPPH) and ferric reducing antioxidant power (FRAP)) were determined for correlation among these components and inhibitory activities. Samoan noni juice showed the greatest inhibitory effects against α-amylase, whereas chlorophyll extracts showed the greatest inhibitory effect against α-glucosidase. Inhibition of α-glucosidase correlated with TFC (r(2) = 0.766; p < 0.01) and FRAP (r(2) = 0.750; p < 0.01) whereas no correlation was observed for α-amylase inhibition. All supplements inhibited fluorescent protein-bound AGEs, with the greatest effect exerted by Olive Leaf Extract, Blood Sugar Support (IC50 = 0.5 mg/ml). The IC50 values negatively correlated with TPC (r(2) = -0.707; p < 0.001) and DPPH scavenging activities (r(2) = 0.515; p < 0.05). The findings of this study highlight the potential of liquid nutritional supplements in managing and treating type 2 diabetes mellitus.

Description of the Age-Related Eye Disease Study 9-step severity scale applied to participants in the Complications of Age-related Macular Degeneration Prevention Trial.

PubMed

Ying, Gui-shuang; Maguire, Maureen G; Alexander, Judith; Martin, Revell W; Antoszyk, Andrew N

2009-09-01

To describe characteristics of the Age-Related Eye Disease Study (AREDS) 9-step severity scale applied to participants in the Complications of Age-related Macular Degeneration Prevention Trial (CAPT). Eligibility criteria for CAPT required 10 or more large (>or=125 microm) drusen in each eye. Readers graded baseline photographs from all participants and all follow-up photographs from 402 untreated eyes. Drusen and pigment characteristics were used to assign the AREDS scale score. Choroidal neovascularization was identified from fluorescein angiograms. Geographic atrophy involving the macular center was identified from color photographs. Among 1001 untreated eyes, 90% were at steps 5 to 7 at baseline. The 5-year incidence of advanced age-related macular degeneration (AMD) increased with each step from 8% (step 4) to 40% (steps 8 and 9 combined). These rates were similar to those reported in AREDS. Among 261 eyes with all 5 annual photograph gradings available and without progression to advanced AMD, 55% of eyes had scores that indicated improvement at least once. Before progression to advanced AMD, only 32% of 141 eyes either went through step 8 or 9 or had an increase of 2 or more steps from baseline. The AREDS 9-step severity scale was predictive of development of advanced AMD. The AREDS scale has deficiencies as a surrogate outcome for progression to advanced AMD.

in vivo quantification of white matter microstructure for use in aging: A focus on two emerging techniques

PubMed Central

Lamar, Melissa; Zhou, Xiaohong Joe; Charlton, Rebecca A.; Dean, Douglas; Little, Deborah; Deoni, Sean C

2013-01-01

Human brain imaging has seen many advances in the quantification of white matter in vivo. For example, these advances have revealed the association between white matter damage and vascular disease as well as their impact on risk for and development of dementia and depression in an aging population. Current neuroimaging methods to quantify white matter damage provide a foundation for understanding such age-related neuropathology; however, these methods are not as adept at determining the underlying microstructural abnormalities signaling at risk tissue or driving white matter damage in the aging brain. This review will begin with a brief overview of the use of diffusion tensor imaging (DTI) in understanding white matter alterations in aging before focusing in more detail on select advances in both diffusion-based methods and multi-component relaxometry techniques for imaging white matter microstructural integrity within myelin sheaths and the axons they encase. While DTI greatly extended the field of white matter interrogation, these more recent technological advances will add clarity to the underlying microstructural mechanisms that contribute to white matter damage. More specifically, the methods highlighted in this review may prove more sensitive (and specific) for determining the contribution of myelin versus axonal integrity to the aging of white matter in brain. PMID:24080382

Is there an advanced aging effect on the ability to mentally represent action?

PubMed

Gabbard, Carl; Caçola, Priscila; Cordova, Alberto

2011-01-01

Motor programming theory suggests that an integral component in an effective outcome is an adequate action (mental) representation of the movements; a representation reflected in the ability to use motor imagery. Recent reports show a decline with advanced age (>64 years) using a variety of motor simulation tasks. Here, we examined the possible effects of advanced age on motor imagery ability in the context of estimation of reachability--that is, estimating whether an object is within reach or out of grasp. Thirty young adults (mean age: 20) and 23 older adults (mean age: 77) were instructed to estimate, using motor imagery, whether randomly presented targets in peripersonal (within actual reach) and extrapersonal (beyond reach) space were within or out of reach of their dominant limb while seated. Results indicated that the younger group was significantly more accurate than the older adults, p < 0.001. Whereas both groups made more errors in extrapersonal space, the values were significantly higher for the older group; that is, they overestimated to a greater extent. In summary, these findings add to the general notion that there is a decline in the ability to mentally represent action with advanced age. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

The future of ageing.

PubMed

Hayflick, L

2000-11-09

Advances in our knowledge of age-associated diseases have far outpaced advances in our understanding of the fundamental ageing processes that underlie the vulnerability to these pathologies. If we are to increase human life expectancy beyond the fifteen-year limit that would result if today's leading causes of death were resolved, more attention must be paid to basic research on ageing. Determination of longevity must be distinguished from ageing to take us from the common question of why we age to a more revealing question that is rarely posed: why do we live as long as we do? But if the ability to intervene in ageing ever becomes a reality, it will be rife with unintended and undesirable consequences.

Glycation, carbonyl stress and AGEs inhibitors: a patent review.

PubMed

Jahan, Humera; Choudhary, M Iqbal

2015-01-01

The glycation process, comprising a series of reactions, results in the formation of heterogeneous adducts, known as advanced glycation end products (AGEs). AGEs are involved in several pathologies, including diabetes-associated late complications, atherosclerosis, Alzheimer's disease and inflammatory arthritis. Several inhibitors of AGEs and/or reactive carbonyl species have been identified from various sources, including natural products and synthetic molecules, and have been investigated for their mechanism of action. This review covers the literature on AGEs inhibitors published as patents between 2001 and 2014. Initially, the earlier reported molecules with AGEs inhibitory properties, their mechanism of actions and reported adverse effects are discussed. The main focus has been on the chemical structures, methods for evaluation of the activity, modes of action, pharmacokinetics and therapeutic outcomes. The potential of these AGEs inhibitors in the treatment and management of a number of diseases are also discussed in this review. The reactive carbonyl species and AGEs have recently emerged as novel therapeutic targets for the prevention and treatment of several diseases. Currently, the major concerns with the use of AGEs inhibitors as therapeutic agents are low effectiveness, poor pharmacokinetics and undesirable side effects. Many of the AGEs inhibitors reviewed here possess potent antiglycation activity and are devoid of undesirable side effects. These small molecules inhibitors can, therefore, serve as scaffolds for the development and designing of new AGEs inhibitors as clinical agents.

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

Should precise numerical dating overrule glacial geomorphology?

NASA Astrophysics Data System (ADS)

Winkler, Stefan

2016-04-01

Numerical age dating techniques, namely different types of terrestrial cosmogenic nuclide dating (TCND), have achieved an impressive progress in both laboratory precision and regional calibration models during the past few decades. It is now possible to apply precise TCND even to young landforms like Late Holocene moraines, a task seemed hardly achievable just about 15 years ago. An increasing number of studies provide very precise TCND ages for boulders from Late Holocene moraines enabling related reconstruction of glacier chronologies and the interpretation of these glacial landforms in a palaeoclimatological context. These studies may also solve previous controversies about different ages assigned to moraines obtained by different dating techniques, for example relative-age dating techniques or techniques combining relative-age dating with few fixed points derived from numerical age dating. There are a few cases, for example Mueller Glacier and nearby long debris-covered valley glacier in Aoraki/Mt.Cook National Park (Southern Alps, New Zealand), where the apparent "supremacy" of TCND-ages seem to overrule glacial geomorphological principles. Enabled by a comparatively high number of individual boulders precisely dated by TCND, moraine ridges on those glacier forelands have been primarily clustered on basis of these boulder ages rather than on their corresponding morphological position. To the extreme, segments of a particular moraine complex morphologically and sedimentologically proven to be formed during one event have become split and classified as two separate "moraines" on different parts of the glacier foreland. One ledge of another moraine complex contains 2 TCND-sampled boulders apparently representing two separate "moraines"-clusters of an age difference in the order of 1,500 years. Although recently criticism has been raised regarding the non-contested application of the arithmetic mean for calculation of TCND-ages for individual moraines, this problem is still not properly addressed in every case and significant age differences of individual boulders on moraine ridges create uncertainties with their palaeoclimatic interpretation. Referring to the exemplary case of the glacier forelands mentioned above it is argued that prior to any chronological interpretation the geomorphological correlation of individual moraine ridges and complexes need to be established and potential uncertainties clearly addressed. After the TCND-ages have been obtained from sampled boulders and assigned to the moraines any discrepancy needs to be carefully investigated to ensure that misleading ages don't effect subsequent chronological reconstructions and palaeoclimatic interpretations. Even if dating precision has recently considerably increased, moraines should not be clustered into synchronous moraine-groups based on TCND-ages if their morphological position or sedimentology contradicts such classification. Furthermore, the high precision of TCND-ages do often not consider the concept of 'LIA'-type events and different response times of nearby glaciers to the same mass balance/climate signal, therefore potentially overestimating the true number of glacier advances during a specific period. An alternative interpretation of existing TCND-ages reveals fewer advances during the Late Holocene. Summarising, modern TCND-ages are possibly "too precise" in some aspects and wrongly judged as superior to geomorphological evidence. A more critical evaluation would be beneficial to any subsequent attempts of intra-hemispheric and global correlation of glacier chronologies.

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

NASA GRC Stirling Technology Development Overview

NASA Technical Reports Server (NTRS)

Thieme, Lanny G.; Schreiber, Jeffrey G.

2003-01-01

The Department of Energy, Lockheed Martin (LM), Stirling Technology Company, and NASA Glenn Research Center (GRC) are developing a high-efficiency Stirling Radioisotope Generator (SRG) for potential NASA Space Science missions. The SRG is being developed for multimission use, including providing spacecraft onboard electric power for NASA deep space missions and power for unmanned Mars rovers. NASA GRC is conducting an in- house supporting technology project to assist in developing the Stirling convertor for space qualification and mission implementation. Preparations are underway for a thermalhacuum system demonstration and unattended operation during endurance testing of the 55-We Technology Demonstration Convertors. Heater head life assessment efforts continue, including verification of the heater head brazing and heat treatment schedules and evaluation of any potential regenerator oxidation. Long-term magnet aging tests are continuing to characterize any possible aging in the strength or demagnetization resistance of the permanent magnets used in the linear alternator. Testing of the magnet/lamination epoxy bond for performance and lifetime characteristics is now underway. These efforts are expected to provide key inputs as the system integrator, LM, begins system development of the SRG. GRC is also developing advanced technology for Stirling convertors. Cleveland State University (CSU) is progressing toward a multi-dimensional Stirling computational fluid dynamics code, capable of modeling complete convertors. Validation efforts at both CSU and the University of Minnesota are complementing the code development. New efforts have been started this year on a lightweight convertor, advanced controllers, high-temperature materials, and an end-to-end system dynamics model. Performance and mass improvement goals have been established for second- and third-generation Stirling radioisotope power systems.

Advances in facial reanimation.

PubMed

Tate, James R; Tollefson, Travis T

2006-08-01

Facial paralysis often has a significant emotional impact on patients. Along with the myriad of new surgical techniques in managing facial paralysis comes the challenge of selecting the most effective procedure for the patient. This review delineates common surgical techniques and reviews state-of-the-art techniques. The options for dynamic reanimation of the paralyzed face must be examined in the context of several patient factors, including age, overall health, and patient desires. The best functional results are obtained with direct facial nerve anastomosis and interpositional nerve grafts. In long-standing facial paralysis, temporalis muscle transfer gives a dependable and quick result. Microvascular free tissue transfer is a reliable technique with reanimation potential whose results continue to improve as microsurgical expertise increases. Postoperative results can be improved with ancillary soft tissue procedures, as well as botulinum toxin. The paper provides an overview of recent advances in facial reanimation, including preoperative assessment, surgical reconstruction options, and postoperative management.

The role of external beam radiation therapy in well-differentiated thyroid cancer.

PubMed

Hamilton, Sarah N; Tran, Eric; Berthelet, Eric; Wu, Jonn

2017-10-01

This review article explores the use of external beam radiotherapy (EBRT) in well differentiated thyroid cancer. Areas covered: The published literature on EBRT for advanced pT4 disease and macroscopic unresectable disease to improve locoregional control is reviewed. EBRT techniques, volumes and doses are discussed in detail. The potential acute and late toxicities of EBRT are discussed in the context of the published literature. The use of EBRT for patients with metastatic disease is also described. Expert commentary: There is good retrospective evidence for EBRT in the setting of unresectable gross residual well-differentiated thyroid cancer as this can result in long-term local control. However, the benefit of EBRT in patients with locally advanced disease that is completely resected is less clear. The use of EBRT for these patients requires careful consideration of age, pathologic factors, comorbidities and patient preference, preferably by a multi-disciplinary team.

Tissue engineering and regenerative medicine: concepts for clinical application.

PubMed

Atala, Anthony

2004-01-01

Patients suffering from diseased and injured organs may be treated with transplanted organs. However, there is a severe shortage of donor organs that is worsening yearly given the aging population. Scientists in the field of regenerative medicine and tissue engineering apply the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Therapeutic cloning, where the nucleus from a donor cell is transferred into an enucleated oocyte in order to extract pluripotent embryonic stem cells, offers a potentially limitless source of cells for tissue engineering applications. The stem cell field is also advancing rapidly, opening new options for therapy. This paper reviews recent advances that have occurred in regenerative medicine and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure.

Engineering tissues, organs and cells.

PubMed

Atala, Anthony

2007-01-01

Patients suffering from diseased and injured organs may be treated with transplanted organs; however, there is a severe shortage of donor organs that is worsening yearly, given the ageing population. In the field of regenerative medicine and tissue engineering, scientists apply the principles of cell transplantation, materials science and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Therapeutic cloning, where the nucleus from a donor cell is transferred into an enucleated oocyte in order to extract pluripotent embryonic stem cells, offers a potentially limitless source of cells for tissue engineering applications. The stem cell field is also advancing rapidly, opening new options for therapy, including the use of amniotic and placental fetal stem cells. This review covers recent advances that have occurred in regenerative medicine and describes applications of these technologies using chemical compounds that may offer novel therapies for patients with end-stage organ failure. 2007 John Wiley & Sons, Ltd

Sensor-Only System Identification for Structural Health Monitoring of Advanced Aircraft

NASA Technical Reports Server (NTRS)

Kukreja, Sunil L.; Bernstein, Dennis S.

2012-01-01

Environmental conditions, cyclic loading, and aging contribute to structural wear and degradation, and thus potentially catastrophic events. The challenge of health monitoring technology is to determine incipient changes accurately and efficiently. This project addresses this challenge by developing health monitoring techniques that depend only on sensor measurements. Since actively controlled excitation is not needed, sensor-to-sensor identification (S2SID) provides an in-flight diagnostic tool that exploits ambient excitation to provide advance warning of significant changes. S2SID can subsequently be followed up by ground testing to localize and quantify structural changes. The conceptual foundation of S2SID is the notion of a pseudo-transfer function, where one sensor is viewed as the pseudo-input and another is viewed as the pseudo-output, is approach is less restrictive than transmissibility identification and operational modal analysis since no assumption is made about the locations of the sensors relative to the excitation.

Metachronous colon polyps in younger versus older adults: a case-control study.

PubMed

Nagpal, Sajan Jiv Singh; Mukhija, Dhruvika; Sanaka, Madhusudhan; Lopez, Rocio; Burke, Carol A

2018-03-01

The incidence of colorectal cancer in the United States has decreased substantially in individuals aged 50 and older. In contrast, it is increasing in young adults. The polyp characteristics on baseline and follow-up colonoscopy in young adults are not well characterized. We describe the polyp characteristics on baseline and follow-up colonoscopy in adults <40 years and determined factors associated with the occurrence of metachronous, advanced neoplasia or high-risk (HR) polyp features. We compared the occurrence of metachronous advanced neoplasia in young adults with those 50 years and older to assess whether postpolypectomy surveillance guidelines seem appropriate for polyp-bearing adults less than age 40 years. Patients <40 years of age with >1 polyp removed on colonoscopy followed by a postpolypectomy colonoscopy were eligible. The primary outcome was the occurrence of advanced neoplasia or HR polyp features on follow-up colonoscopy. Secondary endpoints included factors associated with metachronous advanced neoplasia in young adults. The occurrence of metachronous advanced neoplasia in young adults was compared with a cohort of patients aged 50 years and older. Included were 128 patients with a mean age of 34.9 years; 124 patients (97%) had adenomas and 7% had sessile serrated polyps (SSPs). Advanced neoplasia was seen in 35% of patients at baseline. The median follow-up time was 33.6 months. Metachronous advanced neoplasia was identified in 7% of patients on follow-up colonoscopy. Baseline factors associated with metachronous advanced neoplasia included the presence of an SSP (hazard ratio, 7.8; 95% CI, 1.09-56.3; P = .041) with a trend in those with advanced neoplasia (hazard ratio, 3.4; 95% confidence interval, .89-12.8; P = .072). The occurrence of metachronous advanced neoplasia did not differ between the young and older cohorts (7% vs 12.2%, P = .58); however, young adults were less likely to have HR polyp features on follow-up (8.6% vs 20.3%, P = .008). More than 1 in 3 adults <40 years old undergoing colonoscopy had advanced neoplasia on baseline colonoscopy. The occurrence of metachronous advanced neoplasia in young adults is similar to older adults and appears to be associated with the size, pathology, and number of baseline polyps. Our data suggest young polyp-bearing adults may undergo postpolypectomy colonoscopy at intervals currently recommended by national guidelines. Confirmation in larger studies is warranted. Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

DAMPs, ageing, and cancer: The 'DAMP Hypothesis'.

PubMed

Huang, Jin; Xie, Yangchun; Sun, Xiaofang; Zeh, Herbert J; Kang, Rui; Lotze, Michael T; Tang, Daolin

2015-11-01

Ageing is a complex and multifactorial process characterized by the accumulation of many forms of damage at the molecular, cellular, and tissue level with advancing age. Ageing increases the risk of the onset of chronic inflammation-associated diseases such as cancer, diabetes, stroke, and neurodegenerative disease. In particular, ageing and cancer share some common origins and hallmarks such as genomic instability, epigenetic alteration, aberrant telomeres, inflammation and immune injury, reprogrammed metabolism, and degradation system impairment (including within the ubiquitin-proteasome system and the autophagic machinery). Recent advances indicate that damage-associated molecular pattern molecules (DAMPs) such as high mobility group box 1, histones, S100, and heat shock proteins play location-dependent roles inside and outside the cell. These provide interaction platforms at molecular levels linked to common hallmarks of ageing and cancer. They can act as inducers, sensors, and mediators of stress through individual plasma membrane receptors, intracellular recognition receptors (e.g., advanced glycosylation end product-specific receptors, AIM2-like receptors, RIG-I-like receptors, and NOD1-like receptors, and toll-like receptors), or following endocytic uptake. Thus, the DAMP Hypothesis is novel and complements other theories that explain the features of ageing. DAMPs represent ideal biomarkers of ageing and provide an attractive target for interventions in ageing and age-associated diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

Characteristics of and differences between Pasifika women and New Zealand European women diagnosed with breast cancer in New Zealand.

PubMed

Brown, Charis; Lao, Chunhuan; Lawrenson, Ross; Tin Tin, Sandar; Schaaf, Michelle; Kidd, Jacquie; Allan-Moetaua, Anne; Herman, Josephine; Raamsroop, Reena; Campbell, Ian; Elwood, Mark

2017-12-15

Breast cancer in New Zealand-based Pasifika women is a significant issue. Although Pasifika women have a lower incidence of breast cancer compared to New Zealand European women, they have higher breast cancer mortality and lower five-year survival. The aim of this study was to describe the characteristics and tumour biology of Pasifika women and to compare New Zealand European women to identify what factors impact on early (Stage 1 and 2) vs advanced stage (Stage 3 and 4) at diagnosis. Data on all Pasifika and New Zealand European women diagnosed with breast cancer (C50) during the period 1 June 2000 to 31 May 2013 was extracted from the Auckland and Waikato Breast Cancer Registries. Descriptive tables and Chi-square test were used to examine differences in characteristics and tumour biology between Pasifika and New Zealand European women. Logistic regression was used to identify factors that contributed to an increased risk of advanced stage at diagnosis. A significantly higher proportion of Pasifika women had advanced disease at diagnosis compared to New Zealand European women (33.3% and 18.3%, respectively). Cancer biology in Pasifika women was more likely to be: 1) HER2+, 2) ER/PR negative and 3) have a tumour size of ≥50mm. Pasifika women live in higher deprivation areas of 9-10 compared to New Zealand European women (55% vs 14%, respectively) and were less likely to have their cancer identified through screening. Logistic regression showed that if Pasifika women were on the screen-detected pathway they had similar odds (not sig.) of having advanced disease at diagnosis to New Zealand European women. Mode of detection, deprivation, age and some biological factors contributed to the difference in odds ratio between Pasifika and New Zealand European women. For those of screening age, adherence to the screening programme and improvements in access to earlier diagnosis for Pasifika women under the current screening age have the potential to make a substantial difference in the number of Pasifika women presenting with late-stage disease.

Consequences of advanced aging on renal function in chronic hyperandrogenemic female rat model: implications for aging women with polycystic ovary syndrome.

PubMed

Patil, Chetan N; Racusen, Lorraine C; Reckelhoff, Jane F

2017-11-01

Polycystic ovary syndrome (PCOS) is the most common endocrine and reproductive disorder in premenopausal women, characterized by hyperandrogenemia, metabolic syndrome, and inflammation. Women who had PCOS during their reproductive years remain hyperandrogenemic after menopause. The consequence of chronic hyperandrogenemia with advanced aging has not been studied to our knowledge. We have characterized a model of hyperandrogenemia in female rats and have aged them to 22-25 months to mimic advanced aging in hyperandrogenemic women, and tested the hypothesis that chronic exposure to hyperandrogenemia with aging has a deleterious effect on renal function. Female rats were chronically implanted with dihydrotestosterone pellets (DHT 7.5 mg/90 days) that were changed every 85 days or placebo pellets, and renal function was measured by clearance methods. Aging DHT-treated females had a threefold higher level of DHT with significantly higher body weight, mean arterial pressure, left kidney weight, proteinuria, and kidney injury molecule-1 (KIM-1), than did age-matched controls. In addition, DHT-treated-old females had a 60% reduction in glomerular filtration rate, 40% reduction in renal plasma flow, and significant reduction in urinary nitrate and nitrite excretion (UNOxV), an index of nitric oxide production. Morphological examination of kidneys showed that old DHT-treated females had significant focal segmental glomerulosclerosis, global sclerosis, and interstitial fibrosis compared to controls. Thus chronic hyperandrogenemia that persists into old age in females is associated with renal injury. These data suggest that women with chronic hyperandrogenemia such as in PCOS may be at increased risk for development of chronic kidney disease with advanced age. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

A survey of current trends in computational drug repositioning.

PubMed

Li, Jiao; Zheng, Si; Chen, Bin; Butte, Atul J; Swamidass, S Joshua; Lu, Zhiyong

2016-01-01

Computational drug repositioning or repurposing is a promising and efficient tool for discovering new uses from existing drugs and holds the great potential for precision medicine in the age of big data. The explosive growth of large-scale genomic and phenotypic data, as well as data of small molecular compounds with granted regulatory approval, is enabling new developments for computational repositioning. To achieve the shortest path toward new drug indications, advanced data processing and analysis strategies are critical for making sense of these heterogeneous molecular measurements. In this review, we show recent advancements in the critical areas of computational drug repositioning from multiple aspects. First, we summarize available data sources and the corresponding computational repositioning strategies. Second, we characterize the commonly used computational techniques. Third, we discuss validation strategies for repositioning studies, including both computational and experimental methods. Finally, we highlight potential opportunities and use-cases, including a few target areas such as cancers. We conclude with a brief discussion of the remaining challenges in computational drug repositioning. Published by Oxford University Press 2015. This work is written by US Government employees and is in the public domain in the US.

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.

[Pathogenetic associations of periodontal diseases with somatic therapeutic pathology, comorbid conditions in patients of advanced and senile age: state-of-the-art review. Part 1. Associations of periodontal diseases with somatic therapeutic pathology in patients of advanced and senile age].

PubMed

Ar'eva, G T; Solov'ev, M M; Ar'ev, A L; Ryzhak, G A

2014-01-01

The state-of-the-art review of literature on existing views on the association of periodontal diseases with somatic therapeutic pathology (first part of the review) and comorbid conditions (second part of the review) is submitted. The conclusion about need of carrying out the further multicenter researches which purpose is development of new integrated indicators, in a complex and comprehensively characterizing not only the periodontal status, but also set of available somatic therapeutic pathology, especially at pa- tients of advanced and senile age is drawn.

Neuroimaging explanations of age-related differences in task performance.

PubMed

Steffener, Jason; Barulli, Daniel; Habeck, Christian; Stern, Yaakov

2014-01-01

Advancing age affects both cognitive performance and functional brain activity and interpretation of these effects has led to a variety of conceptual research models without always explicitly linking the two effects. However, to best understand the multifaceted effects of advancing age, age differences in functional brain activity need to be explicitly tied to the cognitive task performance. This work hypothesized that age-related differences in task performance are partially explained by age-related differences in functional brain activity and formally tested these causal relationships. Functional MRI data was from groups of young and old adults engaged in an executive task-switching experiment. Analyses were voxel-wise testing of moderated-mediation and simple mediation statistical path models to determine whether age group, brain activity and their interaction explained task performance in regions demonstrating an effect of age group. Results identified brain regions whose age-related differences in functional brain activity significantly explained age-related differences in task performance. In all identified locations, significant moderated-mediation relationships resulted from increasing brain activity predicting worse (slower) task performance in older but not younger adults. Findings suggest that advancing age links task performance to the level of brain activity. The overall message of this work is that in order to understand the role of functional brain activity on cognitive performance, analysis methods should respect theoretical relationships. Namely, that age affects brain activity and brain activity is related to task performance.

[Pharmacological therapy of age-related macular degeneration based on etiopathogenesis].

PubMed

Fischer, Tamás

2015-11-15

It is of great therapeutic significance that disordered function of the vascular endothelium which supply the affected ocular structures plays a major role in the pathogenesis and development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfunction, and age-related macular degeneration is accompanied by a general inflammatory response. According to current concept, age-related macular degeneration is a local manifestation of systemic vascular disease. This recognition could have therapeutic implications because restoration of endothelial dysfunction can restabilize the condition of chronic vascular disease including age-related macular degeneration as well. Restoration of endothelial dysfunction by pharmaacological or non pharmacological interventions may prevent the development or improve endothelial dysfunction, which result in prevention or improvement of age related macular degeneration as well. Medicines including inhibitors of the renin-angiotensin system (converting enzyme inhibitors, angiotensin-receptor blockers and renin inhibitors), statins, acetylsalicylic acid, trimetazidin, third generation beta-blockers, peroxisome proliferator-activated receptor gamma agonists, folate, vitamin D, melatonin, advanced glycation end-product crosslink breaker alagebrium, endothelin-receptor antagonist bosentan, coenzyme Q10; "causal" antioxidant vitamins, N-acetyl-cysteine, resveratrol, L-arginine, serotonin receptor agonists, tumor necrosis factor-alpha blockers, specific inhibitor of the complement alternative pathway, curcumin and doxycyclin all have beneficial effects on endothelial dysfunction. Restoration of endothelial dysfunction can restabilize chronic vascular disease including age-related macular degeneration as well. Considering that the human vascular system is consubstantial, medicines listed above should be given to patients (1) who have no macular degeneration but have risk factors for the disease and are older than 50 years; (2) who have been diagnosed with unilateral age-related macular degeneration in order to prevent damage of the contralateral eye; (3) who have bilateral age-related macular degeneration in order to avert deterioration and in the hope of a potential improvement. However, randomised prospective clinical trials are still needed to elucidate the potential role of these drug treatments in the prevention and treatment of age-related macular degeneration.

Little Ice Age mapping as a tool for identifying hazard in the paraglacial environment: The case study of Trentino (Eastern Italian Alps)

NASA Astrophysics Data System (ADS)

Zanoner, Thomas; Carton, Alberto; Seppi, Roberto; Carturan, Luca; Baroni, Carlo; Salvatore, Maria Cristina; Zumiani, Matteo

2017-10-01

The Little Ice Age (LIA) is a well-recognized climatic event during which the glaciers in the Alps advanced and reached their maximum Holocene extent. During their retreat following the LIA, the glaciers left large areas of loose or poorly consolidated glacial deposits in their forelands, which are subject to paraglacial reworking and may represent potential hazards for human infrastructures. In this study, we present a regional scale mapping of the LIA and post-LIA glacial deposits and a reconstruction of the maximum LIA extents of glaciers in the same area. This work is motivated by a local law requiring the classification of areas subject to natural hazards in Trentino (Italian Alps). Results highlight that glaciers shrunk by 63% from the LIA maximum, leaving 30 km2 of unconsolidated deposits, which are subject to geomorphic paraglacial processes. Potentially hazardous consequences can occur, in particular, during high-magnitude instantaneous events, causing debris and mud flows, mass wasting from debris-covered ice, and floods from small moraine-dammed lakes.

Deaths from homicides: a historical series.

PubMed

Costa, Flávia Azevedo de Mattos Moura; da Trindade, Ruth França Cizino; dos Santos, Claudia Benedita

2014-01-01

to describe mortality from homicides in Itabuna, in the State of Bahia. study with hybrid, ecological and time-trend design. The mortality coefficients per 1,000 inhabitants, adjusted by the direct technique, proportional mortality by sex and age range, and Potential Years of Life Lost were all calculated. since 2005, the external causes have moved from third to second most-common cause of death, with homicides being responsible for the increase. In the 13 years analyzed, homicides have risen 203%, with 94% of these deaths occurring among the male population. Within this group, the growth occurred mainly in the age range from 15 to 29 years of age. It was ascertained that 83% of the deaths were caused by firearms; 57.2% occurred in public thoroughfares; and 98.4% in the urban zone. In 2012, the 173 homicides resulted in 7,837 potential years of life lost, with each death causing, on average, the loss of 45.3 years. mortality by homicide in a medium-sized city in Bahia reaches levels observed in the big cities of Brazil in the 1980s, evidencing that the phenomenon of criminality - formerly predominant only in the big urban centers - is advancing into the rural area of Brazil, causing changes in the map of violent homicide in Brazil.

Rapamycin: An InhibiTOR of Aging Emerges From the Soil of Easter Island

PubMed Central

Arriola Apelo, Sebastian I.

2016-01-01

Rapamycin (sirolimus) is a macrolide immunosuppressant that inhibits the mechanistic target of rapamycin (mTOR) protein kinase and extends lifespan in model organisms including mice. Although rapamycin is an FDA-approved drug for select indications, a diverse set of negative side effects may preclude its wide-scale deployment as an antiaging therapy. mTOR forms two different protein complexes, mTORC1 and mTORC2; the former is acutely sensitive to rapamycin whereas the latter is only chronically sensitive to rapamycin in vivo. Over the past decade, it has become clear that although genetic and pharmacological inhibition of mTORC1 extends lifespan and delays aging, inhibition of mTORC2 has negative effects on mammalian health and longevity and is responsible for many of the negative side effects of rapamycin. In this review, we discuss recent advances in understanding the molecular and physiological effects of rapamycin treatment, and we discuss how the use of alternative rapamycin treatment regimens or rapamycin analogs has the potential to mitigate the deleterious side effects of rapamycin treatment by more specifically targeting mTORC1. Although the side effects of rapamycin are still of significant concern, rapid progress is being made in realizing the revolutionary potential of rapamycin-based therapies for the treatment of diseases of aging. PMID:27208895

THE INFLUENCE OF ADVANCED AGE ON THE HEPATIC AND RENAL TOXICITY OF CHLOROFORM

EPA Science Inventory

THE INFLUENCE OF ADVANCED AGE ON THE HEPATIC AND RENAL TOXICITY OF CHLOROFORM (CHC13). A McDonald, Y M Sey and J E Simmons. NHEERL, ORD, U.S. EPA, RTP, NC.
Disinfection, by chlorination or by ozonation followed by treatment with either chlorine or chloramine, of water containi...

Advancing Paternal Age and Simplex Autism

ERIC Educational Resources Information Center

Puleo, Connor Morrow; Schmeidler, James; Reichenberg, Abraham; Kolevzon, Alexander; Soorya, Latha V.; Buxbaum, Joseph D.; Silverman, Jeremy M.

2012-01-01

De novo events appear more common in female and simplex autism spectrum disorder (ASD) cases and may underlie greater ASD risk in older fathers' offspring. This study examined whether advancing paternal age predicts an increase in simplex (n = 90) versus multiplex ASD cases (n = 587) in 677 participants (340 families). Whether or not controlling…

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

DNA-aptamers raised against AGEs as a blocker of various aging-related disorders.

PubMed

Yamagishi, Sho-Ichi; Taguchi, Kensei; Fukami, Kei

2016-08-01

A non-enzymatic reaction between sugars or aldehydes and the amino groups of proteins, lipids and nucleic acids contributes to the aging of macromolecules, which could impair their structural integrity and function. This process begins with the conversion of reversible Schiff base adducts, and then to more stable, covalently-bound Amadori rearrangement products. Over a course of days to weeks, these early glycation products undergo further reactions, such as rearrangements and dehydration to become irreversibly crossed-linked, fluorescent protein derivatives termed advanced glycation end products (AGEs). The formation and accumulation of AGEs have been known to progress in a physiological aging process and at an accelerated rate under hyperglycemic, inflammatory and oxidative stress conditions. There is a growing body of evidence that AGEs and their receptor RAGE interaction play a role in the pathogenesis of various devastating disorders, including cardiovascular disease, Alzheimer's disease, insulin resistance, osteoporosis and cancer growth and metastasis. Furthermore, diet has been recently recognized as a major environmental source of AGEs that could also elicit pro-inflammatory reactions, thereby being involved in organ damage in vivo. Therefore, inhibition of AGE formation and/or blockade of the interaction of AGEs with RAGE may be a novel therapeutic target for aging-related disorders. This article discusses a potential utility of DNA-aptamers raised against AGEs for preventing aging and/or diabetes-associated organ damage, especially focusing on diabetic microvascular complications, vascular remodeling, metabolic derangements, and melanoma growth and expansion in animal models.

New age constraints for the Saalian glaciation in northern central Europe: Implications for the extent of ice sheets and related proglacial lake systems

NASA Astrophysics Data System (ADS)

Lang, Jörg; Lauer, Tobias; Winsemann, Jutta

2018-01-01

A comprehensive palaeogeographic reconstruction of ice sheets and related proglacial lake systems for the older Saalian glaciation in northern central Europe is presented, which is based on the integration of palaeo-ice flow data, till provenance, facies analysis, geomorphology and new luminescence ages of ice-marginal deposits. Three major ice advances with different ice-advance directions and source areas are indicated by palaeo-ice flow directions and till provenance. The first ice advance was characterised by a southwards directed ice flow and a dominance of clasts derived from southern Sweden. The second ice advance was initially characterised by an ice flow towards the southwest. Clasts are mainly derived from southern and central Sweden. The latest stage in the study area (third ice advance) was characterised by ice streaming (Hondsrug ice stream) in the west and a re-advance in the east. Clasts of this stage are mainly derived from eastern Fennoscandia. Numerical ages for the first ice advance are sparse, but may indicate a correlation with MIS 8 or early MIS 6. New pIRIR290 luminescence ages of ice-marginal deposits attributed to the second ice advance range from 175 ± 10 to 156 ± 24 ka and correlate with MIS 6. The ice sheets repeatedly blocked the main river-drainage pathways and led to the formation of extensive ice-dammed lakes. The formation of proglacial lakes was mainly controlled by ice-damming of river valleys and major bedrock spillways; therefore the lake levels and extends were very similar throughout the repeated ice advances. During deglaciation the lakes commonly increased in size and eventually drained successively towards the west and northwest into the Lower Rhine Embayment and the North Sea. Catastrophic lake-drainage events occurred when large overspill channels were suddenly opened. Ice-streaming at the end of the older Saalian glaciation was probably triggered by major lake-drainage events.

Casualisation of the teaching workforce: implications for nursing education.

PubMed

Halcomb, Elizabeth J; Andrew, Sharon; Peters, Kath; Salamonson, Yenna; Jackson, Debra

2010-08-01

Internationally, nursing faculty shortages have been reported and there is a potential for them to worsen into the next decade as existing faculty age. To, in part, address this issue, across disciplines there is clearly an international trend towards the increasing casualisation of the higher education workforce. Despite the potential impact of this two-tiered workforce structure, there has been limited examination of the discipline specific issues related to the employment of a growing number of sessional nursing staff. This paper provides a critical review of the literature related to the employment of sessional teachers in higher education. The paper advances the discourse around the role and implications of employing sessional teachers in undergraduate nursing schools. Recommendations for supporting sessional staff and further research are presented. Copyright 2009 Elsevier Ltd. All rights reserved.

Advanced Robotics for Air Force Operations

DTIC Science & Technology

1989-06-01

evaluated current and potential uses of advanced robotics to support Air Force systems, (2) recommended the most effective aplications of advanced robotics...manpower. Such a robot system would The boom would not only transfer fuel, be considerably more mobile and effi- 10 ADVANCED ROBOTICS FOR AIR FORCE...increased manpower resources in war tive clothing reduce vision, hearing, and make this an attractive potential appli- mobility , which further reduce

Recent advances in detection of AGEs: Immunochemical, bioanalytical and biochemical approaches.

PubMed

Ashraf, Jalaluddin Mohd; Ahmad, Saheem; Choi, Inho; Ahmad, Nashrah; Farhan, Mohd; Tatyana, Godovikova; Shahab, Uzma

2015-12-01

Advanced glycation end products (AGEs) are a cohort of heterogeneous compounds that are formed after the nonenzymatic glycation of proteins, lipids and nucleic acids. Accumulation of AGEs in the body is implicated in various pathophysiological conditions like diabetes, cardiovascular diseases and atherosclerosis. Numerous studies have reported the connecting link between AGEs and the various complications associated with diseases. Hence, detection and measurement of AGEs becomes centrally important to understand and manage the menace created by AGEs inside the body. In recent years, an increasing number of immunotechniques as well as bioanalytical techniques have been developed to efficiently measure the levels of AGEs, but most of them are still far away from being clinically consistent, as relative disparity and ambiguity masks their standardization. This article is designed to critically review the recent advances and the emerging techniques for detection of AGEs. It is an attempt to summarize the major techniques that exist currently for the detection of AGEs both qualitatively and quantitatively. This review primarily focuses on the detection and quantification of AGEs which are formed in vivo. Immunochemical approach though costly but most effective and accurate method to measure the level of AGEs. Literature review suggests that detection of autoantibody targeting AGEs is a promising way that can be utilized for detection of AGEs. Future research efforts should be dedicated to develop this method in order to push forward the clinical applications of detection of AGEs. © 2015 International Union of Biochemistry and Molecular Biology.

Enhanced external counterpulsation (EECP) decreases advanced glycation end products and proinflammatory cytokines in patients with non-insulin-dependent type II diabetes mellitus for up to 6 months following treatment.

PubMed

Sardina, Paloma D; Martin, Jeffrey S; Dzieza, Wojciech K; Braith, Randy W

2016-10-01

Enhanced external counterpulsation (EECP) is a noninvasive, non-pharmacologic intervention proven to increase nitric oxide bioavailability in patients with coronary artery disease. The purpose of the present study was to evaluate the potential clinical benefits of EECP on advanced glycation end products (AGEs) and proinflammatory cytokine concentrations in patients with a clinical diagnosis of type II diabetes mellitus (T2DM). Thirty subjects (60.7 ± 1.9 years) with T2DM were randomly assigned (2:1 ratio) to receive either 35 1-h sessions of EECP (n = 20) or time-matched standard care (n = 10). AGEs, receptors for AGEs (RAGEs), soluble vascular cell adhesion molecules-1 (sVCAM-1), and 8-iso-prostaglandin 2α (8-iso-PGF2α) were evaluated before and at 48 h, 2 weeks, 3, and 6 months following EECP treatment or time-matched control. EECP significantly decreased AGEs and RAGEs at all follow-up measurement time points. AGEs and RAGEs were decreased at 48 h (-75 and -16 %), 2 weeks (-87 and -28 %), 3 months (-89 and -29 %), and 6 months (-92 and -20 %) following EECP treatment, respectively. sVCAM-1 and 8-iso-PGF2α were significantly decreased at 48 h (-30 and -49 %) and 2 weeks (-22 and -27 %) following EECP, respectively. sVCAM-1 (-27 %) remained significantly reduced at 3 months following EECP. Nitrite/nitrate (NOx) was significantly increased at 48 h (+48.4 %) and 2 weeks (+51.9 %) following EECP treatment. Our findings provide novel evidence that EECP decreases AGE/RAGE concentrations, inflammation, and oxidative stress in patients with T2DM that persist for up to 6 months following treatment.

Early Formation of Serum Advanced Glycation End-Products in Children with Type 1 Diabetes Mellitus: Relationship with Glycemic Control.

PubMed

Jaisson, Stéphane; Souchon, Pierre-François; Desmons, Aurore; Salmon, Anne-Sophie; Delemer, Brigitte; Gillery, Philippe

2016-05-01

To quantify serum advanced glycation end-products (AGEs) at the onset of type 1 diabetes mellitus and to determine their potential usefulness as retrospective indicators of glycemic balance. Carboxymethyllysine (CML) and pentosidine concentrations were determined by liquid chromatography-tandem mass spectrometry in 3 groups of children with type 1 diabetes mellitus: group (Gr) 1, subjects included at disease onset (n = 36); Gr2, subjects with diabetes of 5 years duration (n = 48); Gr3, subjects with diabetes of 10 years duration and in control subjects (n = 33). Hemoglobin A1c (HbA1c) values were recorded over the entire course of treatment for assessing long-term glycemic balance. Serum AGE concentrations were increased in all groups of subjects with diabetes compared with control subjects, but were highest in Gr1 (for CML: 0.155, 0.306, 0.219, and 0.224 mmol/mol Lys in control, Gr1, Gr2, and Gr3 subjects, respectively; for pentosidine: 312, 492, 365, and 403 nmol/mol Lys, respectively). AGE concentrations were closely correlated with HbA1c values (r = 0.78 for CML; r = 0.49 for pentosidine). In Gr2 and Gr3, the overall glycemic balance estimated by average HbA1c values was positively correlated with CML and pentosidine concentrations, especially in the first year of follow-up. Our results indicate that AGE concentrations are elevated in serum at the time of diabetes mellitus diagnosis, suggesting that the deleterious role of AGEs in the development of long-term complications should be taken into account even at the initial stages of the disease. Moreover, in some circumstances, AGEs could serve as surrogate markers of HbA1c for monitoring glycemic control. Copyright © 2016 Elsevier Inc. All rights reserved.

Advanced Age is Not a Contraindication for Treatment With Curative Intent in Esophageal Cancer.

PubMed

Voncken, Francine E M; van der Kaaij, Rosa T; Sikorska, Karolina; van Werkhoven, Erik; van Dieren, Jolanda M; Grootscholten, Cecile; Snaebjornsson, Petur; van Sandick, Johanna W; Aleman, Berthe M P

2017-07-31

The objective of this study is to compare long-term outcomes between younger and older (70 y and above) esophageal cancer patients treated with curative intent. Overall survival (OS), disease-free survival (DFS), and locoregional recurrence-free interval were compared between older (70 y and above) and younger (below 70 y) esophageal cancer patients treated between 1998 and 2013. Treatment consisted of neoadjuvant chemoradiotherapy with surgery or definitive chemoradiotherapy: 36 to 50.4 Gy in 18 to 28 fractions combined with 5-fluorouracil/cisplatin or carboplatin/paclitaxel. The study comprised 253 patients, of whom 76 were 70 years and older. Median age was 64 years (range, 41 to 83). Most patients had stage II-IIIA disease (83%). Planned treatment was neoadjuvant chemoradiotherapy with surgery for 169 patients (41 patients aged 70 y and older) and definitive chemoradiotherapy for 84 patients (31 patients aged 70 y and older). The compliance to radiotherapy was 92%, with no difference between older and younger patients. In 33 patients (13 patients aged 70 y and older) planned surgery was not performed. Median follow-up was 4.9 years. Three-year OS was 42%. The multivariable analysis showed no statistical difference in OS or in DFS comparing older and younger patients: OS (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.61-1.28), DFS (HR, 0.87; 95% CI, 0.60-1.25). Elderly showed a longer locoregional recurrence-free interval; HR, 0.53 (95% CI, 0.30-0.92; P=0.02) and a higher pathologic complete response rate (50% vs. 25%; P=0.02). Long-term outcomes of older esophageal cancer patients (70 y and above) selected for treatment with neoadjuvant chemoradiotherapy followed by surgery or definitive chemoradiotherapy were comparable with the outcomes of their younger counterparts. Advanced age alone should not be a contraindication for potentially curative chemoradiotherapy-based treatment in esophageal cancer patients.

Caloric restriction and intermittent fasting: Two potential diets for successful brain aging

PubMed Central

Martin, Bronwen; Mattson, Mark P.; Maudsley, Stuart

2008-01-01

The vulnerability of the nervous system to advancing age is all too often manifest in neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. In this review article we describe evidence suggesting that two dietary interventions, caloric restriction (CR) and intermittent fasting (IF), can prolong the health-span of the nervous system by impinging upon fundamental metabolic and cellular signaling pathways that regulate life-span. CR and IF affect energy and oxygen radical metabolism, and cellular stress response systems, in ways that protect neurons against genetic and environmental factors to which they would otherwise succumb during aging. There are multiple interactive pathways and molecular mechanisms by which CR and IF benefit neurons including those involving insulin-like signaling, FoxO transcription factors, sirtuins and peroxisome proliferator-activated receptors. These pathways stimulate the production of protein chaperones, neurotrophic factors and antioxidant enzymes, all of which help cells cope with stress and resist disease. A better understanding of the impact of CR and IF on the aging nervous system will likely lead to novel approaches for preventing and treating neurodegenerative disorders. PMID:16899414

Intelligence and cortical thickness in children with complex partial seizures.

PubMed

Tosun, Duygu; Caplan, Rochelle; Siddarth, Prabha; Seidenberg, Michael; Gurbani, Suresh; Toga, Arthur W; Hermann, Bruce

2011-07-15

Prior studies on healthy children have demonstrated regional variations and a complex and dynamic relationship between intelligence and cerebral tissue. Yet, there is little information regarding the neuroanatomical correlates of general intelligence in children with epilepsy compared to healthy controls. In vivo imaging techniques, combined with methods for advanced image processing and analysis, offer the potential to examine quantitative mapping of brain development and its abnormalities in childhood epilepsy. A surface-based, computational high resolution 3-D magnetic resonance image analytic technique was used to compare the relationship of cortical thickness with age and intelligence quotient (IQ) in 65 children and adolescents with complex partial seizures (CPS) and 58 healthy controls, aged 6-18 years. Children were grouped according to health status (epilepsy; controls) and IQ level (average and above; below average) and compared on age-related patterns of cortical thickness. Our cross-sectional findings suggest that disruption in normal age-related cortical thickness expression is associated with intelligence in pediatric CPS patients both with average and below average IQ scores. Copyright © 2011 Elsevier Inc. All rights reserved.

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

Colonic diverticulosis is not a risk factor for colonic adenoma.

PubMed

Hong, Wandong; Dong, Lemei; Zippi, Maddalena; Stock, Simon; Geng, Wujun; Xu, Chunfang; Zhou, Mengtao

2018-01-01

Colonic diverticulosis may represent a risk factor for colonic adenomas by virtue of the fact that evolving data suggest that these 2 conditions may share common risk factors such as Western dietary pattern and physical inactivity. This study aims to investigate the association between colonic diverticulosis and colonic adenomas in mainland China. We conducted a cross-sectional study on patients who underwent colonoscopic examination between October 2013 and December 2014 in a university hospital in mainland China. Age, gender, colonic adenomas, advanced adenomas, and distribution of diverticulosis were recorded during the procedures. Multivariate logistic regression and stratified analysis were used to evaluate the associations between the prevalence of diverticulosis and age, sex, and presence of colonic adenomas and advanced adenomas. A total of 17,456 subjects were enrolled. The prevalence of colonic diverticulosis and adenoma was 2.4% and 13.2%, respectively. With regard to distribution of diverticula, most (365/424, 86.1%) were right-sided. Multiple logistic regression analysis suggested that age and male gender were independent risk factors for adenoma and advanced adenoma. There was no relationship between diverticulosis or location of diverticulosis and presence of adenoma and advanced adenoma adjusting by age and gender. In a stratified analysis according to age and gender, similar results were also noted. There was no statistical relationship between diverticulosis and the risk of adenoma and advanced adenoma. Our results may not be generalized to the Western population due to the fact that left-sided diverticular cases were very small in our study.

Advanced paternal age increases the risk of schizophrenia and obsessive-compulsive disorder in a Chinese Han population.

PubMed

Wu, Yuejing; Liu, Xiang; Luo, Hongrong; Deng, Wei; Zhao, Gaofeng; Wang, Qiang; Zhang, Lan; Ma, Xiaohong; Liu, Xiehe; Murray, Robin A; Collier, David A; Li, Tao

2012-08-15

Using the Structured Clinical Interview for DSM-IV, patient and non-patient version (SCID-P/NP), this study investigated 351 patients with schizophrenia, 122 with obsessive-compulsive disorder (OCD), and 238 unrelated healthy volunteers in a Chinese Han population. The relative risks posed by advanced paternal age for schizophrenia and OCD in offspring were computed under logistic regression analyses and adjusted for the participant's sex, age and co-parent age at birth. Compared to the offspring with paternal age of 25-29 years old, the relative risks rose from 2.660 to 10.183 in the paternal age range of 30-34 and ≥35. The relative risks for OCD increased from 2.225 to 5.413 in 30-34 and ≥35. For offspring with paternal age of <25, the odds ratios of developing schizophrenia and OCD were 0.628 and 0.289 respectively, whereas an association between increased maternal age and risk for schizophrenia/OCD was not seen. Interaction analysis showed an interaction effect between paternal age and maternal age at birth. Such a tendency of risk affected by parental age for schizophrenia and OCD existed after splitting out the data of early onset patients. Sex-specific analyses found that the relative risks for schizophrenia with paternal age of 30-34 and ≥35 in male offspring were 2.407 and 10.893, and in female offspring were 3.080 and 9.659. The relative risks for OCD with paternal age of 30-34 and ≥35 in male offspring were 3.493 and 7.373, and in female offspring 2.005 and 4.404. The mean paternal age of schizophrenia/OCD patients born before the early 1980s was much greater than that of patients who were born after then. The findings illustrated that advanced paternal age is associated with increased risk for both schizophrenia and OCD in a Chinese Han population, prominently when paternal age is over 35. Biological and non-biological mechanisms may both be involved in the effects of advanced paternal age on schizophrenia and OCD. Copyright © 2012. Published by Elsevier Ireland Ltd.

New stratigraphic constraints on Holocene glacier advances at Mt. Baker, Washington

NASA Astrophysics Data System (ADS)

Clark, D.; Ryane, C.; Tucker, D.; Davis, T.; Bowerman, N.; Osborn, G.; Clague, J.; Menounos, B.; Scott, K.; Guilderson, T.; Riedel, J.; Steig, E.

2007-12-01

New data from a lake sediment core and moraine exposures at Mt. Baker, WA, indicate that a purported early Holocene glacier advance occurred earlier, likely at the end of the Pleistocene. Previous workers used 14C ages associated with small cirque moraines on the SW flank of Mt. Baker, along with the apparent absence of a distinctive scoria (set SC; 8850 14C yr BP, ~9900 cal yr BP) from other moraines on Mt. Baker, as evidence for an advance at ~8400 14C yr BP (~9450 cal yr BP). Such an advance is important to test because it would contrast with glacial records throughout most of the rest of western North America. A 1.2-m sediment core collected from Pocket Lake, which is dammed by one of the previously dated cirque moraines, contains three tephras: Baker set BA (~5800 14C yr BP; 6600 cal yr BP), Mazama ash (6800 14C yr BP; 7600 cal yr BP), and a basal set of ash beds that are tentatively identified as Baker set SC. The lowest macrofossil in the core, ~2 cm above the top of the basal ash beds, yielded an age of 7640 ± 50 14C yr BP (~8400 cal yr BP), consistent with the tephra being SC. Initial geochemical analyses of the tephra also support this identification. These findings indicate that the previous age on the cirque moraine, from organics near the surface of the till, provides a minimum rather than a direct age for the advance that formed the moraine. A 14C age of 11,400 ± 110 14C yr BP (~13,300 cal yr BP) on bulk sediments below the basal ash is likely contaminated and therefore too old. Tephra overlying other ridges at Mt. Baker that were previously identified as post-SC, early-Holocene moraines has been identified as set SC. The ridges thus are actually pre-SC rather than post-SC in age; they may not be moraines in any event. Meanwhile, abundant 14C ages on tills below Deming Glacier indicate both Younger Dryas and Neoglacial advances, but no early Holocene advances. Together, these observations indicate that glaciers in the Mt. Baker area advanced during the YD, were of minimal extent during the early Holocene, and readvanced during the Neoglacial. The similarity of glacier fluctuations here to those in British Columbia and elsewhere in the North Cascades suggests a coherent history of Holocene climate change over a broad area of the northern Cordillera.

Development of somatosensory-evoked potentials in foetal sheep: effects of betamethasone.

PubMed

Anegroaie, P; Frasch, M G; Rupprecht, S; Antonow-Schlorke, I; Müller, T; Schubert, H; Witte, O W; Schwab, M

2017-05-01

Antenatal glucocorticoids are used to accelerate foetal lung maturation in babies threatened with premature labour. We examined the influence of glucocorticoids on functional and structural maturation of the central somatosensory pathway in foetal sheep. Somatosensory-evoked potentials (SEP) reflect processing of somatosensory stimuli. SEP latencies are determined by afferent stimuli transmission while SEP amplitudes reveal cerebral processing. After chronic instrumentation of foetal sheep, mothers received saline (n = 9) or three courses of betamethasone (human equivalent dose of 2 × 110 μg kg -1 betamethasone i.m. 24 h apart, n = 12) at 0.7, 0.75 and 0.8 of gestational age. Trigeminal SEP were evoked prior to, 4 and 24 h after each injection and at 0.8 of gestational age before brains were histologically processed. Somatosensory-evoked potentials were already detectable at 0.7 of gestation age. The early and late responses N20 and N200 were the only reproducible peaks over the entire study period. With advancing gestational age, SEP latencies decreased but amplitudes remained unchanged. Acutely, betamethasone did not affect SEP latencies and amplitudes 4 and 24 h following administration. Chronically, betamethasone delayed developmental decrease in the N200 but not N20 latency by 2 weeks without affecting amplitudes. In parallel, betamethasone decreased subcortical white matter myelination but did not affect network formation and synaptic density in the somatosensory cortex. Somatosensory stimuli are already processed by the foetal cerebral cortex at the beginning of the third trimester. Subsequent developmental decrease in SEP latencies suggests ongoing maturation of afferent sensory transmission. Antenatal glucocorticoids affect structural and functional development of the somatosensory system with specific effects at subcortical level. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

The McGill Geriatric Lithium-Induced Diabetes Insipidus Clinical Study (McGLIDICS).

PubMed

Rej, Soham; Segal, Marilyn; Low, Nancy C P; Mucsi, Istvan; Holcroft, Christina; Shulman, Kenneth; Looper, Karl

2014-06-01

Despite being a common and potentially serious condition, nephrogenic diabetes insipidus (NDI) remains poorly understood in older lithium users. Our main objective was to compare the prevalence of NDI symptoms and decreased urine osmolality ([UOsm] < 300 milli-Osmoles [mOsm/kg]) among geriatric and adult lithium users. We also assessed NDI symptoms, serum sodium (Na+), and urine specific gravity (USG) as possible surrogate measures of decreased UOsm, and ascertained whether potential etiologic factors independently correlated with decreased UOsm. This was a cross-sectional study of 100 consecutive outpatients treated with lithium from 6 tertiary care clinics, of which 45 were geriatric (aged 65 years and older) and 55 adult (aged 18 to 64 years). Patients completed a symptom questionnaire and underwent laboratory tests, including UOsm, serum Na+, and USG. Geriatric and adult lithium users had similar rates of decreased UOsm (12.5%, compared with 17.9%, P = 0.74), but geriatric patients reported less symptoms (P < 0.05). Although UOsm did not correlate with symptoms or current serum Na+, USG of less than 1.010 was suggestive of UOsm of less than 300 mOsm/kg. Age, lithium duration, and serum lithium level were independently associated with UOsm. The prevalence of decreased UOsm is similar in geriatric and adult lithium users, but older patients are less likely to report urinary and thirst symptoms. Although subjective symptoms do not correlate with UOsm, USG may be a cost-efficient clinical surrogate measure for UOsm. We suggest clinicians increase their vigilance for decreased UOsm, especially in lithium users with advanced age, longer duration of lithium exposure, and higher lithium levels. This may potentially prevent lithium intoxication, falls, hypernatremic events, and renal dysfunction.

Advanced glycoxidation and lipoxidation end products (AGEs and ALEs): an overview of their mechanisms of formation.

PubMed

Vistoli, G; De Maddis, D; Cipak, A; Zarkovic, N; Carini, M; Aldini, G

2013-08-01

Advanced lipoxidation end products (ALEs) and advanced glycation end products (AGEs) have a pathogenetic role in the development and progression of different oxidative-based diseases including diabetes, atherosclerosis, and neurological disorders. AGEs and ALEs represent a quite complex class of compounds that are formed by different mechanisms, by heterogeneous precursors and that can be formed either exogenously or endogenously. There is a wide interest in AGEs and ALEs involving different aspects of research which are essentially focused on set-up and application of analytical strategies (1) to identify, characterize, and quantify AGEs and ALEs in different pathophysiological conditions; (2) to elucidate the molecular basis of their biological effects; and (3) to discover compounds able to inhibit AGEs/ALEs damaging effects not only as biological tools aimed at validating AGEs/ALEs as drug target, but also as promising drugs. All the above-mentioned research stages require a clear picture of the chemical formation of AGEs/ALEs but this is not simple, due to the complex and heterogeneous pathways, involving different precursors and mechanisms. In view of this intricate scenario, the aim of the present review is to group the main AGEs and ALEs and to describe, for each of them, the precursors and mechanisms of formation.

Basic and Clinical Research Against Advanced Glycation End Products (AGEs): New Compounds to Tackle Cardiovascular Disease and Diabetic Complications.

PubMed

Nenna, Antonio; Spadaccio, Cristiano; Lusini, Mario; Ulianich, Luca; Chello, Massimo; Nappi, Francesco

2015-01-01

Diabetes is a major risk factor for cardiovascular disease, and recent advances in research indicate that a detailed understanding of the pathophysiology of its effects is mandatory to reduce diabetes-related mortality and morbidity. Advanced Glycation End Products (AGEs) play a central role in the genesis and progression of complications of both type 1 and type 2 diabetes mellitus, and have been found to be important even in non-diabetic patients as a marker of cardiovascular disease. AGEs have a profound impact on patient's prognosis regardless of the glycemic control, and therefore pharmacologic approaches against AGEs accumulation have been proposed over the years to treat cardiovascular diseases, parallel to a more detailed understanding of AGEs pathophysiology. Compounds with anti-AGEs effects are currently under investigation in both pre-clinical and clinical scenarios, and many of the drugs previously used to treat specific diseases have been found to have AGE-inhibitory effects. Some products are still in "bench evaluation", whereas others have been already investigated in clinical trials with conflicting evidences. This review aims at summarizing the mechanisms of AGEs formation and accumulation, and the most relevant issues in pre-clinical and clinical experiences in anti-AGEs treatment in cardiovascular research.

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

In vivo quantification of white matter microstructure for use in aging: a focus on two emerging techniques.

PubMed

Lamar, Melissa; Zhou, Xiaohong Joe; Charlton, Rebecca A; Dean, Douglas; Little, Deborah; Deoni, Sean C

2014-02-01

Human brain imaging has seen many advances in the quantification of white matter in vivo. For example, these advances have revealed the association between white matter damage and vascular disease as well as their impact on risk for and development of dementia and depression in an aging population. Current neuroimaging methods to quantify white matter damage provide a foundation for understanding such age-related neuropathology; however, these methods are not as adept at determining the underlying microstructural abnormalities signaling at risk tissue or driving white matter damage in the aging brain. This review will begin with a brief overview of the use of diffusion tensor imaging (DTI) in understanding white matter alterations in aging before focusing in more detail on select advances in both diffusion-based methods and multi-component relaxometry techniques for imaging white matter microstructural integrity within myelin sheaths and the axons they encase. Although DTI greatly extended the field of white matter interrogation, these more recent technological advances will add clarity to the underlying microstructural mechanisms that contribute to white matter damage. More specifically, the methods highlighted in this review may prove more sensitive (and specific) for determining the contribution of myelin versus axonal integrity to the aging of white matter in brain. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Aging and wave-component latency delays in oVEMP and cVEMP: a systematic review with meta-analysis.

PubMed

Macambira, Ysa Karen Dos Santos; Carnaúba, Aline Tenório Lins; Fernandes, Luciana Castelo Branco Camurça; Bueno, Nassib Bezerra; Menezes, Pedro de Lemos

The natural aging process may result in morphological changes in the vestibular system and in the afferent neural pathway, including loss of hair cells, decreased numbers of vestibular nerve cells, and loss of neurons in the vestibular nucleus. Thus, with advancing age, there should be a decrease in amplitudes and an increase in latencies of the vestibular evoked myogenic potentials, especially the prolongation of p13 latency. Moreover, many investigations have found no significant differences in latencies with advancing age. To determine if there are significant differences in the latencies of cervical and ocular evoked myogenic potentials between elderly and adult patients. This is a systematic review with meta-analysis of observational studies, comparing the differences of these parameters between elderly and young adults, without language or date restrictions, in the following databases: Pubmed, ScienceDirect, SCOPUS, Web of Science, SciELO and LILACS, in addition to the gray literature databases: OpenGrey.eu and DissOnline, as well as Research Gate. The n1 oVEMP latencies had a mean delay in the elderly of 2.32ms with 95% CI of 0.55-4.10ms. The overall effect test showed p=0.01, disclosing that such difference was significant. The heterogeneity found was I 2 =96% (p<0.001). Evaluation of p1 latency was not possible due to the low number of articles selected for this condition. cVEMP analysis was performed in 13 articles. For the p13 component, the mean latency delay in the elderly was 1.34ms with 95% CI of 0.56-2.11ms. The overall effect test showed a p<0.001, with heterogeneity value I 2 =92% (p<0.001). For the n23 component, the mean latency delay for the elderly was 2.82ms with 95% CI of 0.33-5.30ms. The overall effect test showed p=0.03. The heterogeneity found was I 2 =99% (p<0.001). The latency of oVEMP n1 wave component and latencies of cVEMP p13 and n23 wave components are longer in the elderly aged >60 years than in young adults. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Elixir of Life: Thwarting Aging With Regenerative Reprogramming.

PubMed

Beyret, Ergin; Martinez Redondo, Paloma; Platero Luengo, Aida; Izpisua Belmonte, Juan Carlos

2018-01-05

All living beings undergo systemic physiological decline after ontogeny, characterized as aging. Modern medicine has increased the life expectancy, yet this has created an aged society that has more predisposition to degenerative disorders. Therefore, novel interventions that aim to extend the healthspan in parallel to the life span are needed. Regeneration ability of living beings maintains their biological integrity and thus is the major leverage against aging. However, mammalian regeneration capacity is low and further declines during aging. Therefore, modalities that reinforce regeneration can antagonize aging. Recent advances in the field of regenerative medicine have shown that aging is not an irreversible process. Conversion of somatic cells to embryonic-like pluripotent cells demonstrated that the differentiated state and age of a cell is not fixed. Identification of the pluripotency-inducing factors subsequently ignited the idea that cellular features can be reprogrammed by defined factors that specify the desired outcome. The last decade consequently has witnessed a plethora of studies that modify cellular features including the hallmarks of aging in addition to cellular function and identity in a variety of cell types in vitro. Recently, some of these reprogramming strategies have been directly used in animal models in pursuit of rejuvenation and cell replacement. Here, we review these in vivo reprogramming efforts and discuss their potential use to extend the longevity by complementing or augmenting the regenerative capacity. © 2017 American Heart Association, Inc.

The downregulation of thioredoxin accelerated Neuro2a cell apoptosis induced by advanced glycation end product via activating several pathways.

PubMed

Ren, Xiang; Ma, Haiying; Qiu, Yuanyuan; Liu, Bo; Qi, Hui; Li, Zeyu; Kong, Hui; Kong, Li

2015-08-01

Thioredoxin (Trx), a 12 kDa protein, has different functions in different cellular environments, playing important anti-oxidative and anti-apoptotic roles and regulating the expression of transcription factors. Advanced glycation end products (AGEs) are a heterogeneous group of irreversible adducts from glucose-protein condensation reactions and are considered crucial to the development of diabetic nephropathy, retinopathy, neurodegeneration and atherosclerosis. The aim of this study was to use a Trx inhibitor to investigate the effects and mechanism of Trx down-regulation on AGE-induced Neuro2a cell apoptosis. Neuro2a cells were cultured in vitro and treated with different conditions. The apoptosis and proliferation of Neuro2a cells were detected using flow cytometry, DNA-Ladder and CCK8 assays. Rho 123 was used to detect the mitochondrial membrane potential. ROS generation and caspase3 activity were detected using a DCFH-DA probe and micro-plate reader. Western blotting and real-time PCR were used to detect the expression of proteins and genes. We found that the down-regulation of thioredoxin could accelerate AGE-induced apoptosis in Neuro2a cells. A possible underlying mechanism is that the down-regulation of thioredoxin stimulated the up-regulation of ASK1, p-JNK, PTEN, and Txnip, as well as the down-regulation of p-AKT, ultimately increasing ROS levels and caspase3 activity. Copyright © 2015. Published by Elsevier Ltd.

Tissue repair genes: the TiRe database and its implication for skin wound healing.

PubMed

Yanai, Hagai; Budovsky, Arie; Tacutu, Robi; Barzilay, Thomer; Abramovich, Amir; Ziesche, Rolf; Fraifeld, Vadim E

2016-04-19

Wound healing is an inherent feature of any multicellular organism and recent years have brought about a huge amount of data regarding regular and abnormal tissue repair. Despite the accumulated knowledge, modulation of wound healing is still a major biomedical challenge, especially in advanced ages. In order to collect and systematically organize what we know about the key players in wound healing, we created the TiRe (Tissue Repair) database, an online collection of genes and proteins that were shown to directly affect skin wound healing. To date, TiRe contains 397 entries for four organisms: Mus musculus, Rattus norvegicus, Sus domesticus, and Homo sapiens. Analysis of the TiRe dataset of skin wound healing-associated genes showed that skin wound healing genes are (i) over-conserved among vertebrates, but are under-conserved in invertebrates; (ii) enriched in extracellular and immuno-inflammatory genes; and display (iii) high interconnectivity and connectivity to other proteins. The latter may provide potential therapeutic targets. In addition, a slower or faster skin wound healing is indicative of an aging or longevity phenotype only when assessed in advanced ages, but not in the young. In the long run, we aim for TiRe to be a one-station resource that provides researchers and clinicians with the essential data needed for a better understanding of the mechanisms of wound healing, designing new experiments, and the development of new therapeutic strategies. TiRe is freely available online at http://www.tiredb.org.

Prognostic factors in relation to racial disparity in advanced colorectal cancer survival.

PubMed

Wallace, Kristin; Sterba, Katherine R; Gore, Elena; Lewin, David N; Ford, Marvella E; Thomas, Melanie B; Alberg, Anthony J

2013-12-01

Colorectal cancer mortality rates are significantly greater in AA than in EA individuals, and the disparity is worsening. We investigated the relationship between race and metastatic CRC (mCRC) survival in younger and older patients. Using data from the Hollings Cancer Center (Charleston, SC), we studied the role of clinical, pathologic, and treatment-related factors on the disparity in survival. We carried out a retrospective cohort study of 82 mCRC patients (26 AA, 56 EA). The data source was medical record data from June 1, 2004 through May 31, 2008 with follow-up through June 30, 2010. Using Kaplan-Meier methods, we generated median survival time according to race and age (< 61, ≥ 61 years). Cox proportional hazards regression models were used to model the risk of death according to race. The median age was 56.7 years for AA and 61.6 years for EA patients. Compared with EA, median survival in AA patients was 59% worse in younger patients (12.7 vs. 31.0 months) and 29% worse in older patients (11.7 vs. 16.4 months). The risk of death among younger AA compared with EA patients was 2.45 (95% confidence interval [CI], 1.15-5.23) and among older patients was 1.16 (95% CI, 0.49-2.73). Our results highlight the importance of considering younger age, clinical prognostic markers, and tumor phenotypes as potential sources of the disparity in advanced stage CRC. Copyright © 2013 Elsevier Inc. All rights reserved.

Tissue repair genes: the TiRe database and its implication for skin wound healing

PubMed Central

Yanai, Hagai; Budovsky, Arie; Tacutu, Robi; Barzilay, Thomer; Abramovich, Amir; Ziesche, Rolf; Fraifeld, Vadim E.

2016-01-01

Wound healing is an inherent feature of any multicellular organism and recent years have brought about a huge amount of data regarding regular and abnormal tissue repair. Despite the accumulated knowledge, modulation of wound healing is still a major biomedical challenge, especially in advanced ages. In order to collect and systematically organize what we know about the key players in wound healing, we created the TiRe (Tissue Repair) database, an online collection of genes and proteins that were shown to directly affect skin wound healing. To date, TiRe contains 397 entries for four organisms: Mus musculus, Rattus norvegicus, Sus domesticus, and Homo sapiens. Analysis of the TiRe dataset of skin wound healing-associated genes showed that skin wound healing genes are (i) over-conserved among vertebrates, but are under-conserved in invertebrates; (ii) enriched in extracellular and immuno-inflammatory genes; and display (iii) high interconnectivity and connectivity to other proteins. The latter may provide potential therapeutic targets. In addition, a slower or faster skin wound healing is indicative of an aging or longevity phenotype only when assessed in advanced ages, but not in the young. In the long run, we aim for TiRe to be a one-station resource that provides researchers and clinicians with the essential data needed for a better understanding of the mechanisms of wound healing, designing new experiments, and the development of new therapeutic strategies. TiRe is freely available online at http://www.tiredb.org. PMID:27049721

Quaternary glacial, lacustrine, and fluvial interactions in the western Noatak basin, Northwest Alaska

USGS Publications Warehouse

Hamilton, T.D.

2001-01-01

The 130 km long Noatak basin is surrounded by mountains of the western Brooks Range. Middle and late Pleistocene glaciers flowing southeast into the basin dammed a succession of proglacial lakes defined by shorelines, outlet channels and upper limits of wave erosion. More than 60 bluffs along the Noatak River and its principal tributaries expose glacial and glaciolacustrine sediments that exhibit cut-and-fill relationships with interglacial and interstadial river-channel and floodplain deposits. This report focuses on the western Noatak basin, where high bluffs created by deep postglacial erosion record four major glacial advances. During the Cutler advance, a floating ice tongue terminated in a large proglacial lake that filled the Noatak basin. The retreating glacier abandoned a trough along the valley center that subsequently filled with about 40m of sediment during several younger glaciations and probably two major interglacial episodes. Alluvium that formed near the beginning of the younger interglaciation contains the 140,000 yr old Old Crow tephra. The subsequent closely spaced Okak and Makpik advances are clearly younger than the maximum of the last interglaciation, but they preceded a middle Wisconsin (36-30 ka) nonglacial interval in the Noatak basin. The Okak advance terminated in an extensive lake, whereas glaciers of the Makpik and the subsequent Anisak advances flowed into much narrower lakes that filled only the basin center. The Anisak advance, bracketed by radiocarbon ages of about 35 and 13.6 ka, represents the Last Glacial Maximum (LGM) in the western Noatak basin. Correlations with the oldest and youngest glacial deposits of the central Brooks Range are clear, but relationships to events of intermediate age are more tenuous. Early Pleistocene and older glacial advances from the central Brooks Range must have filled the Noatak basin and overflowed northward through Howard Pass. A younger glacial advance, of inferred middle Pleistoscene (Sagavanirktok River) age, extended down the Noatak valley into the basin center, but its deposits are deeply buried beneath the basin floor and must be older than the Cutler moraine. The Cutler advance may have been synchronous with the older of two advances of Itkillik I age in the Atongarak Creek area, but other evidence indicates that the Okak-Makpik moraine succession more likely was synchronous with the two Atongarak Creek moraines. Radiocarbon ages, surface morphology, soil and weathering profiles, and lake-level history all support correlation of the last (Anisak) major glacial advance in the western basin with the Douglas Creek moraine farther east and with Itkillik II (late Wisconsin) glaciation of the central Brooks Range. ?? 2000 Elsevier Science Ltd.

Telomere-driven diseases and telomere-targeting therapies

PubMed Central

2017-01-01

Telomeres, the protective ends of linear chromosomes, shorten throughout an individual’s lifetime. Telomere shortening is proposed to be a primary molecular cause of aging. Short telomeres block the proliferative capacity of stem cells, affecting their potential to regenerate tissues, and trigger the development of age-associated diseases. Mutations in telomere maintenance genes are associated with pathologies referred to as telomere syndromes, including Hoyeraal-Hreidarsson syndrome, dyskeratosis congenita, pulmonary fibrosis, aplastic anemia, and liver fibrosis. Telomere shortening induces chromosomal instability that, in the absence of functional tumor suppressor genes, can contribute to tumorigenesis. In addition, mutations in telomere length maintenance genes and in shelterin components, the protein complex that protects telomeres, have been found to be associated with different types of cancer. These observations have encouraged the development of therapeutic strategies to treat and prevent telomere-associated diseases, namely aging-related diseases, including cancer. Here we review the molecular mechanisms underlying telomere-driven diseases and highlight recent advances in the preclinical development of telomere-targeted therapies using mouse models. PMID:28254828

The Nucleosome Remodeling and Deacetylase (NuRD) Complex in Development and Disease

PubMed Central

Basta, Jeannine; Rauchman, Michael

2014-01-01

The Nucleosome Remodeling and Deacetylase (NuRD) complex is one of the major chromatin remodeling complexes found in cells. It plays an important role in regulating gene transcription, genome integrity and cell cycle progression. Through its impact on these basic cellular processes, increasing evidence indicates that alterations in the activity of this macromolecular complex can lead to developmental defects, oncogenesis and accelerated ageing. Recent genetic and biochemical studies have elucidated the mechanisms of NuRD action in modifying the chromatin landscape. These advances have the potential to lead to new therapeutic approaches to birth defects and cancer. PMID:24880148

Latest Pleistocene and Holocene Glacier Fluctuations in southernmost Patagonia

NASA Astrophysics Data System (ADS)

Menounos, B.; Maurer, M.; Clague, J. J.; osborn, G.; Ponce, F.; Davis, P. T.; Rabassa, J.; Coronato, A.; Marr, R.

2011-12-01

Summer insolation has been proposed to explain long-term glacier fluctuations during the Holocene. If correct, the record of glacier fluctuations at high latitudes in the Southern Hemisphere should differ from that in the Northern Hemisphere. Testing this insolation hypothesis has been hampered by dating uncertainties of many Holocene glacier chronologies from Patagonia. We report on our ongoing research aimed at developing a regional glacier chronology at the southern end of the Andes north and west of Ushuaia, Argentina. We have found evidence for an advance of cirque glaciers at the end of the Pleistocene; one or locally two closely spaced moraines extend up to 2 km beyond Little Ice Age moraines. Radiocarbon dating of terrestrial macrofossils recovered from basal sediments behind two of these moraines yielded ages of 10,320 ± 25 and 10,330 ± 30 14C yr BP. These moraines may record glacier advances coeval with the Antarctic Cold Reversal; surface exposure dating of these moraines is currently in progress to test this hypothesis. We find no evidence of Holocene moraines older than 6800 14C yr BP, based on the distribution of Hudson tephra of that age. At some sites, there is evidence for an early Neoglacial advance of glaciers slightly beyond (< 0.5 km) Little Ice Age limits. Terrestrial macrofossils at the upper contact of basal till from one site yielded an age of 4505 ± 30 14C yr BP; this age overlaps the most probable age range of early Neoglacial ice expansion in southern Patagonia reported by Porter (2000) and the age of plants killed by expansion of the Quelccaya Ice Cap in Peru. We have documented multiple wood mats with stumps in growth position separated by till units in a 100 m section of the northeast lateral moraine at Stoppani Glacier (54.78 S, 68.98 W), 50 km west of Ushuaia. Ten radiocarbon ages on these wood mats range in age from 3510 ± 15 to 135 ± 15 14C yr BP. The mats decrease in age up-section; many overlap with published age ranges for Neoglacial advances in western Canada. Taken together, these data: a) do not support the summer insolation hypothesis for Holocene glacier fluctuations in southernmost Patagonia; b) confirm paleobotanical evidence for a warm, dry early Holocene; and c) suggest that many Neoglacial advances in southernmost Patagonia and western North America were synchronous.

Aging, age-related macular degeneration, and the response-to-retention of apolipoprotein B-containing lipoproteins

PubMed Central

Curcio, Christine A.; Johnson, Mark; Huang, Jiahn-Dar; Rudolf, Martin

2015-01-01

The largest risk factor for age-related macular degeneration (ARMD) is advanced age. A prominent age-related change in the human retina is the accumulation of histochemically detectable neutral lipid in normal Bruch’s membrane (BrM) throughout adulthood. This change has the potential to have a major impact on physiology of the retinal pigment epithelium (RPE). It occurs in the same compartment as drusen and basal linear deposit, the pathognomonic extracellular, lipid-containing lesions of ARMD. Here we present evidence from light microscopic histochemistry, ultrastructure, lipid profiling of tissues and isolated lipoproteins, and gene expression analysis that this deposition can be accounted for by esterified cholesterol-rich, apolipoprotein B-containing lipoprotein particles constitutively produced by the RPE. This work collectively allows ARMD lesion formation and its aftermath to be conceptualized as a response to the retention of a sub-endothelial apolipoprotein B lipoprotein, similar to a widely accepted model of atherosclerotic coronary artery disease (CAD) (Tabas et al., 2007). This approach provides a wide knowledge base and sophisticated clinical armamentarium that can be readily exploited for the development of new model systems and the future benefit of ARMD patients. PMID:19698799

Modifiable risk factors for impaired fertility in women: what nurse practitioners need to know.

PubMed

Kelly-Weeder, Susan; O'Connor, Alane

2006-06-01

To provide an overview of impaired fertility in childbearing-aged women, to review the current research on modifiable lifestyle risk factors implicated in its development, and to suggest strategies for nurse practitioners (NPs) to assist women in behavioral changes that will allow them to protect their fertility. Original research articles and comprehensive review articles identified through Medline, CINAHL, and OVID databases. Research has shown that advancing age, a history of a sexually transmitted infection and/or pelvic inflammatory disease, extremes of body weight, and tobacco and caffeine use are potentially modifiable risk factors in the development of impaired fertility. NPs must be aware of the link between these behaviors and the development of impaired fertility in order to assist women in preserving their fertility. Individual counseling, education, and community-wide education strategies are discussed.

Rehabilitative potentialities and successes of aphasia therapy in children and young people after cerebrotraumatic lesions (author's transl).

PubMed

Emich, I F

1980-08-01

Novel verbal and nonverbal therapeutic techniques are described by means of examples. The aphasic clients range from preschool and school children to young people up to the age of 18. Identification and evaluation of main interest areas enabled individualised combinations of therapeutic measure as well as novel play and/or work situations to be developed, which also involved technical devices: animal voice imitation, play telephone, normal telephone, typewriter, electronic pocket calculator, magic screen, keyed instruments (toy piano, etc.). Rhythmically stressed and "sports" speech training (revolving disc, indoor bicycle, "jouk" sport), hydrotherapy, horseback riding, swimming. Age-adapted conversation, storytelling, motivation through joy and success ("circulus hortativus"), music therapy. Even in cases of extremely delayed treatment, advances may be achieved. Special hints: shorthand therapy, pseudo-phenomena, cotherapy, conversion of right-handed to left.

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 directives in patients with advanced cancer receiving active treatment: attitudes, prevalence, and barriers.

PubMed

McDonald, Julie C; du Manoir, Jeanne M; Kevork, Nanor; Le, Lisa W; Zimmermann, Camilla

2017-02-01

The purposes of the study were to assess awareness and prevalence of advance directives (ADs) among patients with advanced cancer undergoing active outpatient care and to determine factors associated with AD completion before and after the diagnosis of cancer. Patients with advanced solid tumor malignancy receiving treatment at the Chemotherapy Day Unit were approached for recruitment. They completed an onsite questionnaire about completion and timing of ADs, demographic information, and perceived health; a review of their medical records was conducted to document their cancer care and co-morbidities. Multinomial logistic regression analysis identified factors associated with the timing of AD completion (pre-cancer, post-cancer, or not at all). Two hundred patients were enrolled, with 193 surveys available for analysis. ADs were completed in 55 % (106/193) of patients, including a living will in 33 % (63/193), a power of attorney in 49 % (95/193), and a do-not-resuscitate (DNR) designation in 18 % (35/193). Most patients (53 %) had completed an AD before being diagnosed with cancer. Higher income (p = 0.02) and age (p = 0.004) were associated with AD completion pre-cancer diagnosis; discussion of end-of-life care (p = 0.02) and palliative care referral (p < 0.0001) were associated with AD completion post-cancer diagnosis. This study demonstrates that different factors may influence the completion of ADs before and after a diagnosis of cancer and highlights the potential for early palliative care to impact the completion of ADs in patients with advanced cancer who are undergoing active cancer treatment.

Reduced temporal processing in older, normal-hearing listeners evident from electrophysiological responses to shifts in interaural time difference.

PubMed

Ozmeral, Erol J; Eddins, David A; Eddins, Ann C

2016-12-01

Previous electrophysiological studies of interaural time difference (ITD) processing have demonstrated that ITDs are represented by a nontopographic population rate code. Rather than narrow tuning to ITDs, neural channels have broad tuning to ITDs in either the left or right auditory hemifield, and the relative activity between the channels determines the perceived lateralization of the sound. With advancing age, spatial perception weakens and poor temporal processing contributes to declining spatial acuity. At present, it is unclear whether age-related temporal processing deficits are due to poor inhibitory controls in the auditory system or degraded neural synchrony at the periphery. Cortical processing of spatial cues based on a hemifield code are susceptible to potential age-related physiological changes. We consider two distinct predictions of age-related changes to ITD sensitivity: declines in inhibitory mechanisms would lead to increased excitation and medial shifts to rate-azimuth functions, whereas a general reduction in neural synchrony would lead to reduced excitation and shallower slopes in the rate-azimuth function. The current study tested these possibilities by measuring an evoked response to ITD shifts in a narrow-band noise. Results were more in line with the latter outcome, both from measured latencies and amplitudes of the global field potentials and source-localized waveforms in the left and right auditory cortices. The measured responses for older listeners also tended to have reduced asymmetric distribution of activity in response to ITD shifts, which is consistent with other sensory and cognitive processing models of aging. Copyright © 2016 the American Physiological Society.

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

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

[Current insights into anemia in old age : Summary of the symposium "Anemia in old age" on the occasion of the annual congress of the German Society for Geriatrics (DGG) 2016 in Stuttgart].

PubMed

Röhrig, Gabriele; Gütgemann, Ines; von Gersdorff, Gero; Polidori, Maria Cristina; Lupescu, Adrian; Lang, Florian; Kolb, Gerald

2018-04-01

Anemia in advanced age is often a multifactorial condition requiring an interdisciplinary approach. The contributions to the opening interdisciplinary symposium on anemia in older subjects focused on physiological and histopathological as well as on nephrological and neurogeriatric aspects and on the therapeutic implications of this underdiagnosed, yet highly frequent disease. The symposium was the kick-off event for the founding of the German Geriatric Society special interest group on anemia in advanced age.

Advancing LGBT Elder Policy and Support Services: The Massachusetts Model.

PubMed

Krinsky, Lisa; Cahill, Sean R

2017-12-01

The Massachusetts-based LGBT Aging Project has trained elder service providers in affirming and culturally competent care for LGBT older adults, supported development of LGBT-friendly meal programs, and advanced LGBT equality under aging policy. Working across sectors, this innovative model launched the country's first statewide Legislative Commission on Lesbian, Gay, Bisexual, and Transgender Aging. Advocates are working with policymakers to implement key recommendations, including cultural competency training and data collection in statewide networks of elder services. The LGBT Aging Project's success provides a template for improving services and policy for LGBT older adults throughout the country.

Society for the advancement of material and process engineering. 41st International SAMPE symposium and exhibition, Volume 41, Books 1 and 2

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

NONE

This document contains reports which were presented at the 41st International Society For The Advancement of Material and Process Engineering Symposium and Exhibition. Topics include: structural integrity of aging aircraft; composite materials development; affordable composites and processes; corrosion characterization of aging aircraft; adhesive advances; composite design; dual use materials and processing; repair of aircraft structures; adhesive inspection; materials systems for infrastructure; fire safety; composite impact/energy absorption; advanced materials for space; seismic retrofit; high temperature resins; preform technology; thermoplastics; alternative energy and transportation; manufacturing; and durability. Individual reports have been processed separately for the United States Department of Energy databases.

Characterizing Pelvic Organ Prolapse in Adult Spina Bifida Patients.

PubMed

Liu, Joceline S; Vo, Amanda X; Doolittle, Johnathan; Hamoui, Nabeel; Lewicky-Gaupp, Christina; Kielb, Stephanie J

2016-11-01

To report the distribution of pelvic organ prolapse (POP) stages in adult spina bifida (SB) patients. The severity of POP in the SB population has not been previously reported. Retrospective review of SB patients ≥18 years with a documented POP quantification examination between 2006 and 2014 were included. Patient demographics, gestation, parity, POP quantification examinations and prolapse symptoms were obtained. Thirty-three SB patients were identified with a mean age of 33.2 years. Five patients (15.2%) had stage 0 prolapse, 12 (36.4%) had stage 1, 12 (36.4%) had stage 2, 3 (9.1%) had stage 3, and 1 (3.0%) had stage 4. Of the 16 patients with advanced POP (stage 2 prolapse or greater), only 6 patients (37.5%) reported symptoms related to POP. All 6 symptomatic patients endorsed sensation of a vaginal bulge. Two of the 6 patients also reported dyspareunia. Additionally, 1 patient with advanced POP presented with vaginal bulge, noted by a caregiver, and cervical bleeding, but was otherwise asymptomatic. Twenty-four patients (72.7%) were nulliparous, and 12 of the 24 nulliparous patients (50%) demonstrated prolapse. Despite young age and frequent nulliparity, patients with SB are more likely to have POP than the general population. Additionally, the majority of SB patients with prolapse are asymptomatic. Assessment of pelvic organ prolapse should be included in the evaluation of adult SB females due to the low rate of symptoms even in the setting of advanced stage prolapse and potential impact on both urinary and bowel function. Copyright © 2016 Elsevier Inc. All rights reserved.

Advancing age increases sperm chromatin damage and impairs fertility in peroxiredoxin 6 null mice

PubMed Central

Ozkosem, Burak; Feinstein, Sheldon I.; Fisher, Aron B.; O’Flaherty, Cristian

2015-01-01

Due to socioeconomic factors, more couples are choosing to delay conception than ever. Increasing average maternal and paternal age in developed countries over the past 40 years has raised the question of how aging affects reproductive success of males and females. Since oxidative stress in the male reproductive tract increases with age, we investigated the impact of advanced paternal age on the integrity of sperm nucleus and reproductive success of males by using a Prdx6−/− mouse model. We compared sperm motility, cytoplasmic droplet retention sperm chromatin quality and reproductive outcomes of young (2-month-old), adult (8-month-old), and old (20-month-old) Prdx6−/− males with their age-matched wild type (WT) controls. Absence of PRDX6 caused age-dependent impairment of sperm motility and sperm maturation and increased sperm DNA fragmentation and oxidation as well as decreased sperm DNA compaction and protamination. Litter size, total number of litters and total number of pups per male were significantly lower in Prdx6−/− males compared to WT controls. These abnormal reproductive outcomes were severely affected by age in Prdx6−/− males. In conclusion, the advanced paternal age affects sperm chromatin integrity and fertility more severely in the absence of PRDX6, suggesting a protective role of PRDX6 in age-associated decline in the sperm quality and fertility in mice. PMID:25796034

Maternal air pollution exposure and preterm birth in Wuxi, China: Effect modification by maternal age.

PubMed

Han, Yingying; Jiang, Panhua; Dong, Tianyu; Ding, Xinliang; Chen, Ting; Villanger, Gro Dehli; Aase, Heidi; Huang, Lu; Xia, Yankai

2018-08-15

Numerous studies have investigated prenatal air pollution and shown that air pollutants have adverse effect on birth outcomes. However, which trimester was the most sensitive and whether the effect was related to maternal age is still ambiguous. This study aims to explore the association between maternal air pollution exposure during pregnancy and preterm birth, and if this relationship is modified by maternal age. In this retrospective cohort study, we examine the causal relationship of prenatal exposure to air pollutants including particulate matters, which are less than 10 µm (PM 10 ), and ozone (O 3 ), which is one of the gaseous pollutants, on preterm birth by gestational age. A total of 6693 pregnant women were recruited from Wuxi Maternal and Child Health Care Hospital. The participants were dichotomized into child-bearing age group (< 35 years old) and advanced age group (> = 35 years old) in order to analyze the effect modification by maternal age. Logistic and linear regression models were performed to assess the risk for preterm birth (gestational age < 37 weeks) caused by prenatal air pollution exposure. With adjustment for covariates, the highest level of PM 10 exposure significantly increased the risk of preterm birth by 1.42-fold (95% CI: 1.10, 1.85) compared those with the lowest level in the second trimester. Trimester-specific PM 10 exposure was positively associated with gestational age, whereas O 3 exposure was associated with gestational age in the early pregnancy. When stratified by maternal age, PM 10 exposure was significantly associated with an increased risk of preterm birth only in the advanced age group during pregnancy (OR:2.15, 95% CI: 1.13, 4.07). The results suggested that PM 10 exposure associated with preterm birth was modified by advanced maternal age (OR interaction = 2.00, 95% CI: 1.02, 3.91, P interaction = 0.032). Prenatal air pollution exposure would increase risk of preterm birth and reduced gestational age. Thus, more attention should be paid to the effects of ambient air pollution exposure on preterm birth especially in pregnant women with advanced maternal age. Copyright © 2018 Elsevier Inc. All rights reserved.

Growth of California red fir advance regeneration after overstory removal and thinning

Treesearch

William W. Oliver

1985-01-01

Advance regeneration is common under decadent, old-growth stands of California red fir (Abies magnifica A. Murr.). Intense competition for the site's resources can create sapling stands of poor vigor and advanced age. When competition is reduced by overstory removal and thinning, suppressed advance regeneration has been shown to respond with...

Advancements in cosmogenic 38Ar exposure dating of terrestrial rocks

NASA Astrophysics Data System (ADS)

Oostingh, K. F.; Jourdan, F.; Danišík, M.; Evans, N. J.

2017-11-01

Cosmogenic exposure dating of Ca-rich minerals using 38Ar on terrestrial rocks could be a valuable new dating tool to determine timescales of geological surface processes on Earth. Here, we show that advancement in analytical precision, using the new generation multi-collector ARGUSVI mass spectrometer on irradiated pyroxene and apatite samples, allows determination of cosmogenic 38Ar abundances above background values, as well as discrimination of 38Ar/36Ar ratios (1σ absolute precision of ±0.3%) from the non-cosmogenic background value. Four statistically significant cosmochron (38Ar/36Ar vs37Ar/36Ar) diagrams could be constructed for southeast Australian pyroxene samples from the Mt Elephant scoria cone for which a combined apparent exposure age of 313 ± 179 ka (2σ) was obtained when using a 38Ar production rate (Ca) of 250 atoms /g Ca/ yr. This exposure age overlaps within error with the known 40Ar/39Ar eruption age of 184 ± 15 ka (2σ). Although apatite shows much larger 38Ar abundances than pyroxene, our modelling and analyses of unirradiated apatite suggest that apatite suffers from both natural and reactor-derived chlorogenic as well as natural nucleogenic contributions of 38Ar. Hence, we suggest that cosmogenic 38Ar exposure dating on irradiated Ca-rich (and eventually K-rich), but Cl-free, terrestrial minerals is a potential valuable and accessible tool to determine geological surface processes on timescales of a few Ma. Calculations show that with the new generation multi-collector mass spectrometers an analytical uncertainty better than 5% (2σ) can be achieved on samples with expected exposure ages of >4 Ma.

Traditional medicines used by Q'eqchi' Maya to treat diabetic symptoms and their antiglycation potential.

PubMed

Ferrier, J; Saleem, A; Carter Ramirez, A; Liu, R; Chen, Eric; Pesek, T; Cal, V; Balick, M; Arnason, J T

2018-06-21

Because of the recent increase in type 2 diabetes and the need for complementary treatments in remote communities in many parts of the world, we undertook a study of treatments for diabetic symptoms used by traditional Q'eqchi' Maya healers of Belize. We used quantitative ethnobotany to rank culturally important taxa and subsequent pharmacological and phytochemical studies to assess bioactivity. Antidiabetic plants identified in field interviews with traditional healers were ranked by syndromic importance value (SIV) based on 15 symptoms of diabetes.. Species ranked with high SIV were tested in an assay relevant to many diabetes complications, the advanced glycation endproduct (AGE) inhibition assay. Active principles were identified by phytochemical analysis and bioassay. We collected over 70 plant species having a promising SIV score. The plants represented a broad range of neotropical taxa. Selected Q'eqchi' antidiabetic plants with high SIV were collected in bulk and tested in the advanced glycation endproduct (AGE) inhibition assay. All plant extracts showed AGE inhibition and the half maximal inhibitory concentration (IC 50 ) ranged from 40.8 to 733µg/mL, while the most active species was Tynanthus guatemalensis Donn (Bignoniaceae). A linear regression showed a significant relationship between 1/ IC 50 and SIV. Phytochemical analysis revealed the presence of verbascoside, as a major component and active principle of the T guatemalensis which had an IC 50 = 5.1µg/mL, comparable to the positive control quercetin. The results reveal a rich botanical tradition of antidiabetic symptom treatments among the Q'eqchi'. Study of highly ranked plants revealed their activity in AGE inhibition correlated with SIV. T. guatemalensis was identified as a promising species for further evaluation and local use. Copyright © 2018. Published by Elsevier B.V.

Age and stress as determinants of the severity of hyperthyroidism caused by Graves' disease in newly diagnosed patients.

PubMed

Vos, Xander G; Smit, Natalie; Endert, Erik; Brosschot, Jos F; Tijssen, Jan G P; Wiersinga, Wilmar M

2009-02-01

The evidence that stress may provoke Graves' hyperthyroidism in genetically susceptible subjects is substantial. Whether exposure to stress is related to the severity of thyrotoxicosis has not been studied. Advancing age is associated with not only less severe Graves' hyperthyroidism but also self-reported stress. We tested the hypothesis whether advancing age is associated with less exposure to stress, resulting in a lower immunological response, and less severe Graves' hyperthyroidism. Cross-sectional multicenter study. Two hundred and sixty-three consecutive untreated patients with a first episode of Graves' hyperthyroidism were included. The severity of Graves' hyperthyroidism was evaluated biochemically (freeT(4)-index and freeT(3)-index, thyrotropin-binding inhibitory immunoglobulin (TBII)) and clinically by the hyperthyroid symptom scale score (HSS score). Stress exposure was quantitated by three questionnaires. Advancing age was associated with less severe Graves' hyperthyroidism, both biochemically by lower serum freeT(3)-index and freeT(4)-index (P<0.01), lower serum TBII (P=0.05), and clinically by lower HSS scores (P=0.04) and smaller goiter size (P<0.01). FreeT(3)-index and freeT(4)-index were directly associated with HSS scores (P<0.01). Stress scores were associated with HSS scores (P<0.01) but not with biochemical severity of Graves' hyperthyroidism. Advancing age was associated with lower scores for stress exposure. Multivariate regression analysis showed that HSS score was independently related to the tendency to report negative feelings (P<0.01) but not to other stress scores and also not to age. Advancing age is associated with less exposure to stress, lower serum TBII and less severe clinical and biochemical Graves' hyperthyroidism. Because no direct relationship exists between stress exposure and TBII or freeT(3)-index and freeT(4)-index, we reject our hypothesis that less stress is causally related to biochemically less severe Graves' hyperthyroidism in old age. HSS score is primarily determined by negative feelings and not by age.

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

Evaluation of Asteraceae herbal extracts in the management of diabetes and obesity. Contribution of caffeoylquinic acids on the inhibition of digestive enzymes activity and formation of advanced glycation end-products (in vitro).

PubMed

Spínola, Vítor; Castilho, Paula C

2017-11-01

The study was performed to assess, for the first time, the in vitro anti-diabetic potential of ten Asteraceae plant extracts to inhibit the activity of digestive enzymes (α-amylase, α-, β-glucosidases and lipase) responsible for hydrolysis/digestion of sugar and lipids. Prevention of advanced glycation end-products (AGEs) formation was evaluated in bovine serum albumin/ribose glycation reaction model. The phytochemical profiles and caffeoylquinic acids (CQAs) contents were determined for the methanolic extract of each plant. Analyzed plant extracts exhibited significant inhibitory activity against key digestive enzymes linked to type II diabetes and obesity. A strong inhibition was observed for glucosidases and mild activity towards amylase and lipase (compared to reference compounds). Moreover, some extracts exhibited potent ability to prevent formation of AGEs, implicated in some diabetic complications. Caffeoylquinic acids were dominant in all plant extracts and findings demonstrate that these compounds are the most relevant hypoglycemic and anti-glycation agents. From the obtained results, Argyranthemum pinnatifidum, Helichrysum melaleucum, and Phagnalon lowei are good candidates for further development of phyto-pharmaceutical preparations as complementary therapy for diabetes and obesity control. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluating predisposition and training in shaping the musician's brain: the need for a developmental perspective.

PubMed

Zuk, Jennifer; Gaab, Nadine

2018-05-24

The study of music training as a model for structural plasticity has evolved significantly over the past 15 years. Neuroimaging studies have identified characteristic structural brain alterations in musicians compared to nonmusicians in school-age children and adults, using primarily cross-sectional designs. Despite this emerging evidence and advances in pediatric neuroimaging techniques, hardly any studies have examined brain development in early childhood (before age 8) in association with musical training, and longitudinal studies starting in infancy or preschool are particularly scarce. Consequently, it remains unclear whether the characteristic "musician brain" is solely the result of musical training, or whether certain predispositions may have an impact on its development. Moving toward a developmental perspective, the present review considers various factors that may contribute to early brain structure prior to the onset of formal musical training. This review introduces a model for potential neurobiological pathways leading to the characteristic "musician brain," which involves a developmental interaction between predisposition and its temporal dynamics, environmental experience, and training-induced plasticity. This perspective illuminates the importance of studying the brain structure associated with musical training through a developmental lens, and the need for longitudinal studies in early childhood to advance our understanding of music training-induced structural plasticity. © 2018 New York Academy of Sciences.

Association of young and advanced age of pregnant women with the risk of isolated congenital abnormalities in Hungary - a population-based case-matched control study.

PubMed

Csermely, Gyula; Susánszky, Éva; Czeizel, Andrew E

2015-03-01

To analyze the possible association of maternal age with the risk of all congenital abnormalities (CAs) in a population-based large case-matched control data set. The Hungarian Case-Control Surveillance of Congenital Abnormalities included 21,494 cases with isolated CA and their 34,311 matched controls. First the distribution of maternal age groups in 24 CA-groups and their matched controls was compared. In the second step, young (19 years or less) and advanced (35 years or more) age groups were compared. Finally, the subgroups of neural-tube defects, congenital heart defects and abdominal wall's CA were evaluated separately. A higher risk of gastroschisis, congenital heart defects, particularly left-sided obstructive defects, undescended testis and clubfoot was found in the youngest age group (19 years or less) of cases. The higher proportion of pregnant women with advanced age (i.e. 35 years or more) showed only a borderline excess in cases with clubfoot. The so-called U-shaped risk of maternal age distribution was found in cases with clubfoot and in the total group of isolated CAs. The maternal age is a contributing factor to the origin of some isolated CAs mainly in young pregnant women.

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.

The Advanced Glaucoma Intervention Study (AGIS): 11. Risk factors for failure of trabeculectomy and argon laser trabeculoplasty.

PubMed

2002-10-01

To investigate the association of pre-intervention and post-intervention patient and eye characteristics with failure of argon laser trabeculoplasty (ALT) and trabeculectomy. Cohort study of participants in the Advanced Glaucoma Intervention Study. This multicenter study took place between 1988 and 2001. Between 1988 and 1992, 789 eyes of 591 patients aged 35 to 80 years with advanced glaucoma were randomized into one of two surgical treatment sequences: argon laser trabeculoplasty (ALT)-trabeculectomy-trabeculectomy or trabeculectomy-ALT-trabeculectomy. Upon study-defined failure (based on maximum medications, sustained intraocular pressure (IOP) elevation, visual field defect, and disk rim deterioration) of each intervention, patients were offered the subsequent intervention. Potential follow-up was 8 to 13 years. This report is based on data from 779 eyes that had at least 3 months of follow-up. The main outcome measures are failure of ALT and trabeculectomy, whether as first or second interventions. Effect size is measured by the hazard ratio (HR) and its corresponding 95% confidence interval (CI) obtained from Cox multiple regression analysis, where HR corresponds to the coefficient of change in risk associated with a unit increase in a factor. For binary factors, this corresponds to the change in risk in eyes with the factor relative to the risk in eyes without the factor. Pre-intervention factors associated with failure of ALT are younger age (HR = 0.98, CI = 0.96-0.99, P =.009) and higher IOP (1.11, 1.08-1.15, P <.001). Pre-intervention factors associated with failure of trabeculectomy are younger age (HR = 0.97, CI = 0.95-0.99, P =.005) and higher IOP (1.04, 1.01-1.06, P =.002), as well as diabetes (2.86, 1.88-4.36, P <.001) and any postoperative complication (1.99, 1.35-2.93, P <.001). Individual postoperative complications significantly associated with increased risk of failure of trabeculectomy are elevated IOP (3.4, 1.9-6.1, P <.001) and marked inflammation (2.4, 1.3-4.6, P =.006). In this study, ALT failure was associated with younger age and higher pre-intervention IOP. Trabeculectomy failure was associated with younger age, higher pre-intervention IOP, diabetes, and one or more postoperative complications, particularly elevated IOP and marked inflammation.

An assessment of advanced technology for industrial cogeneration

NASA Technical Reports Server (NTRS)

Moore, N.

1983-01-01

The potential of advanced fuel utilization and energy conversion technologies to enhance the outlook for the increased use of industrial cogeneration was assessed. The attributes of advanced cogeneration systems that served as the basis for the assessment included their fuel flexibility and potential for low emissions, efficiency of fuel or energy utilization, capital equipment and operating costs, and state of technological development. Over thirty advanced cogeneration systems were evaluated. These cogeneration system options were based on Rankine cycle, gas turbine engine, reciprocating engine, Stirling engine, and fuel cell energy conversion systems. The alternatives for fuel utilization included atmospheric and pressurized fluidized bed combustors, gasifiers, conventional combustion systems, alternative energy sources, and waste heat recovery. Two advanced cogeneration systems with mid-term (3 to 5 year) potential were found to offer low emissions, multi-fuel capability, and a low cost of producing electricity. Both advanced cogeneration systems are based on conventional gas turbine engine/exhaust heat recovery technology; however, they incorporate advanced fuel utilization systems.

Advanced driver assistance systems for teen drivers: Teen and parent impressions, perceived need, and intervention preferences.

PubMed

Weiss, Eve; Fisher Thiel, Megan; Sultana, Nahida; Hannan, Chloe; Seacrist, Thomas

2018-02-28

From the advent of airbags to electronic stability control, technological advances introduced into automobile design have significantly reduced injury and death from motor vehicle crashes. These advances are especially pertinent among teen drivers, a population whose leading cause of death is motor vehicle crashes. Recently developed advanced driver assistance systems (ADAS) have the potential to compensate for skill deficits and reduce overall crash risk. Yet, ADAS is only effective if drivers are willing to use it. Limited research has been conducted on the suitability of ADAS for teen drivers. The goal of this study is to identify teen drivers' perceived need for ADAS, receptiveness to in-vehicle technology, and intervention preferences. The long-term goal is to understand public perceptions and barriers to ADAS use and to help determine how these systems must evolve to meet the needs of the riskiest driving populations. Three focus groups (N = 24) were conducted with licensed teen drivers aged 16-19 years and 2 focus groups with parents of teen drivers (N = 12). Discussion topics included views on how ADAS might influence driving skills and behaviors; trust in technology; and data privacy. Discussions were transcribed; the team used conventional content analysis and open coding methods to identify 12 coding domains and code transcripts with NVivo 10. Interrater reliability testing showed moderate to high kappa scores. Overall, participants recognized potential benefits of ADAS, including improved safety and crash reduction. Teens suggested that ADAS is still developing and therefore has potential to malfunction. Many teens reported a greater trust in their own driving ability over vehicle technology. They expressed that novice drivers should learn to drive on non-ADAS-equipped cars and that ADAS should be considered a supplemental aid. Many teens felt that overreliance on ADAS may increase distracted driving or risky behaviors among teens. Parents also expressed skepticism for the technology but felt that it would likely be a useful support for teen drivers after the initial learning phase. This study elicited important end-user viewpoints by exploring the intersection between advanced automobile safety technology and human perception for the particular use case of teen drivers. For example, despite evidence that teens are the highest risk driving population, teens trust their own driving skills and competence more than in-vehicle technology. This understanding will ultimately advance the safety of teen drivers by identifying barriers to effective ADAS use.