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Sample records for age related increase

  1. CKD increases the risk of age-related macular degeneration.

    PubMed

    Liew, Gerald; Mitchell, Paul; Wong, Tien Yin; Iyengar, Sudha K; Wang, Jie Jin

    2008-04-01

    Age-related macular degeneration is the leading cause of irreversible blindness in the United States and often coexists with chronic kidney disease. Both conditions share common genetic and environmental risk factors. A total of 1183 participants aged 54+ were examined in the population-based, prospective cohort Blue Mountains Eye Study (Australia) to determine if chronic kidney disease increases the risk of age-related macular degeneration. Moderate chronic kidney disease (estimated glomerular filtration rate < 60 ml/min per 1.73 m(2) based on the Cockcroft-Gault equation) was present in 24% of the population (286 of 1183). The 5-yr incidence of early age-related macular degeneration was 3.9% in participants with no/mild chronic kidney disease (35 of 897) and 17.5% in those with moderate chronic kidney disease (50 of 286). After adjusting for age, sex, cigarette smoking, hypertension, complement factor H polymorphism, and other risk factors, persons with moderate chronic kidney disease were 3 times more likely to develop early age-related macular degeneration than persons with no/mild chronic kidney disease (odds ratio = 3.2; 95% confidence interval, 1.8 to 5.7, P < 0.0001). Each SD (14.8 ml/min per 1.73 m(2)) decrease in Cockcroft-Gault estimated glomerular filtration rate was associated with a doubling of the adjusted risk for early age-related macular degeneration (odds ratio = 2.0; 95% confidence interval, 1.5 to 2.8, P < 0.0001). In conclusion, persons with chronic kidney disease have a higher risk of early age-related macular degeneration, suggesting the possibility of shared pathophysiologic mechanisms between the two conditions.

  2. Age-related hearing loss increases cross-modal distractibility.

    PubMed

    Puschmann, Sebastian; Sandmann, Pascale; Bendixen, Alexandra; Thiel, Christiane M

    2014-10-01

    Recent electrophysiological studies have provided evidence that changes in multisensory processing in auditory cortex cannot only be observed following extensive hearing loss, but also in moderately hearing-impaired subjects. How the reduced auditory input affects audio-visual interactions is however largely unknown. Here we used a cross-modal distraction paradigm to investigate multisensory processing in elderly participants with an age-related high-frequency hearing loss as compared to young and elderly subjects with normal hearing. During the experiment, participants were simultaneously presented with independent streams of auditory and visual input and were asked to categorize either the auditory or visual information while ignoring the other modality. Unisensory sequences without any cross-modal input served as control conditions to assure that all participants were able to perform the task. While all groups performed similarly in these unisensory conditions, hearing-impaired participants showed significantly increased error rates when confronted with distracting cross-modal stimulation. This effect could be observed in both the auditory and the visual task. Supporting these findings, an additional regression analysis indicted that the degree of high-frequency hearing loss significantly modulates cross-modal visual distractibility in the auditory task. These findings provide new evidence that already a moderate sub-clinical hearing loss, a common phenomenon in the elderly population, affects the processing of audio-visual information.

  3. Hypermaintenance and hypofunction of aged spermatogonia: insight from age-related increase of Plzf expression.

    PubMed

    Ferder, Ianina C; Wang, Ning

    2015-06-30

    Like stem cells in other tissues, spermatogonia, including spermatogonial stem cells (SSCs) at the foundation of differentiation hierarchy, undergo age-related decline in function. The promyelocytic leukemia zinc finger (Plzf) protein plays an essential role in spermatogonia maintenance by preventing their differentiation. To evaluate whether there is an age-related change in Plzf expression, we found that aged mouse testes exhibited a robust "Plzf overexpression" phenotype, in that they showed not only a higher frequency of Plzf-expressing cells but also an increased level of Plzf expression in these cells. Moreover, some Plzf-expressing cells in aged testes even aberrantly appeared in the differentiating spermatogonia compartment, which is usually low or negative for Plzf expression. Importantly, ectopic Plzf expression in F9 cells suppressed retinoic acid (RA)-induced Stra8 activation, a gene required for meiosis initiation. These data, together with our observation of a lack of meiosis-initiating spermatocytes associated with high Plzf-expressing spermatogonia in the aged testes, particularly in the degenerative seminiferous tubules, suggest that age-related increase in Plzf expression represents a novel molecular signature of spermatogonia aging by functionally arresting their differentiation.

  4. Increased Waist-to-height Ratio May Contribute to Age-related Increase in Cardiovascular Risk Factors

    PubMed Central

    Akhlaghi, Masoumeh; Kamali, Majid; Dastsouz, Farideh; Sadeghi, Fatemeh; Amanat, Sassan

    2016-01-01

    Background: The risk of cardiovascular diseases (CVDs) increases with age. The objective was to determine whether lifestyle and dietary behaviors and anthropometric measures, which are affected by these behaviors, contribute to the increase of CVD risk factors across age categories of 20–50-year-old. Methods: In a cross-sectional design, 437 adults aged 20–50-year-old were selected from households living in Shiraz. Risk factors of CVD, including body mass index (BMI), waist-to-height ratio (WHtR), blood pressure, fasting blood glucose (FBG), serum triglycerides, total cholesterol, and low- and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively) as well as lifestyle behaviors (physical activity and smoking), dietary habits, and food intakes were assessed across the age categories of 20–29, 30–39, and 40–50 years. Linear regression was used to examine the contribution of different variables to the age-related increase of CVD risk factors. Results: All CVD risk factors, except for HDL-C, significantly increased across age categories. Older subjects had healthier dietary habits and food intakes, but they possessed nonsignificantly lower physical activity and higher smoking rate compared to younger adults. Adjusting for physical activity, smoking, and BMI did not change the significant positive association between age and CVD risk factors but adjusting for WHtR disappeared associations for blood pressure, triglycerides, and metabolic syndrome although significant associations remained for FBG and total and LDL-C. Conclusions: Age-related increase of CVD risk factors occurred independent of lifestyle habits. WHtR, but not BMI, may partially contribute to the age-related increase in CVD risk factors. PMID:27195100

  5. Lens opacity based modelling of the age-related straylight increase.

    PubMed

    Rozema, Jos J; Sanchez, Victoria; Artal, Natalia; Gramajo, Ana L; Torres, Eduardo; Luna, Jose D; Iribarren, Rafael; Tassignon, Marie-José; Juarez, Claudio P

    2015-12-01

    This work studies ethnic and geographical differences in the age-related straylight increase by means of a stochastic model and unpublished lens opacity data of 559 residents of Villa Maria (Argentina), as well as data of 912 Indonesian subjects published previously by Husain et al. For both cohorts the prevalence of each type and grade of lens opacity was determined as a function of age, from which a stochastic model was derived capable of simulating the lens opacity prevalence for both populations. These simulated lens opacity data were then converted to estimated straylight by means of an equation derived from previously recorded data of 107 eyes with varying degrees of cataract. Based on these opacity templates 2500 random sets of subject age and lens opacity data were generated by the stochastic model for each dataset, from which estimated straylight could be calculated. For the Argentinian data the estimated straylight was found to closely resemble the published models for age-related straylight increase. For younger eyes the straylight variation of the model was the same as what was previously published (in both cases ±0.200logunits), which doubled in size for older eyes. For the Indonesian data, however, this age-related straylight increase was found to be fundamentally different from the published age model. This suggests that current normative curves for age-related straylight increase may not always be appropriate for non-European populations, and that the inter-individual straylight variations in young, healthy eyes may possibly be due to variations in lens opacities.

  6. Increased bone morphogenetic protein signaling contributes to age-related declines in neurogenesis and cognition

    PubMed Central

    Meyers, Emily A.; Gobeske, Kevin T.; Bond, Allison M.; Jarrett, Jennifer C.; Peng, Chian-Yu; Kessler, John A.

    2015-01-01

    Aging is associated with decreased neurogenesis in the hippocampus and diminished hippocampus-dependent cognitive functions. Expression of bone morphogenetic protein 4 (BMP4) increases with age by more than 10-fold in the mouse dentate gyrus while levels of the BMP inhibitor, noggin, decrease. This results in a profound 30-fold increase in phosphorylated-SMAD1/5/8, the effector of canonical BMP signaling. Just as observed in mice, a profound increase in expression of BMP4 is observed in the dentate gyrus of humans with no known cognitive abnormalities. Inhibition of BMP signaling either by overexpression of noggin or transgenic manipulation not only increases neurogenesis in aging mice, but remarkably, is associated with a rescue of cognitive deficits to levels comparable to young mice. Additive benefits are observed when combining inhibition of BMP signaling and environmental enrichment. These findings indicate that increased BMP signaling contributes significantly to impairments in neurogenesis and to cognitive decline associated with aging, and identify this pathway as a potential druggable target for reversing age-related changes in cognition. PMID:26827654

  7. Age-related increase in brain activity during task-related and -negative networks and numerical inductive reasoning

    PubMed Central

    Sun, Li; Liang, Peipeng; Jia, Xiuqin; Qi, Zhigang; Li, Kuncheng

    2014-01-01

    Objective: Recent neuroimaging studies have shown that elderly adults exhibit increased and decreased activation on various cognitive tasks, yet little is known about age-related changes in inductive reasoning. Methods: To investigate the neural basis for the aging effect on inductive reasoning, 15 young and 15 elderly subjects performed numerical inductive reasoning while in a magnetic resonance (MR) scanner. Results: Functional magnetic resonance imaging (fMRI) analysis revealed that numerical inductive reasoning, relative to rest, yielded multiple frontal, temporal, parietal, and some subcortical area activations for both age groups. In addition, the younger participants showed significant regions of task-induced deactivation, while no deactivation occurred in the elderly adults. Direct group comparisons showed that elderly adults exhibited greater activity in regions of task-related activation and areas showing task-induced deactivation (TID) in the younger group. Conclusions: Our findings suggest an age-related deficiency in neural function and resource allocation during inductive reasoning. PMID:25337240

  8. Prevalence of insomnia-related symptoms continues to increase in the Finnish working-age population.

    PubMed

    Kronholm, Erkki; Partonen, Timo; Härmä, Mikko; Hublin, Christer; Lallukka, Tea; Peltonen, Markku; Laatikainen, Tiina

    2016-08-01

    In 2008, we published epidemiological data from 1972 to 2005 that suggested an increase in insomnia-related symptoms among the working-age population. The results were based on the National FINRISK (FR) Study samples of the Finnish adult population aged 25-64, and on the Finnish Quality of Work Life Surveys (FQWLS), carried out among Finnish salary earners. Both of these ongoing studies have since provided two new estimates of insomnia-related symptoms. Chronic insomnia-related symptoms were 9.0% (95% CI 8.3-9.7), 9.6% (95% CI 8.8-10.4) in FR 2007 and 2012, respectively; and 9.1% (95% CI 8.3-10.0), 9.2% (95% CI 8.4-10.1) in FQWLS 2008 and 2013, respectively. Occasional insomnia-related symptoms were 45.3% (95% CI 44.1-46.6), 42.5% (95% CI 41.1-43.9) in FR 2007 and 2012, respectively; and 40.3% (95% CI 38.8-41.7), 44.8% (95% CI 41.1-43.9) in FQWLS 2008 and 2013, respectively. The new estimates further strengthen the interpretation of the ongoing increase in occasional insomnia-related symptoms among the Finnish general adult population. The increase in occasional symptoms was most prominent among employees. However, chronic insomnia symptoms showed no further increase.

  9. Age-related decline in cardiac autonomic function is not attenuated with increased physical activity

    PubMed Central

    Njemanze, Hugo; Warren, Charlotte; Eggett, Christopher; MacGowan, Guy A.; Bates, Matthew G D; Siervo, Mario; Ivkovic, Srdjan; Trenell, Michael I.; Jakovljevic, Djordje G.

    2016-01-01

    Age and physical inactivity are important risk factors for cardiovascular mortality. Heart rate response to exercise (HRRE) and heart rate recovery (HRR), measures of cardiac autonomic function, are strong predictors of mortality. The present study defined the effect of age and physical activity on HRRE and HRR. Healthy women (N=72) grouped according to age (young, 20-30 years; middle, 40-50 years; and older, 65-81 years) and daily physical activity (low active <7500, high active >12,500 steps/day) performed a maximal cardiopulmonary exercise test. The HRRE was defined as an increase in heart rate from rest to 1, 3 and 5 minutes of exercise and at 1/3 of total exercise time, and HRR as the difference in heart rate between peak exercise and 1, 2, and 3 minutes later. Age was associated with a significant decline in HRRE at 1 min and 1/3 of exercise time (r= − 0.27, p=0.04, and r=−0.39, p=0.02) and HRR at 2 min and 3 min (r=−0.35, p=0.01, and r=−0.31, p=0.02). There was no significant difference in HRRE and HRR between high and low-active middle-age and older women (p>0.05). Increased level of habitual physical activity level appears to have a limited effect on age-related decline in cardiac autonomic function in women. PMID:27705949

  10. No evidence of age-related increases in unconscious plagiarism during free recall.

    PubMed

    Perfect, Timothy John; Defeldre, Anne-Catherine; Elliman, Rachel; Dehon, Hedwige

    2011-07-01

    In three experiments younger and older participants took part in a group generation task prior to a delayed recall task. In each, participants were required to recall the items that they had generated, avoiding plagiarism errors. All studies showed the same pattern: older adults did not plagiarise their partners any more than younger adults did. However, older adults were more likely than younger adults to intrude with entirely novel items not previously generated by anyone. These findings stand in opposition to the single previous demonstration of age-related increases in plagiarism during recall.

  11. Increased choroidal mast cells and their degranulation in age-related macular degeneration

    PubMed Central

    Bhutto, Imran A; McLeod, D Scott; Jing, Tian; Sunness, Janet S.; Seddon, Johanna M.; Lutty, Gerard A

    2016-01-01

    Background/Aims Inflammation has been implicated in age-related macular degeneration (AMD). This study investigates the association of mast cells (MCs), a resident choroidal inflammatory cell, with pathological changes in AMD. Methods Human donor eyes included aged controls (n=10), clinically diagnosed with early AMD (n=8), geographic atrophy (GA, n=4), and exudative AMD (n=11). The choroids were excised and incubated alkaline phosphatase (APase; blood vessels) and nonspecific esterase activities (MCs). Degranulated (DG) and nondegranulated (NDG) MCs in four areas of posterior choroid (nasal, nonmacular, paramacular, and submacular) were counted in flat mounts (4∼6 fields/area). Choroids were subsequently embedded in JB-4 and sectioned for histological analyses. Results The number of MCs was significantly increased in all choroidal areas in early AMD (p=0.0006) and in paramacular area in exudative AMD (139.44±55.3 cells/mm2; p=0.0091) and GA (199.08±82.0 cells/mm2; p=0.0019) compared to the aged controls. DG MCs was also increased in paramacular (p=0.001) and submacula choroid (p=0.02) in all forms of AMD. Areas with the greatest numbers of DG MC had loss of choriocapillaris (CC). Sections revealed that the MCs were widely distributed in Sattler's and Haller's layer in the choroidal stroma in aged controls, whereas MCs were frequently found in close proximity to CC in GA and exudative AMD and in choroidal neovascularization (CNV). Conclusion Increased MC numbers and degranulation were observed in all AMD choroids. These results suggest that MC degranulation may contribute to the pathogenesis of AMD: death of CC and RPE and CNV formation. The proteolytic enzymes released from MC granules may result in thinning of AMD choroid. PMID:26931413

  12. Age-related increases in right frontal activation during task switching are mediated by reaction time and white matter microstructure.

    PubMed

    Zhu, Z; Hakun, J G; Johnson, N F; Gold, B T

    2014-10-10

    Age-related increases in right frontal cortex activation are a common finding in the neuroimaging literature. However, neurocognitive factors contributing to right frontal over-recruitment remain poorly understood. Here we investigated the influence of age-related reaction time (RT) slowing and white matter (WM) microstructure reductions as potential explanatory factors for age-related increases in right frontal activation during task switching. Groups of younger (N=32) and older (N=33) participants completed a task switching paradigm while functional magnetic resonance imaging (fMRI) was performed, and rested while diffusion tensor imaging (DTI) was performed. Two right frontal regions of interest (ROIs), the dorsolateral prefrontal cortex (DLPFC) and insula, were selected for further analyses from a common network of regions recruited by both age groups during task switching. Results demonstrated age-related activation increases in both ROIs. In addition, the older adult group showed longer RT and decreased fractional anisotropy in regions of the corpus callosum with direct connections to the fMRI ROIs. Subsequent mediation analyses indicated that age-related increases in right insula activation were mediated by RT slowing and age-related increases in right DLPFC activation were mediated by WM microstructure. Our results suggest that age-related RT slowing and WM microstructure declines contribute to age-related increases in right frontal activation during cognitive task performance.

  13. Age-related increase in top-down activation of visual features

    PubMed Central

    Madden, David J.; Spaniol, Julia; Bucur, Barbara; Whiting, Wythe L.

    2007-01-01

    Previous research suggests that, during visual search and discrimination tasks, older adults place greater emphasis than younger adults on top-down attention. This experiment investigated the relative contribution of target activation and distractor inhibition to this age difference. Younger and older adults performed a singleton discrimination task in which either an E or an R target (colour singleton) was present among distractor letters. Relative to a baseline condition in which the colours of the targets and distractors remained constant, an age-related slowing of performance was evident when either the colour of the target or that of the distractors varied across trials. The age-related slowing was more pronounced in response to target colour variation, suggesting that older adults place relatively greater emphasis on the top-down activation of target features. PMID:17455072

  14. Age-related increase of thromboxane B2 and risk of cardiovascular disease in atrial fibrillation

    PubMed Central

    Farcomeni, Alessio; Nocella, Cristina; Bartimoccia, Simona; Carnevale, Roberto; Violi, Francesco

    2016-01-01

    Aging is strictly associated with an increased incidence of cardiovascular events (CVEs) in the general population. Mechanisms underlying the risk of CVEs are still unclear. Platelet activation contributes to the onset of cardiovascular complications. The incidence of atrial fibrillation (AF) increases with age, and the natural history of AF is often complicated by CVEs. We prospectively investigated the relationship between age, urinary thromboxane (Tx) B2, which reflects platelet activation, and CVEs in 833 AF patients. Median TxB2 level was 120 [66-200] ng/mg of urinary creatinine. At multivariable linear regression analysis, age (B: 0.097, p=0.005) and previous MI/CHD (B: 0.069, p=0.047) were associated with log-TxB2 levels. When we divided our population into age classes (i.e. < 60, 60-69, 70-79, ≥ 80 years), we found a significant difference in TxB2 levels across classes (p=0.005), with a significant elevation at 74.6 years. During a mean follow-up of 40.9 months, 128 CVEs occurred; the rate of CVEs significantly increased with age classes (Log-rank test, p < 0.001). TxB2 levels were higher in patients with, compared to those without, CVEs in patients aged 70-79 (p < 0.001) and ≥ 80 (p = 0.020) years. In conclusion, TxB2 levels enhance by increasing age, suggesting that platelet activation contributes to CVEs in elderly patients with AF. PMID:27270651

  15. Better stay together: pair bond duration increases individual fitness independent of age-related variation

    PubMed Central

    Sánchez-Macouzet, Oscar; Rodríguez, Cristina; Drummond, Hugh

    2014-01-01

    Prolonged pair bonds have the potential to improve reproductive performance of socially monogamous animals by increasing pair familiarity and enhancing coordination and cooperation between pair members. However, this has proved very difficult to test robustly because of important confounds such as age and reproductive experience. Here, we address limitations of previous studies and provide a rigorous test of the mate familiarity effect in the socially monogamous blue-footed booby, Sula nebouxii, a long-lived marine bird with a high divorce rate. Taking advantage of a natural disassociation between age and pair bond duration in this species, and applying a novel analytical approach to a 24 year database, we found that those pairs which have been together for longer establish their clutches five weeks earlier in the season, hatch more of their eggs and produce 35% more fledglings, regardless of age and reproductive experience. Our results demonstrate that pair bond duration increases individual fitness and further suggest that synergistic effects between a male and female's behaviour are likely to be involved in generating a mate familiarity effect. These findings help to explain the age- and experience-independent benefits of remating and their role in life-history evolution. PMID:24827435

  16. MYBL2 haploinsufficiency increases susceptibility to age-related haematopoietic neoplasia

    PubMed Central

    Clarke, M; Dumon, S; Ward, C; Jäger, R; Freeman, S; Dawood, B; Sheriff, L; Lorvellec, M; Kralovics, R; Frampton, J; García, P

    2013-01-01

    The haematopoietic system is prone to age-related disorders ranging from deficits in functional blood cells to the development of neoplastic states. Such neoplasms often involve recurrent cytogenetic abnormalities, among which a deletion in the long arm of chromosome 20 (del20q) is common in myeloid malignancies. The del20q minimum deleted region contains nine genes, including MYBL2, which encodes a key protein involved in the maintenance of genome integrity. Here, we show that mice expressing half the normal levels of Mybl2 (Mybl2+/Δ) develop a variety of myeloid disorders upon ageing. These include myeloproliferative neoplasms, myelodysplasia (MDS) and myeloid leukaemia, mirroring the human conditions associated with del20q. Moreover, analysis of gene expression profiles from patients with MDS demonstrated reduced levels of MYBL2, regardless of del20q status and demonstrated a strong correlation between low levels of MYBL2 RNA and reduced expression of a subset of genes related to DNA replication and checkpoint control pathways. Paralleling the human data, we found that these pathways are also disturbed in our Mybl2+/Δ mice. This novel mouse model, therefore, represents a valuable tool for studying the initiation and progression of haematological malignancies during ageing, and may provide a platform for preclinical testing of therapeutic approaches. PMID:22910183

  17. Quest for Cells Responsible for Age-related Increase of Salivary Glycine and Proline.

    PubMed

    Hino, Shunsuke; Nishiyama, Akira; Matsuta, Tomohiko; Horie, Norio; Shimoyama, Tetsuo; Tanaka, Shoji; Sakagami, Hiroshi

    2016-01-01

    We have previously reported that salivary glycine and proline levels are increased to nearly butanoate level in elderly people. In order to identify the source of glycine and proline, we performed high-performance liquid chromatography analysis of amino acid production to a total of seven oral cells before and after stimulation with inflammation inducers. We found that production of amino acids (per a given number of cells) by normal oral mesenchymal cells (gingival fibroblast, pulp cell, periodontal ligament fibroblast) was approximately three-fold that of oral squamous cell carcinoma cell lines (HSC-2, HSC-3, HSC-4, Ca9-22), and that production of glycine and especially proline by all these seven cells was much lower than that of glutamine and glutamic acid. Treatment of three oral mesenchymal cells with interleukin (IL)-1β or lipopoly-saccharide (LPS) reproducibly increased the production of glutamic acid and glutamine, but not that of glycine and proline. Glycine and proline only marginally stimulated the IL-8 production by IL-1β-stimulated gingival fibroblast, whereas glycine dose-dependently inhibited the nitric oxide production by lipopolysaccharide-stimulated mouse macrophage-like RAW264.7 cells. These data demonstrated that normal oral mesenchymal cells are not the major source of glycine and proline that accumulates in the saliva of aged people, suggesting the involvement of the deregulation of collagen metabolism during aging.

  18. Absence of DJ-1 causes age-related retinal abnormalities in association with increased oxidative stress.

    PubMed

    Bonilha, Vera L; Bell, Brent A; Rayborn, Mary E; Samuels, Ivy S; King, Anna; Hollyfield, Joe G; Xie, Chengsong; Cai, Huaibin

    2017-03-01

    Oxidative stress alters physiological function in most biological tissues and can lead to cell death. In the retina, oxidative stress initiates a cascade of events leading to focal loss of RPE and photoreceptors, which is thought to be a major contributing factor to geographic atrophy. Despite these implications, the molecular regulation of RPE oxidative stress under normal and pathological conditions remains largely unknown. A better understanding of the mechanisms involved in regulating RPE and photoreceptors oxidative stress response is greatly needed. To this end we evaluated photoreceptor and RPE changes in mice deficient in DJ-1, a protein that is thought to be important in protecting cells from oxidative stress. Young (3 months) and aged (18 months) DJ-1 knockout (DJ-1 KO) and age-matched wild-type mice were examined. In both group of aged mice, scanning laser ophthalmoscopy (SLO) showed the presence of a few autofluorescent foci. The 18 month-old DJ-1 KO retinas were also characterized by a noticeable increase in RPE fluorescence to wild-type. Optical coherence tomography (OCT) imaging demonstrated that all retinal layers were present in the eyes of both DJ-1 KO groups. ERG comparisons showed that older DJ-1 KO mice had reduced sensitivity under dark- and light-adapted conditions compared to age-matched control. Histologically, the RPE contained prominent vacuoles in young DJ-1 KO group with the appearance of enlarged irregularly shaped RPE cells in the older group. These were also evident in OCT and in whole mount RPE/choroid preparations labeled with phalloidin. Photoreceptors in the older DJ-1 KO mice displayed decreased immunoreactivity to rhodopsin and localized reduction in cone markers compared to the wild-type control group. Lower levels of activated Nrf2 were evident in retina/RPE lysates in both young and old DJ-1 KO mouse groups compared to wild-type control levels. Conversely, higher levels of protein carbonyl derivatives and i

  19. Age-Related Changes to Speech Breathing with Increased Vocal Loudness

    ERIC Educational Resources Information Center

    Huber, Jessica E.; Spruill, John, III

    2008-01-01

    Purpose: The present study examines the effect of normal aging on respiratory support for speech when utterance length is controlled. Method: Fifteen women (M = 71 years of age) and 10 men (M = 73 years of age) produced 2 sentences of different lengths in 4 loudness conditions while respiratory kinematics were measured. Measures included those…

  20. Resveratrol prevents age-related memory and mood dysfunction with increased hippocampal neurogenesis and microvasculature, and reduced glial activation.

    PubMed

    Kodali, Maheedhar; Parihar, Vipan K; Hattiangady, Bharathi; Mishra, Vikas; Shuai, Bing; Shetty, Ashok K

    2015-01-28

    Greatly waned neurogenesis, diminished microvasculature, astrocyte hypertrophy and activated microglia are among the most conspicuous structural changes in the aged hippocampus. Because these alterations can contribute to age-related memory and mood impairments, strategies efficacious for mitigating these changes may preserve cognitive and mood function in old age. Resveratrol, a phytoalexin found in the skin of red grapes having angiogenic and antiinflammatory properties, appears ideal for easing these age-related changes. Hence, we examined the efficacy of resveratrol for counteracting age-related memory and mood impairments and the associated detrimental changes in the hippocampus. Two groups of male F344 rats in late middle-age having similar learning and memory abilities were chosen and treated with resveratrol or vehicle for four weeks. Analyses at ~25 months of age uncovered improved learning, memory and mood function in resveratrol-treated animals but impairments in vehicle-treated animals. Resveratrol-treated animals also displayed increased net neurogenesis and microvasculature, and diminished astrocyte hypertrophy and microglial activation in the hippocampus. These results provide novel evidence that resveratrol treatment in late middle age is efficacious for improving memory and mood function in old age. Modulation of the hippocampus plasticity and suppression of chronic low-level inflammation appear to underlie the functional benefits mediated by resveratrol.

  1. The age-related increase in arterial stiffness is augmented in phases according to the severity of hypertension.

    PubMed

    Tomiyama, Hirofumi; Arai, Tomio; Koji, Yutaka; Yambe, Minoru; Motobe, Kohki; Zaydun, Glunisa; Yamamoto, Yoshio; Hori, Saburoh; Yamashina, Akira

    2004-07-01

    Although blood pressure and age are major determinants of arterial stiffness, it is still unclear whether age-related changes in arterial stiffness are similar among subjects with different degrees of severity of hypertension. The present study examined the association between age and pulse wave velocity in subjects with different degrees of hypertension stratified according to the JNC-7 classification (Normal, Prehypertensive, and Stage I or II Hypertensive subjects). A number of 5,312 subjects (age range, 30-79 years) with no atherosclerotic risk factors other than high blood pressure were selected from two cohorts who regularly underwent annual health checkups, including the measurement of brachial-ankle pulse wave velocity (baPWV). baPWV was increased according to the severity of hypertension in all age groups. The association between age and baPWV formed a quadratic curve in each stage in both genders. The steepness of the slope of the quadratic curve increased according to the severity of hypertension. In each stage of hypertension, age and the baPWV were divided into tertiles. After adjustment for systolic and diastolic blood pressure, the odds ratio of having an increased baPWV in the 3rd age tertile (the highest-age group) was found to increase according to the severity of hypertension. In conclusion, the age-related increase of baPWV was shown to be augmented in phases according to the severity of hypertension, and this augmentation occurred even between the Normal and Prehypertensive stages. These results support the JNC-7 recommendations for a strict control of blood pressure even in the elderly.

  2. Initiation of calorie restriction in middle-aged male rats attenuates aging-related motoric decline and bradykinesia without increased striatal dopamine

    PubMed Central

    Salvatore, Michael F.; Terrebonne, Jennifer; Fields, Victoria; Nodurft, Danielle; Runfalo, Cori; Latimer, Brian; Ingram, Donald K.

    2015-01-01

    Aging-related bradykinesia affects ~15% of those reaching age 65 and 50% of those reaching their 80s. Given this high risk and lack of pharmacological therapeutics, non-invasive lifestyle strategies should be identified to diminish its risk and identify the neurobiological targets to reduce aging-related bradykinesia. Early-life, long-term calorie restriction (CR) attenuates aging-related bradykinesia in rodents. Here, we addressed whether CR initiation at middle age could attenuate aging-related bradykinesia and motoric decline measured as rotarod performance. A 30% CR regimen was implemented for 6 months duration in 12-month old male Brown-Norway Fischer 344 F1 hybrid rats after establishing individual baseline locomotor activities. Locomotor capacity was assessed every 6 weeks thereafter. The ad libitum (AL) group exhibited predictably decreased locomotor activity, except movement speed, out to 18 months of age. In contrast, in the CR group, movement number and horizontal activity did not decrease during the 6-month trial and aging-related decline in rotarod performance was attenuated. The response to CR was influenced by baseline locomotor activity. The lower the locomotor activity level at baseline, the greater the response to CR. Rats in the lower 50th percentile surpassed their baseline level of activity, whereas rats in the top 50th percentile decreased at 6 weeks and then returned to baseline by 12 weeks of CR. We hypothesized that nigrostriatal dopamine tissue content would be greater in the CR group and observed a modest increase only in substantia nigra with no group differences in striatum, nucleus accumbens, or ventral tegmental area. These results indicate initiation of CR at middle age may reduce aging-related bradykinesia and, furthermore, subjects with below average locomotor activity may increase baseline activity. Sustaining nigral DA neurotransmission may be one component of preserving locomotor capabilities during aging. PMID:26610387

  3. Age-related increases in F344 rat intestine microsomal quercetin glucuronidation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to establish the extent age modifies intestinal quercetin glucuronidation capacity. Pooled microsomal fractions of three equidistant small intestine (SI) segments from 4, 12, 18, and 28 mo male F344 rats (n=8/group) were employed to model the enzyme kinetics of UDP-gl...

  4. Age-related increase in cross-sensory noise in resting and steady-state cerebral perfusion

    PubMed Central

    Hugenschmidt, Christina E.; Mozolic, Jennifer L.; Tan, Huan; Kraft, Robert A.; Laurienti, Paul J.

    2010-01-01

    Behavioral research indicates that healthy aging is accompanied by maintenance of voluntary attentional function in many situations, suggesting older adults are able to use attention to enhance and suppress neural activity. However, other experiments show increased distractibility with age, suggesting a failure of attention. One hypothesis for these apparently conflicting findings is that older adults experience a greater sensory processing load at baseline compared to younger adults. In this situation, older adults might successfully modulate sensory cortical activity relative to a baseline referent condition, but the increased baseline load results in more activity than younger adults after attentional modulation. This hypothesis was tested by comparing average functional brain activity in auditory cortex using quantitative perfusion imaging during resting state and steady-state visual conditions. It was observed that older adults demonstrated greater processing of task-irrelevant auditory background noise than younger adults in both conditions. As expected, auditory activity was attenuated relative to rest during a visually engaging task for both older and younger participants. However, older adults continued to show greater auditory processing than their younger counterparts even after this task modulation. Furthermore, auditory activity during the visual task was predictive of cross-sensory distraction on a behavioral task in older adults. Together, these findings suggest that older adults are more distractible than younger, and the cause of this increased distractibility may lie in baseline brain functioning. PMID:19415481

  5. Environmental enrichment improves age-related immune system impairment: long-term exposure since adulthood increases life span in mice.

    PubMed

    Arranz, Lorena; De Castro, Nuria M; Baeza, Isabel; Maté, Ianire; Viveros, Maria Paz; De la Fuente, Mónica

    2010-08-01

    Age-related changes in immunity have been shown to highly influence morbidity and mortality. The aim of the present work was to study the effects of environmental enrichment (EE) (8-16 weeks) on several functions and oxidative stress parameters of peritoneal leukocytes, previously described as health and longevity markers, in mice at different ages, namely adult (44 +/- 4 weeks), old (69 +/- 4 weeks), and very old (92 +/- 4 weeks). Mortality rates were monitored in control and enriched animals, and effects on survival of long-term exposure to EE until natural death were determined. The results showed that exposure to EE was efficient in improving the function (i.e., macrophage chemotaxis and phagocytosis, lymphocyte chemotaxis and proliferation, natural killer cell activity, interleukin-2 and tumor necrosis factor-alpha levels) and decreasing the oxidative-inflammatory stress (i.e., lowered oxidized glutathione content, xanthine oxidase activity, expression of Toll-like receptors 2 and 4 on CD4 and CD8 cells, and increased reduced glutathione and glutathione peroxidase and catalase activities) of immune cells. These positive effects of EE were especially remarkable in animals at older ages. Importantly, long-term exposure to EE from adult age and until natural death stands out as a useful strategy to extend longevity. Thus, the present work confirms the importance of maintaining active mental and/or physical activity aiming to improve quality of life in terms of immunity, and demonstrates that this active life must be initiated at early stages of the aging process and preserved until death to improve life span.

  6. Ultra-sensitive sequencing reveals an age-related increase in somatic mitochondrial mutations that are inconsistent with oxidative damage.

    PubMed

    Kennedy, Scott R; Salk, Jesse J; Schmitt, Michael W; Loeb, Lawrence A

    2013-01-01

    Mitochondrial DNA (mtDNA) is believed to be highly vulnerable to age-associated damage and mutagenesis by reactive oxygen species (ROS). However, somatic mtDNA mutations have historically been difficult to study because of technical limitations in accurately quantifying rare mtDNA mutations. We have applied the highly sensitive Duplex Sequencing methodology, which can detect a single mutation among >10(7) wild type molecules, to sequence mtDNA purified from human brain tissue from both young and old individuals with unprecedented accuracy. We find that the frequency of point mutations increases ~5-fold over the course of 80 years of life. Overall, the mutation spectra of both groups are comprised predominantly of transition mutations, consistent with misincorporation by DNA polymerase γ or deamination of cytidine and adenosine as the primary mutagenic events in mtDNA. Surprisingly, G → T mutations, considered the hallmark of oxidative damage to DNA, do not significantly increase with age. We observe a non-uniform, age-independent distribution of mutations in mtDNA, with the D-loop exhibiting a significantly higher mutation frequency than the rest of the genome. The coding regions, but not the D-loop, exhibit a pronounced asymmetric accumulation of mutations between the two strands, with G → A and T → C mutations occurring more often on the light strand than the heavy strand. The patterns and biases we observe in our data closely mirror the mutational spectrum which has been reported in studies of human populations and closely related species. Overall our results argue against oxidative damage being a major driver of aging and suggest that replication errors by DNA polymerase γ and/or spontaneous base hydrolysis are responsible for the bulk of accumulating point mutations in mtDNA.

  7. Will increasing alcohol availability by lowering the minimum legal drinking age decrease drinking and related consequences among youths?

    PubMed

    Wechsler, Henry; Nelson, Toben F

    2010-06-01

    Alcohol use health consequences are considerable; prevention efforts are needed, particularly for adolescents and college students. The national minimum legal drinking age of 21 years is a primary alcohol-control policy in the United States. An advocacy group supported by some college presidents seeks public debate on the minimum legal drinking age and proposes reducing it to 18 years. We reviewed recent trends in drinking and related consequences, evidence on effectiveness of the minimum legal drinking age of 21 years, research on drinking among college students related to the minimum legal drinking age, and the case to lower the minimum legal drinking age. Evidence supporting the minimum legal drinking age of 21 years is strong and growing. A wide range of empirically supported interventions is available to reduce underage drinking. Public health professionals can play a role in advocating these interventions.

  8. Increased serum IgA concentration and plasmablast frequency in patients with age-related macular degeneration.

    PubMed

    Yu, Honghua; Yuan, Ling; Yang, Yahan; Ma, Suihong; Peng, Lianghong; Wang, Yong; Zhang, Chu; Li, Tao

    2016-05-01

    Age-related macular degeneration (AMD) is the leading cause of blindness among senior citizens of developed countries, with currently unknown etiology. Despite the close associations between AMD development and inhibitory complement factor H mutations, the first step of complement activation, which is the antibody response in AMD patients, has not been studied. Here, we obtained blood and tear samples from AMD patients and Non-AMD controls. We found that compared to Non-AMD controls, AMD subjects had increased IgA titers in serum and tear, and had elevated levels of circulating antibody-secreting plasmablasts. The increase in antibody titer was limited to the IgA isotype, since no significant differences were observed in IgM and IgG isotypes between AMD patients and Non-AMD controls. Interestingly, this increased antibody response in AMD patients was correlated with disease severity, as late AMD patients had increased IgA titers in serum and tear, as well as elevated plasmablast frequency after staphylococcal enterotoxin B stimulation, compared to early AMD patients. Together, our results implicated a role of overreactive IgA responses in AMD pathogenesis.

  9. α-adrenergic vasoconstriction contributes to the age-related increase in conduit artery retrograde and oscillatory shear.

    PubMed

    Casey, Darren P; Padilla, Jaume; Joyner, Michael J

    2012-10-01

    Aging is associated with increased retrograde and oscillatory shear in peripheral conduit arteries of humans. Although the mechanisms responsible for these age-related changes are not completely understood, augmented downstream α-adrenergic tone likely plays a significant role in this phenomenon. Therefore, in protocol 1, brachial artery diameter and blood velocity were measured via Doppler ultrasound during (1) rest (control), (2) endogenous norepinephrine release via intra-arterial infusions of tyramine, and (3) α-adrenergic blockade via infusions of phentolamine in young healthy humans (n=12). Tyramine increased brachial artery retrograde (-4.0±1.4 to -9.5±1.4 s(-1)) and oscillatory shear (0.05±0.02 to 0.18±0.05 arbitrary units), whereas phentolamine abolished retrograde and oscillatory shear (P<0.05). Additionally, in protocol 2, we examined brachial artery shear patterns in young (n=12; 29±2 years) and older (n=13; 69±2 years) healthy adults during (1) rest (control), (2) sympathetic activation via lower body negative pressure, and (3) infusion of phentolamine. At rest, older adults exhibited greater brachial artery retrograde and oscillatory shear (-9.9±2.7 s(-1) and 0.11±0.03 arbitrary units, respectively) compared with younger adults (-3.1±1.0 s(-1) and 0.05±0.02 arbitrary units, respectively; P<0.05 for both). Lower body negative pressure increased retrograde and oscillatory shear in young (P<0.05), but not older adults (P=0.85-0.97), such that differences between young and older were eliminated (P>0.05). During infusion of phentolamine, retrograde and oscillatory shear were abolished in young adults (P<0.05) and markedly reduced, yet still persistent, in older adults (P<0.01). Our data indicate that α-adrenergic vasoconstriction is a major contributor to age-related discrepancies in conduit artery shear-rate patterns at rest.

  10. Age-related deficits in selective attention during encoding increase demands on episodic reconstruction during context retrieval: An ERP study

    PubMed Central

    James, Taylor; Strunk, Jonathan; Arndt, Jason; Duarte, Audrey

    2017-01-01

    Previous event-related potential (ERP) and neuroimaging evidence suggests that directing attention toward single item-context associations compared to intra-item features at encoding improves context memory performance and reduces demands on strategic retrieval operations in young and older adults. In everyday situations, however, there are multiple event features competing for our attention. It is not currently known how selectively attending to one contextual feature while attempting to ignore another influences context memory performance and the processes that support successful retrieval in the young and old. We investigated this issue in the current ERP study. Young and older participants studied pictures of objects in the presence of two contextual features: a color and a scene, and their attention was directed to the object’s relationship with one of those contexts. Participants made context memory decisions for both attended and unattended contexts and rated their confidence in those decisions. Behavioral results showed that while both groups were generally successful in applying selective attention during context encoding, older adults were less confident in their context memory decisions for attended features and showed greater dependence in context memory accuracy for attended and unattended contextual features (i.e., hyper-binding). ERP results were largely consistent between age groups but older adults showed a more pronounced late posterior negativity (LPN) implicated in episodic reconstruction processes. We conclude that age-related suppression deficits during encoding result in reduced selectivity in context memory, thereby increasing subsequent demands on episodic reconstruction processes when sought after details are not readily retrieved. PMID:27094851

  11. Age-related macular degeneration phenotypes are associated with increased tumor necrosis-alpha and subretinal immune cells in aged Cxcr5 knockout mice

    PubMed Central

    Huang, Hu; Liu, Ying; Wang, Lei; Li, Wen

    2017-01-01

    The role of chemokine receptor in age-related macular degeneration (AMD) remains elusive. The objective of this study is to investigate the role of chemokine receptor Cxcr5 in the pathogenesis of AMD. Cxcr5 gene expression levels (mRNA and protein) are higher in the retina and retinal pigment epithelium (RPE) of aged C57BL/6 wild type mice than younger ones. Vascular and glial cells express Cxcr5 and its ligand Cxcl13 in mouse retina. Aged Cxcr5 knockout (-/-) mice develop both early and late AMD-like pathological features. White and yellow spots, which look like drusen in humans, were identified with fundscopic examination. Drusen-like sub-RPE deposits with dome-shaped morphology were characterized on the sections. RPE vacuolization, swelling, and sub-RPE basal deposits were illustrated with light and transmission electron microscope (TEM). TEM further illustrated degenerated and disorganized RPE basal infoldings, phagosomes and melanosomes inside RPE, as well as abnormal photoreceptor outer segments. Lipofuscin granules and lipid droplets in the subretinal space, RPE, and choroid were revealed with fluorescence microscope and oil-red-O staining. Increased IgG in RPE/choroid were determined with Western blots (WB). WB and immunofluorescence staining determined RPE zona occuldens (ZO)-1 protein reduction and abnormal subcellular localization. TUNEL staining, outer nuclear layer (ONL) measurement and electroretinogram (ERG) recording indicated that photoreceptors underwent apoptosis, degeneration, and functional impairment. Additionally, spontaneous neovascularization (NV)-like lesions develop in the subretinal space of aged Cxcr5-/- mice. The underlying mechanisms are associated with increased subretinal F4/80+ immune cells, some of which contain RPE marker RPE65, and up-regulation of the multifunctional cytokine tumor necrosis factor-alpha (TNF-α) in RPE/choroid and retina. These findings suggest that Cxcr5 itself may be involved in the protection of RPE and

  12. Age-related macular degeneration phenotypes are associated with increased tumor necrosis-alpha and subretinal immune cells in aged Cxcr5 knockout mice.

    PubMed

    Huang, Hu; Liu, Ying; Wang, Lei; Li, Wen

    2017-01-01

    The role of chemokine receptor in age-related macular degeneration (AMD) remains elusive. The objective of this study is to investigate the role of chemokine receptor Cxcr5 in the pathogenesis of AMD. Cxcr5 gene expression levels (mRNA and protein) are higher in the retina and retinal pigment epithelium (RPE) of aged C57BL/6 wild type mice than younger ones. Vascular and glial cells express Cxcr5 and its ligand Cxcl13 in mouse retina. Aged Cxcr5 knockout (-/-) mice develop both early and late AMD-like pathological features. White and yellow spots, which look like drusen in humans, were identified with fundscopic examination. Drusen-like sub-RPE deposits with dome-shaped morphology were characterized on the sections. RPE vacuolization, swelling, and sub-RPE basal deposits were illustrated with light and transmission electron microscope (TEM). TEM further illustrated degenerated and disorganized RPE basal infoldings, phagosomes and melanosomes inside RPE, as well as abnormal photoreceptor outer segments. Lipofuscin granules and lipid droplets in the subretinal space, RPE, and choroid were revealed with fluorescence microscope and oil-red-O staining. Increased IgG in RPE/choroid were determined with Western blots (WB). WB and immunofluorescence staining determined RPE zona occuldens (ZO)-1 protein reduction and abnormal subcellular localization. TUNEL staining, outer nuclear layer (ONL) measurement and electroretinogram (ERG) recording indicated that photoreceptors underwent apoptosis, degeneration, and functional impairment. Additionally, spontaneous neovascularization (NV)-like lesions develop in the subretinal space of aged Cxcr5-/- mice. The underlying mechanisms are associated with increased subretinal F4/80+ immune cells, some of which contain RPE marker RPE65, and up-regulation of the multifunctional cytokine tumor necrosis factor-alpha (TNF-α) in RPE/choroid and retina. These findings suggest that Cxcr5 itself may be involved in the protection of RPE and

  13. That's a good one! Belief in efficacy of mnemonic strategies contributes to age-related increase in associative memory.

    PubMed

    Daugherty, Ana M; Ofen, Noa

    2015-08-01

    The development of associative memory during childhood may be influenced by metacognitive factors. Here, one aspect of metamemory function--belief in strategy efficacy-was tested for a role in the effective use of encoding strategies. A sample of 61 children and adults (8-25 years of age) completed an associative recognition memory test and were assessed on belief in the efficacy of encoding strategies. Independent of age, belief ratings identified two factors: "deep" and "shallow" encoding strategies. Although the strategy factor structure was stable across age, adolescents and adults were more likely to prefer using a deep encoding strategy, whereas children were equally likely to prefer a shallow strategy. Belief ratings of deep encoding strategies increased with age and, critically, accounted for better associative recognition.

  14. Nutritional Supplementation Inhibits the Increase in Serum Malondialdehyde in Patients with Wet Age-Related Macular Degeneration

    PubMed Central

    Fukukita, Hiroshi; Tsunekawa, Taichi; Kataoka, Keiko; Hwang, Shiang-Jyi; Nagasaka, Yosuke; Ito, Yasuki; Terasaki, Hiroko

    2017-01-01

    Purpose. To compare serum levels of malondialdehyde (MDA) in patients with wet age-related macular degeneration (wAMD), patients with dry AMD (dAMD), and patients without AMD and to evaluate the efficacy of nutritional supplementation for treating elevated serum MDA in patients with wAMD. Methods. MDA levels were measured in sera from 20 patients with wAMD, 20 with dAMD, and 24 without AMD. Patients with wAMD were randomized to receive or not receive nutritional supplementation (10 patients in each group), and MDA levels were measured after 3 months of treatment. Results. MDA levels in patients with wAMD were significantly greater compared with patients without AMD. In eyes with wAMD, there was a significant correlation between MDA levels and choroidal neovascularization lesion area. Serum MDA levels decreased in most patients that received supplementation and significantly increased in those who did not. Conclusion. Baseline serum MDA levels were elevated in patients with wAMD, and MDA levels were directly correlated with choroidal neovascularization lesion area. In addition, nutritional supplementation appeared to exert a protective effect against oxidative stress in patients with wAMD. PMID:28243361

  15. Nutritional Supplementation Inhibits the Increase in Serum Malondialdehyde in Patients with Wet Age-Related Macular Degeneration.

    PubMed

    Matsuura, Toshiyuki; Takayama, Kei; Kaneko, Hiroki; Ye, Fuxiang; Fukukita, Hiroshi; Tsunekawa, Taichi; Kataoka, Keiko; Hwang, Shiang-Jyi; Nagasaka, Yosuke; Ito, Yasuki; Terasaki, Hiroko

    2017-01-01

    Purpose. To compare serum levels of malondialdehyde (MDA) in patients with wet age-related macular degeneration (wAMD), patients with dry AMD (dAMD), and patients without AMD and to evaluate the efficacy of nutritional supplementation for treating elevated serum MDA in patients with wAMD. Methods. MDA levels were measured in sera from 20 patients with wAMD, 20 with dAMD, and 24 without AMD. Patients with wAMD were randomized to receive or not receive nutritional supplementation (10 patients in each group), and MDA levels were measured after 3 months of treatment. Results. MDA levels in patients with wAMD were significantly greater compared with patients without AMD. In eyes with wAMD, there was a significant correlation between MDA levels and choroidal neovascularization lesion area. Serum MDA levels decreased in most patients that received supplementation and significantly increased in those who did not. Conclusion. Baseline serum MDA levels were elevated in patients with wAMD, and MDA levels were directly correlated with choroidal neovascularization lesion area. In addition, nutritional supplementation appeared to exert a protective effect against oxidative stress in patients with wAMD.

  16. Detection of an aging-related increase in advanced glycation end products in fast- and slow-twitch skeletal muscles in the rat.

    PubMed

    Ramamurthy, B; Larsson, L

    2013-06-01

    Glycation, a non-enzymatic addition of reducing sugars to ε-amino groups of proteins, is a post-translational modification that results in the formation of irreversible advanced glycation end products (AGEs). Ageing related decline in myofibrillar protein function is effected by a number of structural and functional modifications including glycation. Functional properties of skeletal muscles, such as maximum velocity of unloaded shortening, are known to be profoundly affected by ageing at the motor unit, cellular and tissue levels. However, the contribution of protein modifications to a decline in muscle function is not well understood. In this study we measured AGEs of intracellular and sarcolemmal proteins, using an anti-AGE antibody in soleus (SOL) and extensor digiotorum longus (EDL) muscles of male and female rats of five different age groups. Using a fluorescent secondary antibody to visualize AGEs in the confocal microscope, we found that myosin is glycated in both fiber types in all age groups; an ageing related increase in AGEs was observed in both intracellular and sarcolemmal regions in all age groups, with the exception of sarcolemma of SOL (unchanged) and EDL (reduced) in female rats; the greatest concentration of AGEs was found intracellularly in the SOL of the oldest age group (27-30) of females. While an ageing related decline in motor properties can be partially attributed to the observed increase in myofibrillar protein glycation, our results also indicate that intracellular and the less well studied sarcolemmal protein modification likely contribute to an aging-related decline in muscle function. Further studies are required to establish a link between the observed ageing related increase in glycation and muscle function at the motor unit, cellular and tissue levels.

  17. Age related increase in mTOR activity contributes to the pathological changes in ovarian surface epithelium

    PubMed Central

    Bajwa, Preety; Nagendra, Prathima B.; Nielsen, Sarah; Sahoo, Subhransu S.; Bielanowicz, Amanda; Lombard, Janine M.; Wilkinson, Erby J.; Miller, Richard A.; Tanwar, Pradeep S.

    2016-01-01

    Ovarian cancer is a disease of older women. However, the molecular mechanisms of ovarian aging and their contribution to the pathogenesis of ovarian cancer are currently unclear. mTOR signalling is a major regulator of aging as suppression of this pathway extends lifespan in model organisms. Overactive mTOR signalling is present in up to 80% of ovarian cancer samples and is associated with poor prognosis. This study examined the role of mTOR signalling in age-associated changes in ovarian surface epithelium (OSE). Histological examination of ovaries from both aged mice and women revealed OSE cell hyperplasia, papillary growth and inclusion cysts. These pathological lesions expressed bonafide markers of ovarian cancer precursor lesions, Pax8 and Stathmin 1, and were presented with elevated mTOR signalling. To understand whether overactive mTOR signalling is responsible for the development of these pathological changes, we analysed ovaries of the Pten trangenic mice and found significant reduction in OSE lesions compared to controls. Furthermore, pharmacological suppression of mTOR signalling significantly decreased OSE hyperplasia in aged mice. Treatment with mTOR inhibitors reduced human ovarian cancer cell viability, proliferation and colony forming ability. Collectively, we have established the role of mTOR signalling in age-related OSE pathologies and initiation of ovarian cancer. PMID:27036037

  18. Impact of Air Pollution on Age and Gender Related Increase in Cough Reflex Sensitivity of Healthy Children in Slovakia

    PubMed Central

    Demoulin-Alexikova, Silvia; Plevkova, Jana; Mazurova, Lenka; Zatko, Tomas; Alexik, Mikulas; Hanacek, Jan; Tatar, Milos

    2016-01-01

    Background: Numerous studies show higher cough reflex sensitivity (CRS) and cough outcomes in children compared to adults and in females compared to males. Despite close link that exists between cough and environment the potential influence of environmental air pollution on age- and gender -related differences in cough has not been studied yet. Purpose: The purpose of our study was to analyse whether the effects of exposure to environmental tobacco smoke (ETS) from parental smoking and PM10 from living in urban area are implied in age- and gender-related differences in cough outcomes of healthy, non-asthmatic children. Assessment of CRS using capsaicin and incidence of dry and wet cough was performed in 290 children (mean age 13.3 ± 2.6 years (138 females/152 males). Results: CRS was significantly higher in girls exposed to ETS [22.3 μmol/l (9.8–50.2 μmol/l)] compared to not exposed girls [79.9 μmol/l (56.4–112.2 μmol/l), p = 0.02] as well as compared to exposed boys [121.4 μmol/l (58.2–253.1 μmol/l), p = 0.01]. Incidence of dry cough lasting more than 3 weeks was significantly higher in exposed compared to not exposed girls. CRS was significantly higher in school-aged girls living in urban area [22.0 μmol/l (10.6–45.6 μmol/l)] compared to school-aged girls living in rural area [215.9 μmol/l (87.3–533.4 μmol/l); p = 0.003], as well as compared to teenage girls living in urban area [108.8 μmol/l (68.7–172.9 μmol/l); p = 0.007]. No CRS differences were found between urban and rural boys when controlled for age group. No CRS differences were found between school-aged and teenage boys when controlled for living area. Conclusions: Our results have shown that the effect of ETS on CRS was gender specific, linked to female gender and the effect of PM10 on CRS was both gender and age specific, related to female gender and school-age. We suggest that age and gender related differences in incidence of cough and CRS might be, at least partially

  19. Recovery of Aging-Related Size Increase of Skin Epithelial Cells: In vivo Mouse and In vitro Human Study

    PubMed Central

    Sokolov, Igor; Guz, Natali V.; Iyer, Swaminathan; Hewitt, Amy; Sokolov, Nina A.; Erlichman, Joseph S.; Woodworth, Craig D.

    2015-01-01

    The size increase of skin epithelial cells during aging is well-known. Here we demonstrate that treatment of aging cells with cytochalasin B substantially decreases cell size. This decrease was demonstrated on a mouse model and on human skin cells in vitro. Six nude mice were treated by topical application of cytochalasin B on skin of the dorsal left midsection for 140 days (the right side served as control for placebo treatment). An average decrease in cell size of 56±16% resulted. A reduction of cell size was also observed on primary human skin epithelial cells of different in vitro age (passages from 1 to 8). A cell strain obtained from a pool of 6 human subjects was treated with cytochalasin B in vitro for 12 hours. We observed a decrease in cell size that became statistically significant and reached 20–40% for cells of older passage (6–8 passages) whereas no substantial change was observed for younger cells. These results may be important for understanding the aging processes, and for cosmetic treatment of aging skin. PMID:25807526

  20. Glutamate Cysteine Ligase Modifier Subunit (Gclm) Null Mice Have Increased Ovarian Oxidative Stress and Accelerated Age-Related Ovarian Failure

    PubMed Central

    Lim, Jinhwan; Nakamura, Brooke N.; Mohar, Isaac; Kavanagh, Terrance J.

    2015-01-01

    Glutathione (GSH) is the one of the most abundant intracellular antioxidants. Mice lacking the modifier subunit of glutamate cysteine ligase (Gclm), the rate-limiting enzyme in GSH synthesis, have decreased GSH. Our prior work showed that GSH plays antiapoptotic roles in ovarian follicles. We hypothesized that Gclm−/− mice have accelerated ovarian aging due to ovarian oxidative stress. We found significantly decreased ovarian GSH concentrations and oxidized GSH/oxidized glutathione redox potential in Gclm−/− vs Gclm+/+ ovaries. Prepubertal Gclm−/− and Gclm+/+ mice had similar numbers of ovarian follicles, and as expected, the total number of ovarian follicles declined with age in both genotypes. However, the rate of decline in follicles was significantly more rapid in Gclm−/− mice, and this was driven by accelerated declines in primordial follicles, which constitute the ovarian reserve. We found significantly increased 4-hydroxynonenal immunostaining (oxidative lipid damage marker) and significantly increased nitrotyrosine immunostaining (oxidative protein damage marker) in prepubertal and adult Gclm−/− ovaries compared with controls. The percentage of small ovarian follicles with increased granulosa cell proliferation was significantly higher in prepubertal and 2-month-old Gclm−/− vs Gclm+/+ ovaries, indicating accelerated recruitment of primordial follicles into the growing pool. The percentages of growing follicles with apoptotic granulosa cells were increased in young adult ovaries. Our results demonstrate increased ovarian oxidative stress and oxidative damage in young Gclm−/− mice, associated with an accelerated decline in ovarian follicles that appears to be mediated by increased recruitment of follicles into the growing pool, followed by apoptosis at later stages of follicular development. PMID:26083875

  1. Rapamycin increases grip strength and attenuates age-related decline in maximal running distance in old low capacity runner rats.

    PubMed

    Xue, Qian-Li; Yang, Huanle; Li, Hui-Fen; Abadir, Peter M; Burks, Tyesha N; Koch, Lauren G; Britton, Steven L; Carlson, Joshua; Chen, Laura; Walston, Jeremy D; Leng, Sean X

    2016-04-01

    Rapamycin is known to extend lifespan. We conducted a randomized placebo-controlled study of enteric rapamycin-treatment to evaluate its effect on physical function in old low capacity runner (LCR) rats, a rat model selected from diverse genetic background for low intrinsic aerobic exercise capacity without genomic manipulation and characterized by increased complex disease risks and aging phenotypes. The study was performed in 12 male and 16 female LCR rats aged 16-22 months at baseline. The treatment group was fed with rapamycin-containing diet pellets at approximately 2.24mg/kg body weight per day and the placebo group with the same diet without rapamycin for six months. Observation was extended for additional 2 months. Physical function measurements include grip strength measured as maximum tensile force using a rat grip strength meter and maximum running distance (MRD) using rat physical treadmill test. The results showed that rapamycin improved grip strength by 13% (p=.036) and 60% (p=.001) from its baseline in female and male rats, respectively. Rapamycin attenuated MRD decline by 66% (p=.001) and 46% (p=.319) in females and males, respectively. These findings provide initial evidence for beneficial effect of rapamycin on physical functioning in an aging rat model of high disease risks with significant implication in humans.

  2. Age-Related Decrease in Heat Shock 70-kDa Protein 8 in Cerebrospinal Fluid Is Associated with Increased Oxidative Stress

    PubMed Central

    Loeffler, David A.; Klaver, Andrea C.; Coffey, Mary P.; Aasly, Jan O.; LeWitt, Peter A.

    2016-01-01

    Age-associated declines in protein homeostasis mechanisms (“proteostasis”) are thought to contribute to age-related neurodegenerative disorders. The increased oxidative stress which occurs with aging can activate a key proteostatic process, chaperone-mediated autophagy. This study investigated age-related alteration in cerebrospinal fluid (CSF) concentrations of heat shock 70-kDa protein 8 (HSPA8), a molecular chaperone involved in proteostatic mechanisms including chaperone-mediated autophagy, and its associations with indicators of oxidative stress (8-hydroxy-2′-deoxyguanosine [8-OHdG] and 8-isoprostane) and total anti-oxidant capacity. We examined correlations between age, HSPA8, 8-OHdG, 8-isoprostane, and total antioxidant capacity (TAC) in CSF samples from 34 healthy subjects ranging from 20 to 75 years of age. Age was negatively associated with HSPA8 (ρ = –0.47; p = 0.005). An age-related increase in oxidative stress was indicated by a positive association between age and 8-OHdG (ρ = 0.61; p = 0.0001). HSPA8 was moderately negatively associated with 8-OHdG (ρ = –0.58; p = 0.0004). Age and HSPA8 were weakly associated with 8-isoprostane and TAC (range of ρ values: –0.15 to 0.16). Our findings in this exploratory study suggest that during healthy aging, CSF HSPA8 may decrease, perhaps due in part to an increase in oxidative stress. Our results also suggest that 8-OHdG may be more sensitive than 8-isoprostane for measuring oxidative stress in CSF. Further studies are indicated to determine if our findings can be replicated with a larger cohort, and if the age-related decrease in HSPA8 in CSF is reflected by a similar change in the brain. PMID:27507943

  3. Age-related increase of reactive oxygen generation in the brains of mammals and birds: is reactive oxygen a signaling molecule to determine the aging process and life span?

    PubMed

    Sasaki, Toru; Unno, Keiko; Tahara, Shoichi; Kaneko, Takao

    2010-07-01

    Since Harman proposed the "free-radical theory of aging", oxidative stress has been postulated to be a major causal factor of senescence. The accumulation of oxidative stress-induced oxidatively modified macromolecules, including protein, DNA and lipid, were found in tissues during the aging process; however, it is not necessarily clear which factor is more critical, an increase in endogenous reactive oxygen and/or a decrease in anti-oxidative defense, to the age-related increase in oxidative damage. To clarify the increasing production of reactive oxygen with age, we examined reactive oxygen-dependent chemiluminescent (CL) signals in ex vivo brain slices prepared from different-aged animal brains during hypoxia-reoxygenation treatment using a novel photonic imaging method. The CL signal was intensified during reoxygenation. The signals in SAMP10 (short-life strain) and SAMR1 (control) brain slices increased with aging. The slope of the increase of CL intensity with age in P10 was steeper than in R1. Age-dependent increase of CL intensity was also observed in C57BL/6 mice, Wistar rats and pigeons; however, superoxide dismutase (SOD) activity in the brain did not change with age. These results suggest that reactive oxygen production itself increased with aging. The rate of age-related increases of CL intensity was inversely related to the maximum lifespan of animals. We speculate that reactive oxygen might be a signaling molecule and its levels in tissue might determine the aging process and lifespan. Decelerating age-related increases of reactive oxygen production are expected to be a potent strategy for anti-aging interventions.

  4. Age-Related Increases in Long-Range Connectivity in Fetal Functional Neural Connectivity Networks In Utero

    PubMed Central

    Thomason, Moriah E.; Grove, Lauren E.; Lozon, Tim A.; Vila, Angela M.; Ye, Yongquan; Nye, Matthew J.; Manning, Janessa H.; Pappas, Athina; Hernandez-Andrade, Edgar; Yeo, Lami; Mody, Swati; Berman, Susan; Hassan, Sonia S.; Romero, Roberto

    2015-01-01

    Formation of operational neural networks is one of the most significant accomplishments of human fetal brain growth. Recent advances in functional magnetic resonance imaging (fMRI) have made it possible to obtain information about brain function during fetal development. Specifically, resting-state fMRI and novel signal covariation approaches have opened up a new avenue for non-invasive assessment of neural functional connectivity (FC) before birth. Early studies in this area have unearthed new insights about principles of prenatal brain function. However, very little is known about the emergence and maturation of neural networks during fetal life. Here, we obtained cross-sectional rs-fMRI data from 39 fetuses between 24 and 38 weeks postconceptual age to examine patterns of connectivity across ten neural FC networks. We identified primitive forms of motor, visual, default mode, thalamic, and temporal networks in the human fetal brain. We discovered the first evidence of increased long-range, cerebral-cerebellar, cortical-subcortical, and intra-hemispheric FC with advancing fetal age. Continued aggregation of data about fundamental neural connectivity systems in utero is essential to establishing principles of connectomics at the beginning of human life. Normative data provides a vital context against which to compare instances of abnormal neurobiological development. PMID:25284273

  5. Age-related increases in long-range connectivity in fetal functional neural connectivity networks in utero.

    PubMed

    Thomason, Moriah E; Grove, Lauren E; Lozon, Tim A; Vila, Angela M; Ye, Yongquan; Nye, Matthew J; Manning, Janessa H; Pappas, Athina; Hernandez-Andrade, Edgar; Yeo, Lami; Mody, Swati; Berman, Susan; Hassan, Sonia S; Romero, Roberto

    2015-02-01

    Formation of operational neural networks is one of the most significant accomplishments of human fetal brain growth. Recent advances in functional magnetic resonance imaging (fMRI) have made it possible to obtain information about brain function during fetal development. Specifically, resting-state fMRI and novel signal covariation approaches have opened up a new avenue for non-invasive assessment of neural functional connectivity (FC) before birth. Early studies in this area have unearthed new insights about principles of prenatal brain function. However, very little is known about the emergence and maturation of neural networks during fetal life. Here, we obtained cross-sectional rs-fMRI data from 39 fetuses between 24 and 38 weeks postconceptual age to examine patterns of connectivity across ten neural FC networks. We identified primitive forms of motor, visual, default mode, thalamic, and temporal networks in the human fetal brain. We discovered the first evidence of increased long-range, cerebral-cerebellar, cortical-subcortical, and intra-hemispheric FC with advancing fetal age. Continued aggregation of data about fundamental neural connectivity systems in utero is essential to establishing principles of connectomics at the beginning of human life. Normative data provides a vital context against which to compare instances of abnormal neurobiological development.

  6. Age-Related Increases in Verbal Knowledge Are Not Associated With Word Finding Problems in the Cam-CAN Cohort: What You Know Won’t Hurt You

    PubMed Central

    James, Lori E.; Abrams, Lise; Tyler, Lorraine K.

    2017-01-01

    Objective: We tested the claim that age-related increases in knowledge interfere with word retrieval, leading to word finding failures. We did this by relating a measure of crystallized intelligence to tip-of-the-tongue (TOT) states and picture naming accuracy. Method: Participants were from a large (N = 708), cross-sectional (aged 18–88 years), population-based sample from the Cambridge Centre for Ageing and Neuroscience cohort (Cam-CAN; www.cam-can.com). They completed (a) the Spot-the-Word Test (STW), a measure of crystallized intelligence in which participants circled the real word in word/nonword pairs, (b) a TOT-inducing task, and (c) a picture naming task. Results: Age and STW independently predicted TOTs, with higher TOTs for older adults and for participants with lower STW scores. Tests of a moderator model examining interactions between STW and age indicated that STW was a significant negative predictor of TOTs in younger adults, but with increasing age, the effect size gradually approached zero. Results using picture naming accuracy replicated these findings. Discussion: These results do not support the hypothesis that lifelong knowledge acquisition leads to interference that causes an age-related increase in TOTs. Instead, crystallized intelligence supports successful word retrieval, although this relationship weakens across adulthood. PMID:27371482

  7. Increased risk for age-related impairment in visual attention associated with mild traumatic brain injury: Evidence from saccadic response times

    PubMed Central

    Barry, David M.; Ettenhofer, Mark L.

    2017-01-01

    It was hypothesized that risk for age-related impairment in attention would be greater among those with remote history of mild TBI than individuals without history of head injury. Twenty-seven adults with remote history of mild TBI and a well-matched comparison group of 54 uninjured controls completed a computerized test of visual attention while saccadic and manual response times were recorded. Within the mild TBI group only, older age was associated with slower saccadic responses and poorer saccadic inhibition. Saccadic slowing was mitigated in situations where the timing and location of attention targets was fully predictable. Mild TBI was not associated with age-related increases in risk for neuropsychological impairment or neurobehavioral symptoms. These results provide preliminary evidence that risk for age-related impairment in visual attention may be higher among those with a history of mild TBI. Saccadic measures may provide enhanced sensitivity to this subtle form of cognitive impairment. PMID:28166259

  8. Age-related switch of bone mass in p47phox deficient mice through increased inflammatory milieu in bone

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bone remodeling is age-dependently regulated and changes dramatically during the course of development. Excessive accumulation of reactive oxygen species (ROS), including superoxide, hydrogen peroxide, and hydroxyl radicals, has been suggested to be the leading cause of many inflammatory and degener...

  9. Age-related increases in calcium-binding protein immunoreactivity in the cochlear nucleus of hearing impaired C57BL/6J mice.

    PubMed

    Idrizbegovic, Esma; Bogdanovic, Nenad; Willott, James F; Canlon, Barbara

    2004-09-01

    Aging C57BL/6J (C57) mice (1-30 months old), were used to study calcium-binding protein immunoreactivity (parvalbumin, calbindin and calretinin) in the cochlear nucleus. A quantitative stereological method, the optical fractionator was used to determine the total number of neurons, and the total number of immunostained neurons in the posteroventral- and dorsal cochlear nuclei (PVCN and DCN). A statistically significant age-related decrease of the total number of neurons was found in the PVCN and DCN using Nissl staining. In the DCN, an age-related increase in the total number of parvalbumin-positive neurons was found, while no changes in the total number of calbindin or calretinin positive neurons were demonstrated. In the PVCN, the total number of parvalbumin, calbindin, or calretinin positive neurons remained stable with increasing age. The percentage of parvalbumin, calbindin, and calretinin positive neurons significantly increased in the DCN, and the percentage of parvalbumin and calbindin-positive neurons increased in the PVCN. These findings imply that there is a relative up-regulation of calcium-binding proteins in neurons that had not previously expressed these proteins. This plastic response in the profoundly hearing impaired C57 mouse may be a survival strategy for cochlear nucleus neurons.

  10. Can heavy isotopes increase lifespan? Studies of relative abundance in various organisms reveal chemical perspectives on aging

    PubMed Central

    2016-01-01

    Stable heavy isotopes co‐exist with their lighter counterparts in all elements commonly found in biology. These heavy isotopes represent a low natural abundance in isotopic composition but impose great retardation effects in chemical reactions because of kinetic isotopic effects (KIEs). Previous isotope analyses have recorded pervasive enrichment or depletion of heavy isotopes in various organisms, strongly supporting the capability of biological systems to distinguish different isotopes. This capability has recently been found to lead to general decline of heavy isotopes in metabolites during yeast aging. Conversely, supplementing heavy isotopes in growth medium promotes longevity. Whether this observation prevails in other organisms is not known, but it potentially bears promise in promoting human longevity. PMID:27554342

  11. A Remarkable Age-Related Increase in SIRT1 Protein Expression against Oxidative Stress in Elderly: SIRT1 Gene Variants and Longevity in Human

    PubMed Central

    Kilic, Ulkan; Gok, Ozlem; Erenberk, Ufuk; Dundaroz, Mehmet Rusen; Torun, Emel; Kucukardali, Yasar; Elibol-Can, Birsen; Uysal, Omer; Dundar, Tolga

    2015-01-01

    Aging is defined as the accumulation of progressive organ dysfunction. Controlling the rate of aging by clarifying the complex pathways has a significant clinical importance. Nowadays, sirtuins have become famous molecules for slowing aging and decreasing age-related disorders. In the present study, we analyzed the SIRT1 gene polymorphisms (rs7895833 A>G, rs7069102 C>G and rs2273773 C>T) and its relation with levels of SIRT1, eNOS, PON-1, cholesterol, TAS, TOS, and OSI to demonstrate the association between genetic variation in SIRT1 and phenotype at different ages in humans. We observed a significant increase in the SIRT1 level in older people and found a significant positive correlation between SIRT1 level and age in the overall studied population. The oldest people carrying AG genotypes for rs7895833 have the highest SIRT1 level suggesting an association between rs7895833 SNP and lifespan longevity. Older people have lower PON-1 levels than those of adults and children which may explain the high levels of SIRT1 protein as a compensatory mechanism for oxidative stress in the elderly. The eNOS protein level was significantly decreased in older people as compared to adults. There was no significant difference in the eNOS level between older people and children. The current study is the first to demonstrate age-related changes in SIRT1 levels in humans and it is important for a much better molecular understanding of the role of the longevity gene SIRT1 and its protein product in aging. It is also the first study presenting the association between SIRT1 expression in older people and rs7895833 in SIRT1 gene. PMID:25785999

  12. An age-related numerical and functional deficit in CD19(+) CD24(hi) CD38(hi) B cells is associated with an increase in systemic autoimmunity.

    PubMed

    Duggal, Niharika A; Upton, Jane; Phillips, Anna C; Sapey, Elizabeth; Lord, Janet M

    2013-10-01

    Autoimmunity increases with aging indicative of reduced immune tolerance, but the mechanisms involved are poorly defined. In recent years, subsets of B cells with immunoregulatory properties have been identified in murine models of autoimmune disorders, and these cells downregulate immune responses via secretion of IL10. In humans, immature transitional B cells with a CD19(+) CD24(hi) CD38(hi) phenotype have been reported to regulate immune responses via IL10 production. We found the frequency and numbers of CD19(+) CD24(hi) CD38(hi) cells were reduced in the PBMC pool with age. IL10 expression and secretion following activation via either CD40, or Toll-like receptors was also impaired in CD19(+) CD24(hi) CD38(hi) B cells from healthy older donors. When investigating the mechanisms involved, we found that CD19(+) CD24(hi) CD38(hi) B-cell function was compromised by age-related effects on both T cells and B cells: specifically, CD40 ligand expression was lower in CD4 T cells from older donors following CD3 stimulation, and signalling through CD40 was impaired in CD19(+) CD24(hi) CD38(hi) B cells from elders as evidenced by reduced phosphorylation (Y705) and activation of STAT3. However, there was no age-associated change in expression of costimulatory molecules CD80 and CD86 on CD19(+) CD24(hi) CD38(hi) cells, suggesting IL10-dependent immune suppression is impaired, but contact-dependent suppressive capacity is intact with age. Finally, we found a negative correlation between CD19(+) CD24(hi) CD38(hi) B-cell IL10 production and autoantibody (Rheumatoid factor) levels in older adults. We therefore propose that an age-related decline in CD19(+) CD24(hi) CD38(hi) B cell number and function may contribute towards the increased autoimmunity and reduced immune tolerance seen with aging.

  13. Age-related eye disease.

    PubMed

    Voleti, Vinod B; Hubschman, Jean-Pierre

    2013-05-01

    As with many organs, compromised function of the eye is accompanied with age and has become increasingly prevalent with the aging population. When decreased visual loss becomes significant, patients' ability to perform activities of daily living becomes compromised. This decrease in function is met with morbidity and mortality, as well as a large socioeconomic burden throughout the world. This review summarizes the most common age-related eye diseases, including cataract, glaucoma, diabetic retinopathy, retinal vein occlusion, and age-related macular degeneration. Although our understanding of the genetic and biochemical pathways of these diseases is sill at its primitive stages, we have become able to help our patients improve the quality of life as they age.

  14. Increased Toxoplasma gondii positivity relative to age in 125 Scottish sheep flocks; evidence of frequent acquired infection

    PubMed Central

    2011-01-01

    Toxoplasma gondii seroprevalence was determined in 3333 sheep sera from 125 distinct sheep flocks in Scotland, with the majority of flocks being represented by 27 samples, which were collected between July 2006 and August 2008. The selected farms give a representative sample of 14 400 sheep holdings identified in the Scottish Government census data from 2004. Overall T. gondii seroprevalence, at individual sheep level, was determined to be 56.6%; each flock tested, had at least a single positive animal and in four flocks all ewes tested positive. The seroprevalence of sheep increased from 37.7% in one year old stock to 73.8% in ewes that were older than six years, showing that acquired infections during the life of the animals is frequent and that environmental contamination by T. gondii oocysts must be significant. The median within-flock seroprevalence varied significantly across Scotland, with the lowest seroprevalence of 42.3% in the South and the highest seroprevalence of 69.2% in the far North of Scotland and the Scottish Islands, while the central part of Scotland had a seroprevalence of 57.7%. This distribution disequilibrium may be due to the spread and survival of oocysts on pasture and lambing areas. A questionnaire accompanying sampling of flocks identified farms that used Toxovax®, a commercial vaccine that protects sheep from abortion due to T. gondii infection. Only 24.7% of farmers used the vaccine and the vaccine did not significantly affect the within flock seroprevalence for T. gondii. The implications for food safety and human infection are discussed. PMID:22189159

  15. Increased sensitivity to age-related differences in brain functional connectivity during continuous multiple object tracking compared to resting-state.

    PubMed

    Dørum, Erlend S; Kaufmann, Tobias; Alnæs, Dag; Andreassen, Ole A; Richard, Geneviève; Kolskår, Knut K; Nordvik, Jan Egil; Westlye, Lars T

    2017-03-01

    Age-related differences in cognitive agility vary greatly between individuals and cognitive functions. This heterogeneity is partly mirrored in individual differences in brain network connectivity as revealed using resting-state functional magnetic resonance imaging (fMRI), suggesting potential imaging biomarkers for age-related cognitive decline. However, although convenient in its simplicity, the resting state is essentially an unconstrained paradigm with minimal experimental control. Here, based on the conception that the magnitude and characteristics of age-related differences in brain connectivity is dependent on cognitive context and effort, we tested the hypothesis that experimentally increasing cognitive load boosts the sensitivity to age and changes the discriminative network configurations. To this end, we obtained fMRI data from younger (n=25, mean age 24.16±5.11) and older (n=22, mean age 65.09±7.53) healthy adults during rest and two load levels of continuous multiple object tracking (MOT). Brain network nodes and their time-series were estimated using independent component analysis (ICA) and dual regression, and the edges in the brain networks were defined as the regularized partial temporal correlations between each of the node pairs at the individual level. Using machine learning based on a cross-validated regularized linear discriminant analysis (rLDA) we attempted to classify groups and cognitive load from the full set of edge-wise functional connectivity indices. While group classification using resting-state data was highly above chance (approx. 70% accuracy), functional connectivity (FC) obtained during MOT strongly increased classification performance, with 82% accuracy for the young and 95% accuracy for the old group at the highest load level. Further, machine learning revealed stronger differentiation between rest and task in young compared to older individuals, supporting the notion of network dedifferentiation in cognitive aging. Task

  16. [Age related macular degeneration].

    PubMed

    Sayen, Alexandra; Hubert, Isabelle; Berrod, Jean-Paul

    2011-02-01

    Age-related macular degeneration (ARMD) is a multifactorial disease caused by a combination of genetic and environmental factors. It is the first cause of blindness in patients over 50 in the western world. The disease has been traditionally classified into early and late stages with dry (atrophic) and wet (neovascular) forms: neovascular form is characterized by new blood vessels development under the macula (choroidal neovascularisation) which lead to a rapid decline of vision associated with metamorphopsia and requiring an urgent ophtalmological examination. Optical coherence tomography is now one of the most important part of the examination for diagnosis and treatment. Patient with age related maculopathy should consider taking a dietary supplement such that used in AREDS. The treatment of the wet ARMD has largely beneficied since year 2006 of anti-VEGF (vascular endothelial growth factor) molecules such as ranibizumab or bevacizumab given as repeated intravitreal injections. A systematic follow up each 4 to 8 week in required for several years. There is no effective treatment at the moment for dry AMD. For patients with binocular visual acuity under 60/200 rehabilitation includes low vision specialist, vision aids and psychological support.

  17. Age-Related Macular Degeneration.

    PubMed

    Mehta, Sonia

    2015-09-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. AMD is diagnosed based on characteristic retinal findings in individuals older than 50. Early detection and treatment are critical in increasing the likelihood of retaining good and functional vision.

  18. The Impacts of Cellular Senescence in Elderly Pneumonia and in Age-Related Lung Diseases That Increase the Risk of Respiratory Infections.

    PubMed

    Yanagi, Shigehisa; Tsubouchi, Hironobu; Miura, Ayako; Matsuo, Ayako; Matsumoto, Nobuhiro; Nakazato, Masamitsu

    2017-02-25

    Pneumonia generates considerable negative impacts on the elderly. Despite the widespread uses of vaccines and appropriate antibiotics, the morbidity and mortality of elderly pneumonia are significantly higher compared to the counterparts of young populations. The definitive mechanisms of high vulnerability in the elderly against pathogen threats are unclear. Age-associated, chronic low-grade inflammation augments the susceptibility and severity of pneumonia in the elderly. Cellular senescence, one of the hallmarks of aging, has its own characteristics, cell growth arrest and senescence-associated secretory phenotype (SASP). These properties are beneficial if the sequence of senescence-clearance-regeneration is transient in manner. However, persisting senescent cell accumulation and excessive SASP might induce sustained low-grade inflammation and disruption of normal tissue microenvironments in aged tissue. Emerging evidence indicates that cellular senescence is a key component in the pathogenesis of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), which are known to be age-related and increase the risk of pneumonia. In addition to their structural collapses, COPD and IPF might increase the vulnerability to pathogen insults through SASP. Here, we discuss the current advances in understanding of the impacts of cellular senescence in elderly pneumonia and in these chronic lung disorders that heighten the risk of respiratory infections.

  19. The Impacts of Cellular Senescence in Elderly Pneumonia and in Age-Related Lung Diseases That Increase the Risk of Respiratory Infections

    PubMed Central

    Yanagi, Shigehisa; Tsubouchi, Hironobu; Miura, Ayako; Matsuo, Ayako; Matsumoto, Nobuhiro; Nakazato, Masamitsu

    2017-01-01

    Pneumonia generates considerable negative impacts on the elderly. Despite the widespread uses of vaccines and appropriate antibiotics, the morbidity and mortality of elderly pneumonia are significantly higher compared to the counterparts of young populations. The definitive mechanisms of high vulnerability in the elderly against pathogen threats are unclear. Age-associated, chronic low-grade inflammation augments the susceptibility and severity of pneumonia in the elderly. Cellular senescence, one of the hallmarks of aging, has its own characteristics, cell growth arrest and senescence-associated secretory phenotype (SASP). These properties are beneficial if the sequence of senescence–clearance–regeneration is transient in manner. However, persisting senescent cell accumulation and excessive SASP might induce sustained low-grade inflammation and disruption of normal tissue microenvironments in aged tissue. Emerging evidence indicates that cellular senescence is a key component in the pathogenesis of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), which are known to be age-related and increase the risk of pneumonia. In addition to their structural collapses, COPD and IPF might increase the vulnerability to pathogen insults through SASP. Here, we discuss the current advances in understanding of the impacts of cellular senescence in elderly pneumonia and in these chronic lung disorders that heighten the risk of respiratory infections. PMID:28245616

  20. n-3 fatty acids effectively improve the reference memory-related learning ability associated with increased brain docosahexaenoic acid-derived docosanoids in aged rats.

    PubMed

    Hashimoto, Michio; Katakura, Masanori; Tanabe, Yoko; Al Mamun, Abdullah; Inoue, Takayuki; Hossain, Shahdat; Arita, Makoto; Shido, Osamu

    2015-02-01

    We investigated whether a highly purified eicosapentaenoic acid (EPA) and a concentrated n-3 fatty acid formulation (prescription TAK-085) containing EPA and docosahexaenoic acid (DHA) ethyl ester could improve the learning ability of aged rats and whether this specific outcome had any relation with the brain levels of EPA-derived eicosanoids and DHA-derived docosanoids. The rats were tested for reference memory errors (RMEs) and working memory errors (WMEs) in an eight-arm radial maze. Fatty acid compositions were analyzed by GC, whereas brain eicosanoid/docosanoids were measured by LC-ESI-MS-MS-based analysis. The levels of lipid peroxides (LPOs) were measured by thiobarbituric acid reactive substances. The administration of TAK-085 at 300 mg·kg⁻¹day⁻¹ for 17 weeks reduced the number of RMEs in aged rats compared with that in the control rats. Both TAK-085 and EPA administration increased plasma EPA and DHA levels in aged rats, with concurrent increases in DHA and decreases in arachidonic acid in the corticohippocampal brain tissues. TAK-085 administration significantly increased the formation of EPA-derived 5-HETE and DHA-derived 7-, 10-, and 17-HDoHE, PD1, RvD1, and RvD2. ARA-derived PGE2, PGD2, and PGF2α significantly decreased in TAK-085-treated rats. DHA-derived mediators demonstrated a significantly negative correlation with the number of RMEs, whereas EPA-derived mediators did not exhibit any relationship. Furthermore, compared with the control rats, the levels of LPO in the plasma, cerebral cortex, and hippocampus were significantly reduced in TAK-085-treated rats. The findings of the present study suggest that long-term EPA+DHA administration may be a possible preventative strategy against age-related cognitive decline.

  1. Increasing Sibling Relative Risk of Survival to Older and Older Ages and the Importance of Precise Definitions of “Aging,” “Life Span,” and “Longevity”

    PubMed Central

    Sebastiani, Paola; Nussbaum, Lisa; Andersen, Stacy L.; Black, Mara J.

    2016-01-01

    The lack of a formal definition of human longevity continues to generate confusion about its genetic and nongenetic determinants. In order to characterize how differences in birth year cohorts and percentiles of survival are associated with familial contribution to variation in survival, we estimated sibling relative risk of living to increasingly rare percentiles of survival based on a dataset of 1,917 validated sibships each containing at least one individual living to age 90 years. About 1,042 of the sibships included at least one individual who survived to age 100 and 511 included at least one individual who survived to age 105 and older. We show that sibling relative risk increases with older ages, sex, and earlier birth year cohorts of the proband and siblings of male 90-year-olds (5th percentile of survival) have 1.73 (95% CI: 1.5; 2.0) times the chance of living to age 90, while siblings of both male and female probands who survived to age 105 years (~0.01 percentile of survival) have 35.6 (95%CI: 15.1; 67.7) times the chance of living to age 105 compared with population controls. These results emphasize the importance of consistently defining the longevity phenotype in terms of rarity of survival for appropriate comparisons across studies. PMID:25814633

  2. An age-related numerical and functional deficit in CD19+CD24hiCD38hi B cells is associated with an increase in systemic autoimmunity

    PubMed Central

    Duggal, Niharika A; Upton, Jane; Phillips, Anna C; Sapey, Elizabeth; Lord, Janet M

    2013-01-01

    Autoimmunity increases with aging indicative of reduced immune tolerance, but the mechanisms involved are poorly defined. In recent years, subsets of B cells with immunoregulatory properties have been identified in murine models of autoimmune disorders, and these cells downregulate immune responses via secretion of IL10. In humans, immature transitional B cells with a CD19+CD24hiCD38hi phenotype have been reported to regulate immune responses via IL10 production. We found the frequency and numbers of CD19+CD24hiCD38hi cells were reduced in the PBMC pool with age. IL10 expression and secretion following activation via either CD40, or Toll-like receptors was also impaired in CD19+CD24hiCD38hi B cells from healthy older donors. When investigating the mechanisms involved, we found that CD19+CD24hiCD38hi B-cell function was compromised by age-related effects on both T cells and B cells: specifically, CD40 ligand expression was lower in CD4 T cells from older donors following CD3 stimulation, and signalling through CD40 was impaired in CD19+CD24hiCD38hi B cells from elders as evidenced by reduced phosphorylation (Y705) and activation of STAT3. However, there was no age-associated change in expression of costimulatory molecules CD80 and CD86 on CD19+CD24hiCD38hi cells, suggesting IL10-dependent immune suppression is impaired, but contact-dependent suppressive capacity is intact with age. Finally, we found a negative correlation between CD19+CD24hiCD38hi B-cell IL10 production and autoantibody (Rheumatoid factor) levels in older adults. We therefore propose that an age-related decline in CD19+CD24hiCD38hi B cell number and function may contribute towards the increased autoimmunity and reduced immune tolerance seen with aging. PMID:23755918

  3. Age-related effects of increased ambient pressure on discrimination reaction time: A study in 105 professional divers at 6.0 atm abs.

    PubMed

    Tikkinen, Janne; Siimes, Martti A

    2015-01-01

    We investigated 105 professional divers using a computerized visual discrimination trial (Cognitrone) to measure the effects of ambient pressure on reaction times. The possible improvement in performance due to practice was anticipated, and the trials were carried out four times prior to pressurization in a hyperbaric chamber. The effect of increased ambient pressure was measured at 6.0 and 1.9 atm abs, and the potential for residual effects was tested after decompression. The results of our study indicate that repeated testing had a systematic influence on the measured time values. The effects of learning, which were independent of diver age, may have independently influenced response times. Exposure to 6.0 atm abs modified the systematic pattern of learning and was associated with increased reaction times. There were also age-related differences in response times associated with exposure to increased ambient pressures. Younger divers were more susceptible to elevated ambient pressure, evidenced by increased response times at 6 atm abs relative to their older colleagues. One out of every four of the younger divers could be considered susceptible to inert gas narcosis (ION) when an increase of one standard deviation/1SD (> 19%) or more in discrimination reaction time is used as an indicator. ION susceptibility appears independent of body composition and physical fitness. The slowed response speed experienced at 6.0 atm abs was of short duration and returned to baseline immediately with decompression. Our results suggest that IGN is demonstrated by an impaired learning process and decreased response speed and that some younger divers appear more susceptible.

  4. Obesity and related consequences to ageing.

    PubMed

    Jura, Magdalena; Kozak, Leslie P

    2016-02-01

    Obesity has become a major public health problem. Given the current increase in life expectancy, the prevalence of obesity also raises steadily among older age groups. The increase in life expectancy is often accompanied with additional years of susceptibility to chronic ill health associated with obesity in the elderly. Both obesity and ageing are conditions leading to serious health problems and increased risk for disease and death. Ageing is associated with an increase in abdominal obesity, a major contributor to insulin resistance and the metabolic syndrome. Obesity in the elderly is thus a serious concern and comprehension of the key mechanisms of ageing and age-related diseases has become a necessary matter. Here, we aimed to identify similarities underlying mechanisms related to both obesity and ageing. We bring together evidence that age-related changes in body fat distribution and metabolism might be key factors of a vicious cycle that can accelerate the ageing process and onset of age-related diseases.

  5. Combined Administration of Levetiracetam and Valproic Acid Attenuates Age Related Hyperactivity of CA3 Place Cells, Reduces Place Field Area, and Increases Spatial Information Content in Aged Rat Hippocampus

    PubMed Central

    Robitsek, RJ; Ratner, MH; Stewart, TM; Eichenbaum, H; Farb, DH

    2015-01-01

    Learning and memory deficits associated with age-related mild cognitive impairment have long been attributed to impaired processing within the hippocampus. Hyperactivity within the hippocampal CA3 region that is associated with aging is mediated in part by a loss of inhibitory interneurons and thought to underlie impaired performance in spatial memory tasks, including the abnormal tendency in aged animals to pattern complete spatial representations. Here, we asked whether the spatial firing patterns of simultaneously recorded CA3 and CA1 neurons in young and aged rats could be manipulated pharmacologically to selectively reduce CA3 hyperactivity and thus, according to hypothesis, the associated abnormality in spatial representations. We used chronically implanted high-density tetrodes to record the spatial firing properties of CA3 and CA1 units during animal exploration for food in familiar and novel environments. Aged CA3 place cells have higher firing rates, larger place fields, less spatial information content, and respond less to a change from a familiar to a novel environment than young CA3 cells. We also find that the combination of levetiracetam (LEV) + valproic acid (VPA), previously shown to act as a cognitive enhancer in tests of spatial memory, attenuate CA3 place cell firing rates, reduce place field area, and increase spatial information content in aged but not young adult rats. This is consistent with drug enhancing the specificity of neuronal firing with respect to spatial location. Contrary to expectation, however, LEV + VPA reduces place cell discrimination between novel and familiar environments, i.e., spatial correlations increase, independent of age even though drug enhances performance in cognitive tasks. The results demonstrate that spatial information content, or the number of bits of information encoded per action potential, may be the key correlate for enhancement of spatial memory by LEV + VPA. PMID:25941121

  6. Combined administration of levetiracetam and valproic acid attenuates age-related hyperactivity of CA3 place cells, reduces place field area, and increases spatial information content in aged rat hippocampus.

    PubMed

    Robitsek, Jonathan; Ratner, Marcia H; Stewart, Tara; Eichenbaum, Howard; Farb, David H

    2015-12-01

    Learning and memory deficits associated with age-related mild cognitive impairment have long been attributed to impaired processing within the hippocampus. Hyperactivity within the hippocampal CA3 region that is associated with aging is mediated in part by a loss of functional inhibitory interneurons and thought to underlie impaired performance in spatial memory tasks, including the abnormal tendency in aged animals to pattern complete spatial representations. Here, we asked whether the spatial firing patterns of simultaneously recorded CA3 and CA1 neurons in young and aged rats could be manipulated pharmacologically to selectively reduce CA3 hyperactivity and thus, according to hypothesis, the associated abnormality in spatial representations. We used chronically implanted high-density tetrodes to record the spatial firing properties of CA3 and CA1 units during animal exploration for food in familiar and novel environments. Aged CA3 place cells have higher firing rates, larger place fields, less spatial information content, and respond less to a change from a familiar to a novel environment than young CA3 cells. We also find that the combination of levetiracetam (LEV) + valproic acid (VPA), previously shown to act as a cognitive enhancer in tests of spatial memory, attenuate CA3 place cell firing rates, reduce place field area, and increase spatial information content in aged but not young adult rats. This is consistent with drug enhancing the specificity of neuronal firing with respect to spatial location. Contrary to expectation, however, LEV + VPA reduces place cell discrimination between novel and familiar environments, i.e., spatial correlations increase, independent of age even though drug enhances performance in cognitive tasks. The results demonstrate that spatial information content, or the number of bits of information encoded per action potential, may be the key correlate for enhancement of spatial memory by LEV + VPA.

  7. Age-Related Macular Degeneration

    MedlinePlus

    ... version of this page please turn Javascript on. Age-related Macular Degeneration About AMD Click for more ... a leading cause of vision loss among people age 60 and older. It causes damage to the ...

  8. Epigenetics of Aging and Aging-related Disease

    PubMed Central

    2014-01-01

    Aging is associated with a wide range of human disorders, including cancer, diabetes, cardiovascular, and neurodegenerative diseases. Long thought to be an inexorable road toward decline and diseases, aging is in fact remarkably plastic. Such plasticity could be harnessed to approach age-related diseases from a novel perspective. Although many studies have focused on the genes that impact aging, the nongenetic regulation of aging is gaining increasing attention. Specifically, aging is associated with profound epigenetic changes, resulting in alterations of gene expression and disturbances in broad genome architecture and the epigenomic landscape. The potential reversibility of these epigenetic changes that occur as a hallmark of aging offers exciting opportunities to alter the trajectory of age-related diseases. This short review highlights key epigenetic players in the regulation of aging, as well as both future goals and challenges to the utilization of epigenetic strategies to delay and reverse the main diseases of aging. PMID:24833581

  9. Epigenetics of aging and aging-related disease.

    PubMed

    Brunet, Anne; Berger, Shelley L

    2014-06-01

    Aging is associated with a wide range of human disorders, including cancer, diabetes, cardiovascular, and neurodegenerative diseases. Long thought to be an inexorable road toward decline and diseases, aging is in fact remarkably plastic. Such plasticity could be harnessed to approach age-related diseases from a novel perspective. Although many studies have focused on the genes that impact aging, the nongenetic regulation of aging is gaining increasing attention. Specifically, aging is associated with profound epigenetic changes, resulting in alterations of gene expression and disturbances in broad genome architecture and the epigenomic landscape. The potential reversibility of these epigenetic changes that occur as a hallmark of aging offers exciting opportunities to alter the trajectory of age-related diseases. This short review highlights key epigenetic players in the regulation of aging, as well as both future goals and challenges to the utilization of epigenetic strategies to delay and reverse the main diseases of aging.

  10. Mitochondrial aging and age-related dysfunction of mitochondria.

    PubMed

    Chistiakov, Dimitry A; Sobenin, Igor A; Revin, Victor V; Orekhov, Alexander N; Bobryshev, Yuri V

    2014-01-01

    Age-related changes in mitochondria are associated with decline in mitochondrial function. With advanced age, mitochondrial DNA volume, integrity and functionality decrease due to accumulation of mutations and oxidative damage induced by reactive oxygen species (ROS). In aged subjects, mitochondria are characterized by impaired function such as lowered oxidative capacity, reduced oxidative phosphorylation, decreased ATP production, significant increase in ROS generation, and diminished antioxidant defense. Mitochondrial biogenesis declines with age due to alterations in mitochondrial dynamics and inhibition of mitophagy, an autophagy process that removes dysfunctional mitochondria. Age-dependent abnormalities in mitochondrial quality control further weaken and impair mitochondrial function. In aged tissues, enhanced mitochondria-mediated apoptosis contributes to an increase in the percentage of apoptotic cells. However, implementation of strategies such as caloric restriction and regular physical training may delay mitochondrial aging and attenuate the age-related phenotype in humans.

  11. In vivo evidence of an age-related increase in ATP cost of contraction in the plantar flexor muscles.

    PubMed

    Layec, Gwenael; Trinity, Joel D; Hart, Corey R; Kim, Seong-Eun; Groot, Henderik Jonathan; Le Fur, Yann; Sorensen, Jacob R; Jeong, Eun-Kee; Richardson, Russell S

    2014-04-01

    Impaired skeletal muscle efficiency potentially contributes to the age-related decline in exercise capacity and may explain the altered haemodynamic response to exercise in the elderly. Thus we examined whether (i) the ATP cost of contraction increases with age, and (ii) this results in altered convective O(2) delivery to maintain microvascular oxygenation in the calf muscle. To this aim, we used an integrative experimental approach combining (31)P-MRS (magnetic resonance spectroscopy), Doppler ultrasound imaging and NIRS (near-IR spectroscopy) during dynamic plantar flexion exercise at 40% of WR(max) (maximal power output) in 20 healthy young and 20 older subjects matched for physical activity. The ATP cost of contraction was significantly higher in the old (7.2±4.1 mM/min per W) compared with the young (2.4±1.9 mM/min per W; P<0.05) and this was only significantly correlated with the plantar flexion WR(max) value in the old subjects (r=-0.52; P<0.05). Even when differences in power output were taken into account, end-exercise blood flow (old, 259±168 ml/min per W and young, 134±40 ml/min per W; P<0.05) and convective O(2) delivery (old, 0.048±0.031 l/min per W and young, 0.026±0.008 l/min per W; P<0.05) were greater in the old in comparison with the young subjects. In contrast, the NIRS oxyhaemoglobin, deoxyhaemoglobin and microvascular oxygenation indices were not significantly different between the groups (P>0.05). Therefore the present study reveals that, although the peripheral haemodynamic responses to plantar flexion exercise appear to be appropriate, the elevated energy cost of contraction and associated reduction in the WR(max) value in this muscle group may play a role in limiting exercise capacity with age.

  12. Increased expressions and activations of apoptosis-related factors in cell signaling during incised skin wound healing in mice: a preliminary study for forensic wound age estimation.

    PubMed

    Zhao, Rui; Guan, Da-Wei; Zhang, Wei; Du, Yu; Xiong, Chang-Yan; Zhu, Bao-Li; Zhang, Jian-Jun

    2009-04-01

    Recent studies have demonstrated that apoptosis plays a pivotal role during skin wound healing and apoptosis-related factors in cell signaling regulate a variety of cellular function. In this study, the expressions of p38MAPK, and JNK, iNOS, eNOS were detected and the activations of caspase-6, -7, -8, -9, and calpain, another signaling pathway of apoptosis, were also investigated by immunohistochemical staining and Western blotting in mice. A time-dependent increase of each protein level was observed by immunohistochemistry and Western blot in mouse skin incision. p38MAPK level peaked at 12 h and 3 d, calpain level peaked at 1 d and 5 d, iNOS level peaked at 1 d and 10 d, while the peak levels of eNOS, caspase-6, -7, -8, and -9 occurred at 3 d and p-JNK at 1 d post-injury. In the early phase of wound healing, infiltrating polymorphonulcear cells were labeled with all the factors except caspase-8. Thereafter, infiltrating mononuclear cells and proliferating spindle-shaped fibroblastic cells showed positive staining for p38MAPK, JNK, calpain, caspases and NOS. The activation of caspase-8, -9, -6, and -7 as detected by Western blot indicated that caspase apoptotic pathway may take effect in cellular elimination during skin wound healing. From the viewpoint of forensic pathology, the time-dependent expressions of the factors in apoptotic pathway during skin incised wound healing may be used as potential markers for wound age estimation.

  13. Pathophysiology of ageing, longevity and age related diseases

    PubMed Central

    Bürkle, Alexander; Caselli, Graziella; Franceschi, Claudio; Mariani, Erminia; Sansoni, Paolo; Santoni, Angela; Vecchio, Giancarlo; Witkowski, Jacek M; Caruso, Calogero

    2007-01-01

    On April 18, 2007 an international meeting on Pathophysiology of Ageing, Longevity and Age-Related Diseases was held in Palermo, Italy. Several interesting topics on Cancer, Immunosenescence, Age-related inflammatory diseases and longevity were discussed. In this report we summarize the most important issues. However, ageing must be considered an unavoidable end point of the life history of each individual, nevertheless the increasing knowledge on ageing mechanisms, allows envisaging many different strategies to cope with, and delay it. So, a better understanding of pathophysiology of ageing and age-related disease is essential for giving everybody a reasonable chance for living a long and enjoyable final part of the life. PMID:17683521

  14. Difficulties in demonstrating long term immunity in FeLV vaccinated cats due to increasing age-related resistance to infection

    PubMed Central

    2012-01-01

    Background Feline leukaemia virus (FeLV) is a pathogen causing fatal illness in cats worldwide, and as such there is a high demand for products to protect against disease. The duration of immunity provided by an inactivated FeLV vaccine, Versifel FeLV, when administered to cats of the target age was determined. Kittens received two vaccinations when aged 7 to 9 weeks old, and were subsequently challenged up to 36 months later with the FeLV-A Glasgow isolate. Results In all studies, all of the younger aged control kittens showed persistent FeLV p27 antigenaemia confirming that the challenge virus was severe and efficacious. In contrast, the control cats did not show the required level of persistent antigenaemia, with a maximum of 45% cats affected in the middle duration study and only 10% in the longer study. However, apart from one animal in the short duration study, all of the cats vaccinated with Versifel FeLV were negative for persistent antigenaemia and can be considered treatment successes. Conclusion In conclusion, we have shown that although age-related resistance to infection with a virulent FeLV challenge is evident from as early as 10 months of age, vaccination with Versifel FeLV may aid in the protection of cats from FeLV related disease up to three years after primary vaccination as kittens. PMID:22839692

  15. Overview of age-related ocular conditions.

    PubMed

    Akpek, Esen K; Smith, Roderick A

    2013-05-01

    The United States is an aging society. The number of Americans 65 years or older is expected to more than double over the next 40 years, from 40.2 million in 2010 to 88.5 million in 2050, with aging baby boomers accounting for most of the increase. As the society ages, the prevalence of age-related diseases, including diseases of the eye, will continue to increase. By 2020, age-related macular degeneration, one of the leading causes of vision loss, is expected to affect 2.95 million individuals in the United States. Likewise, the prevalence of open-angle glaucoma, estimated at 2.2 million in 2000, is projected to increase by 50%, to 3.36 million by 2020. As the eye ages, it undergoes a number of physiologic changes that may increase susceptibility to disease. Environmental and genetic factors are also major contributors to the development of age-related ocular diseases. This article reviews the physiology of the aging eye and the epidemiology and pathophysiology of 4 major age-related ocular diseases: age-related macular degeneration, glaucoma, diabetic retinopathy, and dry eye.

  16. Age-related macular degeneration.

    PubMed

    Cheung, Lily K; Eaton, Angie

    2013-08-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, and the prevalence of the disease increases exponentially with every decade after age 50 years. It is a multifactorial disease involving a complex interplay of genetic, environmental, metabolic, and functional factors. Besides smoking, hypertension, obesity, and certain dietary habits, a growing body of evidence indicates that inflammation and the immune system may play a key role in the development of the disease. AMD may progress from the early form to the intermediate form and then to the advanced form, where two subtypes exist: the nonneovascular (dry) type and the neovascular (wet) type. The results from the Age-Related Eye Disease Study have shown that for the nonneovascular type of AMD, supplementation with high-dose antioxidants (vitamin C, vitamin E, and β-carotene) and zinc is recommended for those with the intermediate form of AMD in one or both eyes or with advanced AMD or vision loss due to AMD in one eye. As for the neovascular type of the advanced AMD, the current standard of therapy is intravitreal injections of vascular endothelial growth factor inhibitors. In addition, lifestyle and dietary modifications including improved physical activity, reduced daily sodium intake, and reduced intake of solid fats, added sugars, cholesterol, and refined grain foods are recommended. To date, no study has demonstrated that AMD can be cured or effectively prevented. Clearly, more research is needed to fully understand the pathophysiology as well as to develop prevention and treatment strategies for this devastating disease.

  17. Prenatal exposure to the brominated flame retardant hexabromocyclododecane (HBCD) impairs measures of sustained attention and increases age-related morbidity in the Long-Evans rat.

    PubMed

    Miller-Rhodes, Patrick; Popescu, Maria; Goeke, Calla; Tirabassi, Toni; Johnson, Lauren; Markowski, Vincent P

    2014-01-01

    Hexabromocyclododecane (HBCD) is a brominated flame retardant that is widely-used in foam building materials and to a lesser extent, furniture and electronic equipment. After decades of use, HBCD and its metabolites have become globally-distributed environmental contaminants that can be measured in the atmosphere, water bodies, wildlife, food staples and human breastmilk. Emerging evidence suggests that HBCD can affect early brain development and produce behavioral consequences for exposed organisms. The current study examined some of the developmental and lifelong neurobehavioral effects of prenatal HBCD exposure in a rat model. Pregnant rats were gavaged with 0, 3, 10, or 30mg/kg HBCD from gestation day 1 to parturition. A functional observation battery was used to assess sensorimotor behaviors in neonates. Locomotor and operant responding under random ratio and Go/no-go schedules of food reinforcement were examined in cohorts of young adult and aged rats. HBCD exposure was associated with increased reactivity to a tailpinch in neonates, decreased forelimb grip strength in juveniles, and impaired sustained attention indicated by Go/no-go responding in aged rats. In addition, HBCD exposure was associated with a significant increase in morbidity in the aged cohort. One health complication, a progressive loss of hindleg function, was observed only in the aged, 3mg/kg HBCD animals. These effects suggest that HBCD is a developmental neurotoxicant that can produce long-term behavioral impairments that emerge at different points in the lifespan following prenatal exposure.

  18. Age-related aspects of addiction

    PubMed Central

    Koechl, Birgit; Unger, Annemarie; Fischer, Gabriele

    2013-01-01

    Research has shown that substance use, abuse and addiction are not limited to a specific age group. Problems related to substance addiction are an important cause of morbidity in the population aged 65 and above, especially the abuse of prescription drugs and legal substances. A lack of evidence-based studies and tailored treatment options for the aging population is evident. Appropriate and effective health-care is an important goal to improve health-related quality of life of elderly people. Research in the increasingly aging population needs to include an age- and gender-sensitive approach. PMID:22722821

  19. Age-related macular degeneration.

    PubMed

    Lim, Laurence S; Mitchell, Paul; Seddon, Johanna M; Holz, Frank G; Wong, Tien Y

    2012-05-05

    Age-related macular degeneration is a major cause of blindness worldwide. With ageing populations in many countries, more than 20% might have the disorder. Advanced age-related macular degeneration, including neovascular age-related macular degeneration (wet) and geographic atrophy (late dry), is associated with substantial, progressive visual impairment. Major risk factors include cigarette smoking, nutritional factors, cardiovascular diseases, and genetic markers, including genes regulating complement, lipid, angiogenic, and extracellular matrix pathways. Some studies have suggested a declining prevalence of age-related macular degeneration, perhaps due to reduced exposure to modifiable risk factors. Accurate diagnosis combines clinical examination and investigations, including retinal photography, angiography, and optical coherence tomography. Dietary anti-oxidant supplementation slows progression of the disease. Treatment for neovascular age-related macular degeneration incorporates intraocular injections of anti-VEGF agents, occasionally combined with other modalities. Evidence suggests that two commonly used anti-VEGF therapies, ranibizumab and bevacizumab, have similar efficacy, but possible differences in systemic safety are difficult to assess. Future treatments include inhibition of other angiogenic factors, and regenerative and topical therapies.

  20. Increased brain-predicted aging in treated HIV disease

    PubMed Central

    Underwood, Jonathan; Caan, Matthan W.A.; De Francesco, Davide; van Zoest, Rosan A.; Leech, Robert; Wit, Ferdinand W.N.M.; Portegies, Peter; Geurtsen, Gert J.; Schmand, Ben A.; Schim van der Loeff, Maarten F.; Franceschi, Claudio; Sabin, Caroline A.; Majoie, Charles B.L.M.; Winston, Alan; Reiss, Peter; Sharp, David J.

    2017-01-01

    Objective: To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. Methods: A large sample of virologically suppressed HIV-positive adults (n = 162, age 45–82 years) and highly comparable HIV-negative controls (n = 105) were recruited as part of the Comorbidity in Relation to AIDS (COBRA) collaboration. Using T1-weighted MRI scans, a machine-learning model of healthy brain aging was defined in an independent cohort (n = 2,001, aged 18–90 years). Neuroimaging data from HIV-positive and HIV-negative individuals were then used to estimate brain-predicted age; then brain-predicted age difference (brain-PAD = brain-predicted brain age − chronological age) scores were calculated. Neuropsychological and clinical assessments were also carried out. Results: HIV-positive individuals had greater brain-PAD score (mean ± SD 2.15 ± 7.79 years) compared to HIV-negative individuals (−0.87 ± 8.40 years; b = 3.48, p < 0.01). Increased brain-PAD score was associated with decreased performance in multiple cognitive domains (information processing speed, executive function, memory) and general cognitive performance across all participants. Brain-PAD score was not associated with age, duration of HIV infection, or other HIV-related measures. Conclusion: Increased apparent brain aging, predicted using neuroimaging, was observed in HIV-positive adults, despite effective viral suppression. Furthermore, the magnitude of increased apparent brain aging related to cognitive deficits. However, predicted brain age difference did not correlate with chronological age or duration of HIV infection, suggesting that HIV disease may accentuate rather than accelerate brain aging. PMID:28258081

  1. Co-morbidities in persons infected with HIV: increased burden with older age and negative effects on health-related quality of life.

    PubMed

    Rodriguez-Penney, Alan T; Iudicello, Jennifer E; Riggs, Patricia K; Doyle, Katie; Ellis, Ronald J; Letendre, Scott L; Grant, Igor; Woods, Steven Paul

    2013-01-01

    This study sought to determine the synergistic effects of age and HIV infection on medical co-morbidity burden, along with its clinical correlates and impact on health-related quality of life (HRQoL) across the lifespan in HIV. Participants included 262 individuals across four groups stratified by age (≤40 and ≥50 years) and HIV serostatus. Medical co-morbidity burden was assessed using a modified version of the Charlson Co-morbidity Index (CCI). Multiple regression accounting for potentially confounding demographic, psychiatric, and medical factors revealed an interaction between age and HIV infection on the CCI, with the highest medical co-morbidity burden in the older HIV+cohort. Nearly half of the older HIV+group had at least one major medical co-morbidity, with the most prevalent being diabetes (17.8%), syndromic neurocognitive impairment (15.4%), and malignancy (12.2%). Affective distress and detectable plasma viral load were significantly associated with the CCI in the younger and older HIV-infected groups, respectively. Greater co-morbidity burden was uniquely associated with lower physical HRQoL across the lifespan. These findings highlight the prevalence and clinical impact of co-morbidities in older HIV-infected adults and underscore the importance of early detection and treatment efforts that might enhance HIV disease outcomes.

  2. [Age-related macular degeneration].

    PubMed

    Budzinskaia, M V

    2014-01-01

    The review provides an update on the pathogenesis and new treatment modalities for neovascular age-related macular degeneration (AMD). The impact of polymorphism in particular genes, including complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2/LOC387715), and serine peptidase (HTRA1), on AMD development is discussed. Clinical presentations of different forms of exudative AMD, that is classic, occult, or more often mixed choroidal neovascularization, retinal angiomatous proliferation, and choroidal polypoidal vasculopathy, are described. Particular attention is paid to the results of recent clinical trials and safety issues around the therapy.

  3. Aging-related inflammation in osteoarthritis.

    PubMed

    Greene, M A; Loeser, R F

    2015-11-01

    It is well accepted that aging is an important contributing factor to the development of osteoarthritis (OA). The mechanisms responsible appear to be multifactorial and may include an age-related pro-inflammatory state that has been termed "inflamm-aging." Age-related inflammation can be both systemic and local. Systemic inflammation can be promoted by aging changes in adipose tissue that result in increased production of cytokines such as interleukin (IL)-6 and tumor necrosis factor-α (TNFα). Numerous studies have shown an age-related increase in blood levels of IL-6 that has been associated with decreased physical function and frailty. Importantly, higher levels of IL-6 have been associated with an increased risk of knee OA progression. However, knockout of IL-6 in male mice resulted in worse age-related OA rather than less OA. Joint tissue cells, including chondrocytes and meniscal cells, as well as the neighboring infrapatellar fat in the knee joint, can be a local source of inflammatory mediators that increase with age and contribute to OA. An increased production of pro-inflammatory mediators that include cytokines and chemokines, as well as matrix-degrading enzymes important in joint tissue destruction, can be the result of cell senescence and the development of the senescence-associated secretory phenotype (SASP). Further studies are needed to better understand the basis for inflamm-aging and its role in OA with the hope that this work will lead to new interventions targeting inflammation to reduce not only joint tissue destruction but also pain and disability in older adults with OA.

  4. Testofen, a specialised Trigonella foenum-graecum seed extract reduces age-related symptoms of androgen decrease, increases testosterone levels and improves sexual function in healthy aging males in a double-blind randomised clinical study.

    PubMed

    Rao, Amanda; Steels, Elizabeth; Inder, Warrick J; Abraham, Suzanne; Vitetta, Luis

    2016-06-01

    This study examined the effect of Testofen, a specialised Trigonella foenum-graecum seed extract on the symptoms of possible androgen deficiency, sexual function and serum androgen concentrations in healthy aging males. This was a double-blind, randomised, placebo-controlled trial involving 120 healthy men aged between 43 and 70 years of age. The active treatment was standardised Trigonella foenum-graecum seed extract at a dose of 600 mg/day for 12 weeks. The primary outcome measure was the change in the Aging Male Symptom questionnaire (AMS), a measure of possible androgen deficiency symptoms; secondary outcome measures were sexual function and serum testosterone. There was a significant decrease in AMS score over time and between the active and placebo groups. Sexual function improved, including number of morning erections and frequency of sexual activity. Both total serum testosterone and free testosterone increased compared to placebo after 12 weeks of active treatment. Trigonella foenum-graecum seed extract is a safe and effective treatment for reducing symptoms of possible androgen deficiency, improves sexual function and increases serum testosterone in healthy middle-aged and older men.

  5. Increased sensitivity to nitrazepam in old age.

    PubMed

    Castleden, C M; George, C F; Marcer, D; Hallett, C

    1977-01-01

    The effects of a single 10 mg oral dose of nitrazepam were compared with those of a placebo in healthy young and old people. Both the young and the elderly slept better on three successive nights after nitrazepam but they felt less awake at 12 and 36 hours (P less than 0-01). Elderly people made significantly more mistakes in a psychomotor test than did the young, despite similar plasma concentrations of nitrazepam and half lives in the two groups. This difference in response to psychomotor testing is probably explained by an increased sensitivity of the ageing brain to the action of nitrazepam.

  6. Age-related macular degeneration

    PubMed Central

    Querques, Giuseppe; Avellis, Fernando Onofrio; Querques, Lea; Bandello, Francesco; Souied, Eric H

    2011-01-01

    Clinical question: Is there any new knowledge about the pathogenesis and treatment of age-related macular degeneration (AMD)? Results: We now understand better the biochemical and pathological pathways involved in the genesis of AMD. Treatment of exudative AMD is based on intravitreal injection of new antivascular endothelial growth factor drugs for which there does not yet exist a unique recognized strategy of administration. No therapies are actually available for atrophic AMD, despite some experimental new pharmacological approaches. Implementation: strategy of administration, safety of intravitreal injection PMID:21654887

  7. Increases in Cognitive and Linguistic Processing Primarily Account for Increases in Speaking Rate with Age

    ERIC Educational Resources Information Center

    Nip, Ignatius S. B.; Green, Jordan R.

    2013-01-01

    Age-related increases of speaking rate are not fully understood, but have been attributed to gains in biologic factors and learned skills that support speech production. This study investigated developmental changes in speaking rate and articulatory kinematics of participants aged 4 ("N" = 7), 7 ("N" = 10), 10…

  8. Prosocial Behavior Increases with Age across Five Economic Games.

    PubMed

    Matsumoto, Yoshie; Yamagishi, Toshio; Li, Yang; Kiyonari, Toko

    2016-01-01

    Ontogenic studies of human prosociality generally agree on that human prosociality increases from early childhood through early adulthood; however, it has not been established if prosociality increases beyond early adulthood. We examined a sample of 408 non-student residents from Tokyo, Japan, who were evenly distributed across age (20-59) and sex. Participants played five economic games each separated by a few months. We demonstrated that prosocial behavior increased with age beyond early adulthood and this effect was shown across all five economic games. A similar, but weaker, age-related trend was found in one of three social value orientation measures of prosocial preferences. We measured participants' belief that manipulating others is a wise strategy for social success, and found that this belief declined with age. Participants' satisfaction with the unilateral exploitation outcome of the prisoner's dilemma games also declined with age. These two factors-satisfaction with the DC outcome in the prisoner's dilemma games and belief in manipulation-mediated the age effect on both attitudinal and behavioral prosociality. Participants' age-related socio-demographic traits such as marriage, having children, and owning a house weakly mediated the age effect on prosociality through their relationships with satisfaction with the DC outcome and belief in manipulation.

  9. Driving and Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Owsley, Cynthia; McGwin, Gerald, Jr.

    2008-01-01

    This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety,…

  10. Increases in cognitive and linguistic processing primarily account for increases in speaking rate with age.

    PubMed

    Nip, Ignatius S B; Green, Jordan R

    2013-01-01

    Age-related increases of speaking rate are not fully understood, but have been attributed to gains in biologic factors and learned skills that support speech production. This study investigated developmental changes in speaking rate and articulatory kinematics of participants aged 4 (N = 7), 7 (N = 10), 10 (N = 9), 13 (N = 7), 16 (N = 9) years, and young adults (N = 11) in speaking tasks varying in task demands. Speaking rate increased with age, with decreases in pauses and articulator displacements but not increases in articulator movement speed. Movement speed did not appear to constrain the speaking. Rather, age-related increases in speaking rate are due to gains in cognitive and linguistic processing and speech motor control.

  11. Increasing Student Involvement in Cognitive Aging Research

    ERIC Educational Resources Information Center

    Henkel, Linda A.

    2006-01-01

    The involvement of undergraduates in research on aging has benefits for the students and for the faculty mentors, as well as for their departments, their universities, and the field of gerontology at large. This article reports on the application of a 3-year Academic Research Enhancement Award (AREA) by the National Institute on Aging awarded to…

  12. Methamphetamine increases basal ganglia iron to levels observed in aging.

    PubMed

    Melega, William P; Laćan, Goran; Harvey, Dennis C; Way, Baldwin M

    2007-10-29

    Increases in basal ganglia iron are well documented for neurodegenerative diseases but have not been associated with methamphetamine (METH). In this study, vervet monkeys that received two doses of METH (2 mg/kg, intramuscularly, 6 h apart) showed at 1 month, iron increases in substantia nigra pars reticulata and globus pallidus, with concurrent increases of ferritin-immunoreactivity and decreases of tyrosine hydroxylase-immunoreactivity in substantia nigra. At 1.5 years, substantia nigra tyrosine hydroxylase-immunoreactivity had recovered while iron and ferritin-immunoreactivity increases persisted. Globus pallidus and substantia nigra iron levels of the adult METH-exposed animals (age 5-9 years) were now comparable with those of drug-naive, aged animals (19-22 years), suggesting an aging-related condition that might render those regions more vulnerable to oxidative stress.

  13. [Age-related macular degeneration (AMD)].

    PubMed

    Michels, Stephan; Kurz-Levin, Malaika

    2009-03-01

    Today age-related macular degeneration (AMD) is the most frequent cause for legal blindness in western industrialized countries. The prevalence of this disease rises with increasing age. A multifactorial pathogenesis of AMD is postulated including genetic predisposition and environmental risk factors. The most relevant modifiable risk factor is smoking. Up to today there is no cure of this chronic disease. Prophylaxis, including a healthy diet and antioxidants as nutrional supplements for selected patients, aims to slow down the disease progression. Significant progress has been made in the treatment of the neovascular form of the disease using inhibitors of the vascular endothelial growth factor (VEGF).

  14. 1'-Acetoxychavicol acetate ameliorates age-related spatial memory deterioration by increasing serum ketone body production as a complementary energy source for neuronal cells.

    PubMed

    Kojima-Yuasa, Akiko; Yamamoto, Tomiya; Yaku, Keisuke; Hirota, Shiori; Takenaka, Shigeo; Kawabe, Kouichi; Matsui-Yuasa, Isao

    2016-09-25

    1'-Acetoxychavicol acetate (ACA) is naturally obtained from the rhizomes and seeds of Alpinia galangal. Here, we examined the effect of ACA on learning and memory in senescence-accelerated mice prone 8 (SAMP8). In mice that were fed a control diet containing 0.02% ACA for 25 weeks, the learning ability in the Morris water maze test was significantly enhanced in comparison with mice that were fed the control diet alone. In the Y-maze test, SAMP8 mice showed decreased spontaneous alterations in comparison with senescence-accelerated resistant/1 (SAMR1) mice, a homologous control, which was improved by ACA pretreatment. Serum metabolite profiles were obtained by GC-MS analysis, and each metabolic profile was plotted on a 3D score plot. Based upon the diagram, it can be seen that the distribution areas for the three groups were completely separate. Furthermore, the contents of β-hydroxybutyric acid and palmitic acid in the serum of SAMP8-ACA mice were higher than those of SAMP8-control mice and SAMR1-control mice. We also found that SAMR1 mice did not show histological abnormalities, whereas histological damage in the CA1 region of the hippocampus in SAMP8-control mice was observed. However, SAMP8-ACA mice were observed in a similar manner as SAMR1 mice. These findings confirm that ACA increases the serum concentrations of β-hydroxybutyric acid and palmitic acid levels and thus these fuels might contribute to the maintenance of the cognitive performance of SAMP8 mice.

  15. [Treatment options for age-related infertility].

    PubMed

    Belaisch-Allart, Joëlle

    2010-06-20

    There has been a consistent trend towards delayed childbearing in most Western countries. Treatment options for age-related infertility includes controlled ovarian hyperstimulation with intrauterine insemination and in vitro fertilization (IVF). A sharp decline in pregnancy rate with advancing female age is noted with assisted reproductive technologies (ART) including IVF. Evaluation and treatment of infertility should not be delayed in women 35 years and older. No treatment other than oocyte donation has been shown to be effective for women over 40 and for those with compromised ovarian reserve, but its pratice is not easy in France hence the procreative tourism. As an increasing number of couples choose to postpone childbearing, they should be informed that maternal age is an important risk factor for failure to conceive.

  16. Aging and Alcohol Abuse: Increasing Counselor Awareness

    ERIC Educational Resources Information Center

    Williams, June M.; Ballard, Mary B.; Alessi, Hunter

    2005-01-01

    Alcohol abuse in older adulthood is a rapidly growing but often hidden problem. The authors provide an overview of the issues related to older adult alcohol abuse through a discussion of physiological, psychological, and social risk factors; an examination of appropriate assessment procedures; and an overview of factors related to treatment.

  17. Age-Associated Increase in BMP Signaling Inhibits Hippocampal Neurogenesis.

    PubMed

    Yousef, Hanadie; Morgenthaler, Adam; Schlesinger, Christina; Bugaj, Lukasz; Conboy, Irina M; Schaffer, David V

    2015-05-01

    Hippocampal neurogenesis, the product of resident neural stem cell proliferation and differentiation, persists into adulthood but decreases with organismal aging, which may contribute to the age-related decline in cognitive function. The mechanisms that underlie this decrease in neurogenesis are not well understood, although evidence in general indicates that extrinsic changes in an aged stem cell niche can contribute to functional decline in old stem cells. Bone morphogenetic protein (BMP) family members are intercellular signaling proteins that regulate stem and progenitor cell quiescence, proliferation, and differentiation in various tissues and are likewise critical regulators of neurogenesis in young adults. Here, we establish that BMP signaling increases significantly in old murine hippocampi and inhibits neural progenitor cell proliferation. Furthermore, direct in vivo attenuation of BMP signaling via genetic and transgenic perturbations in aged mice led to elevated neural stem cell proliferation, and subsequent neurogenesis, in old hippocampi. Such advances in our understanding of mechanisms underlying decreased hippocampal neurogenesis with age may offer targets for the treatment of age-related cognitive decline.

  18. Vestibular Perceptual Thresholds Increase above the Age of 40

    PubMed Central

    Bermúdez Rey, María Carolina; Clark, Torin K.; Wang, Wei; Leeder, Tania; Bian, Yong; Merfeld, Daniel M.

    2016-01-01

    We measured vestibular perceptual thresholds in 105 healthy humans (54F/51M) ranging from 18 to 80 years of age. Direction-recognition thresholds were measured using standard methods. The motion consisted of single cycles of sinusoidal acceleration at 0.2 Hz for roll tilt and 1.0 Hz for yaw rotation about an earth-vertical axis, inter-aural earth-horizontal translation (y-translation), inferior–superior earth-vertical translation (z-translation), and roll tilt. A large subset of this population (99 of 105) also performed a modified Romberg test of standing balance. Despite the relatively large population (54F/51M), we found no difference between thresholds of male and female subjects. After pooling across sex, we found that thresholds increased above the age of 40 for all five motion directions investigated. The data were best modeled by a two-segment age model that yielded a constant baseline below an age cutoff of about 40 and a threshold increase above the age cutoff. For all subjects who passed all conditions of the balance test, the baseline thresholds were 0.97°/s for yaw rotation, 0.66°/s for 1-Hz roll tilt, 0.35°/s for 0.2-Hz roll tilt, 0.58 cm/s for y-translation, and 1.24 cm/s for z-translation. As a percentage of the baseline, the fitted slopes (indicating the threshold increase each decade above the age cutoff) were 83% for z-translation, 56% for 1-Hz roll tilt, 46% for y-translation, 32% for 0.2-Hz roll tilt, and 15% for yaw rotation. Even taking age and other factors into consideration, we found a significant correlation of balance test failures with increasing roll-tilt thresholds. PMID:27752252

  19. Vestibular Perceptual Thresholds Increase above the Age of 40.

    PubMed

    Bermúdez Rey, María Carolina; Clark, Torin K; Wang, Wei; Leeder, Tania; Bian, Yong; Merfeld, Daniel M

    2016-01-01

    We measured vestibular perceptual thresholds in 105 healthy humans (54F/51M) ranging from 18 to 80 years of age. Direction-recognition thresholds were measured using standard methods. The motion consisted of single cycles of sinusoidal acceleration at 0.2 Hz for roll tilt and 1.0 Hz for yaw rotation about an earth-vertical axis, inter-aural earth-horizontal translation (y-translation), inferior-superior earth-vertical translation (z-translation), and roll tilt. A large subset of this population (99 of 105) also performed a modified Romberg test of standing balance. Despite the relatively large population (54F/51M), we found no difference between thresholds of male and female subjects. After pooling across sex, we found that thresholds increased above the age of 40 for all five motion directions investigated. The data were best modeled by a two-segment age model that yielded a constant baseline below an age cutoff of about 40 and a threshold increase above the age cutoff. For all subjects who passed all conditions of the balance test, the baseline thresholds were 0.97°/s for yaw rotation, 0.66°/s for 1-Hz roll tilt, 0.35°/s for 0.2-Hz roll tilt, 0.58 cm/s for y-translation, and 1.24 cm/s for z-translation. As a percentage of the baseline, the fitted slopes (indicating the threshold increase each decade above the age cutoff) were 83% for z-translation, 56% for 1-Hz roll tilt, 46% for y-translation, 32% for 0.2-Hz roll tilt, and 15% for yaw rotation. Even taking age and other factors into consideration, we found a significant correlation of balance test failures with increasing roll-tilt thresholds.

  20. Overcoming Age-Related Differences

    ERIC Educational Resources Information Center

    Agullo, Gloria Luque

    2006-01-01

    One of the most controversial issues in foreign language (FL) teaching is the age at which language learning should start. Nowadays it is recognized that in second language contexts maturational constraints make an early start advisable, but there is still disagreement regarding the problem of when to start or the best way to learn in foreign…

  1. Preventing painful age-related bone fractures: Anti-sclerostin therapy builds cortical bone and increases the proliferation of osteogenic cells in the periosteum of the geriatric mouse femur.

    PubMed

    Thompson, Michelle L; Chartier, Stephane R; Mitchell, Stefanie A; Mantyh, Patrick W

    2016-01-01

    Age-related bone fractures are usually painful and have highly negative effects on a geriatric patient's functional status, quality of life, and survival. Currently, there are few analgesic therapies that fully control bone fracture pain in the elderly without significant unwanted side effects. However, another way of controlling age-related fracture pain would be to preemptively administer an osteo-anabolic agent to geriatric patients with high risk of fracture, so as to build new cortical bone and prevent the fracture from occurring. A major question, however, is whether an osteo-anabolic agent can stimulate the proliferation of osteogenic cells and build significant amounts of new cortical bone in light of the decreased number and responsiveness of osteogenic cells in aging bone. To explore this question, geriatric and young mice, 20 and 4 months old, respectively, received either vehicle or a monoclonal antibody that sequesters sclerostin (anti-sclerostin) for 28 days. From days 21 to 28, animals also received sustained administration of the thymidine analog, bromodeoxyuridine (BrdU), which labels the DNA of dividing cells. Animals were then euthanized at day 28 and the femurs were examined for cortical bone formation, bone mineral density, and newly borne BrdU+ cells in the periosteum which is a tissue that is pivotally involved in the formation of new cortical bone. In both the geriatric and young mice, anti-sclerostin induced a significant increase in the thickness of the cortical bone, bone mineral density, and the proliferation of newly borne BrdU+ cells in the periosteum. These results suggest that even in geriatric animals, anti-sclerostin therapy can build new cortical bone and increase the proliferation of osteogenic cells and thus reduce the likelihood of painful age-related bone fractures.

  2. Normal aging increases cognitive heterogeneity: analysis of dispersion in WAIS-III scores across age.

    PubMed

    Ardila, Alfredo

    2007-11-01

    Individual differences in cognitive decline during normal aging need further delineation. The purpose of this study was to find the score dispersions in the WAIS-III subtests at different ages. Norms presented in the Administration and Scoring Manual [Wechsler, D. (1997). WAIS-III: Administration and scoring manual. San Antonio: The Psychological Corporation] were used. The WAIS-III was standardized and normalized using 2450 American adults divided into 13 age ranges and 4 education groups. Means and standard deviations for the different WAIS-III subtests were deduced and the ratio Percentage of the mean="(standard deviation/mean)x100" was calculated. It was hypothesized that during normal aging, whereas mean scores decrease, score dispersions increase, pointing to an increased heterogeneity in intellectual abilities in older individuals. In all subtests, except Digit Span, it was found that score dispersions indeed increased during aging. However, in some subtests, increase in dispersion was less than 20% (Block Design, Object Assembly, and Information), whereas in others, increase in dispersion was over 200% (Matrix Reasoning, L-N Sequencing, Digit-Symbol, Picture Completion, and Picture Arrangement). It was proposed that cognitive heterogeneity during normal aging is related to those abilities measured with these latter subtests, basically, executive functions, attention, and selected non-verbal abilities. In other abilities (e.g., visuoconstructive abilities and fund of general information), normal aging is associated with a more homogenous pattern of decline.

  3. Nutrition and age-related eye diseases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vision loss among the elderly is an important health problem. Approximately one person in three has some form of vision-reducing eye disease by the age of 65 [1]. Age-related cataract, age-related macular degeneration (AMD), diabetic retinopathy and glaucoma are the major diseases resulting in visu...

  4. Delirium in the elderly: Current problems with increasing geriatric age.

    PubMed

    Kukreja, Deepti; Günther, Ulf; Popp, Julius

    2015-12-01

    Delirium is an acute disorder of attention and cognition seen relatively commonly in people aged 65 yr or older. The prevalence is estimated to be between 11 and 42 per cent for elderly patients on medical wards. The prevalence is also high in nursing homes and long term care (LTC) facilities. The consequences of delirium could be significant such as an increase in mortality in the hospital, long-term cognitive decline, loss of autonomy and increased risk to be institutionalized. Despite being a common condition, it remains under-recognised, poorly understood and not adequately managed. Advanced age and dementia are the most important risk factors. Pain, dehydration, infections, stroke and metabolic disturbances, and surgery are the most common triggering factors. Delirium is preventable in a large proportion of cases and therefore, it is also important from a public health perspective for interventions to reduce further complications and the substantial costs associated with these. Since the aetiology is, in most cases, multifactorial, it is important to consider a multi-component approach to management, both pharmacological and non-pharmacological. Detection and treatment of triggering causes must have high priority in case of delirium. The aim of this review is to highlight the importance of delirium in the elderly population, given the increasing numbers of ageing people as well as increasing geriatric age.

  5. Increased NGF proforms in aged sympathetic neurons and their targets.

    PubMed

    Bierl, Michael A; Isaacson, Lori G

    2007-01-01

    Target-derived neurotrophins such as nerve growth factor (NGF) and neurotrophin-3 (NT-3) regulate sympathetic neuron survival. Here, NGF and NT-3 protein and transcript were examined in sympathetic neurons and targets in order to determine their role in age-related neuronal atrophy. One obvious alteration was a dramatic increase (up to 50-fold) in NGF protein forms, corresponding to proNGF-B, in the superior cervical ganglion (SCG) and targets where sympathetic innervation shows atrophy. In the iris, where sympathetic innervation is protected into old age, proNGF-B was decreased. Alterations in NGF transcript paralleled changes in NGF protein, albeit to a lesser degree. Though significantly increased in aged SCG, NT-3 protein, found primarily as the 'mature' form, showed only minor changes in most tissues, though NT-3 mRNA generally was decreased. In contrast, both NT-3 transcript and NT-3 precursors were increased in iris. The dramatic increases in proNGF, together with minimal changes in NT-3, suggest that alterations in NGF regulation may contribute to the loss of sympathetic innervation observed in many aged peripheral targets.

  6. What Is Age-Related Macular Degeneration?

    MedlinePlus

    ... of Low Vision Age-Related Macular Degeneration Vision Simulator AMD Pictures and Videos: What Does Macular Degeneration ... degeneration as part of the body's natural aging process. There are different kinds of macular problems, but ...

  7. Preventing painful age-related bone fractures

    PubMed Central

    Thompson, Michelle L; Chartier, Stephane R; Mitchell, Stefanie A

    2016-01-01

    Age-related bone fractures are usually painful and have highly negative effects on a geriatric patient’s functional status, quality of life, and survival. Currently, there are few analgesic therapies that fully control bone fracture pain in the elderly without significant unwanted side effects. However, another way of controlling age-related fracture pain would be to preemptively administer an osteo-anabolic agent to geriatric patients with high risk of fracture, so as to build new cortical bone and prevent the fracture from occurring. A major question, however, is whether an osteo-anabolic agent can stimulate the proliferation of osteogenic cells and build significant amounts of new cortical bone in light of the decreased number and responsiveness of osteogenic cells in aging bone. To explore this question, geriatric and young mice, 20 and 4 months old, respectively, received either vehicle or a monoclonal antibody that sequesters sclerostin (anti-sclerostin) for 28 days. From days 21 to 28, animals also received sustained administration of the thymidine analog, bromodeoxyuridine (BrdU), which labels the DNA of dividing cells. Animals were then euthanized at day 28 and the femurs were examined for cortical bone formation, bone mineral density, and newly borne BrdU+ cells in the periosteum which is a tissue that is pivotally involved in the formation of new cortical bone. In both the geriatric and young mice, anti-sclerostin induced a significant increase in the thickness of the cortical bone, bone mineral density, and the proliferation of newly borne BrdU+ cells in the periosteum. These results suggest that even in geriatric animals, anti-sclerostin therapy can build new cortical bone and increase the proliferation of osteogenic cells and thus reduce the likelihood of painful age-related bone fractures. PMID:27837171

  8. Age-related crosslink in skin collagen

    SciTech Connect

    Yamauchi, M.; Mechanic, G.

    1986-05-01

    A stable crosslinking amino acid was isolated from mature bovine skin collagen and its structure was identified as histidinohydroxylysinonorleucine (HHL) using fast atom bombardment mass spectrometry and /sup 1/H, /sup 13/C-NMR. This newly identified crosslink has a linkage between C-2 histidine and C-6 of lysine in the latter's portion of hydroxylysinonorleucine. Quantitative studies using various aged samples of cow and human skin collagen indicated that this acid-heat stable nonreducible compound was the major age-related crosslink. In case of cow skin collagen, for example, during early embryonic development (3 and 5 month old embryos) the content of HHL stayed less than 0.01 residue/mole of collagen, however from the middle of gestation period (7 month old embryo) through the maturation stage it showed rapid increase with age and reached approximately 0.5 residues/mole of collagen in the 3 year old animal. Small increments (up to 0.65 res/mole of collagen) were observed in the 9 year old cow. The amounts of the crosslink unlike pyridinoline do not decrease with aging. Similar patterns were observed in human skin collagen.

  9. Age-related consequences of childhood obesity.

    PubMed

    Kelsey, Megan M; Zaepfel, Alysia; Bjornstad, Petter; Nadeau, Kristen J

    2014-01-01

    The severity and frequency of childhood obesity has increased significantly over the past three to four decades. The health effects of increased body mass index as a child may significantly impact obese youth as they age. However, many of the long-term outcomes of childhood obesity have yet to be studied. This article examines the currently available longitudinal data evaluating the effects of childhood obesity on adult outcomes. Consequences of obesity include an increased risk of developing the metabolic syndrome, cardiovascular disease, type 2 diabetes and its associated retinal and renal complications, nonalcoholic fatty liver disease, obstructive sleep apnea, polycystic ovarian syndrome, infertility, asthma, orthopedic complications, psychiatric disease, and increased rates of cancer, among others. These disorders can start as early as childhood, and such early onset increases the likelihood of early morbidity and mortality. Being obese as a child also increases the likelihood of being obese as an adult, and obesity in adulthood also leads to obesity-related complications. This review outlines the evidence for childhood obesity as a predictor of adult obesity and obesity-related disorders, thereby emphasizing the importance of early intervention to prevent the onset of obesity in childhood.

  10. Age Related Changes in Preventive Health Behavior.

    ERIC Educational Resources Information Center

    Leventhal, Elaine A.; And Others

    Health behavior may be influenced by age, beliefs, and symptomatology. To examine age-related health beliefs and behaviors with respect to six diseases (the common cold, colon-rectal cancer, lung cancer, heart attack, high blood pressure, and senility), 396 adults (196 males, 200 females) divided into three age groups completed a questionnaire…

  11. Global Metabolic Profiling of Plasma Shows that Three-Year Mild-Caloric Restriction Lessens an Age-Related Increase in Sphingomyelin and Reduces L-leucine and L-phenylalanine in Overweight and Obese Subjects.

    PubMed

    Kim, Minjoo; Lee, Sang-Hyun; Lee, Jong Ho

    2016-12-01

    The effect of weight loss from long-term, mild-calorie diets (MCD) on plasma metabolites is unknown. This study was to examine whether MCD-induced weight reduction caused changes in the extended plasma metabolites. Overweight and obese subjects aged 40-59 years consumed a MCD (approximately 100 kcal/day deficit, n=47) or a weight-maintenance diet (control, n=47) in a randomized, controlled design with a three-year clinical intervention period and plasma samples were analyzed by using UPLC-LTQ-Orbitrap mass spectrometry. The three-year MCD intervention resulted in weight loss (-8.87%) and significant decreases in HOMA-IR and TG. The three-year follow-up of the MCD group showed reductions in the following 13 metabolites: L-leucine; L-phenylalanine; 9 lysoPCs; PC (18:0/20:4); and SM (d18:0/16:1). The three-year MCD group follow-up identified increases in palmitic amide, oleamide, and PC (18:2/18:2). Considering the age-related alterations in the identified metabolites, the MCD group showed a greater decrease in L-leucine, L-phenylalanine, and SM (d18:0/16:1) compared with those of the control group. Overall, the change (Δ) in BMI positively correlated with the ΔTG, ΔHOMA-IR, ΔL-leucine, and ΔSM (d18:0/16:1). The ΔHOMA-IR positively correlated with ΔTG, ΔL-leucine, ΔL-phenylalanine, and ΔSM (d18:0/16:1). The weight loss resulting from three-year mild-caloric restriction lessens the age-related increase in SM and reduces L-leucine and L-phenylalanine in overweight and obese subjects. These changes were coupled with improved insulin resistance (ClinicalTrials.gov: NCT02081898).

  12. Global Metabolic Profiling of Plasma Shows that Three-Year Mild-Caloric Restriction Lessens an Age-Related Increase in Sphingomyelin and Reduces L-leucine and L-phenylalanine in Overweight and Obese Subjects

    PubMed Central

    Kim, Minjoo; Lee, Sang-Hyun; Lee, Jong Ho

    2016-01-01

    The effect of weight loss from long-term, mild-calorie diets (MCD) on plasma metabolites is unknown. This study was to examine whether MCD-induced weight reduction caused changes in the extended plasma metabolites. Overweight and obese subjects aged 40-59 years consumed a MCD (approximately 100 kcal/day deficit, n=47) or a weight-maintenance diet (control, n=47) in a randomized, controlled design with a three-year clinical intervention period and plasma samples were analyzed by using UPLC-LTQ-Orbitrap mass spectrometry. The three-year MCD intervention resulted in weight loss (-8.87%) and significant decreases in HOMA-IR and TG. The three-year follow-up of the MCD group showed reductions in the following 13 metabolites: L-leucine; L-phenylalanine; 9 lysoPCs; PC (18:0/20:4); and SM (d18:0/16:1). The three-year MCD group follow-up identified increases in palmitic amide, oleamide, and PC (18:2/18:2). Considering the age-related alterations in the identified metabolites, the MCD group showed a greater decrease in L-leucine, L-phenylalanine, and SM (d18:0/16:1) compared with those of the control group. Overall, the change (Δ) in BMI positively correlated with the ΔTG, ΔHOMA-IR, ΔL-leucine, and ΔSM (d18:0/16:1). The ΔHOMA-IR positively correlated with ΔTG, ΔL-leucine, ΔL-phenylalanine, and ΔSM (d18:0/16:1). The weight loss resulting from three-year mild-caloric restriction lessens the age-related increase in SM and reduces L-leucine and L-phenylalanine in overweight and obese subjects. These changes were coupled with improved insulin resistance (ClinicalTrials.gov: NCT02081898). PMID:28053823

  13. Age-related changes in triathlon performances.

    PubMed

    Lepers, R; Sultana, F; Bernard, T; Hausswirth, C; Brisswalter, J

    2010-04-01

    The aim of this study was two-fold: i) to analyse age-related declines in swimming, cycling, and running performances for Olympic and Ironman triathlons, and ii) to compare age-related changes in these three disciplines between the Olympic and Ironman triathlons. Swimming, cycling, running and total time performances of the top 10 males between 20 and 70 years of age (in 5 years intervals) were analysed for two consecutive world championships (2006 and 2007) for Olympic and Ironman distances. There was a lesser age-related decline in cycling performance (p<0.01) compared with running and swimming after 55 years of age for Olympic distance and after 50 years of age for Ironman distance. With advancing age, the performance decline was less pronounced (p<0.01) for Olympic than for Ironman triathlon in cycling (>55 years) and running (>50 years), respectively. In contrast, an age-related decline in swimming performance seemed independent of triathlon distance. The age-related decline in triathlon performance is specific to the discipline, with cycling showing less declines in performance with age than swimming and running. The magnitude of the declines in cycling and running performance at Ironman distance is greater than at Olympic distance, suggesting that task duration exerts an important influence on the magnitude of the age-associated changes in triathlon performance.

  14. The neural control of bimanual movements in the elderly: Brain regions exhibiting age-related increases in activity, frequency-induced neural modulation, and task-specific compensatory recruitment.

    PubMed

    Goble, Daniel J; Coxon, James P; Van Impe, Annouchka; De Vos, Jeroen; Wenderoth, Nicole; Swinnen, Stephan P

    2010-08-01

    Coordinated hand use is an essential component of many activities of daily living. Although previous studies have demonstrated age-related behavioral deficits in bimanual tasks, studies that assessed the neural basis underlying such declines in function do not exist. In this fMRI study, 16 old and 16 young healthy adults performed bimanual movements varying in coordination complexity (i.e., in-phase, antiphase) and movement frequency (i.e., 45, 60, 75, 90% of critical antiphase speed) demands. Difficulty was normalized on an individual subject basis leading to group performances (measured by phase accuracy/stability) that were matched for young and old subjects. Despite lower overall movement frequency, the old group "overactivated" brain areas compared with the young adults. These regions included the supplementary motor area, higher order feedback processing areas, and regions typically ascribed to cognitive functions (e.g., inferior parietal cortex/dorsolateral prefrontal cortex). Further, age-related increases in activity in the supplementary motor area and left secondary somatosensory cortex showed positive correlations with coordinative ability in the more complex antiphase task, suggesting a compensation mechanism. Lastly, for both old and young subjects, similar modulation of neural activity was seen with increased movement frequency. Overall, these findings demonstrate for the first time that bimanual movements require greater neural resources for old adults in order to match the level of performance seen in younger subjects. Nevertheless, this increase in neural activity does not preclude frequency-induced neural modulations as a function of increased task demand in the elderly.

  15. A ketogenic diet increases succinic dehydrogenase activity in aging cardiomyocytes.

    PubMed

    Balietti, Marta; Fattoretti, Patrizia; Giorgetti, Belinda; Casoli, Tiziana; Di Stefano, Giuseppina; Solazzi, Moreno; Platano, Daniela; Aicardi, Giorgio; Bertoni-Freddari, Carlo

    2009-08-01

    Impairment of energy metabolism and an increase of reactive oxygen species (ROS) production seem to play a major role in age-related apoptotic loss of cardiomyocytes. Succinic dehydrogenase (SDH) is an important marker of the mitochondrial capability to provide an adequate amount of ATP. Moreover, because of its unique redox properties, SDH activity contributes to maintain the reduced state of the ubiquinone pool. Recent reports have shown that ketone body intake improves cardiac metabolic efficiency and exerts a cardioprotective antioxidant action, we therefore performed a cytochemical investigation of SDH activity in cardiomyocytes of late-adult (19-month-old) rats fed for 8 weeks with a medium-chain triglycerides ketogenic diet (MCT-KD). Young, age-matched and old animals fed with a standard chow were used as controls. The overall area of the precipitates (PA) from SDH activity and the area of the SDH-positive mitochondria (MA) were measured. The percent ratios PA/MA and MA/total myocardial tissue area (MA/TA) were the parameters taken into account. We found that PA/MA was significantly higher in young control rats and in MCT-KD-fed rats versus late-adult and old control rats and in young control versus MCT-KD-fed rats. MA/TA of MCT-KD-fed rats was significantly higher versus age-matched and old control rats and tended to be higher versus young control rats; this parameter was significantly higher in young versus old control rats. Thus, MCT-KD intake partially recovers age-related decrease of SDH activity and increases the myocardial area occupied by metabolically active mitochondria. These effects might counteract metabolic alterations leading to apoptosis-induced myocardial atrophy and failure during aging.

  16. Children and Adolescent Obesity Associates with Pressure-Dependent and Age-Related Increase in Carotid and Femoral Arteries' Stiffness and Not in Brachial Artery, Indicative of Nonintrinsic Arterial Wall Alteration

    PubMed Central

    García-Espinosa, Victoria; Curcio, Santiago; Castro, Juan Manuel; Arana, Maite; Giachetto, Gustavo; Chiesa, Pedro; Zócalo, Yanina

    2016-01-01

    Aim. To analyze if childhood obesity associates with changes in elastic, transitional, and/or muscular arteries' stiffness. Methods. 221 subjects (4–15 years, 92 females) were assigned to normal weight (NW, n = 137) or obesity (OB, n = 84) groups, considering their body mass index z-score. Age groups were defined: 4–8; 8–12; 12–15 years old. Carotid, femoral, and brachial artery local stiffness was determined through systodiastolic pressure-diameter and stress-strain relationships. To this end, arterial diameter and peripheral and aortic blood pressure (BP) levels and waveforms were recorded. Carotid-femoral, femoropedal, and carotid-radial pulse wave velocities were determined to evaluate aortic, lower-limb, and upper-limb regional arterial stiffness, respectively. Correlation analysis between stiffness parameters and BP was done. Results. Compared to NW, OB subjects showed higher peripheral and central BP and carotid and femoral stiffness, reaching statistical significance in subjects aged 12 and older. Arterial stiffness differences disappeared when levels were normalized for BP. There were no differences in intrinsic arterial wall stiffness (elastic modulus), BP stiffness relationships, and regional stiffness parameters. Conclusion. OB associates with BP-dependent and age-related increase in carotid and femoral (but not brachial) stiffness. Stiffness changes would not be explained by intrinsic arterial wall alterations but could be associated with the higher BP levels observed in obese children. PMID:27066273

  17. Age-related eye disease and gender.

    PubMed

    Zetterberg, Madeleine

    2016-01-01

    Worldwide, the prevalence of moderate to severe visual impairment and blindness is 285 millions, with 65% of visually impaired and 82% of all blind people being 50 years and older. Meta-analyses have shown that two out of three blind people are women, a gender discrepancy that holds true for both developed and developing countries. Cataract accounts for more than half of all blindness globally and gender inequity in access to cataract surgery is the major cause of the higher prevalence of blindness in women. In addition to gender differences in cataract surgical coverage, population-based studies on the prevalence of lens opacities indicate that women have a higher risk of developing cataract. Laboratory as well as epidemiologic studies suggest that estrogen may confer antioxidative protection against cataractogenesis, but the withdrawal effect of estrogen in menopause leads to increased risk of cataract in women. For the other major age-related eye diseases; glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy, data are inconclusive. Due to anatomic factors, angle closure glaucoma is more common in women, whereas the dominating glaucoma type; primary open-angle glaucoma (POAG), is more prevalent in men. Diabetic retinopathy also has a male predominance and vascular/circulatory factors have been implied both in diabetic retinopathy and in POAG. For AMD, data on gender differences are conflicting although some studies indicate increased prevalence of drusen and neovascular AMD in women. To conclude, both biologic and socioeconomic factors must be considered when investigating causes of gender differences in the prevalence of age-related eye disease.

  18. Age-Related Changes in Creative Thinking

    ERIC Educational Resources Information Center

    Roskos-Ewoldsen, Beverly; Black, Sheila R.; Mccown, Steven M.

    2008-01-01

    Age-related differences in cognitive processes were used to understand age-related declines in creativity. According to the Geneplore model (Finke, Ward, & Smith, 1992), there are two phases of creativity--generating an idea and exploring the implications of the idea--each with different underlying cognitive processes. These two phases are…

  19. Age-related regulation of genes: slow homeostatic changes and age-dimension technology

    NASA Astrophysics Data System (ADS)

    Kurachi, Kotoku; Zhang, Kezhong; Huo, Jeffrey; Ameri, Afshin; Kuwahara, Mitsuhiro; Fontaine, Jean-Marc; Yamamoto, Kei; Kurachi, Sumiko

    2002-11-01

    Through systematic studies of pro- and anti-blood coagulation factors, we have determined molecular mechanisms involving two genetic elements, age-related stability element (ASE), GAGGAAG and age-related increase element (AIE), a unique stretch of dinucleotide repeats (AIE). ASE and AIE are essential for age-related patterns of stable and increased gene expression patterns, respectively. Such age-related gene regulatory mechanisms are also critical for explaining homeostasis in various physiological reactions as well as slow homeostatic changes in them. The age-related increase expression of the human factor IX (hFIX) gene requires the presence of both ASE and AIE, which apparently function additively. The anti-coagulant factor protein C (hPC) gene uses an ASE (CAGGAG) to produce age-related stable expression. Both ASE sequences (G/CAGAAG) share consensus sequence of the transcriptional factor PEA-3 element. No other similar sequences, including another PEA-3 consensus sequence, GAGGATG, function in conferring age-related gene regulation. The age-regulatory mechanisms involving ASE and AIE apparently function universally with different genes and across different animal species. These findings have led us to develop a new field of research and applications, which we named “age-dimension technology (ADT)”. ADT has exciting potential for modifying age-related expression of genes as well as associated physiological processes, and developing novel, more effective prophylaxis or treatments for age-related diseases.

  20. The DrugAge database of aging-related drugs.

    PubMed

    Barardo, Diogo; Thornton, Daniel; Thoppil, Harikrishnan; Walsh, Michael; Sharifi, Samim; Ferreira, Susana; Anžič, Andreja; Fernandes, Maria; Monteiro, Patrick; Grum, Tjaša; Cordeiro, Rui; De-Souza, Evandro Araújo; Budovsky, Arie; Araujo, Natali; Gruber, Jan; Petrascheck, Michael; Fraifeld, Vadim E; Zhavoronkov, Alexander; Moskalev, Alexey; de Magalhães, João Pedro

    2017-03-16

    Aging is a major worldwide medical challenge. Not surprisingly, identifying drugs and compounds that extend lifespan in model organisms is a growing research area. Here, we present DrugAge (http://genomics.senescence.info/drugs/), a curated database of lifespan-extending drugs and compounds. At the time of writing, DrugAge contains 1316 entries featuring 418 different compounds from studies across 27 model organisms, including worms, flies, yeast and mice. Data were manually curated from 324 publications. Using drug-gene interaction data, we also performed a functional enrichment analysis of targets of lifespan-extending drugs. Enriched terms include various functional categories related to glutathione and antioxidant activity, ion transport and metabolic processes. In addition, we found a modest but significant overlap between targets of lifespan-extending drugs and known aging-related genes, suggesting that some but not most aging-related pathways have been targeted pharmacologically in longevity studies. DrugAge is freely available online for the scientific community and will be an important resource for biogerontologists.

  1. [Depression in Patients with Age-Related Macular Degeneration].

    PubMed

    Narváez, Yamile Reveiz; Gómez-Restrepo, Carlos

    2012-09-01

    Age-related macular degeneration is a cause for disability in the elderly since it greatly affects their quality of life and increases depression likelihood. This article discusses the negative effect depression has on patients with age-related macular degeneration and summarizes the interventions available for decreasing their depression index.

  2. Incentive relativity in middle aged rats.

    PubMed

    Justel, N; Mustaca, A; Boccia, M; Ruetti, E

    2014-01-24

    Response to a reinforcer is affected by prior experience with different reward values of that reward, a phenomenon known as incentive relativity. Two different procedures to study this phenomenon are the incentive downshift (ID) and the consummatory anticipatory negative contrast (cANC), the former is an emotional-cognitive protocol and the latter cognitive one. Aged rodents, as also well described in aged humans, exhibit alterations in cognitive functions. The main goal of this work was to evaluate the effect of age in the incentive' assessment using these two procedures. The results indicated that aged rats had an adequate assessment of the rewards but their performance is not completely comparable to that of young subjects. They recover faster from the ID and they had a cognitive impairment in the cANC. The results are discussed in relation to age-related changes in memory and emotion.

  3. Faster Increases in Human Life Expectancy Could Lead to Slower Population Aging

    PubMed Central

    2015-01-01

    Counterintuitively, faster increases in human life expectancy could lead to slower population aging. The conventional view that faster increases in human life expectancy would lead to faster population aging is based on the assumption that people become old at a fixed chronological age. A preferable alternative is to base measures of aging on people’s time left to death, because this is more closely related to the characteristics that are associated with old age. Using this alternative interpretation, we show that faster increases in life expectancy would lead to slower population aging. Among other things, this finding affects the assessment of the speed at which countries will age. PMID:25876033

  4. Faster increases in human life expectancy could lead to slower population aging.

    PubMed

    Sanderson, Warren C; Scherbov, Sergei

    2015-01-01

    Counterintuitively, faster increases in human life expectancy could lead to slower population aging. The conventional view that faster increases in human life expectancy would lead to faster population aging is based on the assumption that people become old at a fixed chronological age. A preferable alternative is to base measures of aging on people's time left to death, because this is more closely related to the characteristics that are associated with old age. Using this alternative interpretation, we show that faster increases in life expectancy would lead to slower population aging. Among other things, this finding affects the assessment of the speed at which countries will age.

  5. X-82 to Treat Age-related Macular Degeneration

    ClinicalTrials.gov

    2017-01-12

    Age-Related Macular Degeneration (AMD); Macular Degeneration; Exudative Age-related Macular Degeneration; AMD; Macular Degeneration, Age-related, 10; Eye Diseases; Retinal Degeneration; Retinal Diseases

  6. Aging-Related Hormone Changes in Men

    MedlinePlus

    Healthy Lifestyle Men's health Aging-related hormone changes in men — sometimes called male menopause — are different from those ... to erectile dysfunction and other sexual issues. Make healthy lifestyle choices. Eat a healthy diet and include physical ...

  7. Translational strategies in aging and age-related disease.

    PubMed

    Armanios, Mary; de Cabo, Rafael; Mannick, Joan; Partridge, Linda; van Deursen, Jan; Villeda, Saul

    2015-12-01

    Aging is a risk factor for several of the world's most prevalent diseases, including neurodegenerative disorders, cancer, cardiovascular disease and metabolic disease. Although our understanding of the molecular pathways that contribute to the aging process and age-related disease is progressing through the use of model organisms, how to apply this knowledge in the clinic is less clear. In September, Nature Medicine, in collaboration with the Volkswagen Foundation, hosted a conference at the beautiful Herrenhausen Palace in Hannover, Germany with the goal of broadening our understanding of the aging process and its meaning as a 'risk factor' in disease. Here, several of the speakers at that conference answer questions posed by Nature Medicine.

  8. Molecular Diagnostics of Ageing and Tackling Age-related Disease.

    PubMed

    Timmons, James A

    2017-01-01

    As average life expectancy increases there is a greater focus on health-span and, in particular, how to treat or prevent chronic age-associated diseases. Therapies which were able to control 'biological age' with the aim of postponing chronic and costly diseases of old age require an entirely new approach to drug development. Molecular technologies and machine-learning methods have already yielded diagnostics that help guide cancer treatment and cardiovascular procedures. Discovery of valid and clinically informative diagnostics of human biological age (combined with disease-specific biomarkers) has the potential to alter current drug-discovery strategies, aid clinical trial recruitment and maximize healthy ageing. I will review some basic principles that govern the development of 'ageing' diagnostics, how such assays could be used during the drug-discovery or development process. Important logistical and statistical considerations are illustrated by reviewing recent biomarker activity in the field of Alzheimer's disease, as dementia represents the most pressing of priorities for the pharmaceutical industry, as well as the chronic disease in humans most associated with age.

  9. Geroscience approaches to increase healthspan and slow aging

    PubMed Central

    Melov, Simon

    2016-01-01

    For decades, researchers in the biology of aging have focused on defining mechanisms that modulate aging by primarily studying a single metric, sometimes described as the “gold standard” lifespan. Increasingly, geroscience research is turning towards defining functional domains of aging such as the cardiovascular system, skeletal integrity, and metabolic health as being a more direct route to understand why tissues decline in function with age. Each model used in aging research has strengths and weaknesses, yet we know surprisingly little about how critical tissues decline in health with increasing age. Here I discuss popular model systems used in geroscience research and their utility as possible tools in preclinical studies in aging. PMID:27158475

  10. Aging is not a disease: distinguishing age-related macular degeneration from aging.

    PubMed

    Ardeljan, Daniel; Chan, Chi-Chao

    2013-11-01

    Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD.

  11. Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-alpha-phenylnitrone

    SciTech Connect

    Carney, J.M.; Starke-Reed, P.E.; Oliver, C.N.; Landum, R.W.; Cheng, M.S.; Wu, J.F.; Floyd, R.A. )

    1991-05-01

    Oxygen free radicals and oxidative events have been implicated as playing a role in bringing about the changes in cellular function that occur during aging. Brain readily undergoes oxidative damage, so it is important to determine if aging-induced changes in brain may be associated with oxidative events. Previously we demonstrated that brain damage caused by an ischemia/reperfusion insult involved oxidative events. In addition, pretreatment with the spin-trapping compound N-tert-butyl-alpha-phenylnitrone (PBN) diminished the increase in oxidized protein and the loss of glutamine synthetase (GS) activity that accompanied ischemia/reperfusion injury in brain. We report here that aged gerbils had a significantly higher level of oxidized protein as assessed by carbonyl residues and decreased GS and neutral protease activities as compared to young adult gerbils. We also found that chronic treatment with the spin-trapping compound PBN caused a decrease in the level of oxidized protein and an increase in both GS and neutral protease activity in aged Mongolian gerbil brain. In contrast to aged gerbils, PBN treatment of young adult gerbils had no significant effect on brain oxidized protein content or GS activity. Male gerbils, young adults (3 months of age) and retired breeders (15-18 months of age), were treated with PBN for 14 days with twice daily dosages of 32 mg/kg. If PBN administration was ceased after 2 weeks, the significantly decreased level of oxidized protein and increased GS and neutral protease activities in old gerbils changed in a monotonic fashion back to the levels observed in aged gerbils prior to PBN administration. We also report that old gerbils make more errors than young animals and that older gerbils treated with PBN made fewer errors in a radial arm maze test for temporal and spatial memory than the untreated aged controls.

  12. Relative age effect in Japanese male athletes.

    PubMed

    Nakata, Hiroki; Sakamoto, Kiwako

    2011-10-01

    The present study investigated the relative age effect, a biased distribution of elite athletes' birthdates, in Japanese male athletes. Japan applies a unique annual-age grouping for sport and education, which is from April 1 to March 31 of the following year. A total of 4,318 male athletes was evaluated from 12 sports: baseball, soccer, basketball, volleyball, handball, golf, horse racing, rugby, American football, sumo, Ekiden (track and field in long distance), and badminton. They played in the top level of Japanese leagues for each sport in 2010. The distribution of the birth dates was examined in each sport and showed significant relative age effect in baseball, soccer, volleyball, Ekiden, basketball, sumo, and horse racing, but not in all sports. The findings suggest that although the school year in Japan starts on April 1, significant relative age effects are observed in some sporting events.

  13. Gender Relations and Applied Research on Aging

    ERIC Educational Resources Information Center

    Calasanti, Toni

    2010-01-01

    As a concept in gerontology, gender appears as lists of traits learned through socialization when theorized at all. I argue for a framework that theorizes the intersections of relations of gender inequality with those of age. This framework holds that men and women gain resources and bear responsibilities, in relation to one another, by virtue of…

  14. Nut consumption and age-related disease.

    PubMed

    Grosso, G; Estruch, R

    2016-02-01

    Current knowledge on the effects of nut consumption on human health has rapidly increased in recent years and it now appears that nuts may play a role in the prevention of chronic age-related diseases. Frequent nut consumption has been associated with better metabolic status, decreased body weight as well as lower body weight gain over time and thus reduce the risk of obesity. The effect of nuts on glucose metabolism, blood lipids, and blood pressure is still controversial. However, significant decreased cardiovascular risk has been reported in a number of observational and clinical intervention studies. Thus, findings from cohort studies show that increased nut consumption is associated with a reduced risk of cardiovascular disease and mortality (especially that due to cardiovascular-related causes). Similarly, nut consumption has been also associated with reduced risk of certain cancers, such as colorectal, endometrial, and pancreatic neoplasms. Evidence regarding nut consumption and neurological or psychiatric disorders is scarce, but a number of studies suggest significant protective effects against depression, mild cognitive disorders and Alzheimer's disease. The underlying mechanisms appear to include antioxidant and anti-inflammatory actions, particularly related to their mono- and polyunsaturated fatty acids (MUFA and PUFA, as well as vitamin and polyphenol content). MUFA have been demonstrated to improve pancreatic beta-cell function and regulation of postprandial glycemia and insulin sensitivity. PUFA may act on the central nervous system protecting neuronal and cell-signaling function and maintenance. The fiber and mineral content of nuts may also confer health benefits. Nuts therefore show promise as useful adjuvants to prevent, delay or ameliorate a number of chronic conditions in older people. Their association with decreased mortality suggests a potential in reducing disease burden, including cardiovascular disease, cancer, and cognitive impairments.

  15. Age Metallicity Relation in the LMC

    NASA Astrophysics Data System (ADS)

    Kontizas, E.; Dapergolas, A.; Kontizas, M.; Nordström, B.; Andersen, J.; Prantzos, N.; Kaltcheva, N.

    The age metallicity relation (AMR) is known to be very important for understanding the chemical evolution in a galaxy. LMC, our nearest galaxy offers an ideal target for such studies, considering that with the SMC and our Galaxy are an interacting group, influencing each other's star formation rate and production of metals. An observing program for the determination of AMR from a study of small open LMC clusters using Stroemgren phorometry has been initiated. Three observing runs were granted with the 1.5m Danish Telescope at La Silla. We report on our search within 8 clusters, scattered all over the LMC to cover a wide spatial distribution and metallicity. CMDs using Stroemgren photometry have been produced, in order to find the age of the stellar content. The available isochrones used, although very few are able to give us a good age estimate. The calibration of the y, b, v, magnitudes and colours to metallicity used, is the one by Richter et al. (A&A, 1999), to obtain the adopted metallicities of the clusters. Although our sample is still small, a clear trend is observed in AMR showing a significant increase of metallicity with age. Comparison with previous AMRs from other investigations shows good agreement within the errors. The bursting model of chemical evolution by Pagel and Tautvaisiene (MNRAS, 1999) shows that the burst of star formation (SF) produces a change of slope in their AMRs from 2 Gyr to the present time, the burst assumed to occur from -0.4 dex to 0.0 dex. Although our sample is small the observed trend favours the expected change of the AMRs rather towards the 1 Gyr. Therefore our observations support a bursting model of chemical evolution. More obervations are needed and new theoretical models to strengthen these results. Finally it is found that all young metal rich clusters occupy the central LMC regions whereas the old metal poor ones are found in the LMC periphery giving evidence for a metallicity gradient as well. We would like to

  16. Age-related increase in food spilling by laboratory mice may lead to significant overestimation of actual food consumption: implications for studies on dietary restriction, metabolism, and dose calculations.

    PubMed

    Starr, Marlene E; Saito, Hiroshi

    2012-10-01

    It is widely accepted that food consumption in humans declines with advanced age; however, data from mice remain controversial. Based on our previous observation that mice spill a considerable amount of food while eating, we hypothesized that increased food spillage in old mice masks actual food intake. To investigate whether mice exhibit age-associated declines in food consumption, we evaluated the actual food consumption of C57BL/6 mice at various ages by measuring both the amount of food in the food receptacle and the amount dropped to the cage bottom during feeding. We found that old mice dropped significantly more food (36% ± 8%) than young mice (18% ± 5%), which led to overestimations of food consumption, particularly in old mice. Although actual food consumption decreased in very old mice, food intake per body weight did not significantly change. These findings suggest that caution should be taken to accurately quantify food consumption by aged animals.

  17. Pathophysiology of age-related diseases

    PubMed Central

    Campisi, Giuseppina; Chiappelli, Martina; De Martinis, Massimo; Franco, Vito; Ginaldi, Lia; Guiglia, Rosario; Licastro, Federico; Lio, Domenico

    2009-01-01

    A Symposium regarding the Pathophysiology of Successful and Unsuccessful Ageing was held in Palermo, Italy on 7-8 April 2009. Three lectures from that Symposium by G. Campisi, L. Ginaldi and F. Licastro are here summarized. Ageing is a complex process which negatively impacts on the development of various bodily systems and its ability to function. A long life in a healthy, vigorous, youthful body has always been one of humanity's greatest dreams. Thus, a better understanding of the pathophysiology of age-related diseases is urgently required to improve our understanding of maintaining good health in the elderly and to program possible therapeutic intervention. PMID:19737378

  18. Audience Design and Social Relations in Aging.

    PubMed

    Keller-Cohen, Deborah

    2015-10-01

    This study asks two questions: (1) Do older adults modify their language based on age of the listener (audience design)? (2) Does social contact affect audience design in older adults? Older adults (n = 34; mean age = 82) engaged in an instructions task with two fictive listeners (a child and an adult) to test these questions. Results show that older adults used a greater total number of propositions and rapport-building devices and a lower type-token ratio when giving instructions to the child compared to the adult listener. Adults with more social interactions used more propositions when talking to a child. In addition, satisfaction with interactions was significantly positively related to task-tracking devices and negatively related to rapport-building devices by older adults. These results suggest that audience design and social relations are worth further study in language maintenance in older age.

  19. Increase in the age of Olympic swimmers in modern times.

    PubMed

    Mazzilli, Facundo

    2016-11-25

    Mazzilli, F. Increase in the age of Olympic swimmers in modern times. Anecdotal data suggest an increase in the age of Olympic swimmers, but scientific studies in this regard are scarce, despite the importance for coaches of the confirmation of this increase in different styles. To ascertain the reality of this increase, the present study focused on the analysis of the data contained in the reports of the Internal Olympic Games Association, covering different events and styles throughout the history of the Games. Starting with the 1908 Games, a total of 806 swimmers (436 men and 370 women) were included in the study. Of them 137 men and 135 women had won two or more medals. Plots of the age of the swimmer at the time a gold, silver or bronze medal was granted versus year of competition elicited statistical significant increases in 3 events in men and 9 events in women. Interestingly, significant increases were regularly observed in the styles introduced in the sixties and a kind of V-shaped distribution was observed in some of the long established competitions, namely in the 100, 400 and 1500 m freestyle in men, where the point of inflexion seems to occur around 1960. Overall there is a continuing increase in the age of swimmers of ages over 24 years old mirrored by a decrease of those below 20 years and this is accompanied by the increased presence of swimmers that have won medals in 2 or 3 different Games.

  20. [Pathogenesis of age-related macular degeneration].

    PubMed

    Kaarniranta, Kai; Seitsonen, Sanna; Paimela, Tuomas; Meri, Seppo; Immonen, Ilkka

    2009-01-01

    Age-related macular degeneration is a multiform disease of the macula, the region responsible for detailed central vision. In recent years, plenty of new knowledge of the pathogenesis of this disease has been obtained, and the treatment of exudative macular degeneration has greatly progressed. The number of patients with age-related macular degeneration will multiply in the following decades, because knowledge of mechanisms of development of macular degeneration that could be subject to therapeutic measures is insufficient. Central underlying factors are genetic inheritance, exposure of the retina to chronic oxidative stress and accumulation of inflammation-inducing harmful proteins into or outside of retinal cells.

  1. [New aspects in age related macular degeneration].

    PubMed

    Turlea, C

    2012-01-01

    Being the leading cause of blindness in modern world Age Related Macular Degeneration has beneficiated in the last decade of important progress in diagnosis, classification and the discovery of diverse factors who contribute to the etiology of this disease. Treatments have arised who can postpone the irreversible evolution of the disease and thus preserve vision. Recent findings have identified predisposing genetic factors and also inflamatory and imunological parameters that can be modified trough a good and adequate prevention and therapy This articole reviews new aspects of patology of Age Related Macular Degeneration like the role of complement in maintaining inflamation and the role of oxidative stress on different structures of the retina.

  2. Parainflammation, chronic inflammation, and age-related macular degeneration.

    PubMed

    Chen, Mei; Xu, Heping

    2015-11-01

    Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune-privileged tissue as a result of its unique anatomic and physiologic properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate-immune system, particularly microglia and the complement system, undergoes low levels of activation (parainflammation). In many cases, this parainflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration, this parainflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal parainflammation include genetic predisposition, environmental risk factors, and old age. Dysregulated parainflammation (chronic inflammation) in age-related macular degeneration damages the blood retina barrier, resulting in the breach of retinal-immune privilege, leading to the development of retinal lesions. This review discusses the basic principles of retinal innate-immune responses to endogenous chronic insults in normal aging and in age-related macular degeneration and explores the difference between beneficial parainflammation and the detrimental chronic inflammation in the context of age-related macular degeneration.

  3. [Age-related muscle mass loss].

    PubMed

    Czarkowska-Paczek, Bozena; Milczarczyk, Sylwia

    2006-01-01

    One of the signs of advancing age in humans is sarcopenia. The term is used to define the loss of muscle mass and strength that occurs with ageing. Sarcopenia contributes to the decreased capacity of independent living and increased amounts of traumas. Numbers of mechanisms are proposed as a cause of sarcopenia, including changes in protein metabolism, alterations in hormonal and neural functions, impaired regeneration after contraction-induced injuries, mitochondrial abnormalities, oxidative stress and apoptosis in skeletal muscle fibres. Further studies on the mechanisms leading to sarcopenia could provide the basis for prevention and establishment of therapeutic methods that would contribute to an increase in the standard of living among elderly people.

  4. Marginal effect of increasing ageing drivers on injury crashes.

    PubMed

    Tay, Richard

    2008-11-01

    The safety effects of the ageing driving population have been a topic of research interests in health and transportation economics in recent years due to the ageing of the baby boomers. This study adds to the current knowledge by examining the marginal effects of changing the driver mix on injury crashes using data from the Canadian Province of Alberta between 1990 and 2004. Results from a Poisson regression model reveal that increasing the number of young and ageing drivers will result in an increase in the number of injury crashes whereas increasing the number of middle-aged drivers will result in a reduction. These results are in contrast to those obtained in a previous study on the marginal effects of changing the driver mix on fatal crashes in the Australian State of Queensland and some possible explanations for the differing results are provided.

  5. Age-Related Changes in 1/f Neural Electrophysiological Noise.

    PubMed

    Voytek, Bradley; Kramer, Mark A; Case, John; Lepage, Kyle Q; Tempesta, Zechari R; Knight, Robert T; Gazzaley, Adam

    2015-09-23

    Aging is associated with performance decrements across multiple cognitive domains. The neural noise hypothesis, a dominant view of the basis of this decline, posits that aging is accompanied by an increase in spontaneous, noisy baseline neural activity. Here we analyze data from two different groups of human subjects: intracranial electrocorticography from 15 participants over a 38 year age range (15-53 years) and scalp EEG data from healthy younger (20-30 years) and older (60-70 years) adults to test the neural noise hypothesis from a 1/f noise perspective. Many natural phenomena, including electrophysiology, are characterized by 1/f noise. The defining characteristic of 1/f is that the power of the signal frequency content decreases rapidly as a function of the frequency (f) itself. The slope of this decay, the noise exponent (χ), is often <-1 for electrophysiological data and has been shown to approach white noise (defined as χ = 0) with increasing task difficulty. We observed, in both electrophysiological datasets, that aging is associated with a flatter (more noisy) 1/f power spectral density, even at rest, and that visual cortical 1/f noise statistically mediates age-related impairments in visual working memory. These results provide electrophysiological support for the neural noise hypothesis of aging. Significance statement: Understanding the neurobiological origins of age-related cognitive decline is of critical scientific, medical, and public health importance, especially considering the rapid aging of the world's population. We find, in two separate human studies, that 1/f electrophysiological noise increases with aging. In addition, we observe that this age-related 1/f noise statistically mediates age-related working memory decline. These results significantly add to this understanding and contextualize a long-standing problem in cognition by encapsulating age-related cognitive decline within a neurocomputational model of 1/f noise-induced deficits in

  6. Depression in Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Casten, Robin; Rovner, Barry

    2008-01-01

    Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling…

  7. Age related macular degeneration and visual disability.

    PubMed

    Christoforidis, John B; Tecce, Nicola; Dell'Omo, Roberto; Mastropasqua, Rodolfo; Verolino, Marco; Costagliola, Ciro

    2011-02-01

    Age-related macular degeneration (AMD) is the leading cause of central blindness or low vision among the elderly in industrialized countries. AMD is caused by a combination of genetic and environmental factors. Among modifiable environmental risk factors, cigarette smoking has been associated with both the dry and wet forms of AMD and may increase the likelihood of worsening pre-existing AMD. Despite advances, the treatment of AMD has limitations and affected patients are often referred for low vision rehabilitation to help them cope with their remaining eyesight. The characteristic visual impairment for both forms of AMD is loss of central vision (central scotoma). This loss results in severe difficulties with reading that may be only partly compensated by magnifying glasses or screen-projection devices. The loss of central vision associated with the disease has a profound impact on patient quality of life. With progressive central visual loss, patients lose their ability to perform the more complex activities of daily living. Common vision aids include low vision filters, magnifiers, telescopes and electronic aids. Low vision rehabilitation (LVR) is a new subspecialty emerging from the traditional fields of ophthalmology, optometry, occupational therapy, and sociology, with an ever-increasing impact on the usual concepts of research, education, and services for visually impaired patients. Relatively few ophthalmologists practise LVR and fewer still routinely use prismatic image relocation (IR) in AMD patients. IR is a method of stabilizing oculomotor functions with the purpose of promoting better function of preferred retinal loci (PRLs). The aim of vision rehabilitation therapy consists in the achievement of techniques designed to improve PRL usage. The use of PRLs to compensate for diseased foveae has offered hope to these patients in regaining some function. However, in a recently published meta-analysis, prism spectacles were found to be unlikely to be of

  8. Consuming a buttermilk drink containing lutein-enriched egg yolk daily for 1 year increased plasma lutein but did not affect serum lipid or lipoprotein concentrations in adults with early signs of age-related macular degeneration.

    PubMed

    van der Made, Sanne M; Kelly, Elton R; Berendschot, Tos T J M; Kijlstra, Aize; Lütjohann, Dieter; Plat, Jogchum

    2014-09-01

    Dietary lutein intake is postulated to interfere with the development of age-related macular degeneration (AMD). Because egg yolk-derived lutein has a high bioavailability, long-term consumption of lutein-enriched eggs might be effective in preventing AMD development, but alternatively might increase cardiovascular disease risk. Here, we report the effect of 1-y daily consumption of a buttermilk drink containing 1.5 lutein-rich egg yolks on serum lipid and lipoprotein and plasma lutein concentrations. Additionally, subgroups that could potentially benefit the most from the intervention were identified. Men and women who had early signs of AMD in at least 1 eye, but were otherwise healthy, participated in a 1-y randomized, placebo-controlled parallel intervention trial. At the start of the study, 101 participants were included: 52 in the experimental (Egg) group and 49 in the control (Con) group. Final analyses were performed with 45 participants in the Egg group and 43 participants in the Con group. As expected, the increase in plasma lutein concentrations in the Egg group was 83% higher than that in the Con group (P < 0.001). Changes in serum total, HDL, and LDL cholesterol, as well as the ratio of total cholesterol to HDL cholesterol, were not different between the 2 groups. Interestingly, participants classified as cholesterol absorbers had higher serum HDL cholesterol concentrations than participants classified as cholesterol synthesizers or participants with average campesterol-to-lathosterol ratios (P < 0.05) at baseline. In addition, cholesterol absorbers had a 229% higher increase in plasma lutein concentrations than participants who were classified as having an average campesterol-to-lathosterol ratio upon consumption of the lutein-enriched egg yolk drink (P < 0.05). Moreover, the change in serum HDL cholesterol upon consumption was significantly different between these 3 groups (P < 0.05). We suggest that cholesterol absorbers particularly might benefit

  9. Aging increases CCN1 expression leading to muscle senescence.

    PubMed

    Du, Jie; Klein, Janet D; Hassounah, Faten; Zhang, Jin; Zhang, Cong; Wang, Xiaonan H

    2014-01-01

    Using microarray analysis, we found that aging sarcopenia is associated with a sharp increase in the mRNA of the matricellular protein CCN1 (Cyr61/CTGF/Nov). CCN1 mRNA was upregulated 113-fold in muscle of aged vs. young rats. CCN1 protein was increased in aging muscle in both rats (2.8-fold) and mice (3.8-fold). When muscle progenitor cells (MPCs) were treated with recombinant CCN1, cell proliferation was decreased but there was no change in the myogenic marker myoD. However, the CCN1-treated MPCs did express a senescence marker (SA-βgal). Interestingly, we found CCN1 increased p53, p16(Ink4A), and pRP (hypophosphorylated retinoblastoma protein) protein levels, all of which can arrest cell growth in MPCs. When MPCs were treated with aged rodent serum CCN1 mRNA increased by sevenfold and protein increased by threefold suggesting the presence of a circulating regulator. Therefore, we looked for a circulating regulator. Wnt-3a, a stimulator of CCN1 expression, was increased in serum from elderly humans (2.6-fold) and aged rodents (2.0-fold) compared with young controls. We transduced C2C12 myoblasts with wnt-3a and found that CCN1 protein was increased in a time- and dose-dependent manner. We conclude that in aging muscle, the circulating factor wnt-3a acts to increase CCN1 expression, prompting muscle senescence by activating cell arrest proteins.

  10. Statistical physics of age related macular degeneration

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon; Mazzitello, K. I.; Arizmendi, C. M.; Grossniklaus, H. E.

    Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). The RPE is a phagocytic system that is essential for renewal of photoreceptors (rods and cones). With time, incompletely degraded membrane material builds up in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer disease and Parkinson disease. The study of lipofuscin formation and growth is important, because of their association with cellular aging. We introduce a model of non-equilibrium cluster growth and aggregation that we have developed for studying the formation and growth of lipofuscin in the aging RPE. Our results agree with a linear growth of the number of lipofuscin granules with age. We apply the dynamic scaling approach to our model and find excellent data collapse for the cluster size distribution. An unusual feature of our model is that while small particles are removed from the RPE the larger ones become fixed and grow by aggregation.

  11. Growth factors, aging and age-related diseases.

    PubMed

    Balasubramanian, Priya; Longo, Valter D

    2016-06-01

    Simple organisms including yeast and flies with mutations in the IGF-1 and Tor-S6K pathways are dwarfs, are highly protected from toxins, and survive up to 3 times longer. Similarly, dwarf mice with deficiencies in the growth hormone-IGF-I axis are also long lived and protected from diseases. We recently reported that humans with Growth Hormone Receptor Deficiency (GHRD) rarely develop cancer or diabetes. These findings are in agreement with the effect of defects in the Tor-S6K pathways in causing dwarfism and protection of DNA. Because protein restriction reduces both GHR-IGF-1 axis and Tor-S6K activity, we examined links between protein intake, disease, and mortality in over 6000 US subjects in the NHANES CDC database. Respondents aged 50-65 reporting a high protein intake displayed an increase in IGF-I levels, a 75% increased risk of overall mortality and a 3-4 fold increased risk of cancer mortality in agreement with findings in mouse experiments. These studies point to a conserved link between proteins and amino acids, GHR-IGF-1/insulin, Tor-S6k signaling, aging, and diseases.

  12. The age of astronomy-related organizations

    NASA Astrophysics Data System (ADS)

    Heck, A.

    1999-03-01

    The age of currently active astronomy-related organizations is investigated from comprehensive and up-to-date samples. Results for professional institutions, associations, planetariums, and public observatories are commented, as well as specific distributions for astronomy-related publishers and software producers. Some events had a clear impact on the rate of foundation of astronomy-related organizations, such as World War I and II, the beginning of space exploration and the landing of man on the Moon, but not all of them affected in the same way Western Europe and North America. It is still premature to assess the impact of the end of the Cold War. A category such as the software producers would of course not exist nor prosper without the advent of the computer age and the subsequent electronic networking of the planet. Other aspects are discussed in the paper.

  13. Aging and age-related diseases--from endocrine therapy to target therapy.

    PubMed

    Bao, Qi; Pan, Jie; Qi, Hangfei; Wang, Lu; Qian, Huan; Jiang, Fangzhen; Shao, Zheren; Xu, Fengzhi; Tao, Zhiping; Ma, Qi; Nelson, Peter; Hu, Xueqing

    2014-08-25

    Aging represents an important health issue not only for the individual, but also for society in general. Burdens associated with aging are expanding as longevity increases. This has led to an enhanced focus on issues related to aging and age-related diseases. Until recently, anti-aging endocrine-therapy has been largely limited to hormone-replacement therapy (HRT) that is associated with multiple side effects, including an increased risk of cancer. This has greatly limited the application of HRT in anti-aging therapy. Recently, the focus of anti-aging research has expanded from endocrine signaling pathways to effects on regulatory gene networks. In this regard, the GHRH-GH-IGF-1/Insulin, TOR-S6K1,NAD(+)-Sirtuin, P53, Klotho and APOE pathways have been linked to processes associated with age-related diseases, including cancer, cardiovascular disease, diabetes, osteoporosis, and neurodegenerative diseases, all of which directly influence health in aging, and represent key targets in anti-aging therapy.

  14. Stem cell transplantation improves aging-related diseases

    PubMed Central

    Ikehara, Susumu; Li, Ming

    2014-01-01

    Aging is a complex process of damage accumulation, and has been viewed as experimentally and medically intractable. The number of patients with age-associated diseases such as type 2 diabetes mellitus (T2DM), osteoporosis, Alzheimer's disease (AD), Parkinson's disease, atherosclerosis, and cancer has increased recently. Aging-related diseases are related to a deficiency of the immune system, which results from an aged thymus and bone marrow cells. Intra bone marrow-bone marrow transplantation (IBM-BMT) is a useful method to treat intractable diseases. This review summarizes findings that IBM-BMT can improve and treat aging-related diseases, including T2DM, osteoporosis and AD, in animal models. PMID:25364723

  15. The application of information theory for the research of aging and aging-related diseases.

    PubMed

    Blokh, David; Stambler, Ilia

    2016-03-19

    This article reviews the application of information-theoretical analysis, employing measures of entropy and mutual information, for the study of aging and aging-related diseases. The research of aging and aging-related diseases is particularly suitable for the application of information theory methods, as aging processes and related diseases are multi-parametric, with continuous parameters coexisting alongside discrete parameters, and with the relations between the parameters being as a rule non-linear. Information theory provides unique analytical capabilities for the solution of such problems, with unique advantages over common linear biostatistics. Among the age-related diseases, information theory has been used in the study of neurodegenerative diseases (particularly using EEG time series for diagnosis and prediction), cancer (particularly for establishing individual and combined cancer biomarkers), diabetes (mainly utilizing mutual information to characterize the diseased and aging states), and heart disease (mainly for the analysis of heart rate variability). Few works have employed information theory for the analysis of general aging processes and frailty, as underlying determinants and possible early preclinical diagnostic measures for aging-related diseases. Generally, the use of information-theoretical analysis permits not only establishing the (non-linear) correlations between diagnostic or therapeutic parameters of interest, but may also provide a theoretical insight into the nature of aging and related diseases by establishing the measures of variability, adaptation, regulation or homeostasis, within a system of interest. It may be hoped that the increased use of such measures in research may considerably increase diagnostic and therapeutic capabilities and the fundamental theoretical mathematical understanding of aging and disease.

  16. Increased mobilization of aged carbon to rivers by human disturbance

    NASA Astrophysics Data System (ADS)

    Butman, David E.; Wilson, Henry F.; Barnes, Rebecca T.; Xenopoulos, Marguerite A.; Raymond, Peter A.

    2015-02-01

    Approximately 8% of anthropogenic carbon dioxide emissions are estimated to come from land-use change, but this estimate excludes fluxes of terrestrial carbon to aquatic ecosystems from human disturbance. Carbon fluxes from land to rivers have probably increased by 0.1 to 0.2 petagrams of carbon per year as a result of disturbances such as deforestation, agricultural intensification and the injection of human wastewater. Most dissolved organic carbon in rivers originates from young organic carbon from soils and vegetation, but aged carbon removed from the modern carbon cycle is also exported in many systems. Here we analyse a global data set of radiocarbon ages of riverine dissolved organic carbon and spatial data on land cover, population and environmental variables. We find that the age of dissolved organic carbon in rivers increases with population density and the proportion of human-dominated landscapes within a watershed, and decreases with annual precipitation. We reason that disturbance reintroduces aged soil organic matter into the modern carbon cycle, although fossil carbon in fertilizer or petroleum products may also be a source of aged carbon in disturbed watersheds. The total export from the terrestrial environment to freshwater systems remains unknown; nevertheless, our results suggest that 3-9% of dissolved organic carbon in rivers is aged carbon mobilized by human disturbance.

  17. Glial dysfunction causes age-related memory impairment in Drosophila.

    PubMed

    Yamazaki, Daisuke; Horiuchi, Junjiro; Ueno, Kohei; Ueno, Taro; Saeki, Shinjiro; Matsuno, Motomi; Naganos, Shintaro; Miyashita, Tomoyuki; Hirano, Yukinori; Nishikawa, Hiroyuki; Taoka, Masato; Yamauchi, Yoshio; Isobe, Toshiaki; Honda, Yoshiko; Kodama, Tohru; Masuda, Tomoko; Saitoe, Minoru

    2014-11-19

    Several aging phenotypes, including age-related memory impairment (AMI), are thought to be caused by cumulative oxidative damage. In Drosophila, age-related impairments in 1 hr memory can be suppressed by reducing activity of protein kinase A (PKA). However, the mechanism for this effect has been unclear. Here we show that decreasing PKA suppresses AMI by reducing activity of pyruvate carboxylase (PC), a glial metabolic enzyme whose amounts increase upon aging. Increased PC activity causes AMI through a mechanism independent of oxidative damage. Instead, increased PC activity is associated with decreases in D-serine, a glia-derived neuromodulator that regulates NMDA receptor activity. D-serine feeding suppresses both AMI and memory impairment caused by glial overexpression of dPC, indicating that an oxidative stress-independent dysregulation of glial modulation of neuronal activity contributes to AMI in Drosophila.

  18. Prevention of age-related macular degeneration

    PubMed Central

    Koo, Simon Chi Yan; Chan, Clement Wai Nang

    2010-01-01

    Age-related macular degeneration (AMD) is one of the leading causes of blindness in the developed world. Although effective treatment modalities such as anti-VEGF treatment have been developed for neovascular AMD, there is still no effective treatment for geographical atrophy, and therefore the most cost-effective management of AMD is to start with prevention. This review looks at current evidence on preventive measures targeted at AMD. Modalities reviewed include (1) nutritional supplements such as the Age-Related Eye Disease Study (AREDS) formula, lutein and zeaxanthin, omega-3 fatty acid, and berry extracts, (2) lifestyle modifications, including smoking and body-mass-index, and (3) filtering sunlight, i.e. sunglasses and blue-blocking intraocular lenses. In summary, the only proven effective preventive measures are stopping smoking and the AREDS formula. PMID:20862519

  19. [Aged woman's vulnerability related to AIDS].

    PubMed

    Silva, Carla Marins; Lopes, Fernanda Maria do Valle Martins; Vargens, Octavio Muniz da Costa

    2010-09-01

    This article is a systhematic literature review including the period from 1994 to 2009, whose objective was to discuss the aged woman's vulnerability in relation to Acquired Imunodeficiency Syndrome (Aids). The search for scientific texts was accomplished in the following databases: Biblioteca Virtual em Saúde, Scientific Eletronic Library Online (SciELO), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) and Medical Literature Analysis and Retrieval System Online (MEDLINE). The descriptors used were vulnerability, woman and Aids. Eighteen texts were analyzed, including articles in scientific journals, thesis and dissertations. As a conclusion, it was noted that aged women and vulnerability to Aids are directly related, through gender characteristics including submission and that were built historical and socially. We consider as fundamental the development of studies which may generate publications accessible to women, in order to help them see themselves as persons vulnerable to Aids contagion just for being women.

  20. Depression in Age-Related Macular Degeneration.

    PubMed

    Casten, Robin; Rovner, Barry

    2008-01-01

    Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling diseases. This article discusses the effect of depression on vision-related disability in patients with AMD, suggests methods for screening for depression, and summarizes interventions for preventing depression in this high-risk group.

  1. Salmon lice increase the age of returning Atlantic salmon

    PubMed Central

    Vollset, Knut Wiik; Barlaup, Bjørn Torgeir; Skoglund, Helge; Normann, Eirik Straume; Skilbrei, Ove Tommy

    2014-01-01

    The global increase in the production of domestic farmed fish in open net pens has created concerns about the resilience of wild populations owing to shifts in host–parasite systems in coastal ecosystems. However, little is known about the effects of increased parasite abundance on life-history traits in wild fish populations. Here, we report the results of two separate studies in which 379 779 hatchery-reared Atlantic salmon smolts were treated (or not) against salmon lice, marked and released. Adults were later recaptured, and we specifically tested whether the age distribution of the returning spawners was affected by the treatment. The estimates of parasite-induced mortality were 31.9% and 0.6% in the River Vosso and River Dale stock experiments, respectively. Age of returning salmon was on average higher in treated versus untreated fish. The percentages of fish returning after one winter at sea were 37.5% and 29.9% for the treated and untreated groups, respectively. We conclude that salmon lice increase the age of returning salmon, either by affecting their age at maturity or by disproportionately increasing mortality in fish that mature early. PMID:24478199

  2. Onset of mortality increase with age and age trajectories of mortality from all diseases in the four Nordic countries

    PubMed Central

    Dolejs, Josef; Marešová, Petra

    2017-01-01

    Background The answer to the question “At what age does aging begin?” is tightly related to the question “Where is the onset of mortality increase with age?” Age affects mortality rates from all diseases differently than it affects mortality rates from nonbiological causes. Mortality increase with age in adult populations has been modeled by many authors, and little attention has been given to mortality decrease with age after birth. Materials and methods Nonbiological causes are excluded, and the category “all diseases” is studied. It is analyzed in Denmark, Finland, Norway, and Sweden during the period 1994–2011, and all possible models are screened. Age trajectories of mortality are analyzed separately: before the age category where mortality reaches its minimal value and after the age category. Results Resulting age trajectories from all diseases showed a strong minimum, which was hidden in total mortality. The inverse proportion between mortality and age fitted in 54 of 58 cases before mortality minimum. The Gompertz model with two parameters fitted as mortality increased with age in 17 of 58 cases after mortality minimum, and the Gompertz model with a small positive quadratic term fitted data in the remaining 41 cases. The mean age where mortality reached minimal value was 8 (95% confidence interval 7.05–8.95) years. The figures depict an age where the human population has a minimal risk of death from biological causes. Conclusion Inverse proportion and the Gompertz model fitted data on both sides of the mortality minimum, and three parameters determined the shape of the age–mortality trajectory. Life expectancy should be determined by the two standard Gompertz parameters and also by the single parameter in the model c/x. All-disease mortality represents an alternative tool to study the impact of age. All results are based on published data. PMID:28176929

  3. Multifocal electroretinogram: age-related changes for different luminance levels

    PubMed Central

    Gerth, Christina; Garcia, Susan M.; Ma, Lei; Keltner, John L.; Werner, John S.

    2008-01-01

    Background Age-related changes in the first-order multifocal electroretinogram (mfERG) responses were measured for two different luminance levels (200 and 700 cd·m−2). The relative contribution of optical and neural factors to senescent change in response was evaluated. Methods Data were obtained from one eye of each of 71 normal phakic subjects, age 9−80 years. The mfERG responses were recorded with the 7” stimulus-refractor unit (EDI) and VERIS 4.3 using the following protocol: bipolar contact lens, 103 hexagons, consecutive stimulation with 200 and 700 cd·m−2, pupils ≥6 mm, amplification of 105, filter cut-offs at 10 and 300 Hz. Results Age-correlated decreases in amplitude and response density and increases in P1 implicit time were found for both luminance levels. The mean response density (nV·deg−2) was higher for the 700 cd·m−2 stimulus, but the rate of change with age was not significantly different from that obtained with the 200 cd·m−2 stimulus. Implicit time was not significantly different for the two light levels, nor was the rate of change with age. The decrease in response density and the increase in implicit time with age were significant across all retinal regions, dividing the 50 deg stimulus into six concentric rings. Age-related change in response density was greatest for the central retina and decreased with increasing retinal eccentricity. Conclusion Log mfERG response changes linearly as a function of age. Analyses of the effects of reduced ocular media transmission and increased stray light, along with ancillary data obtained from pseudophakes, imply that age-related changes in the mfERG are due to both optical and neural factors. PMID:11935277

  4. Physics of Age Related Macular Degeneration

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon

    2009-11-01

    Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). The RPE is a phagocytic system that is essential for renewal of photoreceptors (rods and cones). With time, incompletely degraded membrane material builds up in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer's disease, and Parkinson's disease. The study of lipofuscin formation and growth is important, because of their association with cellular aging. In this talk I will discuss a model of non-equilibrium cluster growth that we have developed for studying the formation and growth of lipofuscin in AMD [K.I. Mazzitello, C.M. Arizmendi, Fereydoon Family, H. E. Grossniklaus, Physical Review E (2009)]. I will also present an overview of our theoretical and computational efforts in modeling some other aspects of the physics of AMD, including CNV and the breakdown of Bruch's membrane [Ongoing collaboration with Abbas Shirinifard and James A. Glazier, Biocomplexity Institute and Department of Physics, Indiana University, Y. Jiang, Los Alamos, and Hans E. Grossniklaus, Department of Ophthalmology, Emory University].

  5. Mechanisms of age-related bone loss.

    PubMed

    Mosekilde, L

    2001-01-01

    The human skeleton is formed and modelled during childhood and youth through the influence of hormones and daily mechanical usage. Around the age of 20-25 years, the skeleton achieves its maximum mass and strength. Thereafter, and throughout adult life, bone is lost at an almost constant rate due to the dynamic bone turnover process: the remodelling process. During this process, small packets of bone are renewed by teams of bone cells coupled together in time and space. In an adult human skeleton there will be 1-2 million active remodelling sites at any time point. The vast number of turnover units combined with a slightly negative balance at the completion of each process leads to the age-related loss of bone mass mentioned above and, concomitantly, to loss of structural continuity and strength. The magnitude of this loss will be determined by hormonal factors, nutrition and mechanical usage. As a consequence of the remodelling process, the bone tissue of the skeleton will always be younger than the age of the individual. However, as a consequence of the remodelling process, osteopenia and osteoporotic fractures will also occur. In this article, the remodelling-induced changes in the human spine will be used as an example of ageing bone.

  6. Increasing the Value of Age: Guidance in Employers' Age Management Strategies. Research Paper No 44

    ERIC Educational Resources Information Center

    Cedefop - European Centre for the Development of Vocational Training, 2015

    2015-01-01

    The European active population is ageing. In the face of growing skills shortages, both national States and employers need to prolong the working lives of their most experienced workers. While enterprises strive to respond to this challenge, most still have not fully explored the potential of guidance activities in addressing age-related issues in…

  7. Age related changes in steroid receptors on cultured lung fibroblasts

    SciTech Connect

    Barile, F.A.; Bienkowski, R.S.

    1986-03-05

    The number of high affinity glucocorticoid receptors (Ro) on human fetal lung fibroblasts decreases as the cells age in vitro, and it has been suggested that these cell systems may be useful models of age-related changes in vivo. They examined the relation between change in Ro with in vitro aging and donor age. Confluent monolayers of lung fibroblasts at various population doubling levels (PDL), were incubated with (/sup 3/H)-dexamethasone ((/sup 3/H)Dex) either alone or with excess (.01 mM) Dex. Specific binding was calculated as the difference between radioactivity in cells incubated with and without unlabeled Dex; Scatchard plots were used to analyze the data. Ro, measured as fmol (/sup 3/H)Dex/10/sup 6/ cells, for two lines of human fetal cells (HFL-1 and MRC-5) decreased with increasing age in vitro. However, human newborn (CRL-1485) and adult (CCL-201) cells and fetal rabbit cells (FAB-290), showed increases in Ro with continuous passage. For each cell line, the affinity constant (K/sub d/) did not change significantly with passage. They conclude that the direction of changes in steroid receptor levels on cells aging in vitro is influenced by donor age and species. Caution should be used in applying results obtained from model systems to aging organisms.

  8. Age-related changes of serum lipoprotein oxidation in rats.

    PubMed

    Nakamura, Yukiko Kawashima; Omaye, Stanley Teruo

    2004-01-23

    Oxidation of low-density lipoprotein (LDL) may be a prelude to atherogenesis and directly age related. To assess whether there may be relationship between age and plasma lipoprotein (LP) oxidation, we studied copper-mediated LP oxidation isolated from the blood of 2 months, 7 months, and 15 months old rats. We determined whether the susceptibility of LP to oxidation might be related to vitamin C levels in serum, vitamin E levels in LP, or the total antioxidant capacity (TAC) of serum or LP. Serum vitamin C content was inversely related to age, malondialdehyde (MDA) propagation rate, and maximum change of MDA concentrations. However, there were no significant relationships between age and serum TAC, LP TAC, serum vitamin E, or the ratio of LP vitamin E to serum vitamin C content. The lag phase of MDA formation was significantly decreased with age and the ratio of LP vitamin E content to serum vitamin C content, increased with age. Maximum change of MDA concentration was positively correlated with the ratio of LP vitamin E contents to serum vitamin C concentration. Thus, as the rat ages, vitamin C status decreases with an increased LP susceptibility to oxidation. It is tempting to speculate that enhanced LP oxidation in older rats may reflect a reduced amount of recycling of LDL vitamin E by serum vitamin C.

  9. Taste-related sensations in old age.

    PubMed

    Ogawa, T; Annear, M J; Ikebe, K; Maeda, Y

    2017-03-02

    The sense of taste is important as it allows for assessment of nutritional value, safety and quality of foods as well as for food enjoyment and quality of life. Several factors are suggested to be associated with taste sensitivity, and higher prevalence of taste disorder has been reported among older adults. This review focused on the reported causes and correlates of taste decline in older adults, with the aim to consolidating existing evidence and identifying gaps and limitations. Using a scoping review methodology, we sought relevant literature from the last 20 years. Search terms included taste, gustatory sense, older adults and geriatric. Considered research was limited to reports that involved research participants over 60 years old, papers written in English, and manuscripts published after 1995. We have consolidated available evidences on the influences on taste-related sensations among international cohorts of older adults. Influences can be reflected under the topics of physiological changes in the sensory organs, physiological and behavioural variables related to taste sensation. This review identified three areas of historic and current research endeavour related to studies of taste sensation in older subjects: physiological changes in the sensory organs, factors related to the ageing of the individual and behavioural variables affecting taste-related sensation. Key limitations and gaps in the current literature include notable lack of consideration of potential confounding, mediating and moderating effects, while future research is indicated in the areas of measuring the quality of health and life. As global population ageing accelerates in the coming decades, maintaining taste sensations and sensitivity in older adults will be a key measure to ensuring quality of health and life.

  10. Hhip haploinsufficiency sensitizes mice to age-related emphysema.

    PubMed

    Lao, Taotao; Jiang, Zhiqiang; Yun, Jeong; Qiu, Weiliang; Guo, Feng; Huang, Chunfang; Mancini, John Dominic; Gupta, Kushagra; Laucho-Contreras, Maria E; Naing, Zun Zar Chi; Zhang, Li; Perrella, Mark A; Owen, Caroline A; Silverman, Edwin K; Zhou, Xiaobo

    2016-08-09

    Genetic variants in Hedgehog interacting protein (HHIP) have consistently been associated with the susceptibility to develop chronic obstructive pulmonary disease and pulmonary function levels, including the forced expiratory volume in 1 s (FEV1), in general population samples by genome-wide association studies. However, in vivo evidence connecting Hhip to age-related FEV1 decline and emphysema development is lacking. Herein, using Hhip heterozygous mice (Hhip(+/-)), we observed increased lung compliance and spontaneous emphysema in Hhip(+/-) mice starting at 10 mo of age. This increase was preceded by increases in oxidative stress levels in the lungs of Hhip(+/-) vs. Hhip(+/+) mice. To our knowledge, these results provide the first line of evidence that HHIP is involved in maintaining normal lung function and alveolar structures. Interestingly, antioxidant N-acetyl cysteine treatment in mice starting at age of 5 mo improved lung function and prevented emphysema development in Hhip(+/-) mice, suggesting that N-acetyl cysteine treatment limits the progression of age-related emphysema in Hhip(+/-) mice. Therefore, reduced lung function and age-related spontaneous emphysema development in Hhip(+/-) mice may be caused by increased oxidative stress levels in murine lungs as a result of haploinsufficiency of Hhip.

  11. Life stress, glucocorticoid signaling, and the aging epigenome: Implications for aging-related diseases.

    PubMed

    Gassen, Nils C; Chrousos, George P; Binder, Elisabeth B; Zannas, Anthony S

    2017-03-01

    Life stress has been associated with accelerated cellular aging and increased risk for developing aging-related diseases; however, the underlying molecular mechanisms remain elusive. A highly relevant process that may underlie this association is epigenetic regulation. In this review, we build upon existing evidence to propose a model whereby exposure to life stress, in part via its effects on the hypothalamic-pituitary axis and the glucocorticoid signaling system, may alter the epigenetic landscape across the lifespan and, consequently, influence genomic regulation and function in ways that are conducive to the development of aging-related diseases. This model is supported by recent studies showing that life stressors and stress-related phenotypes can accelerate epigenetic aging, a measure that is based on DNA methylation prediction of chronological age and has been associated with several aging-related disease phenotypes. We discuss the implications of this model for the prevention and treatment of aging-related diseases, as well as the challenges and limitations of this line of research.

  12. Age-related deterioration of rod vision in mice.

    PubMed

    Kolesnikov, Alexander V; Fan, Jie; Crouch, Rosalie K; Kefalov, Vladimir J

    2010-08-18

    Even in healthy individuals, aging leads to deterioration in visual acuity, contrast sensitivity, visual field, and dark adaptation. Little is known about the neural mechanisms that drive the age-related changes of the retina and, more specifically, photoreceptors. According to one hypothesis, the age-related deterioration in rod function is due to the limited availability of 11-cis-retinal for rod pigment formation. To determine how aging affects rod photoreceptors and to test the retinoid-deficiency hypothesis, we compared the morphological and functional properties of rods of adult and aged B6D2F1/J mice. We found that the number of rods and the length of their outer segments were significantly reduced in 2.5-year-old mice compared with 4-month-old animals. Aging also resulted in a twofold reduction in the total level of opsin in the retina. Behavioral tests revealed that scotopic visual acuity and contrast sensitivity were decreased by twofold in aged mice, and rod ERG recordings demonstrated reduced amplitudes of both a- and b-waves. Sensitivity of aged rods determined from single-cell recordings was also decreased by 1.5-fold, corresponding to not more than 1% free opsin in these photoreceptors, and kinetic parameters of dim flash response were not altered. Notably, the rate of rod dark adaptation was unaffected by age. Thus, our results argue against age-related deficiency of 11-cis-retinal in the B6D2F1/J mouse rod visual cycle. Surprisingly, the level of cellular dark noise was increased in aged rods, providing an alternative mechanism for their desensitization.

  13. A developmental increase in allostatic load from ages 3 to 11 years is associated with increased schizotypal personality at age 23 years.

    PubMed

    Peskin, Melissa; Raine, Adrian; Gao, Yu; Venables, Peter H; Mednick, Sarnoff A

    2011-11-01

    Although allostatic load has been investigated in mood and anxiety disorders, no prior study has investigated developmental change in allostatic load as a precursor to schizotypal personality. This study employed a multilevel developmental framework to examine whether the development of increased allostatic load, as indicated by impaired sympathetic nervous system habituation from ages 3 to 11 years, predisposes to schizotypal personality at age 23 years. Electrodermal activity to six aversive tones was recorded in 995 subjects at age 3 years and again at 11 years. Habituation slopes at both ages were used to create groups who showed a developmental increase in habituation (decreased allostatic load), and those who showed a developmental decrease in habituation (increased allostatic load). Children who showed a developmental increase in allostatic load from ages 3 to 11 years had higher levels of schizotypal personality at 23 years. A breakdown of total schizotypy scores demonstrated specificity of findings to cognitive-perceptual features of schizotypy. Findings are the first to document a developmental abnormality in allostasis in relation to adult schizotypal personality. The relative failure to develop normal habituation to repeated stressors throughout childhood is hypothesized to result in an accumulation of allostatic load and consequently increased positive symptom schizotypy in adulthood.

  14. Increased centrosome amplification in aged stem cells of the Drosophila midgut

    SciTech Connect

    Park, Joung-Sun; Pyo, Jung-Hoon; Na, Hyun-Jin; Jeon, Ho-Jun; Kim, Young-Shin; Arking, Robert; Yoo, Mi-Ae

    2014-07-25

    Highlights: • Increased centrosome amplification in ISCs of aged Drosophila midguts. • Increased centrosome amplification in ISCs of oxidative stressed Drosophila midguts. • Increased centrosome amplification in ISCs by overexpression of PVR, EGFR, and AKT. • Supernumerary centrosomes can be responsible for abnormal ISC polyploid cells. • Supernumerary centrosomes can be a useful marker for aging stem cells. - Abstract: Age-related changes in long-lived tissue-resident stem cells may be tightly linked to aging and age-related diseases such as cancer. Centrosomes play key roles in cell proliferation, differentiation and migration. Supernumerary centrosomes are known to be an early event in tumorigenesis and senescence. However, the age-related changes of centrosome duplication in tissue-resident stem cells in vivo remain unknown. Here, using anti-γ-tubulin and anti-PH3, we analyzed mitotic intestinal stem cells with supernumerary centrosomes in the adult Drosophila midgut, which may be a versatile model system for stem cell biology. The results showed increased centrosome amplification in intestinal stem cells of aged and oxidatively stressed Drosophila midguts. Increased centrosome amplification was detected by overexpression of PVR, EGFR, and AKT in intestinal stem cells/enteroblasts, known to mimic age-related changes including hyperproliferation of intestinal stem cells and hyperplasia in the midgut. Our data show the first direct evidence for the age-related increase of centrosome amplification in intestinal stem cells and suggest that the Drosophila midgut is an excellent model for studying molecular mechanisms underlying centrosome amplification in aging adult stem cells in vivo.

  15. [The relationship between the polymorphism of immunity genes and both aging and age-related diseases].

    PubMed

    Ruan, Qing-Wei; Yu, Zhuo-Wei; Bao, Zhi-Jun; Ma, Yong-Xing

    2013-07-01

    Aging is acommon, progressive and irreversible state of multi-cell dysfunction. Immune aging mainly includes the declines of regenerative capacity and lymphoid lineage differentiation potential, the hyporesponsive to infection and vaccination, the hyperresponsive in the context of inflammatory pathology, and the increased risk of autoimmunity. The dysfunction of aged immune system accelerates the occurrence of aging and age-related diseases. The mutation of immunity genes that affect immune responses accelerates or slows aging process and age-related diseases. The frequencies of acquired immunity genes, such as immune protective HLA II DRB1*11 and DRB*16-associated haplotype, are increased in the longevity populations. The increased susceptibility of immune inflammatory response, morbidity and mortality in the elderly is often associated with decreased frequencies of anti-inflammatory factor IL-10 -1082G allele, TNF-β1 haplotype cnd10T/C, cnd25G/G, -988C/C, -800G/A, low proinflammatory fator TNFa level related extended TNF-A genotype -1031C/C, -863C/A, -857C/C, IL-6-174 CC and IFN-γ+874 T allele as well. The innate immunity genes, such as highly expressed anti-inflammatory +896 G KIR4 allele, CCR5Δ32 variant, -765 C Cox-2 allele, -1708 G and 21 C 5-Lox alleles are detected in centenarians. In age-related diseases, a higher CMV-specific IgG antibody level in elderly individuals is associated with a decreased frequency of KIR haplotypes KIR2DS5 and A1B10 and an increased frequency of MBL2 haplotypes LYPB, LYQC and HYPD that result in the absence of MBL2 protein. The increased frequencies of CRP ATG haplotypes and CFH 402 His allele indicate high mortality in the elderly. In the present study, we review the advances in the polymorphism and haplotype of innate and adoptive immunity genes, and their association with both aging and age-related diseases. To strengthen the analysis of extended haplotypes, epigenetic studies of immunity genes and genetic study of

  16. Age-related changes in head and eye coordination.

    PubMed

    Proudlock, Frank A; Shekhar, Himanshu; Gottlob, Irene

    2004-01-01

    The effect of ageing upon head movements during gaze shifts is unknown. We have investigated age-related changes in head and eye coordination in a group of healthy volunteers. Horizontal head and eye movements were recorded in 53 subjects, aged between 20 and 83 years, during the performance of saccades, antisaccades, smooth pursuit and a reading task. The subjects were divided into three groups, young subjects (20-40 years), middle-aged subjects (41-60 years) and older subjects (over 60 years). Logarithmic transformations of the head gain were significantly greater in the older subjects compared to the young subjects during the saccadic task (P=0.001), antisaccadic task (P=0.004), smooth pursuit at 20 degrees/s (P=0.001) and 40 degrees/s (P=0.005), but not reading. For saccadic and antisaccadic tasks, the increase in transformed head gain was non-linear with significant differences between older and middle-aged subjects but not middle-aged and young subjects. Head movement tendencies were highly consistent for related tasks. Head movement gain during gaze shifts significantly increases with age, which may contribute to dizziness and balance problems experienced by the elderly.

  17. Aging and factors related to running economy.

    PubMed

    Quinn, Timothy J; Manley, Michelle J; Aziz, Jason; Padham, Jamie L; MacKenzie, Allison M

    2011-11-01

    The purpose of this study was to investigate the relationship that age has on factors affecting running economy (RE) in competitive distance runners. Fifty-one male and female subelite distance runners (Young [Y]: 18-39 years [n = 18]; Master [M]: 40-59 years [n = 22]; and Older [O]: 60-older [n = 11]) were measured for RE, step rate, lactate threshold (LT), VO2max, muscle strength and endurance, flexibility, power, and body composition. An RE test was conducted at 4 different velocities (161, 188, 215, and 241 m·min(-1)), with subjects running for 5 minutes at each velocity. The steady-state VO2max during the last minute of each stage was recorded and plotted vs. speed, and a regression equation was formulated. A 1 × 3 analysis of variance revealed no differences in the slopes of the RE regression lines among age groups (y = 0.1827x - 0.2974; R2 = 0.9511 [Y]; y = 0.1988x - 1.0416; R2 = 0.9697 [M]; y = 0.1727x + 3.0252; R2 = 0.9618 [O]). The VO2max was significantly lower in the O group compared to in the Y and M groups (Y = 64.1 ± 3.2; M = 56.8 ± 2.7; O = 44.4 ± 1.7 mlO2·kg(-1)·min(-1)). The maximal heart rate and velocity @ LT were significantly different among all age groups (Y = 197 ± 4; M = 183 ± 2; O = 170 ± 6 b·min(-1) and Y = 289.7 ± 27.0; M = 251.5 ± 32.9; O = 212.3 ± 24.6 m·min(-1), respectively). The VO2max @ LT was significantly lower in the O group compared to in the Y and M groups (Y = 50.3 ± 2.0; M = 48.8 ± 2.9; O = 34.9 ± 3.2 mlO2·kg(-1)·min(-1)). The O group was significantly lower than in the Y and M groups in flexibility, power, and upper body strength. Multiple regression analyses showed that strength and power were significantly related to running velocity. The results from this cross-sectional analysis suggest that age-related declines in running performance are associated with declines in maximal and submaximal cardiorespiratory variables and declines in strength and power, not because of declines in running economy.

  18. Lack of increase in DNA crosslinking in Drosophila melanogaster with age.

    PubMed

    Massie, H R; Baird, M B; Williams, T R

    1975-01-01

    Adult Drosophila melanogaster fruit flies ranging in age from 2 to 7.5 weeks with a median colony survival time of 6.4 weeks at 25 degrees C showed no increase in DNA crosslinking with age. The purified denatured DNA used for crosslink determinations varied in molecular weight from 2.02 to 3.84 times 10(5) daltons and was crosslinked to the extent of 6.2-8.8% with no age-related trend.

  19. Aging Affects Neural Synchronization to Speech-Related Acoustic Modulations

    PubMed Central

    Goossens, Tine; Vercammen, Charlotte; Wouters, Jan; van Wieringen, Astrid

    2016-01-01

    As people age, speech perception problems become highly prevalent, especially in noisy situations. In addition to peripheral hearing and cognition, temporal processing plays a key role in speech perception. Temporal processing of speech features is mediated by synchronized activity of neural oscillations in the central auditory system. Previous studies indicate that both the degree and hemispheric lateralization of synchronized neural activity relate to speech perception performance. Based on these results, we hypothesize that impaired speech perception in older persons may, in part, originate from deviances in neural synchronization. In this study, auditory steady-state responses that reflect synchronized activity of theta, beta, low and high gamma oscillations (i.e., 4, 20, 40, and 80 Hz ASSR, respectively) were recorded in young, middle-aged, and older persons. As all participants had normal audiometric thresholds and were screened for (mild) cognitive impairment, differences in synchronized neural activity across the three age groups were likely to be attributed to age. Our data yield novel findings regarding theta and high gamma oscillations in the aging auditory system. At an older age, synchronized activity of theta oscillations is increased, whereas high gamma synchronization is decreased. In contrast to young persons who exhibit a right hemispheric dominance for processing of high gamma range modulations, older adults show a symmetrical processing pattern. These age-related changes in neural synchronization may very well underlie the speech perception problems in aging persons. PMID:27378906

  20. Age-Related Changes in Trabecular Meshwork Imaging

    PubMed Central

    Gold, Mark E.; Nagi, Kundandeep S.; Bell, Nicholas P.; Blieden, Lauren S.; Chuang, Alice Z.; Baker, Laura A.; Mankiewicz, Kimberly A.; Feldman, Robert M.

    2013-01-01

    Purpose. To evaluate the normal aging effects on trabecular meshwork (TM) parameters using Fourier domain anterior segment optical coherence tomography (ASOCT) images. Patients and Methods. One eye from 45 participants with open angles was imaged. Two independent readers measured TM area, TM length, and area and length of the TM interface shadow from 3 age groups (18–40, 41–60, and 61–80). Measurements were compared using stepwise regression analysis. Results. The average TM parameters were 0.0487 (±0.0092) mm2 for TM area, 0.5502 (±0.1033) mm for TM length, 0.1623 (±0.341) mm2 for TM interface shadow area, and 0.7755 (±0.1574) mm for TM interface shadow length. Interobserver reproducibility coefficients ranged from 0.45 (TM length) to 0.82 (TM area). TM area and length were not correlated with age. While the TM interface shadow length did not correlate with age, the TM interface shadow area increased with age. Race, sex, intraocular pressure, and gonioscopy score were not correlated with any TM parameters. Conclusion. Although the TM measurements were not correlated with age, the TM interface shadow area increased with age. Further study is required to determine whether there is any relationship between the age-related ASOCT findings of the TM interface shadow area and physiologic function. PMID:24163814

  1. Age-Related Changes in Electroencephalographic Signal Complexity.

    PubMed

    Zappasodi, Filippo; Marzetti, Laura; Olejarczyk, Elzbieta; Tecchio, Franca; Pizzella, Vittorio

    2015-01-01

    The study of active and healthy aging is a primary focus for social and neuroscientific communities. Here, we move a step forward in assessing electrophysiological neuronal activity changes in the brain with healthy aging. To this end, electroencephalographic (EEG) resting state activity was acquired in 40 healthy subjects (age 16-85). We evaluated Fractal Dimension (FD) according to the Higuchi algorithm, a measure which quantifies the presence of statistical similarity at different scales in temporal fluctuations of EEG signals. Our results showed that FD increases from age twenty to age fifty and then decreases. The curve that best fits the changes in FD values across age over the whole sample is a parabola, with the vertex located around age fifty. Moreover, FD changes are site specific, with interhemispheric FD asymmetry being pronounced in elderly individuals in the frontal and central regions. The present results indicate that fractal dimension well describes the modulations of brain activity with age. Since fractal dimension has been proposed to be related to the complexity of the signal dynamics, our data demonstrate that the complexity of neuronal electric activity changes across the life span of an individual, with a steady increase during young adulthood and a decrease in the elderly population.

  2. Age-Related Changes in Electroencephalographic Signal Complexity

    PubMed Central

    Zappasodi, Filippo; Marzetti, Laura; Olejarczyk, Elzbieta; Tecchio, Franca; Pizzella, Vittorio

    2015-01-01

    The study of active and healthy aging is a primary focus for social and neuroscientific communities. Here, we move a step forward in assessing electrophysiological neuronal activity changes in the brain with healthy aging. To this end, electroencephalographic (EEG) resting state activity was acquired in 40 healthy subjects (age 16–85). We evaluated Fractal Dimension (FD) according to the Higuchi algorithm, a measure which quantifies the presence of statistical similarity at different scales in temporal fluctuations of EEG signals. Our results showed that FD increases from age twenty to age fifty and then decreases. The curve that best fits the changes in FD values across age over the whole sample is a parabola, with the vertex located around age fifty. Moreover, FD changes are site specific, with interhemispheric FD asymmetry being pronounced in elderly individuals in the frontal and central regions. The present results indicate that fractal dimension well describes the modulations of brain activity with age. Since fractal dimension has been proposed to be related to the complexity of the signal dynamics, our data demonstrate that the complexity of neuronal electric activity changes across the life span of an individual, with a steady increase during young adulthood and a decrease in the elderly population. PMID:26536036

  3. Loss of Rictor with aging in osteoblasts promotes age-related bone loss

    PubMed Central

    Lai, Pinling; Song, Qiancheng; Yang, Cheng; Li, Zhen; Liu, Sichi; Liu, Bin; Li, Mangmang; Deng, Hongwen; Cai, Daozhang; Jin, Dadi; Liu, Anling; Bai, Xiaochun

    2016-01-01

    Osteoblast dysfunction is a major cause of age-related bone loss, but the mechanisms underlying changes in osteoblast function with aging are poorly understood. This study demonstrates that osteoblasts in aged mice exhibit markedly impaired adhesion to the bone formation surface and reduced mineralization in vivo and in vitro. Rictor, a specific component of the mechanistic target of rapamycin complex 2 (mTORC2) that controls cytoskeletal organization and cell survival, is downregulated with aging in osteoblasts. Mechanistically, we found that an increased level of reactive oxygen species with aging stimulates the expression of miR-218, which directly targets Rictor and reduces osteoblast bone surface adhesion and survival, resulting in a decreased number of functional osteoblasts and accelerated bone loss in aged mice. Our findings reveal a novel functional pathway important for age-related bone loss and support for miR-218 and Rictor as potential targets for therapeutic intervention for age-related osteoporosis treatment. PMID:27735936

  4. Aging on a different scale – chronological versus pathology-related aging

    PubMed Central

    Melis, Joost P.M.; Jonker, Martijs J.; Vijg, Jan; Hoeijmakers, Jan H.J.; Breit, Timo M.; van Steeg, Harry

    2013-01-01

    In the next decades the elderly population will increase dramatically, demanding appropriate solutions in health care and aging research focusing on healthy aging to prevent high burdens and costs in health care. For this, research targeting tissue-specific and individual aging is paramount to make the necessary progression in aging research. In a recently published study we have attempted to make a step interpreting aging data on chronological as well as pathological scale. For this, we sampled five major tissues at regular time intervals during the entire C57BL/6J murine lifespan from a controlled in vivo aging study, measured the whole transcriptome and incorporated temporal as well as physical health aspects into the analyses. In total, we used 18 different age-related pathological parameters and transcriptomic profiles of liver, kidney, spleen, lung and brain and created a database that can now be used for a broad systems biology approach. In our study, we focused on the dynamics of biological processes during chronological aging and the comparison between chronological and pathology-related aging. PMID:24131799

  5. Aging on a different scale--chronological versus pathology-related aging.

    PubMed

    Melis, Joost P M; Jonker, Martijs J; Vijg, Jan; Hoeijmakers, Jan H J; Breit, Timo M; van Steeg, Harry

    2013-10-01

    In the next decades the elderly population will increase dramatically, demanding appropriate solutions in health care and aging research focusing on healthy aging to prevent high burdens and costs in health care. For this, research targeting tissue-specific and individual aging is paramount to make the necessary progression in aging research. In a recently published study we have attempted to make a step interpreting aging data on chronological as well as pathological scale. For this, we sampled five major tissues at regular time intervals during the entire C57BL/6J murine lifespan from a controlled in vivo aging study, measured the whole transcriptome and incorporated temporal as well as physical health aspects into the analyses. In total, we used 18 different age-related pathological parameters and transcriptomic profiles of liver, kidney, spleen, lung and brain and created a database that can now be used for a broad systems biology approach. In our study, we focused on the dynamics of biological processes during chronological aging and the comparison between chronological and pathology-related aging.

  6. Human Aging Is a Metabolome-related Matter of Gender.

    PubMed

    Jové, Mariona; Maté, Ianire; Naudí, Alba; Mota-Martorell, Natalia; Portero-Otín, Manuel; De la Fuente, Mónica; Pamplona, Reinald

    2016-05-01

    A molecular description of the mechanisms by which aging is produced is still very limited. Here, we have determined the plasma metabolite profile by using high-throughput metabolome profiling technologies of 150 healthy humans ranging from 30 to 100 years of age. Using a nontargeted approach, we detected 2,678 metabolite species in plasma, and the multivariate analyses separated perfectly two groups indicating a specific signature for each gender. In addition, there is a set of gender-shared metabolites, which change significantly during aging with a similar tendency. Among the identified molecules, we found vitamin D2-related compound, phosphoserine (40:5), monoacylglyceride (22:1), diacylglyceride (33:2), and resolvin D6, all of them decreasing with the aging process. Finally, we found three molecules that directly correlate with age and seven that inversely correlate with age, independently of gender. Among the identified molecules (6 of 10 according to exact mass and retention time), we found a proteolytic product (l-γ-glutamyl-l-leucine), which increased with age. On the contrary, a hydroxyl fatty acid (25-hydroxy-hexacosanoic), a polyunsaturated fatty acid (eicosapentaenoic acid), two phospholipids (phosphocholine [42:9]and phosphoserine [42:3]) and a prostaglandin (15-keto-prostaglandin F2α) decreased with aging. These results suggest that lipid species and their metabolism are closely linked to the aging process.

  7. Animal models of age related macular degeneration.

    PubMed

    Pennesi, Mark E; Neuringer, Martha; Courtney, Robert J

    2012-08-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations.

  8. Animal models of age related macular degeneration

    PubMed Central

    Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

    2013-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

  9. Normal tear protein profiles and age-related changes.

    PubMed Central

    McGill, J I; Liakos, G M; Goulding, N; Seal, D V

    1984-01-01

    The specific and non-specific tear proteins have been analysed by means of the ELISA technique to establish the normal and age-related values. There is a linear and related decline of lysozyme and lactoferrin with age, and a similar but unrelated reduction in tear volume. IgA levels gradually decline, while caeruloplasmin and IgG both increase after the fifth decade. The results suggest that tear IgG and caeruloplasmin are probably transudates from the serum, that IgA is secreted independently of tear volume, and that lysozyme and lactoferrin are secreted at the same site but independently of tear volume. PMID:6712908

  10. Medical bioremediation of age-related diseases

    PubMed Central

    Mathieu, Jacques M; Schloendorn, John; Rittmann, Bruce E; Alvarez, Pedro JJ

    2009-01-01

    Catabolic insufficiency in humans leads to the gradual accumulation of a number of pathogenic compounds associated with age-related diseases, including atherosclerosis, Alzheimer's disease, and macular degeneration. Removal of these compounds is a widely researched therapeutic option, but the use of antibodies and endogenous human enzymes has failed to produce effective treatments, and may pose risks to cellular homeostasis. Another alternative is "medical bioremediation," the use of microbial enzymes to augment missing catabolic functions. The microbial genetic diversity in most natural environments provides a resource that can be mined for enzymes capable of degrading just about any energy-rich organic compound. This review discusses targets for biodegradation, the identification of candidate microbial enzymes, and enzyme-delivery methods. PMID:19358742

  11. Dietary Approaches that Delay Age-Related Diseases

    PubMed Central

    Everitt, Arthur V; Hilmer, Sarah N; Brand-Miller, Jennie C; Jamieson, Hamish A; Truswell, A Stewart; Sharma, Anita P; Mason, Rebecca S; Morris, Brian J; Le Couteur, David G

    2006-01-01

    Reducing food intake in lower animals such as the rat decreases body weight, retards many aging processes, delays the onset of most diseases of old age, and prolongs life. A number of clinical trials of food restriction in healthy adult human subjects running over 2–15 years show significant reductions in body weight, blood cholesterol, blood glucose, and blood pressure, which are risk factors for the development of cardiovascular disease and diabetes. Lifestyle interventions that lower energy balance by reducing body weight such as physical exercise can also delay the development of diabetes and cardiovascular disease. In general, clinical trials are suggesting that diets high in calories or fat along with overweight are associated with increased risk for cardiovascular disease, type 2 diabetes, some cancers, and dementia. There is a growing literature indicating that specific dietary constituents are able to influence the development of age-related diseases, including certain fats (trans fatty acids, saturated, and polyunsaturated fats) and cholesterol for cardiovascular disease, glycemic index and fiber for diabetes, fruits and vegetables for cardiovascular disease, and calcium and vitamin D for osteoporosis and bone fracture. In addition, there are dietary compounds from different functional foods, herbs, and neutraceuticals such as ginseng, nuts, grains, and polyphenols that may affect the development of age-related diseases. Long-term prospective clinical trials will be needed to confirm these diet—disease relationships. On the basis of current research, the best diet to delay age-related disease onset is one low in calories and saturated fat and high in wholegrain cereals, legumes, fruits and vegetables, and which maintains a lean body weight. Such a diet should become a key component of healthy aging, delaying age-related diseases and perhaps intervening in the aging process itself. Furthermore, there are studies suggesting that nutrition in childhood

  12. Age-related Alterations in the Dynamic Behavior of Microglia

    PubMed Central

    Damani, Mausam R.; Zhao, Lian; Fontainhas, Aurora M.; Amaral, Juan; Fariss, Robert N.; Wong, Wai T.

    2010-01-01

    Summary Microglia, the primary resident immune cells of the CNS, exhibit dynamic behavior involving rapid process motility and cellular migration that is thought to underlie key functions of immune surveillance and tissue repair. Although age-related changes in microglial activation have been implicated in the pathogenesis of neurodegenerative diseases of aging, how dynamic behavior in microglia is influenced by aging is not fully understood. In this study, we employed live imaging of retinal microglia in situ to compare microglial morphology and behavioral dynamics in young and aged animals. We found that aged microglia in the resting state have significantly smaller and less branched dendritic arbors, and also slower process motilities, which likely compromise their ability to continuously survey and interact with their environment. We also found that dynamic microglial responses to injury were age-dependent. While young microglia responded to extracellular ATP, an injury-associated signal, by increasing their motility and becoming more ramified, aged microglia exhibited a contrary response, becoming less dynamic and ramified. In response to laser-induced focal tissue injury, aged microglia demonstrated slower acute responses with lower rates of process motility and cellular migration compared to young microglia. Interestingly, the longer term response of disaggregation from the injury site was retarded in aged microglia, indicating that senescent microglial responses, while slower to initiate, are more sustained. Together, these altered features of microglial behavior at rest and following injury reveal an age-dependent dysregulation of immune response in the CNS that may illuminate microglial contributions to age-related neuroinflammatory degeneration. PMID:21108733

  13. Mechanisms of age-related macular degeneration and therapeutic opportunities.

    PubMed

    van Lookeren Campagne, Menno; LeCouter, Jennifer; Yaspan, Brian L; Ye, Weilan

    2014-01-01

    As the age of the population increases in many nations, age-related degenerative diseases pose significant socioeconomic challenges. One of the key degenerative diseases that compromise quality of life is age-related macular degeneration (AMD). AMD is a multi-faceted condition that affects the central retina, which ultimately leads to blindness in millions of people worldwide. The pathophysiology and risk factors for AMD are complex, and the symptoms manifest in multiple related but distinct forms. The ability to develop effective treatments for AMD will depend on a thorough understanding of the underlying pathophysiology, risk factors, and driver molecular pathways, as well as the ability to develop useful animal models. This review provides an overview of the aforementioned aspects in AMD.

  14. Age-related bone loss in the LOU/c rat model of healthy ageing.

    PubMed

    Duque, Gustavo; Rivas, Daniel; Li, Wei; Li, Ailian; Henderson, Janet E; Ferland, Guylaine; Gaudreau, Pierrette

    2009-03-01

    Inbred albino Louvain (LOU) rats are considered a model of healthy aging due to their increased longevity in the absence of obesity and with a low incidence of common age-related diseases. In this study, we characterized the bone phenotype of male and female LOU rats at 4, 20 and 27 months of age using quantitative micro computed tomographic (mCT) imaging, histology and biochemical analysis of circulating bone biomarkers. Bone quality and morphometry of the distal femora, assessed by mCT, was similar in male and female rats at 4 months of age and deteriorated over time. Histochemical staining of undecalcified bone showed a significant reduction in cortical and trabecular bone by 20 months of age. The reduction in mineralized tissue was accompanied by reduced numbers of osteoblasts and osteoclasts and a significant increase in marrow adiposity. Biochemical markers of bone turnover, C-telopeptide and osteocalcin, correlated with the age-related bone loss whereas the calciotropic hormones PTH and vitamin D remained unchanged over time. In summary, aged LOU rats exhibit low-turnover bone loss and marrow fat infiltration, which are the hallmarks of senile osteoporosis, and thus represent a novel model in which to study the molecular mechanisms leading to this disorder.

  15. Age-related changes in cognitive conflict processing: an event-related potential study.

    PubMed

    Mager, Ralph; Bullinger, Alex H; Brand, Serge; Schmidlin, Maria; Schärli, Heinz; Müller-Spahn, Franz; Störmer, Robert; Falkenstein, Michael

    2007-12-01

    Cognitive tasks involving conflicting stimuli and responses are associated with an early age-related decline in performance. Conflict and conflict-induced interference can be stimulus- or response-related. In classical stimulus-response compatibility tasks, such as the Stroop task, the event-related potential (ERP) usually reveals a greater negativity on incongruent versus congruent trials which has often been linked with conflict processing. However, it is unclear whether this negativity is related to stimulus- or response-related conflict, thus rendering the meaning of age-related changes inconclusive. In the present study, a modified Stroop task was used to focus on stimulus-related interference processes while excluding response-related interference. Since we intended to study work-relevant effects ERPs and performance were determined in young (about 30 years old) and middle-aged (about 50 years old) healthy subjects (total n=80). In the ERP, a broad negativity developed after incongruent versus congruent stimuli between 350 and 650 ms. An age-related increase of the latency and amplitude of this negativity was observed. These results indicate age-related alterations in the processing of conflicting stimuli already in middle age.

  16. Parainflammation, chronic inflammation and age-related macular degeneration

    PubMed Central

    Chen, Mei; Xu, Heping

    2016-01-01

    Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune privileged tissue due to its unique anatomical and physiological properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate immune system, particularly microglia and the complement system, undergo low levels of activation (para-inflammation). In many cases, this para-inflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration (AMD), this para-inflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal para-inflammation include genetic predisposition, environmental risk factors and old age. Dysregulated para-inflammation (chronic inflammation) in AMD damages the blood retina barrier (BRB), resulting in the breach of retinal immune privilege leading to the development of retinal lesions. This review discusses the basic principles of retinal innate immune responses to endogenous chronic insults in normal aging and in AMD, and explores the difference between beneficial para-inflammation and the detrimental chronic inflammation in the context of AMD. PMID:26292978

  17. ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases

    PubMed Central

    Davalli, Pierpaola; Mitic, Tijana; Caporali, Andrea; Lauriola, Angela; D'Arca, Domenico

    2016-01-01

    The aging process worsens the human body functions at multiple levels, thus causing its gradual decrease to resist stress, damage, and disease. Besides changes in gene expression and metabolic control, the aging rate has been associated with the production of high levels of Reactive Oxygen Species (ROS) and/or Reactive Nitrosative Species (RNS). Specific increases of ROS level have been demonstrated as potentially critical for induction and maintenance of cell senescence process. Causal connection between ROS, aging, age-related pathologies, and cell senescence is studied intensely. Senescent cells have been proposed as a target for interventions to delay the aging and its related diseases or to improve the diseases treatment. Therapeutic interventions towards senescent cells might allow restoring the health and curing the diseases that share basal processes, rather than curing each disease in separate and symptomatic way. Here, we review observations on ROS ability of inducing cell senescence through novel mechanisms that underpin aging processes. Particular emphasis is addressed to the novel mechanisms of ROS involvement in epigenetic regulation of cell senescence and aging, with the aim to individuate specific pathways, which might promote healthy lifespan and improve aging. PMID:27247702

  18. Surface L-type Ca2+ channel expression levels are increased in aged hippocampus

    PubMed Central

    Núñez-Santana, Félix Luis; Oh, Myongsoo Matthew; Antion, Marcia Diana; Lee, Amy; Hell, Johannes Wilhelm; Disterhoft, John Francis

    2014-01-01

    Age-related increase in L-type Ca2+ channel (LTCC) expression in hippocampal pyramidal neurons has been hypothesized to underlie the increased Ca2+ influx and subsequent reduced intrinsic neuronal excitability of these neurons that lead to age-related cognitive deficits. Here, using specific antibodies against Cav1.2 and Cav1.3 subunits of LTCCs, we systematically re-examined the expression of these proteins in the hippocampus from young (3 to 4 month old) and aged (30 to 32 month old) F344xBN rats. Western blot analysis of the total expression levels revealed significant reductions in both Cav1.2 and Cav1.3 subunits from all three major hippocampal regions of aged rats. Despite the decreases in total expression levels, surface biotinylation experiments revealed significantly higher proportion of expression on the plasma membrane of Cav1.2 in the CA1 and CA3 regions and of Cav1.3 in the CA3 region from aged rats. Furthermore, the surface biotinylation results were supported by immunohistochemical analysis that revealed significant increases in Cav1.2 immunoreactivity in the CA1 and CA3 regions of aged hippocampal pyramidal neurons. In addition, we found a significant increase in the level of phosphorylated Cav1.2 on the plasma membrane in the dentate gyrus of aged rats. Taken together, our present findings strongly suggest that age-related cognitive deficits cannot be attributed to a global change in L-type channel expression nor to the level of phosphorylation of Cav1.2 on the plasma membrane of hippocampal neurons. Rather, increased expression and density of LTCCs on the plasma membrane may underlie the age-related increase in L-type Ca2+ channel activity in CA1 pyramidal neurons. PMID:24033980

  19. Probing a nonequilibrium einstein relation in an aging colloidal glass.

    PubMed

    Abou, Bérengère; Gallet, François

    2004-10-15

    We present a direct experimental measurement of an effective temperature in a colloidal glass of laponite, using a micrometric bead as a thermometer. The nonequilibrium fluctuation-dissipation relation, in the particular form of a modified Einstein relation, is investigated with diffusion and mobility measurements of the bead embedded in the glass. We observe an unusual nonmonotonic behavior of the effective temperature: starting from the bath temperature, it is found to increase up to a maximum value, and then decrease back, as the system ages. We show that the observed deviation from the Einstein relation is related to the relaxation times previously measured in dynamic light scattering experiments.

  20. Introduction to Aging, Cancer, and Age-related Diseases.

    PubMed

    Perry, Daniel P

    2010-06-01

    A rising tide of chronic age-dependent diseases, co-morbidities, and geriatric syndromes--a veritable Silver Tsunami--will soon present serious challenges for North America, Europe, Japan, and other industrialized nations. Meanwhile, a growing number of scientists, led by biogerontologists, maintain that the key to blunting the societal impact of large-scale decline and disability among older populations lies with better understanding and potential manipulation of biological mechanisms of aging itself. Well-characterized interventions that slow aging and extend health and vigor in animal models may be forerunners of technologies that preserve additional years of healthy productive life in humans. What will it take to validate these momentous insights from biogerontology and their potential applications for human populations? What are the points of resistance for key opinion leaders and policy makers? And how can biogerontologists make common cause with those outside the discipline to inform larger and more politically powerful audiences?

  1. Age-related differences in working memory updating components.

    PubMed

    Linares, Rocío; Bajo, M Teresa; Pelegrina, Santiago

    2016-07-01

    The aim of this study was to investigate possible age-related changes throughout childhood and adolescence in different component processes of working memory updating (WMU): retrieval, transformation, and substitution. A set of numerical WMU tasks was administered to four age groups (8-, 11-, 14-, and 21-year-olds). To isolate the effect of each of the WMU components, participants performed different versions of a task that included different combinations of the WMU components. The results showed an expected overall decrease in response times and an increase in accuracy performance with age. Most important, specific age-related changes in the retrieval component were found, demonstrating that the effect of retrieval on accuracy was larger in children than in adolescents or young adults. These findings indicate that the availability of representations from outside the focus of attention may change with age. Thus, the retrieval component of updating could contribute to the age-related changes observed in the performance of many updating tasks.

  2. Amniotic Epithelial Cells: A New Tool to Combat Aging and Age-Related Diseases?

    PubMed Central

    Di Germanio, Clara; Bernier, Michel; de Cabo, Rafael; Barboni, Barbara

    2016-01-01

    The number of elderly people is growing at an unprecedented rate and this increase of the aging population is expected to have a direct impact on the incidence of age-related diseases and healthcare-associated costs. Thus, it is imperative that new tools are developed to fight and slow age-related diseases. Regenerative medicine is a promising strategy for the maintenance of health and function late in life; however, stem cell-based therapies face several challenges including rejection and tumor transformation. As an alternative, the placenta offers an extraordinary source of fetal stem cells, including the amniotic epithelial cells (AECs), which retain some of the characteristics of embryonic stem cells, but show low immunogenicity, together with immunomodulatory and anti-inflammatory activities. Because of these characteristics, AECs have been widely utilized in regenerative medicine. This perspective highlights different mechanisms triggered by transplanted AECs that could be potentially useful for anti-aging therapies, which include: Graft and differentiation for tissue regeneration in age-related settings, anti-inflammatory behavior to combat “inflammaging,” anti-tumor activity, direct lifespan and healthspan extension properties, and possibly rejuvenation in a manner reminiscent of heterochronic parabiosis. Here, we critically discuss benefits and limitation of AECs-based therapies in age-related diseases. PMID:27921031

  3. Increased human AP endonuclease 1 level confers protection against the paternal age effect in mice

    PubMed Central

    Sanchez, Jamila R.; Reddick, Traci L.; Perez, Marissa; Centonze, Victoria E.; Mitra, Sankar; Izumi, Tadahide; McMahan, C. Alex; Walter, Christi A.

    2015-01-01

    Increased paternal age is associated with a greater risk of producing children with genetic disorders originating from de novo germline mutations. Mice mimic the human condition by displaying an age-associated increase in spontaneous mutant frequency in spermatogenic cells. The observed increase in mutant frequency appears to be associated with a decrease in the DNA repair protein, AP endonuclease1 (APEX1) and Apex1 heterozygous mice display an accelerated paternal age effect as young adults. In this study, we directly tested if APEX1 over-expression in cell lines and transgenic mice could prevent increases in mutagenesis. Cell lines with ectopic expression of APEX1 had increased APEX1 activity and lower spontaneous and induced mutations in the lacI reporter gene relative to the control. Spermatogenic cells obtained from mice transgenic for human APEX1 displayed increased APEX1 activity, were protected from the age-dependent increase in spontaneous germline mutagenesis, and exhibited increased apoptosis in the spermatogonial cell population. These results directly indicate that increases in APEX1 level confer protection against the murine paternal age effect, thus highlighting the role of APEX1 in preserving reproductive health with increasing age and in protection against genotoxin-induced mutagenesis in somatic cells. PMID:26201249

  4. Age related prolactin secretion in men after fentanyl anaesthesia.

    PubMed

    Aliberti, Giuseppe; Pulignano, Isabella; Schiappoli, Angelo; Cigognetti, Leonilde; Tritapepe, Luigi; Proietta, Maria

    2002-01-01

    The aim of this study was to investigate the role of age in the hormonal response to opiate anaesthetic fentanyl. In 90 patients undergoing aortocoronary bypass, 59.6 +/- 9.2 years mean age, 35-81 age range, prolactin (PRL), thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH), luteinizing hormone (LH), human growth hormone (HGH), insulin-like growth factor I (IGF I), glucagon and insulin were measured in venous blood samples drawn from fasting patients immediately before, at 8 h in the morning, and 60 min after the induction of anaesthesia with 30 microg/kg intravenous fentanyl bolus, 30 min after a second 7 microg/kg fentanyl bolus. Results showed a higher 60 min PRL peak in older, >65 years, in respect to younger, < or =50 years, patients (57.6 +/- 23.3 vs. 40.6 +/- 13.8 microg/l, P<0.005), with a significant upward trend with age across the entire age span (r=0.32; P<0.002), while no difference by age was found for the basal concentrations. No differences were found between the respective basal and 60 min concentrations for the other hormones investigated. As expected, differences by age were found for FSH, higher in >65 and in 51-65-year-olds than in younger patients (for the basal values, respectively, P<0.02 and P<0.05); IGF I was lower in >65 in respect to < or =50 (P<0.02) and to 51-65-year-old patients (P<0.05), with a significant negative correlation with age (r=-0.33; P<0.005). The study shows an age related increase of PRL concentrations after fentanyl administration. It may be due to the reduction of the hypothalamic dopaminergic tone with aging. IGF I levels have been confirmed to be inversely correlated with age.

  5. Developments in age-related macular degeneration: Diagnosis and treatment.

    PubMed

    Kaufman, Steven R

    2009-03-01

    Age-related macular degeneration (ARMD) is the leading cause of legal blindness of Americans over age 65 years. Severe loss of vision is usually due to exudative ARMD, of which there are about 200,000 new cases in the United States annually. Until recently, only a small fraction of patients benefited from treatment, but advances in the early diagnosis of the disease and major developments in therapy have substantially improved the prognosis of patients with ARMD. Because visual loss substantially reduces quality of life, effective management of ARMD will have increasing public health importance as the population ages. The American Academy of Ophthalmology recommends that people over age 65 years should have a comprehensive eye examination every 1 to 2 years to check for cataracts, macular degeneration, glaucoma, and other conditions. Those who complain of difficulty reading, driving at night, or adapting from sunlight to indoor lighting might have macular degeneration.

  6. Age-related changes in wavelength discrimination

    PubMed Central

    Shinomori, Keizo; Schefrin, Brooke E.; Werner, John S.

    2008-01-01

    Wavelength discrimination functions (420 to 620–650 nm) were measured for four younger (mean 30.9 years) and four older (mean 72.5 years) observers. Stimuli consisted of individually determined isoluminant monochromatic lights (10 Td) presented in each half of a 2° circular bipartite field with use of a Maxwellian-view optical system. A spatial two-alternative forced-choice method was used in combination with a staircase procedure to determine discrimination thresholds across the spectrum. Small but consistent elevations in discrimination thresholds were found for older compared with younger observers. Because the retinal illuminance of the stimuli was equated across all observers, these age-related losses in discrimination are attributable to neural changes. Analyses of these data reveal a significant change in Weber fraction across adulthood for a chromatically opponent pathway receiving primarily antagonistic signals from middle-wavelength-sensitive and long-wavelength-sensitive cones but not for a short-wavelength-sensitive cone pathway. PMID:11205976

  7. Association of Age Related Macular Degeneration and Age Related Hearing Impairment

    PubMed Central

    Ghasemi, Hassan; Pourakbari, Malihe Shahidi; Entezari, Morteza; Yarmohammadi, Mohammad Ebrahim

    2016-01-01

    Purpose: To evaluate the association between age-related macular degeneration (ARMD) and sensory neural hearing impairment (SHI). Methods: In this case-control study, hearing status of 46 consecutive patients with ARMD were compared with 46 age-matched cases without clinical ARMD as a control group. In all patients, retinal involvements were confirmed by clinical examination, fluorescein angiography (FA) and optical coherence tomography (OCT). All participants were examined with an otoscope and underwent audiological tests including pure tone audiometry (PTA), speech reception threshold (SRT), speech discrimination score (SDS), tympanometry, reflex tests and auditory brainstem response (ABR). Results: A significant (P = 0.009) association was present between ARMD, especially with exudative and choroidal neovascularization (CNV) components, and age-related hearing impairment primarily involving high frequencies. Patients had higher SRT and lower SDS against anticipated presbycusis than control subjects. Similar results were detected in exudative, CNV and scar patterns supporting an association between late ARMD with SRT and SDS abnormalities. ABR showed significantly prolonged wave I and IV latency times in ARMD (P = 0.034 and 0.022, respectively). Average latency periods for wave I in geographic atrophy (GA) and CNV, and that for wave IV in drusen patterns of ARMD were significantly higher than controls (P = 0.030, 0.007 and 0.050, respectively). Conclusion: The association between ARMD and age-related SHI may be attributed to common anatomical components such as melanin in these two sensory organs. PMID:27195086

  8. Neuroanatomical Substrates of Age-Related Cognitive Decline

    ERIC Educational Resources Information Center

    Salthouse, Timothy A.

    2011-01-01

    There are many reports of relations between age and cognitive variables and of relations between age and variables representing different aspects of brain structure and a few reports of relations between brain structure variables and cognitive variables. These findings have sometimes led to inferences that the age-related brain changes cause the…

  9. Gadd45 proteins: Relevance to aging, longevity and age-related pathologies

    PubMed Central

    Moskalev, Alexey A.; Smit-McBride, Zeljka; Shaposhnikov, Mikhail V.; Plyusnina, Ekaterina N.; Zhavoronkov, Alex; Budovsky, Arie; Tacutu, Robi; Fraifeld, Vadim E.

    2013-01-01

    The Gadd45 proteins have been intensively studied, in view of their important role in key cellular processes. Indeed, the Gadd45 proteins stand at the crossroad of the cell fates by controlling the balance between cell (DNA) repair, eliminating (apoptosis) or preventing the expansion of potentially dangerous cells (cell cycle arrest, cellular senescence), and maintaining the stem cell pool. However, the biogerontological aspects have not thus far received sufficient attention. Here we analyzed the pathways and modes of action by which Gadd45 members are involved in aging, longevity and age-related diseases. Because of their pleiotropic action, a decreased inducibility of Gadd45 members may have far-reaching consequences including genome instability, accumulation of DNA damage, and disorders in cellular homeostasis – all of which may eventually contribute to the aging process and age-related disorders (promotion of tumorigenesis, immune disorders, insulin resistance and reduced responsiveness to stress). Most recently, the dGadd45 gene has been identified as a longevity regulator in Drosophila. Although further wide-scale research is warranted, it is becoming increasingly clear that Gadd45s are highly relevant to aging, age-related diseases (ARDs) and to the control of life span, suggesting them as potential therapeutic targets in ARDs and pro-longevity interventions. PMID:21986581

  10. Effect of NCAM on aged-related deterioration in vision.

    PubMed

    Luke, Margaret Po-Shan; LeVatte, Terry L; O'Reilly, Amanda M; Smith, Benjamin J; Tremblay, François; Brown, Richard E; Clarke, David B

    2016-05-01

    The neural cell adhesion molecule (NCAM) is involved in developmental processes and age-associated cognitive decline; however, little is known concerning the effects of NCAM in the visual system during aging. Using anatomical, electrophysiological, and behavioral assays, we analyzed age-related changes in visual function of NCAM deficient (-/-) and wild-type mice. Anatomical analyses indicated that aging NCAM -/- mice had fewer retinal ganglion cells, thinner retinas, and fewer photoreceptor cell layers than age-matched controls. Electroretinogram testing of retinal function in young adult NCAM -/- mice showed a 2-fold increase in a- and b-wave amplitude compared with wild-type mice, but the retinal activity dropped dramatically to control levels when the animals reached 10 months. In behavioral tasks, NCAM -/- mice had no visual pattern discrimination ability and showed premature loss of vision as they aged. Together, these findings demonstrate that NCAM plays significant roles in the adult visual system in establishing normal retinal anatomy, physiology and function, and in maintaining vision during aging.

  11. Cold hardiness increases with age in juvenile Rhododendron populations

    PubMed Central

    Lim, Chon-Chong; Krebs, Stephen L.; Arora, Rajeev

    2014-01-01

    Winter survival in woody plants is controlled by environmental and genetic factors that affect the plant’s ability to cold acclimate. Because woody perennials are long-lived and often have a prolonged juvenile (pre-flowering) phase, it is conceivable that both chronological and physiological age factors influence adaptive traits such as stress tolerance. This study investigated annual cold hardiness (CH) changes in several hybrid Rhododendron populations based on Tmax, an estimate of the maximum rate of freezing injury (ion leakage) in cold-acclimated leaves from juvenile progeny. Data from F2 and backcross populations derived from R. catawbiense and R. fortunei parents indicated significant annual increases in Tmax ranging from 3.7 to 6.4°C as the seedlings aged from 3 to 5 years old. A similar yearly increase (6.7°C) was observed in comparisons of 1- and 2-year-old F1 progenies from a R. catawbiense × R. dichroanthum cross. In contrast, CH of the mature parent plants (>10 years old) did not change significantly over the same evaluation period. In leaf samples from a natural population of R. maximum, CH evaluations over 2 years resulted in an average Tmax value for juvenile 2- to 3-year-old plants that was 9.2°C lower than the average for mature (~30 years old) plants. A reduction in CH was also observed in three hybrid rhododendron cultivars clonally propagated by rooted cuttings (ramets)—Tmax of 4-year-old ramets was significantly lower than the Tmax estimates for the 30- to 40-year-old source plants (ortets). In both the wild R. maximum population and the hybrid cultivar group, higher accumulation of a cold-acclimation responsive 25 kDa leaf dehydrin was associated with older plants and higher CH. The feasibility of identifying hardy phenotypes at juvenile period and research implications of age-dependent changes in CH are discussed. PMID:25360138

  12. Divergent Thinking and Age-Related Changes

    ERIC Educational Resources Information Center

    Palmiero, Massimiliano; Di Giacomo, Dina; Passafiume, Domenico

    2014-01-01

    Aging can affect cognition in different ways. The extent to which aging affects divergent thinking is unclear. In this study, younger and older adults were compared at the performance on the Torrance Test of Creative Thinking in visual and verbal form. Results showed that older adults can think divergently as younger participants, although they…

  13. Innate immunity and inflammation in ageing: a key for understanding age-related diseases

    PubMed Central

    Licastro, Federico; Candore, Giuseppina; Lio, Domenico; Porcellini, Elisa; Colonna-Romano, Giuseppina; Franceschi, Claudio; Caruso, Calogero

    2005-01-01

    The process of maintaining life for the individual is a constant struggle to preserve his/her integrity. This can come at a price when immunity is involved, namely systemic inflammation. Inflammation is not per se a negative phenomenon: it is the response of the immune system to the invasion of viruses or bacteria and other pathogens. During evolution the human organism was set to live 40 or 50 years; today, however, the immune system must remain active for much a longer time. This very long activity leads to a chronic inflammation that slowly but inexorably damages one or several organs: this is a typical phenomenon linked to ageing and it is considered the major risk factor for age-related chronic diseases. Alzheimer's disease, atherosclerosis, diabetes and even sarcopenia and cancer, just to mention a few – have an important inflammatory component, though disease progression seems also dependent on the genetic background of individuals. Emerging evidence suggests that pro-inflammatory genotypes are related to unsuccessful ageing, and, reciprocally, controlling inflammatory status may allow a better chance of successful ageing. In other words, age-related diseases are "the price we pay" for a life-long active immune system: this system has also the potential to harm us later, as its fine tuning becomes compromised. Our immune system has evolved to control pathogens, so pro-inflammatory responses are likely to be evolutionarily programmed to resist fatal infections with pathogens aggressively. Thus, inflammatory genotypes are an important and necessary part of the normal host responses to pathogens in early life, but the overproduction of inflammatory molecules might also cause immune-related inflammatory diseases and eventually death later. Therefore, low responder genotypes involved in regulation of innate defence mechanisms, might better control inflammatory responses and age-related disease development, resulting in an increased chance of long life survival

  14. Increasing Body Mass Index Is Inversely Related to Groin Hernias.

    PubMed

    Ravanbakhsh, Samine; Batech, Michael; Tejirian, Talar

    2015-10-01

    Few studies describe the relationship between obesity and groin hernias. Our objective was to investigate the correlation between body mass index (BMI) and groin hernias in a large population. Patients with the diagnosis of inguinal or femoral hernia with and without incarceration or strangulation were identified using the Kaiser Permanente Southern California regional database including 14 hospitals over a 7-year period. Patients were stratified by BMI. There were 47,950 patients with a diagnosis of a groin hernia--a prevalence of 2.28 per cent. Relative to normal BMI (20-24.9 kg/m(2)), lower BMI was associated with an increased risk for hernia diagnosis. With increasing BMI, the risk of incarceration or strangulation increased. Additionally, increasing age, male gender, white race, history of hernia, tobacco use history, alcohol use, and higher comorbidity index increased the chance of a groin hernia diagnosis. Complications were higher for women, patients with comorbidities, black race, and alcohol users. Our study is the largest to date correlating obesity and groin hernias in a diverse United States population. Obesity (BMI ≥ 30 kg/m(2)) is associated with a lower risk of groin hernia diagnosis, but an increased risk of complications. This inverse relationship may be due to limitations of physical exam in obese patients.

  15. Elevated Mutagenesis Does Not Explain the Increased Frequency of Antibiotic Resistant Mutants in Starved Aging Colonies

    PubMed Central

    Katz, Sophia; Hershberg, Ruth

    2013-01-01

    The frequency of mutants resistant to the antibiotic rifampicin has been shown to increase in aging (starved), compared to young colonies of Eschierchia coli. These increases in resistance frequency occur in the absence of any antibiotic exposure, and similar increases have also been observed in response to additional growth limiting conditions. Understanding the causes of such increases in the frequency of resistance is important for understanding the dynamics of antibiotic resistance emergence and spread. Increased frequency of rifampicin resistant mutants in aging colonies is cited widely as evidence of stress-induced mutagenesis (SIM), a mechanism thought to allow bacteria to increase mutation rates upon exposure to growth-limiting stresses. At the same time it has been demonstrated that some rifampicin resistant mutants are relatively fitter in aging compared to young colonies, indicating that natural selection may also contribute to increased frequency of rifampicin resistance in aging colonies. Here, we demonstrate that the frequency of mutants resistant to both rifampicin and an additional antibiotic (nalidixic-acid) significantly increases in aging compared to young colonies of a lab strain of Escherichia coli. We then use whole genome sequencing to demonstrate conclusively that SIM cannot explain the observed magnitude of increased frequency of resistance to these two antibiotics. We further demonstrate that, as was previously shown for rifampicin resistance mutations, mutations conferring nalidixic acid resistance can also increase fitness in aging compared to young colonies. Our results show that increases in the frequency of antibiotic resistant mutants in aging colonies cannot be seen as evidence of SIM. Furthermore, they demonstrate that natural selection likely contributes to increases in the frequency of certain antibiotic resistance mutations, even when no selection is exerted due to the presence of antibiotics. PMID:24244205

  16. Aging Changes in Retinal Microglia and their Relevance to Age-related Retinal Disease.

    PubMed

    Ma, Wenxin; Wong, Wai T

    2016-01-01

    Age-related retinal diseases, such as age-related macular degeneration (AMD) and glaucoma, contain features of chronic retinal inflammation that may promote disease progression. However, the relationship between aging and neuroinflammation is unclear. Microglia are long-lived, resident immune cells of the retina, and mediate local neuroinflammatory reactions. We hypothesize that aging changes in microglia may be causally linked to neuroinflammatory changes underlying age-dependent retinal diseases. Here, we review the evidence for (1) how the retinal microglial phenotype changes with aging, (2) the factors that drive microglial aging in the retina, and (3) aging-related changes in microglial gene expression. We examine how these aspects of microglial aging changes may relate to pathogenic mechanisms of immune dysregulation driving the progression of age-related retinal disease. These relationships can highlight microglial aging as a novel target for the prevention and treatment of retinal disease.

  17. 8 Areas of Age-Related Change

    MedlinePlus

    ... please turn Javascript on. Photo: PhotoDisc 1. Brain: Memory and Alzheimer's Disease (AD) As adults age, many ... Researchers from 12 institutions, including the NIH's National Human Genome Research Institute (NHGRI), recently announced the results ...

  18. Age-related elemental change in bones

    NASA Astrophysics Data System (ADS)

    Wang, C.; Eisa, M. H.; Jin, W.; Shen, H.; Mi, Y.; Gao, J.; Zhou, Y.; Yao, H.; Zhao, Y.

    2008-04-01

    To investigate age dependence of the bone element contents and structure, lumbar and femur from Sprague-Dawley (SD) rats were chosen for their more susceptibility to fracture. These rats were divided into to 5 age groups: 1, 4, 7, 11 and 25 month-age, corresponding human beings from the young to the old. The elements contents were detected by external Proton Induced X-ray emission (PIXE) technique. X-ray Absorption Fine Structure (XAFS) method was also applied to obtain information about calcium (Ca) and phosphor (P) structure. It was found that Ca content, Ca/P ratio, valance state of Ca and P and their coordinate structure remains unaltered with age variance, whereas the content of strontium (Sr) was significantly decreasing. Sr concentration may provide a new parameter for diagnosis of bone disorder.

  19. Effect of age increase on metabolism and toxicity of ethanol in female rats.

    PubMed

    Kim, Young C; Kim, Sung Y; Sohn, Young R

    2003-12-12

    Age-dependent change in the effects of acute ethanol administration on female rat liver was investigated. Female Sprague-Dawley rats, each aged 4, 12, or 50 weeks, received ethanol (2 g/kg) via a catheter inserted into a jugular vein. Ethanol elimination rate (EER), most rapid in the 4 weeks old rats, was decreased as the age advanced. Hepatic alcohol dehydrogenase activity was not altered by age, but microsomal p-nitrophenol hydroxylase activity was significantly greater in the 4 weeks old rats. Relative liver weight decreased with age increase in proportion to reduction of EER. Hepatic triglyceride and malondialdehyde concentrations increased spontaneously in the 50 weeks old nai;ve rats. Ethanol administration (3 g/kg, ip) elevated malondialdehyde and triglyceride contents only in the 4 and the 12 weeks old rats. Hepatic glutathione concentration was increasingly reduced by ethanol with age increase. Ethanol decreased cysteine concentration in the 4 weeks old rats, but elevated it significantly in the older rats. Inhibition of gamma-glutamylcysteine synthetase activity by ethanol was greater with age increase, which appeared to be responsible for the increase in hepatic cysteine. The results indicate that age does not affect the ethanol metabolizing capacity of female rat liver, but the overall ethanol metabolism is decreased in accordance with the reduction of relative liver size. Accordingly induction of acute alcoholic fatty liver is less significant in the old rats. However, progressively greater depletion of glutathione by ethanol in older rats suggests that susceptibility of liver to oxidative damage would be increased as animals grow old.

  20. Relative Age Effect in Masters Sports: Replication and Extension

    ERIC Educational Resources Information Center

    Medic, Nikola; Starkes, Janet L.; Weir, Patricia L.; Young, Bradley W.; Grove, J. Robert

    2009-01-01

    The relative age effect refers to the performance-related advantage of being born early in a cohort or selection year. Until recently it was unknown whether the relative age effect generalizes across the lifespan. Medic, Starkes, and Young (2007) reasoned that the 5-year age categories that are widely used in masters-level sports to organize…

  1. THE ENERGY-REDOX AXIS IN AGING AND AGE-RELATED NEURODEGENERATION

    PubMed Central

    Yap, Li-Peng; Garcia, Jerome V.; Han, Derick; Cadenas, Enrique

    2009-01-01

    Decrease in mitochondrial energy-transducing capacity is a feature of the aging process that accompanies redox alterations, such as increased generation of mitochondrial oxidants, altered GSH status, and increased protein oxidation. The decrease in mitochondrial energy-transducing capacity and altered redox status should be viewed as a concerted process that embodies the mitochondrial energy – redox axis and is linked through various mechanisms including: (a) an inter-convertible reducing equivalents pool (i.e., NAD(P)+/NAD(P)H) and (b) redox-mediated protein post-translational modifications involved in energy metabolism. The energy–redox axis provides the rationale for therapeutic approaches targeted to each or both component(s) of the axis that effectively preserves or improve mitochondrial function and that have implications for aging and age-related neurodegenerative disorders. PMID:19716388

  2. Increases of M2a macrophages and fibrosis in aging muscle are influenced by bone marrow aging and negatively regulated by muscle-derived nitric oxide.

    PubMed

    Wang, Ying; Wehling-Henricks, Michelle; Samengo, Giuseppina; Tidball, James G

    2015-08-01

    Muscle aging is associated with changes in myeloid cell phenotype that may influence age-related changes in muscle structure. We tested whether preventing age-related reductions in muscle neuronal nitric oxide synthase (nNOS) would obviate age-related changes in myeloid cells in muscle. Our findings show that muscle aging is associated with elevations of anti-inflammatory M2a macrophages that can increase muscle fibrosis. Expression of a muscle-specific nNOS transgene in mice prevented age-related increases in M2a macrophages. Transgene expression also reduced expression of collagens and decreased muscle fibrosis. The nNOS transgene prevented age-related increases in arginase-1 but did not influence TGFβ expression, indicating that the transgene may prevent age-related muscle fibrosis by inhibiting the arginase-dependent profibrotic pathway. Although aged satellite cells or fibro-adipogenic precursor (FAPs) cells also promote fibrosis, transgene expression had no effect on the expression of key signaling molecules that regulate fibrogenic activity of those cells. Finally, we tested whether increases in M2a macrophages and the associated increase in fibrosis were attributable to aging of myeloid lineage cells. Young bone marrow cells (BMCs) were transplanted into young or old mice, and muscles were collected 8 months later. Muscles of young mice receiving young BMCs showed no effect on M2a macrophage number or collagen accumulation compared to age-matched, nontransplanted controls. However, muscles of old mice receiving young BMCs showed fewer M2a macrophages and less accumulation of collagen. Thus, the age-related increase in M2a macrophages in aging muscle and the associated muscle fibrosis are determined in part by the age of bone marrow cells.

  3. Bodacious Berry, Potency Wood and the Aging Monster: Gender and Age Relations in Anti-Aging Ads

    ERIC Educational Resources Information Center

    Calasanti, Toni

    2007-01-01

    This paper situates age discrimination within a broader system of age relations that intersects with other inequalities, and then uses that framework to analyze internet advertisements for the anti-aging industry. Such ads reinforce age and gender relations by positing old people as worthwhile only to the extent that they look and act like those…

  4. Aging Chart: a community resource for rapid exploratory pathway analysis of age-related processes

    PubMed Central

    Moskalev, Alexey; Zhikrivetskaya, Svetlana; Shaposhnikov, Mikhail; Dobrovolskaya, Evgenia; Gurinovich, Roman; Kuryan, Oleg; Pashuk, Aleksandr; Jellen, Leslie C.; Aliper, Alex; Peregudov, Alex; Zhavoronkov, Alex

    2016-01-01

    Aging research is a multi-disciplinary field encompassing knowledge from many areas of basic, applied and clinical research. Age-related processes occur on molecular, cellular, tissue, organ, system, organismal and even psychological levels, trigger the onset of multiple debilitating diseases and lead to a loss of function, and there is a need for a unified knowledge repository designed to track, analyze and visualize the cause and effect relationships and interactions between the many elements and processes on all levels. Aging Chart (http://agingchart.org/) is a new, community-curated collection of aging pathways and knowledge that provides a platform for rapid exploratory analysis. Building on an initial content base constructed by a team of experts from peer-reviewed literature, users can integrate new data into biological pathway diagrams for a visible, intuitive, top-down framework of aging processes that fosters knowledge-building and collaboration. As the body of knowledge in aging research is rapidly increasing, an open visual encyclopedia of aging processes will be useful to both the new entrants and experts in the field. PMID:26602690

  5. Age-related differences in recovery from simulated jet lag.

    PubMed

    Moline, M L; Pollak, C P; Monk, T H; Lester, L S; Wagner, D R; Zendell, S M; Graeber, R C; Salter, C A; Hirsch, E

    1992-02-01

    Six healthy young men and eight early middle-aged men were isolated from environmental time cues for 15 days. For the first 6-7 days (one or two nights adaptation, four nights baseline), their sleep and meals were scheduled to approximate their habitual patterns. Their daily routines were then shifted 6 hours earlier by terminating the sixth or seventh sleep episode 6 hours early. The new schedules were followed for the next 8 or 9 days. Important age-related differences in adjustment to this single 6-hour schedule shift were found. For the first 4-day interval after the shift, middle-aged subjects had larger increases of waking time during the sleep period and earlier termination of sleep than young subjects. They also reported larger decreases in alertness and well-being and larger increases in sleepiness, weariness and effort required to perform daily functions. The rate of adjustment of the circadian core temperature rhythm to the new schedule did not differ between groups. These results suggest that the symptoms reported by the middle-aged subjects may be due mainly to difficulty maintaining sleep at early times of the circadian day. The compensatory response to sleep deprivation may also be less robust in middle-aged individuals traveling eastbound.

  6. Thyroid function and aging: gender-related differences.

    PubMed

    da Costa, V M; Moreira, D G; Rosenthal, D

    2001-10-01

    The effects of aging on human or animal thyroid function are still not well defined. We evaluated some aspects of thyroid function during aging using an animal model (young and old Dutch-Miranda rats). In old rats of both genders, serum thyroxine (T4) decreased but serum thyrotrophin (TSH) remained unaltered, suggesting a disturbance in the pituitary-thyroid feedback mechanism during aging. Serum tri-iodothyronine (T3) only decreased in old males, possibly because female rats are almost twice as efficient in hepatic T4 to T3 deiodination. Thyroidal T4-5'-deiodinase activity did not change much during aging, although it decreased slightly in males. Thyroidal iodothyronine-deiodinase type I mRNA expression but not total thyroidal enzymatic activity were higher in female than in male rats. Thus, ovarian/testicular hormones may modulate the expression and/or the activity of hepatic and thyroidal type I iodothyronine-deiodinase. Thyroperoxidase (TPO) and thyroglobulin (Tg) expression were higher in young male rats than in females. In males, TPO and Tg gene expression decreased with aging, suggesting that androgens might increase their expression. Our results showed that aging induces real changes in rat thyroid gland function and regulation, affecting at least pituitary, thyroid and liver functions. Furthermore, some of these changes were gender related, indicating that gonadal hormones may modulate thyroid gland function and regulation.

  7. Effects of Age-Related Macular Degeneration on Postural Sway

    PubMed Central

    Chatard, Hortense; Tepenier, Laure; Jankowski, Olivier; Aussems, Antoine; Allieta, Alain; Beydoun, Talal; Salah, Sawsen; Bucci, Maria P.

    2017-01-01

    Purpose: To compare the impact of unilateral vs. bilateral age-related macular degeneration (AMD) on postural sway, and the influence of different visual conditions. The hypothesis of our study was that the impact of AMD will be different between unilateral and bilateral AMD subjects compared to age-matched healthy elderly. Methods: Postural stability was measured with a platform (TechnoConcept®) in 10 elderly unilateral AMD subjects (mean age: 71.1 ± 4.6 years), 10 elderly bilateral AMD subjects (mean age: 70.8 ± 6.1 years), and 10 healthy age-matched control subjects (mean age: 69.8 ± 6.3 years). Four visual conditions were tested: both eyes viewing condition (BEV), dominant eye viewing (DEV), non-dominant eye viewing (NDEV), and eyes closed (EC). We analyzed the surface area, the length, the mean speed, the anteroposterior (AP), and mediolateral (ML) displacement of the center of pressure (CoP). Results: Bilateral AMD subjects had a surface area (p < 0.05) and AP displacement of the CoP (p < 0.01) higher than healthy elderly. Unilateral AMD subjects had more AP displacement of the CoP (p < 0.05) than healthy elderly. Conclusions: We suggest that ADM subjects could have poor postural adaptive mechanisms leading to increase their postural instability. Further studies will aim to improve knowledge on such issue and to develop reeducation techniques in these patients.

  8. Statins for age-related macular degeneration

    PubMed Central

    Gehlbach, Peter; Li, Tianjing; Hatef, Elham

    2016-01-01

    Background Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries. Recent epidemiologic, genetic, and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. Objectives The objective of this review was to examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and progression of AMD. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2014), EMBASE (January 1980 to June 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to June 2014), PubMed (January 1946 to June 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 June 2014. Selection criteria We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Two authors independently evaluated the search results against the selection criteria, abstracted data, and assessed risk of bias. We did not perform meta-analysis due to heterogeneity in the interventions and outcomes among the

  9. The relevance of aging-related changes in brain function to rehabilitation in aging-related disease

    PubMed Central

    Crosson, Bruce; McGregor, Keith M.; Nocera, Joe R.; Drucker, Jonathan H.; Tran, Stella M.; Butler, Andrew J.

    2015-01-01

    The effects of aging on rehabilitation of aging-related diseases are rarely a design consideration in rehabilitation research. In this brief review we present strong coincidental evidence from these two fields suggesting that deficits in aging-related disease or injury are compounded by the interaction between aging-related brain changes and disease-related brain changes. Specifically, we hypothesize that some aphasia, motor, and neglect treatments using repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in stroke patients may address the aging side of this interaction. The importance of testing this hypothesis and addressing the larger aging by aging-related disease interaction is discussed. Underlying mechanisms in aging that most likely are relevant to rehabilitation of aging-related diseases also are covered. PMID:26074807

  10. The role of epigenetics in age-related macular degeneration.

    PubMed

    Gemenetzi, M; Lotery, A J

    2014-12-01

    It is becoming increasingly evident that epigenetic mechanisms influence gene expression and can explain how interactions between genetics and the environment result in particular phenotypes during development. The extent to which this epigenetic effect contributes to phenotype heritability in age-related macular degeneration (AMD) is currently ill defined. However, emerging evidence suggests that epigenetic changes are relevant to AMD and as such provide an exciting new avenue of research for AMD. This review addresses information on the impact of posttranslational modification of the genome on the pathogenesis of AMD, such as DNA methylation changes affecting antioxidant gene expression, hypoxia-regulated alterations in chromatin structure, and histone acetylation status in relation to angiogenesis and inflammation. It also contains information on the role of non-coding RNA-mediated gene regulation in AMD at a posttranscriptional (before translation) level. Our aim was to review the epigenetic mechanisms that cause heritable changes in gene activity without changing the DNA sequence. We also describe some long-term alterations in the transcriptional potential of a cell, which are not necessarily heritable but remains to be defined in the future. Increasing understanding of the significance of common and rare genetic variants and their relationship to epigenetics and environmental influences may help in establishing methods to assess the risk of AMD. This in turn may allow new therapeutic interventions for the leading cause of central vision impairment in patients over the age of 50 years in developed countries. Search strategy We searched the MEDLINE/PubMed database following MeSH suggestions for articles including the terms: 'ocular epigenetic mechanisms', 'human disease epigenetics', and 'age-related macular degeneration genetics'. The headline used to locate related articles in PubMed was 'epigenetics in ocular disease', and to restrict search, we used the

  11. Preferential retrotransposition in aging yeast mother cells is correlated with increased genome instability.

    PubMed

    Patterson, Melissa N; Scannapieco, Alison E; Au, Pak Ho; Dorsey, Savanna; Royer, Catherine A; Maxwell, Patrick H

    2015-10-01

    Retrotransposon expression or mobility is increased with age in multiple species and could promote genome instability or altered gene expression during aging. However, it is unclear whether activation of retrotransposons during aging is an indirect result of global changes in chromatin and gene regulation or a result of retrotransposon-specific mechanisms. Retromobility of a marked chromosomal Ty1 retrotransposon in Saccharomyces cerevisiae was elevated in mother cells relative to their daughter cells, as determined by magnetic cell sorting of mothers and daughters. Retromobility frequencies in aging mother cells were significantly higher than those predicted by cell age and the rate of mobility in young populations, beginning when mother cells were only several generations old. New Ty1 insertions in aging mothers were more strongly correlated with gross chromosome rearrangements than in young cells and were more often at non-preferred target sites. Mother cells were more likely to have high concentrations and bright foci of Ty1 Gag-GFP than their daughter cells. Levels of extrachromosomal Ty1 cDNA were also significantly higher in aged mother cell populations than their daughter cell populations. These observations are consistent with a retrotransposon-specific mechanism that causes retrotransposition to occur preferentially in yeast mother cells as they begin to age, as opposed to activation by phenotypic changes associated with very old age. These findings will likely be relevant for understanding retrotransposons and aging in many organisms, based on similarities in regulation and consequences of retrotransposition in diverse species.

  12. Increased Risk of Dementia Among Sleep-Related Movement Disorders

    PubMed Central

    Lin, Chun-Chieh; Chou, Chung-Hsing; Fan, Yu-Ming; Yin, Jiu-Haw; Chung, Chi-Hsiang; Chien, Wu-Chien; Sung, Yueh-Feng; Tsai, Chia-Kuang; Lin, Guan-Yu; Lin, Yu-Kai; Lee, Jiunn-Tay

    2015-01-01

    Abstract Sleep-related movement disorders (SRMD) are sleep disorders. As poor sleep quality is associated with cognitive impairment, we hypothesized that SRMD patients were exposed to a great risk for developing dementia. The present study was aimed to retrospectively examine the association of SRMD and dementia risk. A retrospective longitudinal study was conducted using the data obtained from the Longitudinal Health Insurance Database (LHID) in Taiwan. The study cohort enrolled 604 patients with SRMD who were initially diagnosed and 2416 patients who were randomly selected and age/gender matched with the study group. SRMD, dementia, and other confounding factors were defined according to International Classification of Diseases Clinical Modification Codes. Cox proportional-hazards regressions were employed to examine adjusted hazard ratios (HR) after adjusting with confounding factors. Our data revealed that patients with SRMD had a 3.952 times (95% CI = 1.124–4.767) higher risk to develop all-cause dementia compared with individuals without SRMD. The results showed that SRMD patients aged 45 to 64 exhibited highest risk of developing all-cause dementia (HR: 5.320, 95% CI = 1.770–5.991), followed by patients age ≥65 (HR: 4.123, 95% CI = 2.066–6.972) and <45 (HR: 3.170, 95% CI = 1.050–4.128), respectively. Females with SRMD were at greater risk to develop all-cause dementia (HR: 4.372, 95% CI = 1.175–5.624). The impact of SRMD on dementia risk was progressively increased by various follow-up time intervals (<1 year, 1–2 years, and ≥2 years). The results suggest that SRMD is linked to an increased risk for dementia with gender-dependent and time-dependent characteristics. PMID:26705224

  13. Age-Related Changes in Visual Pseudoneglect

    ERIC Educational Resources Information Center

    Schmitz, Remy; Peigneux, Philippe

    2011-01-01

    Pseudoneglect is a slight but consistent leftward attentional bias commonly observed in healthy young populations, purportedly explained by right hemispheric dominance. It has been suggested that normal aging might be associated with a decline of the right hemisphere. According to this hypothesis, a few studies have shown that elderly tend to…

  14. Nutritional interventions protect against age-related deficits in behavior: from animals to humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aged rats show impaired performance on motor and cognitive tasks. Similar changes in behavior occur in humans with age, and the development of methods to retard or reverse these age-related neuronal and behavioral deficits could increase healthy aging and decrease health care costs. In the present s...

  15. Age-related decline in global form suppression.

    PubMed

    Wiegand, Iris; Finke, Kathrin; Töllner, Thomas; Starman, Kornelija; Müller, Hermann J; Conci, Markus

    2015-12-01

    Visual selection of illusory 'Kanizsa' figures, an assembly of local elements that induce the percept of a whole object, is facilitated relative to configurations composed of the same local elements that do not induce a global form--an instance of 'global precedence' in visual processing. Selective attention, i.e., the ability to focus on relevant and ignore irrelevant information, declines with increasing age; however, how this deficit affects selection of global vs. local configurations remains unknown. On this background, the present study examined for age-related differences in a global-local task requiring selection of either a 'global' Kanizsa- or a 'local' non-Kanizsa configuration (in the presence of the respectively other configuration) by analyzing event-related lateralizations (ERLs). Behaviorally, older participants showed a more pronounced global-precedence effect. Electrophysiologically, this effect was accompanied by an early (150-225 ms) 'positivity posterior contralateral' (PPC), which was elicited for older, but not younger, participants, when the target was a non-Kanizsa configuration and the Kanizsa figure a distractor (rather than vice versa). In addition, timing differences in the subsequent (250-500 ms) posterior contralateral negativity (PCN) indicated that attentional resources were allocated faster to Kanizsa, as compared to non-Kanizsa, targets in both age groups, while the allocation of spatial attention seemed to be generally delayed in older relative to younger age. Our results suggest that the enhanced global-local asymmetry in the older age group originated from less effective suppression of global distracter forms on early processing stages--indicative of older observers having difficulties with disengaging from a global default selection mode and switching to the required local state of attentional resolution.

  16. Risk of inhibitor development in mild haemophilia A increases with age.

    PubMed

    Mauser-Bunschoten, E P; Den Uijl, I E M; Schutgens, R E G; Roosendaal, G; Fischer, K

    2012-03-01

    Mild haemophilia A is a rare disease with a relatively mild phenotype. Treatment with factor VIII (FVIII) is indicated after trauma or for surgery only. FVIII infusion may result in the development of inhibiting antibodies against FVIII. This study describes the relation between age and other risk factors for inhibitor development in mild haemophilia. A retrospective cohort study was conducted among all patients with mild haemophilia (FVIII 0.05-0.40 IU mL(-1)) registered at the van Creveldkliniek, University Medical Centre Utrecht, The Netherlands. Data on peak treatment with FVIII, gene mutation and history of inhibitor development were obtained from patient files from the period between 1st January 1970 and 31st December 2009. A total of 231 out of 297 (78%) patients had at least one exposure to FVIII, of whom 14 (6.1%) developed an inhibitor to FVIII at a median age of 66 years after a median of 50 exposure days (ED). Age at first exposure, age at peak treatment, number of peak treatments and Arg593Cys mutation were significantly associated with the development of an inhibitor, while continuous infusion with FVIII was not. Although the incidence of inhibitors in mild haemophilia is low, it increases with age and peak treatments. With increasing age patients with mild haemophilia will suffer from co-morbidity more frequently, requiring surgical interventions and exposing them to an increased risk of inhibitor development. Especially patients with a change of arginine in cysteine at 593 are at risk for inhibitor development.

  17. Age-related differences in pulmonary effects of acute and ...

    EPA Pesticide Factsheets

    Ozone (O3) is known to induce adverse pulmonary and systemic health effects. Importantly, children and older persons are considered at-risk populations for O3-induced dysfunction, yet the mechanisms accounting for the age-related pulmonary responses to O3 are uncertain. In this study, we examined age-related susceptibility to O3 using 1 mo (adolescent), 4 mo (young adult), 12 mo (adult) and 24 mo (senescent) male Brown Norway rats exposed to filtered air or O3 (0.25and 1.00 ppm), 6 h/day, two days/week for 1 week (acute) or 13 weeks (subchronic). Ventilatory function, assessed by whole-body plethysmography, and bronchoalveolar lavage fluid (BALF) biomarkers of injury and inflammation were used to examine O3-induced pulmonary effects.Relaxation time declined in all ages following the weekly exposures; however, this effect persisted only in the 24 mo rats following a five days recovery, demonstrating an inability to induce adaptation commonly seen with repeated O3 exposures. PenH was increased in all groups with an augmented response in the 4 mo rats following the subchronic O3 exposures. O3 led to increased breathing frequency and minute volume in the 1 and 4 mo animals. Markers ofpulmonary permeability were increased in all age groups. Elevations in BALF γ-glutamyl transferase activity and lung inflammation following an acute O3 exposure were noted in only the 1 and 4 mo rats, which likely received an increased effective O3 dose. These data demonstrate that ado

  18. Age-related forgetting in locomotor adaptation.

    PubMed

    Malone, Laura A; Bastian, Amy J

    2016-02-01

    The healthy aging process affects the ability to learn and remember new facts and tasks. Prior work has shown that motor learning can be adversely affected by non-motor deficits, such as time. Here we investigated how age, and a dual task influence the learning and forgetting of a new walking pattern. We studied healthy younger (<30 yo) and older adults (>50 yo) as they alternated between 5-min bouts of split-belt treadmill walking and resting. Older subjects learned a new walking pattern at the same rate as younger subjects, but forgot some of the new pattern during the rest breaks. We tested if forgetting was due to reliance on a cognitive strategy that was not fully engaged after rest breaks. When older subjects performed a dual cognitive task to reduce strategic control of split-belt walking, their adaptation rate slowed, but they still forgot much of the new pattern during the rest breaks. Our results demonstrate that the healthy aging process is one component that weakens motor memories during rest breaks and that this phenomenon cannot be explained solely by reliance on a conscious strategy in older adults.

  19. Visual steady state in relation to age and cognitive function.

    PubMed

    Horwitz, Anna; Dyhr Thomsen, Mia; Wiegand, Iris; Horwitz, Henrik; Klemp, Marc; Nikolic, Miki; Rask, Lene; Lauritzen, Martin; Benedek, Krisztina

    2017-01-01

    Neocortical gamma activity is crucial for sensory perception and cognition. This study examines the value of using non-task stimulation-induced EEG oscillations to predict cognitive status in a birth cohort of healthy Danish males (Metropolit) with varying cognitive ability. In particular, we examine the steady-state VEP power response (SSVEP-PR) in the alpha (8Hz) and gamma (36Hz) bands in 54 males (avg. age: 62.0 years) and compare these with 10 young healthy participants (avg. age 27.6 years). Furthermore, we correlate the individual alpha-to-gamma difference in relative visual-area power (ΔRV) with cognitive scores for the older adults. We find that ΔRV decrease with age by just over one standard deviation when comparing young with old participants (p<0.01). Furthermore, intelligence is significantly negatively correlated with ΔRV in the older adult cohort, even when processing speed, global cognition, executive function, memory, and education (p<0.05). In our preferred specification, an increase in ΔRV of one standard deviation is associated with a reduction in intelligence of 48% of a standard deviation (p<0.01). Finally, we conclude that the difference in cerebral rhythmic activity between the alpha and gamma bands is associated with age and cognitive status, and that ΔRV therefore provide a non-subjective clinical tool with which to examine cognitive status in old age.

  20. Visual steady state in relation to age and cognitive function

    PubMed Central

    Dyhr Thomsen, Mia; Wiegand, Iris; Horwitz, Henrik; Klemp, Marc; Nikolic, Miki; Rask, Lene; Lauritzen, Martin; Benedek, Krisztina

    2017-01-01

    Neocortical gamma activity is crucial for sensory perception and cognition. This study examines the value of using non-task stimulation-induced EEG oscillations to predict cognitive status in a birth cohort of healthy Danish males (Metropolit) with varying cognitive ability. In particular, we examine the steady-state VEP power response (SSVEP-PR) in the alpha (8Hz) and gamma (36Hz) bands in 54 males (avg. age: 62.0 years) and compare these with 10 young healthy participants (avg. age 27.6 years). Furthermore, we correlate the individual alpha-to-gamma difference in relative visual-area power (ΔRV) with cognitive scores for the older adults. We find that ΔRV decrease with age by just over one standard deviation when comparing young with old participants (p<0.01). Furthermore, intelligence is significantly negatively correlated with ΔRV in the older adult cohort, even when processing speed, global cognition, executive function, memory, and education (p<0.05). In our preferred specification, an increase in ΔRV of one standard deviation is associated with a reduction in intelligence of 48% of a standard deviation (p<0.01). Finally, we conclude that the difference in cerebral rhythmic activity between the alpha and gamma bands is associated with age and cognitive status, and that ΔRV therefore provide a non-subjective clinical tool with which to examine cognitive status in old age. PMID:28245274

  1. Mechanism of Inflammation in Age-Related Macular Degeneration

    PubMed Central

    Parmeggiani, Francesco; Romano, Mario R.; Costagliola, Ciro; Semeraro, Francesco; Incorvaia, Carlo; D'Angelo, Sergio; Perri, Paolo; De Palma, Paolo; De Nadai, Katia; Sebastiani, Adolfo

    2012-01-01

    Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease. PMID:23209345

  2. Mechanism of inflammation in age-related macular degeneration.

    PubMed

    Parmeggiani, Francesco; Romano, Mario R; Costagliola, Ciro; Semeraro, Francesco; Incorvaia, Carlo; D'Angelo, Sergio; Perri, Paolo; De Palma, Paolo; De Nadai, Katia; Sebastiani, Adolfo

    2012-01-01

    Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease.

  3. Auditory white noise reduces age-related fluctuations in balance.

    PubMed

    Ross, J M; Will, O J; McGann, Z; Balasubramaniam, R

    2016-09-06

    Fall prevention technologies have the potential to improve the lives of older adults. Because of the multisensory nature of human balance control, sensory therapies, including some involving tactile and auditory noise, are being explored that might reduce increased balance variability due to typical age-related sensory declines. Auditory white noise has previously been shown to reduce postural sway variability in healthy young adults. In the present experiment, we examined this treatment in young adults and typically aging older adults. We measured postural sway of healthy young adults and adults over the age of 65 years during silence and auditory white noise, with and without vision. Our results show reduced postural sway variability in young and older adults with auditory noise, even in the absence of vision. We show that vision and noise can reduce sway variability for both feedback-based and exploratory balance processes. In addition, we show changes with auditory noise in nonlinear patterns of sway in older adults that reflect what is more typical of young adults, and these changes did not interfere with the typical random walk behavior of sway. Our results suggest that auditory noise might be valuable for therapeutic and rehabilitative purposes in older adults with typical age-related balance variability.

  4. Relative Age Affects Marathon Performance in Male and Female Athletes

    PubMed Central

    Connick, Mark J.; Beckman, Emma M.; Tweedy, Sean M.

    2015-01-01

    Marathon runners are ranked in 5-year age groups. However the extent to which 5-year groupings facilitates equitable competition has not been evaluated. The aim of this study was to evaluate the effect of relative age in male and female marathon running. Marathon finishing times for the top ten male (aged 20-69 years) and female athletes (aged 20-64 years) were obtained from the 2013 New York and Chicago marathons. Intra-class and inter-class validity were evaluated by comparing performances within (intra-class) and between (inter-class) the 5-year age groups. Results showed intra-class effects in all male age groups over 50 years, in all female age groups over 40 years, and in male and female 20-24 age groups (p < 0.05). Inter-class differences existed between the 20-24 and 25-29 age groups in both males and females, between all male age groups over 50 years, and between all female age groups over 40 years (p < 0.05). This study provided the first evaluation of the effects of relative age in male and female marathon running. The results provide preliminary but compelling evidence that the relatively older male athletes in age groups over 50 years and the relatively older females in age groups over 40 years are competitively disadvantaged compared to the younger athletes in these age groups. Key points Results showed a curvilinear relationship between age and marathon running performance with the negative effect of age becoming more pronounced in older runners. Relative age effects were found in all age groups over age 50 years in males and over age 40 years in females indicating that the relatively older runners were competitively disadvantaged compared to the relatively younger runners in these age groups. Relative age affected the 20-24 age classification which is consistent with the hypothesis that marathon performance improves until peak performance occurs in the 25-29 age classification. PMID:26336355

  5. Relative Age Affects Marathon Performance in Male and Female Athletes.

    PubMed

    Connick, Mark J; Beckman, Emma M; Tweedy, Sean M

    2015-09-01

    Marathon runners are ranked in 5-year age groups. However the extent to which 5-year groupings facilitates equitable competition has not been evaluated. The aim of this study was to evaluate the effect of relative age in male and female marathon running. Marathon finishing times for the top ten male (aged 20-69 years) and female athletes (aged 20-64 years) were obtained from the 2013 New York and Chicago marathons. Intra-class and inter-class validity were evaluated by comparing performances within (intra-class) and between (inter-class) the 5-year age groups. Results showed intra-class effects in all male age groups over 50 years, in all female age groups over 40 years, and in male and female 20-24 age groups (p < 0.05). Inter-class differences existed between the 20-24 and 25-29 age groups in both males and females, between all male age groups over 50 years, and between all female age groups over 40 years (p < 0.05). This study provided the first evaluation of the effects of relative age in male and female marathon running. The results provide preliminary but compelling evidence that the relatively older male athletes in age groups over 50 years and the relatively older females in age groups over 40 years are competitively disadvantaged compared to the younger athletes in these age groups. Key pointsResults showed a curvilinear relationship between age and marathon running performance with the negative effect of age becoming more pronounced in older runners.Relative age effects were found in all age groups over age 50 years in males and over age 40 years in females indicating that the relatively older runners were competitively disadvantaged compared to the relatively younger runners in these age groups.Relative age affected the 20-24 age classification which is consistent with the hypothesis that marathon performance improves until peak performance occurs in the 25-29 age classification.

  6. Cumulative Lead Exposure and Age-related Hearing Loss: The VA Normative Aging Study

    PubMed Central

    Park, Sung Kyun; Elmarsafawy, Sahar; Mukherjee, Bhramar; Spiro, Avron; Vokonas, Pantel S.; Nie, Huiling; Weisskopf, Marc G.; Schwartz, Joel; Hu, Howard

    2010-01-01

    Although lead has been associated with hearing loss in occupational settings and in children, little epidemiologic research has been conducted on the impact of cumulative lead exposure on age-related hearing loss in the general population. We determined whether bone lead levels, a marker of cumulative lead exposure, are associated with decreased hearing ability in 448 men from the Normative Aging Study, seen between 1962 and 1996 (2,264 total observations). Air conduction hearing thresholds were measured at 0.25 to 8 kHz and pure tone averages (PTA) (mean of 0.5, 1, 2 and 4 kHz) were computed. Tibia and patella lead levels were measured using K x-ray fluorescence between 1991 and 1996. In cross-sectional analyses, after adjusting for potential confounders including occupational noise, patella lead levels were significantly associated with poorer hearing thresholds at 2, 3, 4, 6 and 8 kHz and PTA. The odds of hearing loss significantly increased with patella lead levels. We also found significant positive associations between tibia lead and the rate change in hearing thresholds at 1, 2, and 8 kHz and PTA in longitudinal analyses. Our results suggest that chronic low-level lead exposure may be an important risk factor for age-related hearing loss and reduction of lead exposure could help prevent or delay development of age-related hearing loss. PMID:20638461

  7. Low Calorie Diet Affects Aging-Related Factors

    MedlinePlus

    ... Issue Past Issues Research News From NIH Low Calorie Diet Affects Aging-Related Factors Past Issues / Summer ... learn more about the effects of sustained low-calorie diets in humans on factors affecting aging. This ...

  8. Validation of anti-aging drugs by treating age-related diseases.

    PubMed

    Blagosklonny, Mikhail V

    2009-03-28

    Humans die from age-related diseases, which are deadly manifestations of the aging process. In order to extend life span, an anti-aging drug must delay age-related diseases. All together age-related diseases are the best biomarker of aging. Once a drug is used for treatment of any one chronic disease, its effect against other diseases (atherosclerosis, cancer, prostate enlargement, osteoporosis, insulin resistance, Alzheimer's and Parkinson's diseases, age-related macular degeneration) may be evaluated in the same group of patients. If the group is large, then the anti-aging effect could be validated in a couple of years. Startlingly, retrospective analysis of clinical and preclinical data reveals four potential anti-aging modalities.

  9. Evidence for a major gene influencing 7-year increases in diastolic blood pressure with age

    SciTech Connect

    Li Shu-Chuan Cheng; Carmelli, D.; Hunt, S.C.

    1995-11-01

    The contribution of genetic factors to blood pressure levels is well established. The contribution of genes to the longitudinal change in blood pressure has been less well studied, because of the lack of longitudinal family data. The present study investigated a possible major-gene effect on the observed increase with age in diastolic blood pressure (DBP) levels. Subjects included 965 unmedicated adults (age {ge}18 years) in 73 pedigrees collected in Utah as part of a longitudinal cardiovascular family study. Segregation analysis of DBP change over 7.2 years of follow-up identified a recessive major-gene effect with a gene frequency of p = .23. There was also a significant age effect on the genotypic means, which decreased expression of the major gene at older ages. For those inferred to have the genotype responsible for large DBP increases, DBP increased 32.3%, compared with a 1.5% increase in the nonsusceptible group (P < .0001). The relative risk of developing hypertension between the susceptible and nonsusceptible groups after 7.2 years was 2.4 (P = .006). Baseline DBP reactivities to mental arithmetic (P < .0001) and isometric hand-grip (P < .0001) stress tests were greatest in those assigned to the susceptible genotype. We conclude that age-related changes in DBP are influenced by a major gene. Characteristics of this major-gene effect for greater age-related blood pressure increases include greater reactivity to mental and physical stressors. The present study thus provides evidence for genetic control of changes in blood pressure, in addition to the previously suggested genetic control of absolute blood pressure level. 28 refs., 6 tabs.

  10. Age-Related Factors That Influence Fertility

    MedlinePlus

    ... Job listings, application forms & job-related information Meetings, Conferences & Events Upcoming & past scientific meetings & public events Partnering & Donations Guidance on partnering, guidelines for donations Search Email Page Print Page Health & Research A-Z ...

  11. Age-related and death-related differences in emotional complexity.

    PubMed

    Palgi, Yuval; Shrira, Amit; Ben-Ezra, Menachem; Spalter, Tal; Kavé, Gitit; Shmotkin, Dov

    2014-06-01

    The present study aimed to examine an aspect of emotional complexity as seen in covariation between retrospective judgments of positive and negative affects. We assume that individuals can experience positive affect independently of negative affect. Theories argue that emotional complexity increases in old age, but research shows mixed evidence. Additionally, emotional complexity has been shown to decrease in situations prevalent in old age, such as physical illness and disability. Integrating distinct effects of age and distance to death, we propose that emotional complexity may remain intact or even increase in old age, and yet it decreases in light of functional deterioration shortly before death. The current research examined whether emotional complexity decreases as a function of subjective perception of closeness to death (subjective survival probability) or actual closeness to death. We used 3 large-scale databases: 2 cross-sectional (SHARE, N = 17,437, mean age = 64; HRS, N = 6,032, mean age = 67) and 1 longitudinal (CALAS, N = 1,310, mean age at baseline = 83). Hierarchical multiple regressions and multilevel models showed that respondents who perceived themselves as closer to death or were actually closer to death showed lower emotional complexity (a stronger negative correlation between positive and negative affects). Age and emotional complexity were unrelated or positively related, depending on the sample. Findings remained the same after controlling for demographic characteristics, as well as physical and cognitive functioning. The results indicate that both subjective and objective closeness to death are associated with lower emotional complexity. This death-related decrease in emotional complexity is discussed within current theories of aging.

  12. iPSC technology to study human aging and aging-related disorders.

    PubMed

    Liu, Guang-Hui; Ding, Zhichao; Izpisua Belmonte, Juan Carlos

    2012-12-01

    A global aging population, normally accompanied by a high incidence of aging-associated diseases, has prompted a renewed interest in basic research on human aging. Although encouraging progress has been achieved using animal models, the underlying fundamental mechanisms of aging remain largely unknown. Here, we review the human induced pluripotent stem cell (hiPSC)-based models of aging and aging-related diseases. These models seek to advance our knowledge of aging molecular mechanisms and help to develop strategies for treating aging-associated human diseases.

  13. Increase in Metabolic Syndrome-Related Hospitalizations in Relation to Environmental Sources of Persistent Organic Pollutants

    PubMed Central

    Sergeev, Alexander V.; Carpenter, David O.

    2011-01-01

    Evidence from cell studies indicates that persistent organic pollutants (POP) can induce insulin resistance, an essential component of the metabolic syndrome (MetS). We hypothesized that residential proximity to environmental sources of POP would be associated with the MetS in the population. The present study examined the association between residency in a zip code containing or abutting environmental sources of POP and MetS-related hospitalization rates. Hospitalization data were obtained from the New York Statewide Planning and Research Cooperative System. Relative risks (RR) were calculated as hospitalization rate ratios. Adjusted RR and their 95% confidence intervals (CI) were estimated by multivariable Poisson regression. A higher proportion of African Americans resided in POP zip codes compared to Caucasians (25.9% and 24.3%, respectively, p < 0.01). Residence in POP zip codes was associated with a statistically significant 39.2% increase in MetS-related hospitalization rates, adjusted for race, gender, and age (adjusted RR = 1.392, 95% CI: 1.032–1.879, p = 0.030). Increase in age was independently associated with higher MetS-related hospitalization rates (p for trend < 0.001). Our findings contribute to the body of evidence supporting the hypothesis of POP constituting an environmental risk factor for the MetS. Further studies investigating exposure to POP and insulin resistance are warranted. PMID:21556177

  14. Memorizing while walking: increase in dual-task costs from young adulthood to old age.

    PubMed

    Lindenberger, U; Marsiske, M; Baltes, P B

    2000-09-01

    The dual task of memorizing word lists while walking was predicted to become more difficult with age because balance and gait are in greater need of "attentional resources." Forty-seven young (ages 20-30 years), 45 middle-aged (40-50), and 48 old (60-70) adults were trained to criterion in a mnemonic technique and instructed to walk quickly and accurately on 2 narrow tracks of different path complexity. Then. participants encoded the word lists while sitting, standing, or walking on either track; likewise, speed and accuracy of walking performance were assessed with and without concurrent memory encoding. Dual-task costs increased with age in both domains; relative to young adults, the effect size of the overall increase was 0.98 standard deviation units for middle-aged and 1.47 standard deviation units for old adults. It is argued that sensory and motor aspects of behavior are increasingly in need of cognitive control with advancing age.

  15. Brain SERT Expression of Male Rats Is Reduced by Aging and Increased by Testosterone Restitution

    PubMed Central

    Herrera-Pérez, José Jaime; Fernández-Guasti, Alonso; Martínez-Mota, Lucía

    2013-01-01

    In preclinical and clinical studies aging has been associated with a deteriorated response to antidepressant treatment. We hypothesize that such impairment is explained by an age-related decrease in brain serotonin transporter (SERT) expression associated with low testosterone (T) levels. The objectives of this study were to establish (1) if brain SERT expression is reduced by aging and (2) if the SERT expression in middle-aged rats is increased by T-restitution. Intact young rats (3–5 months) and gonad-intact middle-aged rats with or without T-restitution were used. The identification of the brain SERT expression was done by immunofluorescence in prefrontal cortex, lateral septum, hippocampus, and raphe nuclei. An age-dependent reduction of SERT expression was observed in all brain regions examined, while T-restitution recovered the SERT expression only in the dorsal raphe of middle-aged rats. This last action seems relevant since dorsal raphe plays an important role in the antidepressant action of selective serotonin reuptake inhibitors. All data suggest that this mechanism accounts for the T-replacement usefulness to improve the response to antidepressants in the aged population. PMID:26317087

  16. Age Related Decline in Postural Control Mechanisms.

    ERIC Educational Resources Information Center

    Stelmach, George E.; And Others

    1989-01-01

    Studied voluntary and reflexive mechanisms of postural control of young (N=8) and elderly (N=8) adults through measurement of reflexive reactions to large-fast and small-slow ankle rotation postural disturbances. Found reflexive mechanisms relatively intact for both groups although elderly appeared more disadvantaged when posture was under the…

  17. Loss of Catecholaminergic Neuromodulation of Persistent Forms of Hippocampal Synaptic Plasticity with Increasing Age

    PubMed Central

    Twarkowski, Hannah; Manahan-Vaughan, Denise

    2016-01-01

    Neuromodulation by means of the catecholaminergic system is a key component of motivation-driven learning and behaviorally modulated hippocampal synaptic plasticity. In particular, dopamine acting on D1/D5 receptors and noradrenaline acting on beta-adrenergic receptors exert a very potent regulation of forms of hippocampal synaptic plasticity that last for very long-periods of time (>24 h), and occur in conjunction with novel spatial learning. Antagonism of these receptors not only prevents long-term potentiation (LTP) and long-term depression (LTD), but prevents the memory of the spatial event that, under normal circumstances, leads to the perpetuation of these plasticity forms. Spatial learning behavior that normally comes easily to rats, such as object-place learning and spatial reference learning, becomes increasingly impaired with aging. Middle-aged animals display aging-related deficits of specific, but not all, components of spatial learning, and one possibility is that this initial manifestation of decrements in learning ability that become apparent in middle-age relate to changes in motivation, attention and/or the regulation by neuromodulatory systems of these behavioral states. Here, we compared the regulation by dopaminergic D1/D5 and beta-adrenergic receptors of persistent LTP in young (2–4 month old) and middle-aged (8–14 month old) rats. We observed in young rats, that weak potentiation that typically lasts for ca. 2 h could be strengthened into persistent (>24 h) LTP by pharmacological activation of either D1/D5 or beta-adrenergic receptors. By contrast, no such facilitation occurred in middle-aged rats. This difference was not related to an ostensible learning deficit: a facilitation of weak potentiation into LTP by spatial learning was possible both in young and middle-aged rats. It was also not directly linked to deficits in LTP: strong afferent stimulation resulted in equivalent LTP in both age groups. We postulate that this change in

  18. The genetics of age-related macular degeneration.

    PubMed

    Gorin, M B; Breitner, J C; De Jong, P T; Hageman, G S; Klaver, C C; Kuehn, M H; Seddon, J M

    1999-11-03

    Age-related macular degeneration (AMD) is increasingly recognized as a complex genetic disorder in which one or more genes contribute to an individual's susceptibility for developing the condition. Twin and family studies as well as population-based genetic epidemiologic methods have convincingly demonstrated the importance of genetics in AMD, though the extent of heritability, the number of genes involved, and the phenotypic and genetic heterogeneity of the condition remain unresolved. The extent to which other hereditary macular dystrophies such as Stargardts disease, familial radial drusen (malattia leventinese), Best's disease, and peripherin/RDS-related dystrophy are related to AMD remains unclear. Alzheimer's disease, another late onset, heterogeneous degenerative disorder of the central nervous system, offers a valuable model for identifying the issues that confront AMD genetics.

  19. Slowing Down: Age-Related Neurobiological Predictors of Processing Speed

    PubMed Central

    Eckert, Mark A.

    2011-01-01

    Processing speed, or the rate at which tasks can be performed, is a robust predictor of age-related cognitive decline and an indicator of independence among older adults. This review examines evidence for neurobiological predictors of age-related changes in processing speed, which is guided in part by our source based morphometry findings that unique patterns of frontal and cerebellar gray matter predict age-related variation in processing speed. These results, together with the extant literature on morphological predictors of age-related changes in processing speed, suggest that specific neural systems undergo declines and as a result slow processing speed. Future studies of processing speed – dependent neural systems will be important for identifying the etiologies for processing speed change and the development of interventions that mitigate gradual age-related declines in cognitive functioning and enhance healthy cognitive aging. PMID:21441995

  20. The Relative Age Effect among Female Brazilian Youth Volleyball Players

    ERIC Educational Resources Information Center

    Okazaki, Fabio H. A.; Keller, Birgit; Fontana, Fabio E.; Gallagher, Jere D.

    2011-01-01

    In sports, the relative age effect (RAE) refers to performance disadvantages of children born late in the competition year compared to those with birthdays soon after the cutoff date. This effect is derived from age grouping, a strategy commonly used in youth sport programs. The purpose of age grouping is to decrease possible cognitive, physical,…

  1. Age-Related Differences in Idiom Production in Adulthood

    ERIC Educational Resources Information Center

    Conner, Peggy S.; Hyun, Jungmoon; O'Connor Wells, Barbara; Anema, Inge; Goral, Mira; Monereau-Merry, Marie-Michelle; Rubino, Daniel; Kuckuk, Raija; Obler, Loraine K.

    2011-01-01

    To investigate whether idiom production was vulnerable to age-related difficulties, we asked 40 younger (ages 18-30) and 40 older healthy adults (ages 60-85) to produce idiomatic expressions in a story-completion task. Younger adults produced significantly more correct idiom responses (73%) than did older adults (60%). When older adults generated…

  2. Hypoxia-Inducible Histone Lysine Demethylases: Impact on the Aging Process and Age-Related Diseases

    PubMed Central

    Salminen, Antero; Kaarniranta, Kai; Kauppinen, Anu

    2016-01-01

    Hypoxia is an environmental stress at high altitude and underground conditions but it is also present in many chronic age-related diseases, where blood flow into tissues is impaired. The oxygen-sensing system stimulates gene expression protecting tissues against hypoxic insults. Hypoxia stabilizes the expression of hypoxia-inducible transcription factor-1α (HIF-1α), which controls the expression of hundreds of survival genes related to e.g. enhanced energy metabolism and autophagy. Moreover, many stress-related signaling mechanisms, such as oxidative stress and energy metabolic disturbances, as well as the signaling cascades via ceramide, mTOR, NF-κB, and TGF-β pathways, can also induce the expression of HIF-1α protein to facilitate cell survival in normoxia. Hypoxia is linked to prominent epigenetic changes in chromatin landscape. Screening studies have indicated that the stabilization of HIF-1α increases the expression of distinct histone lysine demethylases (KDM). HIF-1α stimulates the expression of KDM3A, KDM4B, KDM4C, and KDM6B, which enhance gene transcription by demethylating H3K9 and H3K27 sites (repressive epigenetic marks). In addition, HIF-1α induces the expression of KDM2B and KDM5B, which repress transcription by demethylating H3K4me2,3 sites (activating marks). Hypoxia-inducible KDMs support locally the gene transcription induced by HIF-1α, although they can also control genome-wide chromatin landscape, especially KDMs which demethylate H3K9 and H3K27 sites. These epigenetic marks have important role in the control of heterochromatin segments and 3D folding of chromosomes, as well as the genetic loci regulating cell type commitment, proliferation, and cellular senescence, e.g. the INK4 box. A chronic stimulation of HIF-1α can provoke tissue fibrosis and cellular senescence, which both are increasingly present with aging and age-related diseases. We will review the regulation of HIF-1α-dependent induction of KDMs and clarify their role in

  3. Mitochondrial proteomic profiling reveals increased carbonic anhydrase II in aging and neurodegeneration

    PubMed Central

    Pollard, Amelia; Shephard, Freya; Freed, James; Liddell, Susan; Chakrabarti, Lisa

    2016-01-01

    Carbonic anhydrase inhibitors are used to treat glaucoma and cancers. Carbonic anhydrases perform a crucial role in the conversion of carbon dioxide and water into bicarbonate and protons. However, there is little information about carbonic anhydrase isoforms during the process of ageing. Mitochondrial dysfunction is implicit in ageing brain and muscle. We have interrogated isolated mitochondrial fractions from young adult and middle aged mouse brain and skeletal muscle. We find an increase of tissue specific carbonic anhydrases in mitochondria from middle-aged brain and skeletal muscle. Mitochondrial carbonic anhydrase II was measured in the Purkinje cell degeneration (pcd5J) mouse model. In pcd5J we find mitochondrial carbonic anhydrase II is also elevated in brain from young adults undergoing a process of neurodegeneration. We show C.elegans exposed to carbonic anhydrase II have a dose related shorter lifespan suggesting that high CAII levels are in themselves life limiting. We show for the first time that the mitochondrial content of brain and skeletal tissue are exposed to significantly higher levels of active carbonic anhydrases as early as in middle-age. Carbonic anhydrases associated with mitochondria could be targeted to specifically modulate age related impairments and disease. PMID:27743511

  4. The role of epigenetics in age-related macular degeneration

    PubMed Central

    Gemenetzi, M; Lotery, A J

    2014-01-01

    It is becoming increasingly evident that epigenetic mechanisms influence gene expression and can explain how interactions between genetics and the environment result in particular phenotypes during development. The extent to which this epigenetic effect contributes to phenotype heritability in age-related macular degeneration (AMD) is currently ill defined. However, emerging evidence suggests that epigenetic changes are relevant to AMD and as such provide an exciting new avenue of research for AMD. This review addresses information on the impact of posttranslational modification of the genome on the pathogenesis of AMD, such as DNA methylation changes affecting antioxidant gene expression, hypoxia-regulated alterations in chromatin structure, and histone acetylation status in relation to angiogenesis and inflammation. It also contains information on the role of non-coding RNA-mediated gene regulation in AMD at a posttranscriptional (before translation) level. Our aim was to review the epigenetic mechanisms that cause heritable changes in gene activity without changing the DNA sequence. We also describe some long-term alterations in the transcriptional potential of a cell, which are not necessarily heritable but remains to be defined in the future. Increasing understanding of the significance of common and rare genetic variants and their relationship to epigenetics and environmental influences may help in establishing methods to assess the risk of AMD. This in turn may allow new therapeutic interventions for the leading cause of central vision impairment in patients over the age of 50 years in developed countries. Search strategy We searched the MEDLINE/PubMed database following MeSH suggestions for articles including the terms: ‘ocular epigenetic mechanisms', ‘human disease epigenetics', and ‘age-related macular degeneration genetics'. The headline used to locate related articles in PubMed was ‘epigenetics in ocular disease', and to restrict search, we used

  5. Younger age increases the risk of early prosthesis failure following primary total knee replacement for osteoarthritis

    PubMed Central

    2010-01-01

    Background and purpose Total knee replacements (TKRs) are being increasingly performed in patients aged ≤ 65 years who often have high physical demands. We investigated the relation between age of the patient and prosthesis survival following primary TKR using nationwide data collected from the Finnish Arthroplasty Register. Materials From Jan 1, 1997 through Dec 31, 2003, 32,019 TKRs for primary or secondary osteoarthritis were reported to the Finnish Arthroplasty Register. The TKRs were followed until the end of 2004. During the follow-up, 909 TKRs were revised, 205 (23%) due to infection and 704 for other reasons. Results Crude overall implant survival improved with increasing age between the ages of 40 and 80. The 5-year survival rates were 92% and 95% in patients aged ≤ 55 and 56–65 years, respectively, compared to 97% in patients who were > 65 years of age (p < 0.001). The difference was mainly attributable to reasons other than infections. Sex, diagnosis, type of TKR (condylar, constrained, or hinge), use of patellar component, and fixation method were also associated with higher revision rates. However, the differences in prosthesis survival between the age groups ≤ 55, 56–65, and > 65 years remained after adjustment for these factors (p < 0.001). Interpretation Young age impairs the prognosis of TKR and is associated with increased revision rates for non-infectious reasons. Diagnosis, sex, type of TKR, use of patellar component, and fixation method partly explain the differences, but the effects of physical activity, patient demands, and obesity on implant survival in younger patients warrant further research. PMID:20809740

  6. Relative Age Effects in Dutch Adolescents: Concurrent and Prospective Analyses

    PubMed Central

    Jeronimus, Bertus F.; Stavrakakis, Nikolaos; Veenstra, René; Oldehinkel, Albertine J.

    2015-01-01

    The literature on relative age position effects is rather inconsistent. In this study we examined intra-classroom age position (or relative age) effects on Dutch adolescents’ school progress and performance (as rated by teachers), physical development, temperamental development (fear and frustration), and depressive symptoms, all adjusted for age at the time of measurement. Data were derived from three waves of Tracking Adolescents' Individuals Lives Survey (TRAILS) of 2230 Dutch adolescents (baseline mean age 11.1, SD = 0.6, 51% girls). Albeit relative age predicted school progress (grade retention ORs = 0.83 for each month, skipped grade OR = 1.47, both p<.001), our key observation is the absence of substantial developmental differences as a result of relative age position in Dutch adolescents with a normative school trajectory, in contrast to most literature. For adolescents who had repeated a grade inverse relative age effects were observed, in terms of physical development and school performance, as well as on depressive symptoms, favoring the relatively young. Cross-cultural differences in relative age effect may be partly explained by the decision threshold for grade retention. PMID:26076384

  7. Caloric restriction increases ketone bodies metabolism and preserves blood flow in aging brain

    PubMed Central

    Lin, Ai-Ling; Zhang, Wei; Gao, Xiaoli; Watts, Lora

    2015-01-01

    Caloric restriction (CR) has been shown to increase the life span and health span of a broad range of species. However, CR effects on in vivo brain functions are far from explored. In this study, we used multimetric neuroimaging methods to characterize the CR-induced changes of brain metabolic and vascular functions in aging rats. We found that old rats (24 months of age) with CR diet had reduced glucose uptake and lactate concentration, but increased ketone bodies level, compared with the age-matched and young (5 months of age) controls. The shifted metabolism was associated with preserved vascular function: old CR rats also had maintained cerebral blood flow relative to the age-matched controls. When investigating the metabolites in mitochondrial tricarboxylic acid cycle, we found that citrate and α-ketoglutarate were preserved in the old CR rats. We suggest that CR is neuroprotective; ketone bodies, cerebral blood flow, and α-ketoglutarate may play important roles in preserving brain physiology in aging. PMID:25896951

  8. Age-Associated Increases in Pulmonary Artery Systolic Pressure in the General Population

    PubMed Central

    Lam, Carolyn S. P.; Borlaug, Barry A.; Kane, Garvan C.; Enders, Felicity T.; Rodeheffer, Richard J.; Redfield, Margaret M.

    2009-01-01

    Background In contrast to the wealth of data on isolated systolic hypertension involving the systemic circulation in the elderly, much less is known about age-related change in pulmonary artery systolic pressure (PASP) and its prognostic impact in the general population. We sought to define the relationship between PASP and age, evaluate which factors influence PASP and determine if PASP is independently predictive of mortality in the community. Methods and Results A random sample of Olmsted County, MN general population (N=2042) underwent echocardiography and spirometry and was followed for a median of 9 years. PASP was measured from the tricuspid regurgitation velocity. Left ventricular diastolic pressure was estimated using Doppler echocardiography (E/e' ratio) and arterial stiffening was assessed using the brachial artery pulse pressure. Among 1413 (69%) subjects with measurable PASP (63±11y; 43% male), PASP (median, 25th-75th percentile) was 26 (24-30) mmHg and increased with age (r=0.31; p<0.001). Independent predictors of PASP were age, pulse pressure and mitral E/e' (all p≤0.003). Increasing PASP was associated with higher mortality (hazard ratio 2.73 per 10 mmHg; p<0.001). In subjects without cardiopulmonary disease (any heart failure, coronary artery disease, hypertension, diabetes mellitus or chronic obstructive lung disease), the age-adjusted hazard ratio was 2.74 per 10 mmHg (p=0.016). Conclusions We provide the first population-based evidence of age-related increase in pulmonary artery pressure, its association with increasing left heart diastolic pressures and systemic vascular stiffening, as well as its negative impact on survival. Pulmonary artery pressure may serve as a novel cardiovascular risk factor and potential therapeutic target. PMID:19433755

  9. The role of hydrogen sulfide in aging and age-related pathologies

    PubMed Central

    Perridon, Bernard W.; Leuvenink, Henri G.D.; Hillebrands, Jan-Luuk; van Goor, Harry; Bos, Eelke M.

    2016-01-01

    When humans grow older, they experience inevitable and progressive loss of physiological function, ultimately leading to death. Research on aging largely focuses on the identification of mechanisms involved in the aging process. Several proposed aging theories were recently combined as the ‘hallmarks of aging’. These hallmarks describe (patho-)physiological processes that together, when disrupted, determine the aging phenotype. Sustaining evidence shows a potential role for hydrogen sulfide (H2S) in the regulation of aging. Nowadays, H2S is acknowledged as an endogenously produced signaling molecule with various (patho-) physiological effects. H2S is involved in several diseases including pathologies related to aging. In this review, the known, assumed and hypothetical effects of hydrogen sulfide on the aging process will be discussed by reviewing its actions on the hallmarks of aging and on several age-related pathologies. PMID:27683311

  10. A Context for Teaching Aging-Related Public Policy.

    ERIC Educational Resources Information Center

    Brown, David K.

    1999-01-01

    Describes two points of view regarding age-related public programs (Medicaid, Medicare, Social Security): that of devolutionists who would curtail them and safety netters who maintain the government's role is indispensable. Uses Relative Deprivation theory as a framework for teaching public policy about aging. (SK)

  11. How Pervasive Are Relative Age Effects in Secondary School Education?

    ERIC Educational Resources Information Center

    Cobley, Stephen; McKenna, Jim; Baker, Joeseph; Wattie, Nick

    2009-01-01

    Relative age effects (RAEs; R. H. Barnsley, A. H. Thompson, & P. E. Barnsley, 1985) convey school attainment (dis)advantages depending on whether one is relatively older or younger within annually age-grouped cohorts. In the present study, the authors examined the pervasiveness of RAEs by examining (a) attainment in 4 secondary school…

  12. Relative Weights of the Backpacks of Elementary-Aged Children

    ERIC Educational Resources Information Center

    Bryant, Benjamin P.; Bryant, Judith B.

    2014-01-01

    The purpose of the study was to describe the range of relative backpack weights of one group of elementary-aged children and the extent to which they exceeded recommended levels. A second purpose was to explore whether gender and age help predict the relative weight of children's backpacks. Ninety-five 8- to 12-year-old elementary school students…

  13. Unique Relations of Age and Delinquency with Cognitive Control

    ERIC Educational Resources Information Center

    Iselin, Anne-Marie R.; DeCoster, Jamie

    2012-01-01

    Context processing has significant empirical support as an explanation of age- and psychopathology-related deficiencies in cognitive control. We examined whether context processing generalizes to younger individuals who are in trouble with the law. We tested whether age and delinquency might have unique relations to context processing skills in…

  14. The Digital Ageing Atlas: integrating the diversity of age-related changes into a unified resource.

    PubMed

    Craig, Thomas; Smelick, Chris; Tacutu, Robi; Wuttke, Daniel; Wood, Shona H; Stanley, Henry; Janssens, Georges; Savitskaya, Ekaterina; Moskalev, Alexey; Arking, Robert; de Magalhães, João Pedro

    2015-01-01

    Multiple studies characterizing the human ageing phenotype have been conducted for decades. However, there is no centralized resource in which data on multiple age-related changes are collated. Currently, researchers must consult several sources, including primary publications, in order to obtain age-related data at various levels. To address this and facilitate integrative, system-level studies of ageing we developed the Digital Ageing Atlas (DAA). The DAA is a one-stop collection of human age-related data covering different biological levels (molecular, cellular, physiological, psychological and pathological) that is freely available online (http://ageing-map.org/). Each of the >3000 age-related changes is associated with a specific tissue and has its own page displaying a variety of information, including at least one reference. Age-related changes can also be linked to each other in hierarchical trees to represent different types of relationships. In addition, we developed an intuitive and user-friendly interface that allows searching, browsing and retrieving information in an integrated and interactive fashion. Overall, the DAA offers a new approach to systemizing ageing resources, providing a manually-curated and readily accessible source of age-related changes.

  15. Age-related changes in conditioned flavor preference in rats.

    PubMed

    Renteria, Adam F; Silbaugh, Bryant C; Tolentino, Jerlyn C; Gilbert, Paul E

    2008-03-17

    Age-related changes have been documented in regions of the brain shown to process reward information. However, few studies have examined the effects of aging on associative memory for reward. The present study tested 7- and 24-month-old rats on a conditioned flavor preference task. Half of the rats in each age group received an unsweetened grape-flavored solution (CS-) on odd-numbered days and a sweetened cherry-flavored solution (CS+) on even-numbered days. The remaining rats in each age group received a sweetened grape-flavored solution (CS+) on odd-numbered days and an unsweetened cherry-flavored solution (CS-) on even-numbered days. During the acquisition phase of testing, the designated solution (CS+ or CS-) was presented to each rat for 15 min daily across six consecutive days. On the preference phase, each rat received unsweetened cherry and unsweetened grape-flavored solutions simultaneously for 15 min daily across four consecutive days. The 7-month-old rats showed a significant preference for the flavor that was previously sweetened during the acquisition phase (CS+) compared to the previously unsweetened solution (CS-) when the two unsweetened solutions were presented simultaneously during the preference phase of testing. In contrast, the 24-month-old rats did not show a preference and consumed roughly equal amounts of the previously sweetened (CS+) and unsweetened (CS-) solutions. Thus, the data suggest that the ability to form flavor-reward associations declines with increasing age, resulting in impaired conditioned flavor preference.

  16. The incidence of cervical spondylosis decreases with aging in the elderly, and increases with aging in the young and adult population: a hospital-based clinical analysis

    PubMed Central

    Wang, Chuanling; Tian, Fuming; Zhou, Yingjun; He, Wenbo; Cai, Zhiyou

    2016-01-01

    Background and purpose Cervical spondylosis is well accepted as a common degenerative change in the cervical spine. Compelling evidence has shown that the incidence of cervical spondylosis increases with age. However, the relationship between age and the incidence of cervical spondylosis remains obscure. It is essential to note the relationship between age and the incidence of cervical spondylosis through more and more clinical data. Methods In the case-controlled study reported here, retrospective clinical analysis of 1,276 cases of cervical spondylosis has been conducted. We analyzed the general clinical data, the relationship between age and the incidence of cervical spondylosis, and the relationship between age-related risk factors and the incidence of cervical spondylosis. A chi-square test was used to analyze the associations between different variables. Statistical significance was defined as a P-value of less than 0.05. Results The imaging examination demonstrated the most prominent characteristic features of cervical spondylosis: bulge or herniation at C3-C4, C4-C5, and C5-C6. The incidence of cervical spondylosis increased with aging before age 50 years and decreased with aging after age 50 years, especially in the elderly after 60 years old. The occurrence rate of bulge or herniation at C3-C4, C4-C5, C5-C6, and C6-C7 increased with aging before age 50 years and decreased with aging after age 50 years, especially after 60 years. Moreover, the incidence of hyperosteogeny and spinal stenosis increased with aging before age 60 years and decreased with aging after age 60 years, although there was no obvious change in calcification. The age-related risk factors, such as hypertension, hyperlipidemia, diabetes, cerebral infarct, cardiovascular diseases, smoking, and drinking, have no relationship with the incidence of cervical spondylosis. Conclusion A decreasing proportion of cervical spondylosis with aging occurs in the elderly, while the proportion of

  17. Increasing wealth inequality may increase interpersonal hostility: The relationship between personal relative deprivation and aggression.

    PubMed

    Greitemeyer, Tobias; Sagioglou, Christina

    2017-01-31

    In most Western societies, wealth inequality is increasing, which in turn could increase people's belief that one's standing is relatively disadvantaged. Based on relative deprivation theory, we argue that such an experience of personal relative deprivation should causally lead to greater interpersonal hostility. Indeed, three experiments show that participants in a personal relative deprivation condition reported higher levels of aggressive affect and behaved more aggressively than participants in a personal relative gratification condition. Compared to a control condition, participants experiencing personal relative deprivation were more aggressive rather than participants experiencing personal relative gratification being less aggressive. However, personal relative deprivation increased aggressive behavior only toward targets that were the source for participants' experience of disadvantage, but it did not increase aggression toward neutral targets.

  18. The burden of age-related macular degeneration.

    PubMed

    Schmier, Jordana K; Jones, Mechelle L; Halpern, Michael T

    2006-01-01

    As age-related macular degeneration (AMD) becomes more prevalent as a result of longer life expectancy and the number of elderly people worldwide, it will become increasingly important to understand its potential health and economic impact for appropriate healthcare planning. This review identified published literature on costs and resource use associated with AMD. Despite the increasing prevalence of AMD, the worldwide burden of illness is unknown. Several studies of direct medical costs, both those associated with ophthalmic care and those associated with other care, have been conducted and have identified increased medical care associated with AMD. Direct non-medical costs include the cost for vision aids; while these costs may be substantial, they are difficult to quantify as no comprehensive sources track the distribution or use of vision aids. Because AMD is uncommon among people of working age, there is less concern regarding the impact of indirect (workplace) costs among AMD patients. However, indirect costs are incurred by caregivers who leave the workforce early or change their work patterns in order to provide assistance to AMD patients; the magnitude of caregiver-related costs is unknown. The cost effectiveness of some interventions for AMD has been explored. Supplementation with zinc and antioxidants for non-exudative (dry) AMD has been shown to result in an acceptable cost per QALY and is considered cost effective. Studies suggest that laser photocoagulation is cost effective but that photodynamic therapy with verteporfin appears to be cost effective only among patients with good visual acuity at baseline or when models extend longer than 5 years. Further research is needed to integrate the information on various components of AMD-related costs into a comprehensive burden of illness estimate and to evaluate basic utility assumptions in existing models.

  19. Rapid Assessment of Age-Related Differences in Standing Balance

    PubMed Central

    Kalisch, Tobias; Kattenstroth, Jan-Christoph; Noth, Sebastian; Tegenthoff, Martin; Dinse, Hubert R.

    2011-01-01

    As life expectancy continues to rise, in the future there will be an increasing number of older people prone to falling. Accordingly, there is an urgent need for comprehensive testing of older individuals to collect data and to identify possible risk factors for falling. Here we use a low-cost force platform to rapidly assess deficits in balance under various conditions. We tested 21 healthy older adults and 24 young adults during static stance, unidirectional and rotational displacement of their centre of pressure (COP). We found an age-related increase in postural sway during quiet standing and a reduction of maximal COP displacement in unidirectional and rotational displacement tests. Our data show that even low-cost computerized assessment tools allow for the comprehensive testing of balance performance in older subjects. PMID:21629742

  20. Undergraduate Students' Perceptions and Behaviors Related to the Aged and to Aging Processes

    ERIC Educational Resources Information Center

    Van Dussen, Daniel J.; Weaver, Robert R.

    2009-01-01

    Aging education is relatively new to the university, and our understanding of the perspectives students bring to aging populations is correspondingly limited. This investigation surveys 546 students at a midsized, Midwestern university to explore students' views toward elders, toward serving elders, and toward the relevance of aging education for…

  1. Genetic risk factors and age-related macular degeneration (AMD)

    PubMed Central

    Mousavi, Maryam; Armstrong, Richard A.

    2013-01-01

    Age related macular degeneration (AMD) is the leading cause of blindness in individuals older than 65 years of age. It is a multifactorial disorder and identification of risk factors enables individuals to make lifestyle choices that may reduce the risk of disease. Collaboration between geneticists, ophthalmologists, and optometrists suggests that genetic risk factors play a more significant role in AMD than previously thought. The most important genes are associated with immune system modulation and the complement system, e.g., complement factor H (CFH), factor B (CFB), factor C3, and serpin peptidase inhibitor (SERPING1). Genes associated with membrane transport, e.g., ATP-binding cassette protein (ABCR) and voltage-dependent calcium channel gamma 3 (CACNG3), the vascular system, e.g., fibroblast growth factor 2 (FGF2), fibulin-5, lysyl oxidase-like gene (LOXL1) and selectin-P (SELP), and with lipid metabolism, e.g., apolipoprotein E (APOE) and hepatic lipase (LIPC) have also been implicated. In addition, several other genes exhibit some statistical association with AMD, e.g., age-related maculopathy susceptibility protein 2 (ARMS2) and DNA excision repair protein gene (ERCC6) but more research is needed to establish their significance. Modifiable risk factors for AMD should be discussed with patients whose lifestyle and/or family history place them in an increased risk category. Furthermore, calculation of AMD risk using current models should be recommended as a tool for patient education. It is likely that AMD management in future will be increasingly influenced by assessment of genetic risk as such screening methods become more widely available.

  2. Increased ghrelin signaling prolongs survival in mouse models of human aging through activation of sirtuin1

    PubMed Central

    Fujitsuka, N; Asakawa, A; Morinaga, A; Amitani, M S; Amitani, H; Katsuura, G; Sawada, Y; Sudo, Y; Uezono, Y; Mochiki, E; Sakata, I; Sakai, T; Hanazaki, K; Yada, T; Yakabi, K; Sakuma, E; Ueki, T; Niijima, A; Nakagawa, K; Okubo, N; Takeda, H; Asaka, M; Inui, A

    2016-01-01

    Caloric restriction (CR) is known to retard aging and delay functional decline as well as the onset of diseases in most organisms. Ghrelin is secreted from the stomach in response to CR and regulates energy metabolism. We hypothesized that in CR ghrelin has a role in protecting aging-related diseases. We examined the physiological mechanisms underlying the ghrelin system during the aging process in three mouse strains with different genetic and biochemical backgrounds as animal models of accelerated or normal human aging. The elevated plasma ghrelin concentration was observed in both klotho-deficient and senescence-accelerated mouse prone/8 (SAMP8) mice. Ghrelin treatment failed to stimulate appetite and prolong survival in klotho-deficient mice, suggesting the existence of ghrelin resistance in the process of aging. However, ghrelin antagonist hastened death and ghrelin signaling potentiators rikkunshito and atractylodin ameliorated several age-related diseases with decreased microglial activation in the brain and prolonged survival in klotho-deficient, SAMP8 and aged ICR mice. In vitro experiments, the elevated sirtuin1 (SIRT1) activity and protein expression through the cAMP–CREB pathway was observed after ghrelin and ghrelin potentiator treatment in ghrelin receptor 1a-expressing cells and human umbilical vein endothelial cells. Furthermore, rikkunshito increased hypothalamic SIRT1 activity and SIRT1 protein expression of the heart in the all three mouse models of aging. Pericarditis, myocardial calcification and atrophy of myocardial and muscle fiber were improved by treatment with rikkunshito. Ghrelin signaling may represent one of the mechanisms activated by CR, and potentiating ghrelin signaling may be useful to extend health and lifespan. PMID:26830139

  3. Age-related changes in emotional face processing across childhood and into young adulthood: evidence from event-related potentials

    PubMed Central

    MacNamara, Annmarie; Vergés, Alvaro; Kujawa, Autumn; Fitzgerald, Kate D.; Monk, Christopher S.; Phan, K. Luan

    2016-01-01

    Socio-emotional processing is an essential part of development, and age-related changes in its neural correlates can be observed. The late positive potential (LPP) is a measure of motivated attention that can be used to assess emotional processing; however, changes in the LPP elicited by emotional faces have not been assessed across a wide age range in childhood and young adulthood. We used an emotional face matching task to examine behavior and event-related potentials (ERPs) in 33 youth aged 7 to 19 years old. Younger children were slower when performing the matching task. The LPP elicited by emotional faces but not control stimuli (geometric shapes) decreased with age; by contrast, an earlier ERP (the P1) decreased with age for both faces and shapes, suggesting increased efficiency of early visual processing. Results indicate age-related attenuation in emotional processing that may stem from increased efficiency and regulatory control when performing a socio-emotional task. PMID:26220144

  4. Methylglyoxal alters glucose metabolism and increases AGEs content in C6 glioma cells.

    PubMed

    Hansen, Fernanda; de Souza, Daniela Fraga; Silveira, Simone da Luz; Hoefel, Ana Lúcia; Fontoura, Júlia Bijoldo; Tramontina, Ana Carolina; Bobermin, Larissa Daniele; Leite, Marina Concli; Perry, Marcos Luiz Santos; Gonçalves, Carlos Alberto

    2012-12-01

    Methylglyoxal is a dicarbonyl compound that is physiologically produced by enzymatic and non-enzymatic reactions. It can lead to cytotoxicity, which is mainly related to Advanced Glycation End Products (AGEs) formation. Methylglyoxal and AGEs are involved in the pathogenesis of Neurodegenerative Diseases (ND) and, in these situations, can cause the impairment of energetic metabolism. Astroglial cells play critical roles in brain metabolism and the appropriate functioning of astrocytes is essential for the survival and function of neurons. However, there are only a few studies evaluating the effect of methylglyoxal on astroglial cells. The aim of this study was to evaluate the effect of methylglyoxal exposure, over short (1 and 3 h) and long term (24 h) periods, on glucose, glycine and lactate metabolism in C6 glioma cells, as well as investigate the glyoxalase system and AGEs formation. Glucose uptake and glucose oxidation to CO(2) increased in 1 h and the conversion of glucose to lipids increased at 3 h. In addition, glycine oxidation to CO(2) and conversion of glycine to lipids increased at 1 h, whereas the incorporation of glycine in proteins decreased at 1 and 3 h. Methylglyoxal decreased glyoxalase I and II activities and increased AGEs content within 24 h. Lactate oxidation and lactate levels were not modified by methylglyoxal exposure. These data provide evidence that methylglyoxal may impair glucose metabolism and can affect glyoxalase activity. In periods of increased methylglyoxal exposure, such alterations could be exacerbated, leading to further increases in intracellular methylglyoxal and AGEs, and therefore triggering and/or worsening ND.

  5. Myosteatosis increases with aging and is associated with incident diabetes in African ancestry men

    PubMed Central

    Miljkovic, I; Kuipers, AL; Cvejkus, R; Bunker, CH; Patrick, AL; Gordon, CL; Zmuda, JM

    2015-01-01

    Objective Skeletal muscle fat infiltration (known as myosteatosis) is greater in African compared with European ancestry men and may play an important role in the development of type 2 diabetes (T2D). However, prospective studies examining the magnitude of changes in myosteatosis with aging and their metabolic consequences are sparse. Methods We examined longitudinal changes in peripheral quantitative computed tomography measured calf myosteatosis [inter-muscular fat (mm2) and skeletal muscle density as a measure of intra-muscular fat (mg/cm3)] in 1,515 Afro-Caribbean men aged 40+ years recruited without regard to their health status. Results During an average of 6.2 years of follow-up, we observed an age-related increase in inter-muscular fat and a decrease in skeletal muscle density (all P<0.0001), which remained significant in those who lost weight, gained weight, or remained weight-stable (all P<0.0001). In addition, muscle density loss accelerated with increasing age (P<0.0001). Increased inter-muscular fat during follow-up was associated with an increased incident risk of T2D independent of factors known to be associated with T2D (Odds ratios per 1-SD increase in inter-muscular fat=1.29; 95% CI=1.08-1.53). Conclusions Our findings suggest that both inter- and intra- muscular fat increase with advancing age and that inter-muscular fat contributes to development of T2D among African ancestry men. PMID:26694517

  6. Age-Related Macular Degeneration: A Scientometric Analysis

    PubMed Central

    Ramin, Shahrokh; Soheilian, Masoud; Habibi, Gholamreza; Ghazavi, Roghayeh; Gharebaghi, Reza; Heidary, Fatemeh

    2015-01-01

    Age-related macular degeneration (ARMD) is a major cause of central blindness among working aged adults across the world. Systematic research planning on any subject, including ARMD is in need of solid data regarding previous efforts in this field and to identify the gaps in the research. This study aimed to elucidate the most important trends, directions, and gap in this subject. The data extracted from the Institute for Scientific Information were used to perform a bibliometric analysis of the scientific productions (1993–2013) about ARMD. Specific parameters related to ARMD were analyzed to obtain a view of the topic’s structure, history, and document relationships. Additionally, the trends and authors in the most influential publications were analyzed. The number of articles in this field was found constantly increasing. Most highly cited articles addressed genetic epidemiology and clinical research topics in this field. During the past 3 years, there has been a trend toward biomarker research. Through performing the first scientometric survey on ARMD research, we analyzed the characteristics of papers and the trends in scientific production. We also identified some of the critical gaps in the current research efforts that would help in large-scale research strategic planning. PMID:26060829

  7. Flavonoids and Age Related Disease: Risk, benefits and critical windows

    PubMed Central

    Prasain, JK; Carlson, SH; Wyss, JM

    2010-01-01

    Plant derived products are consumed by a large percentage of the population to prevent, delay and ameliorate disease burden; however, relatively little is known about the efficacy, safety and underlying mechanisms of these traditional health products, especially when taken in concert with pharmaceutical agents. The flavonoids are a group of plant metabolites that are common in the diet and appear to provide some health benefits. While flavonoids are primarily derived from soy, many are found in fruits, nuts and more exotic sources, e.g., kudzu. Perhaps the strongest evidence for the benefits of flavonoids in diseases of aging relates to their effect on components of the metabolic syndrome. Flavonoids from soy, grape seed, kudzu and other sources all lower arterial pressure in hypertensive animal models and in a limited number of tests in humans. They also decrease the plasma concentration of lipids and buffer plasma glucose. The underlying mechanisms appear to include antioxidant actions, central nervous system effects, gut transport alterations, fatty acid sequestration and processing, PPAR activation and increases in insulin sensitivity. In animal models of disease, dietary flavonoids also demonstrate a protective effect against cognitive decline, cancer and metabolic disease. However, research also indicates that the flavonoids can be detrimental in some settings and, therefore, are not universally safe. Thus, as the population ages, it is important to determine the impact of these agents on prevention/attenuation of disease, including optimal exposure (intake, timing/duration) and potential contraindications. PMID:20181448

  8. Age-Related Changes in Demand–Withdraw Communication Behaviors

    PubMed Central

    Holley, Sarah R.; Haase, Claudia M.; Levenson, Robert W.

    2013-01-01

    Demand–withdraw communication is a set of conflict-related behaviors in which one partner blames or pressures while the other partner withdraws or avoids. The present study examined age-related changes in these behaviors longitudinally over the course of later life stages. One hundred twenty-seven middle-aged and older long-term married couples were observed at 3 time points across 13 years as they engaged in a conversation about an area of relationship conflict. Husbands’ and wives’ demand–withdraw behaviors (i.e., blame, pressure, withdrawal, avoidance) were objectively rated by trained coders at each time point. Data were analyzed using dyad-level latent growth curve models in a structural equation modeling framework. For both husbands and wives, the results showed a longitudinal pattern of increasing avoidance behavior over time and stability in all other demand and withdraw behaviors. This study supports the notion that there is an important developmental shift in the way that conflict is handled in later life. PMID:23913982

  9. Age-related synthesis of glucocorticoids in thymocytes

    SciTech Connect

    Qiao Shengjun Chen Liying; Okret, Sam; Jondal, Mikael

    2008-10-01

    Glucocorticoids (GCs) are primarily synthesized in the adrenal glands but an ectopic production has also been reported in the brain, the gastrointestinal tract and in thymic epithelial cells (TEC). Here we show that thymocytes express genes encoding for all enzymes required for de novo GC synthesis and produce the hormone as demonstrated by both a GC specific reporter assay and a corticosterone specific ELISA assay. Interestingly, GC synthesis is detectable in cells from young mice (4 weeks) and thereafter increases during aging (14-22 weeks) together with an increased gene expression of the rate-limiting enzymes StAR and CYP11A1. Hormone production occurred at a thymocyte differentiation stage characterized by being double positive for the CD4 and CD8 surface markers but was found to be unrelated to CD69 expression, a marker for thymocytes undergoing positive selection. No GC synthesis was found in resting or anti-CD3 activated CD4 and CD8 positive T cells isolated from the spleen. Thymocyte-derived GC had an anti-proliferative effect on a GR-transfected cell line and induced apoptosis in thymocytes. The age- and differentiation stage-related GC synthesis in thymocytes may play a role in the involution process that the thymus gland undergoes.

  10. Neuroanatomy accounts for age-related changes in risk preferences

    PubMed Central

    Grubb, Michael A.; Tymula, Agnieszka; Gilaie-Dotan, Sharon; Glimcher, Paul W.; Levy, Ifat

    2016-01-01

    Many decisions involve uncertainty, or ‘risk', regarding potential outcomes, and substantial empirical evidence has demonstrated that human aging is associated with diminished tolerance for risky rewards. Grey matter volume in a region of right posterior parietal cortex (rPPC) is predictive of preferences for risky rewards in young adults, with less grey matter volume indicating decreased tolerance for risk. That grey matter loss in parietal regions is a part of healthy aging suggests that diminished rPPC grey matter volume may have a role in modulating risk preferences in older adults. Here we report evidence for this hypothesis and show that age-related declines in rPPC grey matter volume better account for age-related changes in risk preferences than does age per se. These results provide a basis for understanding the neural mechanisms that mediate risky choice and a glimpse into the neurodevelopmental dynamics that impact decision-making in an aging population. PMID:27959326

  11. Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice

    PubMed Central

    Bitto, Alessandro; Ito, Takashi K; Pineda, Victor V; LeTexier, Nicolas J; Huang, Heather Z; Sutlief, Elissa; Tung, Herman; Vizzini, Nicholas; Chen, Belle; Smith, Kaleb; Meza, Daniel; Yajima, Masanao; Beyer, Richard P; Kerr, Kathleen F; Davis, Daniel J; Gillespie, Catherine H; Snyder, Jessica M; Treuting, Piper M; Kaeberlein, Matt

    2016-01-01

    The FDA approved drug rapamycin increases lifespan in rodents and delays age-related dysfunction in rodents and humans. Nevertheless, important questions remain regarding the optimal dose, duration, and mechanisms of action in the context of healthy aging. Here we show that 3 months of rapamycin treatment is sufficient to increase life expectancy by up to 60% and improve measures of healthspan in middle-aged mice. This transient treatment is also associated with a remodeling of the microbiome, including dramatically increased prevalence of segmented filamentous bacteria in the small intestine. We also define a dose in female mice that does not extend lifespan, but is associated with a striking shift in cancer prevalence toward aggressive hematopoietic cancers and away from non-hematopoietic malignancies. These data suggest that a short-term rapamycin treatment late in life has persistent effects that can robustly delay aging, influence cancer prevalence, and modulate the microbiome. DOI: http://dx.doi.org/10.7554/eLife.16351.001 PMID:27549339

  12. Malaria in school-age children in Africa: an increasingly important challenge

    PubMed Central

    Nankabirwa, Joaniter; Brooker, Simon J; Clarke, Sian E; Fernando, Deepika; Gitonga, Caroline W; Schellenberg, David; Greenwood, Brian

    2014-01-01

    School-age children have attracted relatively little attention as a group in need of special measures to protect them against malaria. However, increasing success in lowering the level of malaria transmission in many previously highly endemic areas will result in children acquiring immunity to malaria later in life than has been the case in the past. Thus, it can be anticipated that in the coming years there will be an increase in the incidence of both uncomplicated and severe malaria in school-age children in many previously highly endemic areas. In this review, which focuses primarily on Africa, recent data on the prevalence of malaria parasitaemia and on the incidence of clinical malaria in African school-age children are presented and evidence that malaria adversely effects school performance is reviewed. Long-lasting insecticide treated bednets (LLIN) are an effective method of malaria control but several studies have shown that school-age children use LLINs less frequently than other population groups. Antimalarial drugs are being used in different ways to control malaria in school-age children including screening and treatment and intermittent preventive treatment. Some studies of chemoprevention in school-age children have shown reductions in anaemia and improved school performance but this has not been the case in all trials and more research is needed to identify the situations in which chemoprevention is likely to be most effective and, in these situations, which type of intervention should be used. In the longer term, malaria vaccines may have an important role in protecting this important section of the community from malaria. Regardless of the control approach selected, it is important this is incorporated into the overall programme of measures being undertaken to enhance the health of African school-age children. PMID:25145389

  13. Malaria in school-age children in Africa: an increasingly important challenge.

    PubMed

    Nankabirwa, Joaniter; Brooker, Simon J; Clarke, Sian E; Fernando, Deepika; Gitonga, Caroline W; Schellenberg, David; Greenwood, Brian

    2014-11-01

    School-age children have attracted relatively little attention as a group in need of special measures to protect them against malaria. However, increasing success in lowering the level of malaria transmission in many previously highly endemic areas will result in children acquiring immunity to malaria later in life than has been the case in the past. Thus, it can be anticipated that in the coming years there will be an increase in the incidence of both uncomplicated and severe malaria in school-age children in many previously highly endemic areas. In this review, which focuses primarily on Africa, recent data on the prevalence of malaria parasitaemia and on the incidence of clinical malaria in African school-age children are presented and evidence that malaria adversely effects school performance is reviewed. Long-lasting insecticide treated bednets (LLIN) are an effective method of malaria control but several studies have shown that school-age children use LLINs less frequently than other population groups. Antimalarial drugs are being used in different ways to control malaria in school-age children including screening and treatment and intermittent preventive treatment. Some studies of chemoprevention in school-age children have shown reductions in anaemia and improved school performance but this has not been the case in all trials and more research is needed to identify the situations in which chemoprevention is likely to be most effective and, in these situations, which type of intervention should be used. In the longer term, malaria vaccines may have an important role in protecting this important section of the community from malaria. Regardless of the control approach selected, it is important this is incorporated into the overall programme of measures being undertaken to enhance the health of African school-age children.

  14. Epigenome-Wide Scans Identify Differentially Methylated Regions for Age and Age-Related Phenotypes in a Healthy Ageing Population

    PubMed Central

    Yang, Tsun-Po; Pidsley, Ruth; Nisbet, James; Glass, Daniel; Mangino, Massimo; Zhai, Guangju; Zhang, Feng; Valdes, Ana; Shin, So-Youn; Dempster, Emma L.; Murray, Robin M.; Grundberg, Elin; Hedman, Asa K.; Nica, Alexandra; Small, Kerrin S.; Dermitzakis, Emmanouil T.; McCarthy, Mark I.; Mill, Jonathan; Spector, Tim D.; Deloukas, Panos

    2012-01-01

    Age-related changes in DNA methylation have been implicated in cellular senescence and longevity, yet the causes and functional consequences of these variants remain unclear. To elucidate the role of age-related epigenetic changes in healthy ageing and potential longevity, we tested for association between whole-blood DNA methylation patterns in 172 female twins aged 32 to 80 with age and age-related phenotypes. Twin-based DNA methylation levels at 26,690 CpG-sites showed evidence for mean genome-wide heritability of 18%, which was supported by the identification of 1,537 CpG-sites with methylation QTLs in cis at FDR 5%. We performed genome-wide analyses to discover differentially methylated regions (DMRs) for sixteen age-related phenotypes (ap-DMRs) and chronological age (a-DMRs). Epigenome-wide association scans (EWAS) identified age-related phenotype DMRs (ap-DMRs) associated with LDL (STAT5A), lung function (WT1), and maternal longevity (ARL4A, TBX20). In contrast, EWAS for chronological age identified hundreds of predominantly hyper-methylated age DMRs (490 a-DMRs at FDR 5%), of which only one (TBX20) was also associated with an age-related phenotype. Therefore, the majority of age-related changes in DNA methylation are not associated with phenotypic measures of healthy ageing in later life. We replicated a large proportion of a-DMRs in a sample of 44 younger adult MZ twins aged 20 to 61, suggesting that a-DMRs may initiate at an earlier age. We next explored potential genetic and environmental mechanisms underlying a-DMRs and ap-DMRs. Genome-wide overlap across cis-meQTLs, genotype-phenotype associations, and EWAS ap-DMRs identified CpG-sites that had cis-meQTLs with evidence for genotype–phenotype association, where the CpG-site was also an ap-DMR for the same phenotype. Monozygotic twin methylation difference analyses identified one potential environmentally-mediated ap-DMR associated with total cholesterol and LDL (CSMD1). Our results suggest that in a

  15. Age-related changes to the neural correlates of working memory which emerge after midlife.

    PubMed

    Macpherson, Helen N; White, David J; Ellis, Kathryn A; Stough, Con; Camfield, David; Silberstein, Richard; Pipingas, Andrew

    2014-01-01

    Previous research has indicated that the neural processes which underlie working memory change with age. Both age-related increases and decreases to cortical activity have been reported. This study investigated which stages of working memory are most vulnerable to age-related changes after midlife. To do this we examined age-differences in the 13 Hz steady state visually evoked potential (SSVEP) associated with a spatial working memory delayed response task. Participants were 130 healthy adults separated into a midlife (40-60 years) and an older group (61-82 years). Relative to the midlife group, older adults demonstrated greater bilateral frontal activity during encoding and this pattern of activity was related to better working memory performance. In contrast, evidence of age-related under activation was identified over left frontal regions during retrieval. Findings from this study suggest that after midlife, under-activation of frontal regions during retrieval contributes to age-related decline in working memory performance.

  16. The Role of Social Activity in Age-Cognition Relations

    ERIC Educational Resources Information Center

    Soubelet, Andrea

    2013-01-01

    The goal of the current project was to examine whether engaging in social activity may moderate or mediate the relation between age and cognitive functioning. A large age range sample of adults performed a variety of cognitive tests and completed a social activities questionnaire. Results did not support the moderator hypothesis, as age…

  17. Nutritional influences on epigenetics and age-related disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nutritional epigenetics has emerged as a novel mechanism underlying gene–diet interactions, further elucidating the modulatory role of nutrition in aging and age-related disease development. Epigenetics is defined as a heritable modification to the DNA that regulates chromosome architecture and modu...

  18. Age-Related Differences in Moral Identity across Adulthood

    ERIC Educational Resources Information Center

    Krettenauer, Tobias; Murua, Lourdes Andrea; Jia, Fanli

    2016-01-01

    In this study, age-related differences in adults' moral identity were investigated. Moral identity was conceptualized a context-dependent self-structure that becomes differentiated and (re)integrated in the course of development and that involves a broad range of value-orientations. Based on a cross-sectional sample of 252 participants aged 14 to…

  19. Computer Use and the Relation between Age and Cognitive Functioning

    ERIC Educational Resources Information Center

    Soubelet, Andrea

    2012-01-01

    This article investigates whether computer use for leisure could mediate or moderate the relations between age and cognitive functioning. Findings supported smaller age differences in measures of cognitive functioning for people who reported spending more hours using a computer. Because of the cross-sectional design of the study, two alternative…

  20. Nutritional modulation of age-related macular degeneration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30-50 million individuals and clinical hallmarks of AMD are observed in at least one third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated wi...

  1. Birth Order, Age-Spacing, IQ Differences, and Family Relations.

    ERIC Educational Resources Information Center

    Pfouts, Jane H.

    1980-01-01

    Very close age spacing was an obstacle to high academic performance for later borns. In family relations and self-esteem, first borns scored better and performed in school as well as their potentially much more able younger siblings, regardless of age spacing. (Author)

  2. Age-Related Differences in Nonverbal Decoding Ability.

    ERIC Educational Resources Information Center

    Liebermann, Devorah A.; And Others

    1988-01-01

    Reports a study comparing the nonverbal decoding ability (under auditory, visual, and audio-visual conditions) of college age females with elderly females, in order to identify preliminary nonverbal differences which may be related to aging. Finds that the elderly were significantly less skilled in decoding nonverbal behaviors across all…

  3. The Age-related Positivity Effect and Tobacco Warning Labels

    PubMed Central

    Roberts, Megan E.; Peters, Ellen; Ferketich, Amy K.; Klein, Elizabeth G.

    2016-01-01

    Objectives This study tested whether age is a factor in viewing time for tobacco warning labels. The approach drew from previous work demonstrating an age-related positivity effect, whereby older adults show preferences toward positive and away from negative stimuli. Methods Participants were 295 daily smokers from Appalachian Ohio (age range: 21–68). All participants took part in an eye-tracking paradigm that captured the attention paid to elements of health warning labels in the context of magazine advertisements. Participants also reported on their past cessation attempts and their beliefs about the dangers of smoking. Results Consistent with theory on age-related positivity, older age predicted weaker beliefs about smoking risks, but only among those with no past-year quit attempts. In support of our primary hypothesis, older age was also related to a lower percentage of time spent viewing tobacco warning labels, both overall (text + image) and for the graphic image alone. These associations remained after controlling for cigarettes smoked per day. Conclusions Overall, findings suggest that age is an important consideration for the design of future graphic warning labels and other tobacco risk communications. For older adults, warning labels may need to be tailored to overcome the age-related positivity effect. PMID:27617273

  4. Ageing and apoE change DHA homeostasis: relevance to age-related cognitive decline.

    PubMed

    Hennebelle, Marie; Plourde, Mélanie; Chouinard-Watkins, Raphaël; Castellano, Christian-Alexandre; Barberger-Gateau, Pascale; Cunnane, Stephen C

    2014-02-01

    Epidemiological studies fairly convincingly suggest that higher intakes of fatty fish and n-3 fatty acids are associated with reduced risk of Alzheimer's disease (AD). DHA in plasma is normally positively associated with DHA intake. However, despite being associated with lower fish and DHA intake, unexpectedly, plasma (or brain) DHA is frequently not lower in AD. This review will highlight some metabolic and physiological factors such as ageing and apoE polymorphism that influence DHA homeostasis. Compared with young adults, blood DHA is often slightly but significantly higher in older adults without any age-related cognitive decline. Higher plasma DHA in older adults could be a sign that their fish or DHA intake is higher. However, our supplementation and carbon-13 tracer studies also show that DHA metabolism, e.g. transit through the plasma, apparent retroconversion and β-oxidation, is altered in healthy older compared with healthy young adults. ApoE4 increases the risk of AD, possibly in part because it too changes DHA homeostasis. Therefore, independent of differences in fish intake, changing DHA homeostasis may tend to obscure the relationship between DHA intake and plasma DHA which, in turn, may contribute to making older adults more susceptible to cognitive decline despite older adults having similar or sometimes higher plasma DHA than in younger adults. In conclusion, recent development of new tools such as isotopically labelled DHA to study DHA metabolism in human subjects highlights some promising avenues to evaluate how and why DHA metabolism changes during ageing and AD.

  5. Metabolomics of human brain aging and age-related neurodegenerative diseases.

    PubMed

    Jové, Mariona; Portero-Otín, Manuel; Naudí, Alba; Ferrer, Isidre; Pamplona, Reinald

    2014-07-01

    Neurons in the mature human central nervous system (CNS) perform a wide range of motor, sensory, regulatory, behavioral, and cognitive functions. Such diverse functional output requires a great diversity of CNS neuronal and non-neuronal populations. Metabolomics encompasses the study of the complete set of metabolites/low-molecular-weight intermediates (metabolome), which are context-dependent and vary according to the physiology, developmental state, or pathologic state of the cell, tissue, organ, or organism. Therefore, the use of metabolomics can help to unravel the diversity-and to disclose the specificity-of metabolic traits and their alterations in the brain and in fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of aging and neurodegenerative diseases. Here, we review the current applications of metabolomics in studies of CNS aging and certain age-related neurodegenerative diseases such as Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Neurometabolomics will increase knowledge of the physiologic and pathologic functions of neural cells and will place the concept of selective neuronal vulnerability in a metabolic context.

  6. The Relative Age Effect and Its Influence on Academic Performance

    PubMed Central

    Navarro, Juan-José; García-Rubio, Javier; Olivares, Pedro R.

    2015-01-01

    performance. Conclusions The RAE remains, even with residual values, an explanatory factor in academic performance even in eighth graders. Since the RAE decreases as the influence of schooling increases, the potential adverse effects for some students would be placed in previous and initial moments of formal schooling. These findings may be useful into taking steps towards flexibilisation on age of entry in compulsory schooling. Moreover, the need to implement early, comprehensive evaluation systems which include aspects related to neurodevelopment in order to provide maximum information to parents and educators is also drawn. PMID:26517552

  7. BOLD Variability is Related to Dopaminergic Neurotransmission and Cognitive Aging.

    PubMed

    Guitart-Masip, Marc; Salami, Alireza; Garrett, Douglas; Rieckmann, Anna; Lindenberger, Ulman; Bäckman, Lars

    2016-05-01

    Dopamine (DA) losses are associated with various aging-related cognitive deficits. Typically, higher moment-to-moment brain signal variability in large-scale patterns of voxels in neocortical regions is linked to better cognitive performance and younger adult age, yet the physiological mechanisms regulating brain signal variability are unknown. We explored the relationship among adult age, DA availability, and blood oxygen level-dependent (BOLD) signal variability, while younger and older participants performed a spatial working memory (SWM) task. We quantified striatal and extrastriatal DA D1 receptor density with [(11)C]SCH23390 and positron emission tomography in all participants. We found that BOLD variability in a neocortical region was negatively related to age and positively related to SWM performance. In contrast, BOLD variability in subcortical regions and bilateral hippocampus was positively related to age and slower responses, and negatively related to D1 density in caudate and dorsolateral prefrontal cortex. Furthermore, BOLD variability in neocortical regions was positively associated with task-related disengagement of the default-mode network, a network whose activation needs to be suppressed for efficient SWM processing. Our results show that age-related DA losses contribute to changes in brain signal variability in subcortical regions and suggest a potential mechanism, by which neocortical BOLD variability supports cognitive performance.

  8. Neuroanatomical substrates of age-related cognitive decline

    PubMed Central

    Salthouse, Timothy A.

    2011-01-01

    There are many reports of relations between age and cognitive variables and of relations between age and variables representing different aspects of brain structure, and a few reports of relations between brain structure variables and cognitive variables. These findings have sometimes led to inferences that the age-related brain changes cause the age-related cognitive changes. Although this conclusion may well be true, it is widely recognized that simple correlations are not sufficient to warrant causal conclusions, and other types of correlational information, such as mediation and correlations between longitudinal brain changes and longitudinal cognitive changes, also have limitations with respect to causal inferences. These issues are discussed, and the existing results on relations of regional volume, white matter hyperintensities, and DTI measures of white matter integrity to age and to measures of cognitive functioning are reviewed. It is concluded that at the current time the evidence that these aspects of brain structure are neuroanatomical substrates of age-related cognitive decline is weak. The final section contains several suggestions concerned with measurement and methodology that may lead to stronger conclusions in the future. PMID:21463028

  9. Relationship Between Age, Tenure, and Disability Duration in Persons With Compensated Work-Related Conditions

    PubMed Central

    Besen, Elyssa; Young, Amanda E.; Gaines, Brittany; Pransky, Glenn

    2016-01-01

    Objective: The aim of the study was to examine the relationships among age, tenure, and the length of disability following a work-related injury/illness. Methods: This study utilized 361,754 administrative workers’ compensation claims. The relationships between age, tenure, and disability duration was estimated with random-effects models. Results: The age-disability duration relationship was stronger than the tenure-disability duration relationship. An interaction was observed between age and tenure. At younger ages, disability duration varied little based on tenure. In midlife, disability duration was greater for workers with lower tenure than for workers with higher tenure. At the oldest ages, disability duration increased as tenure increased. Conclusions: Findings indicate that age is a more important factor in disability duration than tenure; however, the relationship between age and disability duration varies based on tenure, suggesting that both age and tenure are important influences in the work-disability process. PMID:26645384

  10. Diversity of gut microbiota increases with aging and starvation in the desert locust.

    PubMed

    Dillon, Rod J; Webster, Gordon; Weightman, Andrew J; Keith Charnley, A

    2010-01-01

    Here we report the effects of starvation and insect age on the diversity of gut microbiota of adult desert locusts, Schistocerca gregaria, using denaturing gradient gel electrophoretic (DGGE) analysis of bacterial 16S rRNA genes. Sequencing of excised DGGE bands revealed the presence of only one potentially novel uncultured member of the Gammaproteobacteria in the guts of fed, starved, young or old locusts. Most of the 16S rRNA gene sequences were closely related to known cultured bacterial species. DGGE profiles suggested that bacterial diversity increased with insect age and did not provide evidence for a characteristic locust gut bacterial community. Starved insects are often more prone to disease, probably because they compromise on immune defence. However, the increased diversity of Gammaproteobacteria in starved locusts shown here may improve defence against enteric threats because of the role of gut bacteria in colonization resistance.

  11. The genetics of age-related macular degeneration.

    PubMed

    Guymer, Robyn

    2001-07-01

    AIM: To review the genetics of age-related macular degeneration (AMD). The pathogenesis of AMD, the leading cause of severe visual disability and blindness in our community, remains unknown. However, AMD is regarded as a genetic disease where family history of AMD is a significant risk factor for the disease. Understanding the genetic factors associated with AMD offers the greatest chance for understanding the underlying disease processes. METHODS: Through a review of the literature and the use of original research findings, the current knowledge of the genetics of AMD is explored. CONCLUSION: AMD is increasing in prevalence and remains a major challenge for eye heath providers. Finding the genes that are associated with AMD offers the greatest chance for the development of preventative strategies and treatments.

  12. Meta-analysis of Gene Expression in the Mouse Liver Reveals Biomarkers Associated with Inflammation Increased Early During Aging

    EPA Science Inventory

    Aging is associated with a predictable loss of cellular homeostasis, a decline in physiological function and an increase in various diseases. We hypothesized that similar age-related gene expression profiles would be observed in mice across independent studies. Employing a metaan...

  13. Diminished acute phase response and increased hepatic inflammation of aged rats in response to intraperitoneal injection of lipopolysaccharide.

    PubMed

    Gomez, Christian R; Acuña-Castillo, Claudio; Pérez, Claudio; Leiva-Salcedo, Elías; Riquelme, Denise M; Ordenes, Gamaliel; Oshima, Kiyoko; Aravena, Mauricio; Pérez, Viviana I; Nishimura, Sumiyo; Sabaj, Valeria; Walter, Robin; Sierra, Felipe

    2008-12-01

    Aging is associated with a deterioration of the acute phase response to inflammatory challenges. However, the nature of these defects remains poorly defined. We analyzed the hepatic inflammatory response after intraperitoneal administration of lipopolysaccharide (LPS) given to Fisher 344 rats aged 6, 15, and 22-23 months. Induction of the acute phase proteins (APPs), haptoglobin, alpha-1-acid glycoprotein, and T-kininogen was reduced and/or retarded with aging. Initial induction of interleukin-6 in aged rats was normal, but the later response was increased relative to younger counterparts. An exacerbated hepatic injury was observed in aged rats receiving LPS, as evidenced by the presence of multiple microabscesses in portal tracts, confluent necrosis, higher neutrophil accumulation, and elevated serum levels of alanine aminotransferase, relative to younger animals. Our results suggest that aged rats displayed a reduced expression of APPs and increased hepatic injury in response to the inflammatory insult.

  14. Age-related changes in long-term average spectra of children's voices.

    PubMed

    Sergeant, Desmond; Welch, Graham Frederick

    2008-11-01

    This paper forms part of a larger study into the nature of singing development in children. The focus here is on an investigation of age-related changes in long-term average spectra (LTAS). Three hundred and twenty children in age groups 4-11 years learned a song. Each child was then digitally recorded singing alone. LTAS curves were calculated from the recordings of each voice and perceived age was estimated by a panel of independent judges. Progressive statistically significant changes were observed in the LTAS as a function of increasing age of the children. These took the form of increases in spectral energy in all frequencies below 5.75 kHz, with concomitant reductions of energy in frequency regions above this point. Increases with age were also found in overall intensity levels of the vocal products. Four experienced listeners audited the voice samples and made estimates of the children's ages. The level of accuracy of age-estimates was remarkably high for children in the youngest age groups, but was reduced with voice samples from older children. Maturation and developing competence of the vocal system, both in growth of lung capacity and at a laryngeal level, are implicated in the generation of age-related spectral changes. Perceived child singer age appears to be less closely related to spectral characteristics (as defined within LTAS) with increasing age of children.

  15. Age-related change of endocytic receptors megalin and cubilin in the kidney in rats.

    PubMed

    Odera, Keiko; Goto, Sataro; Takahashi, Ryoya

    2007-10-01

    Megalin and cubilin are the major endocytic receptors responsible for resorption of glomerular filtrate proteins, particularly albumin, in the renal proximal tubule. In order to better understand the mechanism of the development of albuminuria with age in rats, we investigated age-related change of the amount and cellular localization of both receptors in the kidney. Immunoblot analysis of the kidney extracts showed that the amount of megalin significantly decreased with age. Although there was no age-related change in the amount of intact cubilin, the amount of cubilin fragments increased with age. Immunohistochemical study revealed that megalin and cubilin were predominantly localized in brush border membrane of proximal tubular cells in young rats, but the receptors tended to diffuse into the cytoplasm in the old rats. Interestingly, low but significant amounts of megalin and cubilin were present in the glomerular cells in addition to the proximal tubular cells. The quantity of receptors progressively increased in the glomerulus with age. This age-related increase might be to compensate for the age-related defect of the uptake of albumin by the proximal tubules. Thus, although it is unclear whether megalin and cubilin in the glomerulus contribute to the uptake of albumin in primary urine, the age-related increase in the amount of albumin in urine might at least partly be due to quantitative and qualitative alterations of both receptors in the proximal tubule.

  16. Alfacalcidol increases cancellous bone in low turnover, fatty marrow sites in aged, orchidectomized rats.

    PubMed

    Tian, X Y; Chen, H Y; Setterberg, R B; Li, M; Jee, W S S

    2009-01-01

    The objectives of this study were to determine the responses of cancellous bone in the distal tibial metaphysis (DTM), a low turnover, fatty (yellow) marrow site, to sham-aged, orchidectomy (ORX) and alfacalcidol treatment in sham-aged and ORX rats. Eighteen-month-old male sham and ORX rats were treated with 0.1 and 0.2 microg/kg alfacalcidol 5 days/wk p.o. for 12 weeks, double fluorescent labeled, and the DTM were processed for bone histomorphometry analyses. The current study found the DTM in sham-aged male rats were resistant to age-related and ORX-induced cancellous bone loss and alfacalcidol-induced bone gain, findings that differ from that in the proximal tibial metaphysis (PTM) and lumbar vertebral body (LVB), two high turnover, red marrow bone sites. However, alfacalcidol treatment increased DTM bone mass in ORX rats where bone turnover was elevated by androgen deficiency. These results in concert with the previously positive findings in red marrow bone sites following alfacalcidol treatment suggest that alfacalcidol is more effective in increasing cancellous bone mass in the skeletal sites with higher bone turnover.

  17. Aging assessment of reactor instrumentation and protection system components. Aging-related operating experiences

    SciTech Connect

    Gehl, A.C.; Hagen, E.W.

    1992-07-01

    A study of the aging-related operating experiences throughout a five-year period (1984--1988) of six generic instrumentation modules (indicators, sensors, controllers, transmitters, annunciators, and recorders) was performed as a part of the Nuclear Plant Aging Research Program. The effects of aging from operational and environmental stressors were characterized from results depicted in Licensee Event Reports (LERs). The data are graphically displayed as frequency of events per plant year for operating plant ages from 1 to 28 years to determine aging-related failure trend patterns. Three main conclusions were drawn from this study: (1) Instrumentation and control (I&C) modules make a modest contribution to safety-significant events: 17% of LERs issued during 1984--1988 dealt with malfunctions of the six I&C modules studied, and 28% of the LERs dealing with these I&C module malfunctions were aging related (other studies show a range 25--50%); (2) Of the six modules studied, indicators, sensors, and controllers account for the bulk (83%) of aging-related failures; and (3) Infant mortality appears to be the dominant aging-related failure mode for most I&C module categories (with the exception of annunciators and recorders, which appear to fail randomly).

  18. Health- and Disease-Related Biomarkers in Aging Research

    PubMed Central

    Thompson, Hilaire J.; Voss, Joachim G.

    2011-01-01

    This article focuses on a synthesis of knowledge about healthy aging research in human beings and then synthesized nurse-led research in gerontology and geriatrics that use biomarkers. Healthy aging research has attracted considerable attention in the biomedical and basic sciences within the context of four major areas: (a) genetic variations as an expression of successful or unsuccessful aging; (b) caloric restriction as an intervention to slow the progression of aging; (c) immunological aging; (d) neurobiology of the aging brain. A systematic review of the literature was performed to identify nurse-led geriatric-related biomarker research. Nurse researchers who have chosen to integrate biomarkers as part of their research studies have been working in six focal areas, which are reviewed: health promotion within risk populations, cancer, vascular disease, Alzheimer’s disease, caregiving, and complementary therapies. The article provides a discussion of contributions to date, identifying existing gaps and future research opportunities. PMID:20077975

  19. Frontotemporal Network Connectivity during Memory Encoding Is Increased with Aging and Disrupted by Beta-Amyloid

    PubMed Central

    Jagust, William J.

    2013-01-01

    Approximately 30% of cognitively normal older adults harbor brain β-amyloid (Aβ), a prominent feature of Alzheimer's disease associated with neural alterations and episodic memory decline. We examined how aging and Aβ deposition affect neural function during memory encoding of visual scenes using functional magnetic resonance imaging (fMRI) in humans. Thirty-six cognitively normal older people underwent fMRI scanning, and positron emission tomography with [11C] Pittsburgh compound B to measure fibrillar brain Aβ; 15 young subjects were studied with fMRI. Older adults without Aβ deposition showed reduced regional brain activation (compared with young subjects) with decreased task-independent functional connectivity between parahippocampal gyrus and prefrontal cortex. In this network, task-related connectivity was increased compared with young subjects, and the degree of connectivity was related to memory performance. In contrast, older individuals with Aβ deposition showed no such increased task-related network connectivity, but did display increased regional activity unassociated with performance. These findings suggest that network connectivity plays a significant role in compensating for reduced regional activity during successful memory encoding in aging without Aβ deposition, while in those with Aβ this network compensation fails and is accompanied by inefficient regional hyperactivation. PMID:24259567

  20. Therapeutic Modalities of Exudative Age-related Macular Degeneration

    PubMed Central

    Mavija, Milka; Alimanovic, Emina; Jaksic, Vesna; Kasumovic, Sanja Sefic; Cekic, Sonja; Stamenkovic, Miroslav

    2014-01-01

    Introduction: Age-related macular degeneration (AMD) is a leading cause of irreversible serious vision damage in persons over 50 years of age. In treating AMD many medicaments are applied such as inhibitors of vascular endothelial growth factor (VEGF), have been very carefully included over the last few years after a series of study research. Aims: To analyze the past methods of treatment, discuss emerging therapies which could advance the treatment of exudative AMD. The past anti-VEGF therapies require frequent repetitions of administration, with uncertain visual acuity recovery, as not all patients react to anti-VEGF therapy. Consequently, there is a need to find out additional therapies which could improve the treatment of exudative AMD. The real aim in the treating of AMD is to prevent CNV development. Methods: A survey of the current clinical research and results in the field of the present and future treatments of exudative AMD. Results: There are many areas of research into new methods of the exudative AMD treatment. Conclusion: The future therapies for exudative AMD treatment have a potential not only to reduce the frequency of administration and follow-up visits, but also to improve effects of treatment by targeting additional ways of CNV development, increasing the aptitude of target binding and extending durability of treatment. PMID:25568535

  1. Age-dependent increase in the expression of antioxidant-like protein-1 in the gerbil hippocampus

    PubMed Central

    Park, Jin-A; Park, Joon Ha; Ahn, Ji Hyeon; Kim, Jong-Dai; Won, Moo-Ho; Lee, Choong-Hyun

    2016-01-01

    Antioxidant-like protein-1 (AOP-1) reduces the intracellular level of reactive oxygen species. In the present study, the age-related change in AOP-1 expression in the hippocampus among young, adult and aged gerbils was compared using western blot analysis and immunohistochemistry. The results demonstrated that the protein expression of AOP-1 was gradually and significantly increased in the hippocampus during the normal aging process. In addition, the age-dependent increase in AOP-1 immunoreactivity was also observed in pyramidal neurons of the hippocampus proper; however, in the dentate gyrus, AOP-1 immunoreactivity was not altered during the normal aging process. These results indicated that the expression of AOP-1 is significantly increased in the hippocampus proper, but not in the dentate gyrus, during the normal aging process. PMID:27511601

  2. Increases in norepinephrine release and ovarian cyst formation during ageing in the rat

    PubMed Central

    Acuña, Eric; Fornes, Romina; Fernandois, Daniela; Garrido, Maritza P; Greiner, Monika; Lara, Hernan E; Paredes, Alfonso H

    2009-01-01

    Background Depletion of ovarian follicles is associated with the end of reproductive function in ageing females. Recently, it has been described that this process parallels increases in the concentration of norepinephrine (NE) in the rat ovary. In sexually mature rats, experimentally-induced increases in the sympathetic tone of the ovary is causally related to ovarian cyst formation and deranged follicular development. Thus, there is a possibility that increased ovarian NE concentrations represent changes in the activity of sympathetic nerves, which consequently participate in the process of ovarian cyst formation observed during ageing in the human and experimental animal models. Methods Sprague-Dawley rats between 6 and 14 months old were used to analyse the capacity of the ovary to release 3H-NE recently incorporated under transmural depolarisation in relation to changes in the ovarian follicular population. Morphometric analysis of ovarian follicles and real time PCR for Bcl2 and Bax mRNA were used to assess follicular atresia. Results From 8 months old, the induced release of recently incorporated 3H-norepinephrine (3H-NE) from the ovary and ovarian NE concentrations increased, reaching their peak values at 12 months old and remained elevated up to 14 months old. Increases in sympathetic nerve activity paralleled changes in the follicular population, as well as disappearance of the corpus luteum. In contrast, luteinised follicles, precystic follicles, and cystic follicles increased. During this period, the relationship between Bax and Bcl2 mRNAs (the proapoptotic/antiapoptotic signals) increased, suggesting atresia as the principal mechanism contributing to the decreased follicular population. When NE tone was increased, the mRNA ratio favoured Bcl2 to Bax and antiapoptotic signals dominated this period of development. Thus, these changing ratios could be responsible for the increase in luteinised follicles, as well as precystic and cystic follicles

  3. [Dementia and lifestyle-related diseases in Japanese aging society].

    PubMed

    Iwamoto, Toshihiko

    2011-05-01

    Recently, the number of elderly patients with dementia has been increasing in Japan because of both the extension of average life expectancy and a considerable rise in the incidence of dementia with age. For these reasons, dementia in Japan has become common, and more than half of all cases are Alzheimer disease. This disease has typically been considered to be a degenerative disorder due to genetic abnormalities, but recent epidemiological studies have indicated that lifestyle-related diseases such as hypertension, diabetes, dyslipidemia, and obesity in midlife could accelerate the dementing process, via either vascular changes in cerebral infarction or Alzheimer-related pathological changes with plaque and tangle formations which result in dementia in later life. Furthermore, several studies have suggested that a high intake of vegetables and fish, an active daily life, and lifelong education might positively influence cognitive function as neuroprotective factors. Therefore, we should try to prevent dementia based on the clinical and hygienic management of the lifestyles and lifestyle-related diseases, even in the youth.

  4. Cellular senescence in aging and age-related disease: from mechanisms to therapy

    PubMed Central

    Childs, Bennett G; Durik, Matej; Baker, Darren J; van Deursen, Jan M

    2016-01-01

    Cellular senescence, a process that imposes permanent proliferative arrest on cells in response to various stressors, has emerged as a potentially important contributor to aging and age-related disease, and it is an attractive target for therapeutic exploitation. A wealth of information about senescence in cultured cells has been acquired over the past half century; however, senescence in living organisms is poorly understood, largely because of technical limitations relating to the identification and characterization of senescent cells in tissues and organs. Furthermore, newly recognized beneficial signaling functions of senescence suggest that indiscriminately targeting senescent cells or modulating their secretome for anti-aging therapy may have negative consequences. Here we discuss current progress and challenges in understanding the stressors that induce senescence in vivo, the cell types that are prone to senesce, and the autocrine and paracrine properties of senescent cells in the contexts of aging and age-related diseases as well as disease therapy. PMID:26646499

  5. Cellular senescence in aging and age-related disease: from mechanisms to therapy.

    PubMed

    Childs, Bennett G; Durik, Matej; Baker, Darren J; van Deursen, Jan M

    2015-12-01

    Cellular senescence, a process that imposes permanent proliferative arrest on cells in response to various stressors, has emerged as a potentially important contributor to aging and age-related disease, and it is an attractive target for therapeutic exploitation. A wealth of information about senescence in cultured cells has been acquired over the past half century; however, senescence in living organisms is poorly understood, largely because of technical limitations relating to the identification and characterization of senescent cells in tissues and organs. Furthermore, newly recognized beneficial signaling functions of senescence suggest that indiscriminately targeting senescent cells or modulating their secretome for anti-aging therapy may have negative consequences. Here we discuss current progress and challenges in understanding the stressors that induce senescence in vivo, the cell types that are prone to senesce, and the autocrine and paracrine properties of senescent cells in the contexts of aging and age-related diseases as well as disease therapy.

  6. Relative age effects in Japanese baseball: an historical analysis.

    PubMed

    Nakata, Hiroki; Sakamoto, Kiwako

    2013-08-01

    The present study investigated the existence of the relative age effect, a biased distribution of birth dates, in Japanese professional baseball players born from 1911 to 1980. Japan applies a unique annual-age grouping for sport and education, which is from April 1 to March 31 of the following year. Thus, athletes were divided into four groups based on their month of birth; quarters Q1 (April-June), Q2 (July-September), Q3 (October-December), and Q4 (January-March of the following year). There were statistically biased distributions of birth dates among players born in the 1940s and subsequent decades (medium effects), and similar (but small) relative age effects were observed among players born in the 1910s, 1920s, and 1930s. The magnitude of the relative age effect changed with time, and socio-cultural factors such as international competition and media coverage may have contributed greatly to this effect.

  7. Effects of increased paternal age on sperm quality, reproductive outcome and associated epigenetic risks to offspring.

    PubMed

    Sharma, Rakesh; Agarwal, Ashok; Rohra, Vikram K; Assidi, Mourad; Abu-Elmagd, Muhammad; Turki, Rola F

    2015-04-19

    Over the last decade, there has been a significant increase in average paternal age when the first child is conceived, either due to increased life expectancy, widespread use of contraception, late marriages and other factors. While the effect of maternal ageing on fertilization and reproduction is well known and several studies have shown that women over 35 years have a higher risk of infertility, pregnancy complications, spontaneous abortion, congenital anomalies, and perinatal complications. The effect of paternal age on semen quality and reproductive function is controversial for several reasons. First, there is no universal definition for advanced paternal ageing. Secondly, the literature is full of studies with conflicting results, especially for the most common parameters tested. Advancing paternal age also has been associated with increased risk of genetic disease. Our exhaustive literature review has demonstrated negative effects on sperm quality and testicular functions with increasing paternal age. Epigenetics changes, DNA mutations along with chromosomal aneuploidies have been associated with increasing paternal age. In addition to increased risk of male infertility, paternal age has also been demonstrated to impact reproductive and fertility outcomes including a decrease in IVF/ICSI success rate and increasing rate of preterm birth. Increasing paternal age has shown to increase the incidence of different types of disorders like autism, schizophrenia, bipolar disorders, and childhood leukemia in the progeny. It is thereby essential to educate the infertile couples on the disturbing links between increased paternal age and rising disorders in their offspring, to better counsel them during their reproductive years.

  8. Non-parametric estimation of age-related centiles over wide age ranges.

    PubMed

    Pan, H Q; Goldstein, H; Yang, Q

    1990-01-01

    A new method for estimating age-related centile curves has been developed, which is suitable for measurement covering a wide age range. The method was used to calculate weight centile curves of 8995 children from birth to 6 years obtained by the Collaborating Centre for Physical Growth and Psychosocial Development of Children in Shanghai, China.

  9. Age-related differences in neurotoxicity produced by organophosphorus and N-methyl carbamate pesticides

    EPA Science Inventory

    Potential pesticide effects in infants and toddlers have received much attention in the scientific literature and the public media, including the concern for increased response to acute or shortterm exposures. Age-related differences in the acute neurotoxicity of acetylcholinest...

  10. beta. -adrenergic receptor-mediated hepatic glycogenolysis is increased in aged male rats

    SciTech Connect

    Herring, P.A.; Graham, S.M.; Arinze, I.J.

    1986-03-05

    The effect of age on catecholamine-stimulated glycogenolysis was studied in isolated hepatocytes prepared from 3, 12, and 24 month-old rats. Glucose release was stimulated by epinephrine and norepinephrine, this was inhibited by phentolamine and prazosin. Isoproterenol (ISO) stimulated glycogenolysis only in cells from 24 month-old rats, this was blocked by propranolol. In liver plasma membranes, binding of (/sup 3/H)yohimbine (100-130 fmol/mg protein) did not change with age, whereas (/sup 3/H)prazosin binding decreased from 870 fmol/mg at 3 months to 435 fmol/mg at 12 months, but subsequently rose to 656 fmol/mg at 24 months. (/sup 125/I)Cyanopindolol binding increased from 8 fmol/mg at 3 months to 19 fmol/mg at 24 months. The proportion of ..beta..-receptors in the high affinity state increased from 28% at 3 months to 42% at 24 months. ISO stimulated adenylate cyclase at 24 months but not at 3 months. Basal, fluoride-, GTP-, and Gpp(NH)p-stimulated activities were 1.4- to 2.4-fold greater at 24 months than at 3 months. These results suggest an age-related increase in the sensitivity of adenylate cyclase to ..beta..-receptor stimulation.

  11. Intrinsic stiffness of extracellular matrix increases with age in skeletal muscles of mice.

    PubMed

    Wood, Lauren K; Kayupov, Erdan; Gumucio, Jonathan P; Mendias, Christopher L; Claflin, Dennis R; Brooks, Susan V

    2014-08-15

    Advanced age is associated with increases in muscle passive stiffness, but the contributors to the changes remain unclear. Our purpose was to determine the relative contributions of muscle fibers and extracellular matrix (ECM) to muscle passive stiffness in both adult and old animals. Passive mechanical properties were determined for isolated individual muscle fibers and bundles of muscle fibers that included their associated ECM, obtained from tibialis anterior muscles of adult (8-12 mo old) and old (28-30 mo old) mice. Maximum tangent moduli of individual muscle fibers from adult and old muscles were not different at any sarcomere length tested. In contrast, the moduli of bundles of fibers from old mice was more than twofold greater than that of fiber bundles from adult muscles at sarcomere lengths >2.5 μm. Because ECM mechanical behavior is determined by the composition and arrangement of its molecular constituents, we also examined the effect of aging on ECM collagen characteristics. With aging, muscle ECM hydroxyproline content increased twofold and advanced glycation end-product protein adducts increased threefold, whereas collagen fibril orientation and total ECM area were not different between muscles from adult and old mice. Taken together, these findings indicate that the ECM of tibialis anterior muscles from old mice has a higher modulus than the ECM of adult muscles, likely driven by an accumulation of densely packed extensively crosslinked collagen.

  12. Mass spectrometry-based proteomic analysis of middle-aged vs. aged vastus lateralis reveals increased levels of carbonic anhydrase isoform 3 in senescent human skeletal muscle.

    PubMed

    Staunton, Lisa; Zweyer, Margit; Swandulla, Dieter; Ohlendieck, Kay

    2012-10-01

    The age-related loss of skeletal muscle mass and associated progressive decline in contractile strength is a serious pathophysiological issue in the elderly. In order to investigate global changes in the skeletal muscle proteome after the fifth decade of life, this study analysed total extracts from human vastus lateralis muscle by fluorescence difference in-gel electrophoresis. Tissue specimens were derived from middle-aged (47-62 years) vs. aged (76-82 years) individuals and potential changes in the protein expression profiles were compared between these two age groups by a comprehensive gel electrophoresis-based survey. Age-dependent alterations in the concentration of 19 protein spots were revealed and mass spectrometry identified these components as being involved in the excitation-contraction-relaxation cycle, muscle metabolism, ion handling and the cellular stress response. This indicates a generally perturbed protein expression pattern in senescent human muscle. Increased levels of mitochondrial enzymes and isoform switching of the key contractile protein, actin, support the idea of glycolytic-to-oxidative and fast-to-slow transition processes during muscle aging. Importantly, the carbonic anhydrase (CA)3 isoform displayed an increased abundance during muscle aging, which was independently verified by immunoblotting of differently aged human skeletal muscle samples. Since the CA3 isoform is relatively muscle-specific and exhibits a fibre type-specific expression pattern, this enzyme may represent an interesting new biomarker of sarcopenia. Increased levels of CA are indicative of an increased demand of CO₂-removal in senescent muscle, and also suggest age-related fibre type shifting to slower-contracting muscles during human aging.

  13. Tooth Size Variation Related to Age in Amboseli Baboons

    PubMed Central

    Galbany, Jordi; Dotras, Laia; Alberts, Susan C.; Pérez-Pérez, Alejandro

    2011-01-01

    We measured the molar size from a single population of wild baboons from Amboseli (Kenya), both females (n = 57) and males (n = 50). All the females were of known age; the males represented a mix of known-age individuals (n = 31) and individuals with ages estimated to within 2 years (n = 19). The results showed a significant reduction in the mesiodistal length of teeth in both sexes as a function of age. Overall patterns of age-related change in tooth size did not change whether we included or excluded the individuals of estimated age, but patterns of statistical significance changed as a result of changed sample sizes. Our results demonstrate that tooth length is directly related to age due to interproximal wearing caused by M2 and M3 compression loads. Dental studies in primates, including both fossil and extant species, are mostly based on specimens obtained from osteological collections of varying origins, for which the age at death of each individual in the sample is not known. Researchers should take into account the phenomenon of interproximal attrition leading to reduced tooth size when measuring tooth length for ondontometric purposes. PMID:21325862

  14. Normalisation against Circadian and Age-Related Disturbances Enables Robust Detection of Gene Expression Changes in Liver of Aged Mice

    PubMed Central

    Fonseca Costa, Sara S.; Wegmann, Daniel; Ripperger, Jürgen A.

    2017-01-01

    The expression of some genes is affected by age. To detect such age-related changes, their expression levels are related to constant marker genes. However, transcriptional noise increasing with advancing age renders difficult the identification of real age-related changes because it may affect the marker genes as well. Here, we report a selection procedure for genes appropriate to normalise the mouse liver transcriptome under various conditions including age. These genes were chosen from an initial set of 16 candidate genes defined based on a RNA-sequencing experiment and published literature. A subset of genes was selected based on rigorous statistical assessment of their variability using both RNA-sequencing and Nanostring hybridization experiments. The robustness of these marker genes was then verified by the analysis of 130 publicly available data sets using the mouse liver transcriptome. Altogether, a set of three genes, Atp5h, Gsk3β, and Sirt2 fulfilled our strict selection criteria in all assessments, while four more genes, Nono, Tprkb, Tspo, and Ttr passed all but one assessment and were included into the final set of marker genes to enhance robustness of normalisation against outliers. Using the geometric mean of expression of the genes to normalise Nanostring hybridization experiments we reliably identified age-related increases in the expression of Casein kinase 1δ and 1ϵ, and Sfpq, while the expression of the glucose transporter Glut2 decreased. The age-related changes were verified by real-time PCR and Western blot analysis. As conclusion, proper normalisation enhances the robustness of quantitative methods addressing age-related changes of a transcriptome. PMID:28068403

  15. Normalisation against Circadian and Age-Related Disturbances Enables Robust Detection of Gene Expression Changes in Liver of Aged Mice.

    PubMed

    Fonseca Costa, Sara S; Wegmann, Daniel; Ripperger, Jürgen A

    2017-01-01

    The expression of some genes is affected by age. To detect such age-related changes, their expression levels are related to constant marker genes. However, transcriptional noise increasing with advancing age renders difficult the identification of real age-related changes because it may affect the marker genes as well. Here, we report a selection procedure for genes appropriate to normalise the mouse liver transcriptome under various conditions including age. These genes were chosen from an initial set of 16 candidate genes defined based on a RNA-sequencing experiment and published literature. A subset of genes was selected based on rigorous statistical assessment of their variability using both RNA-sequencing and Nanostring hybridization experiments. The robustness of these marker genes was then verified by the analysis of 130 publicly available data sets using the mouse liver transcriptome. Altogether, a set of three genes, Atp5h, Gsk3β, and Sirt2 fulfilled our strict selection criteria in all assessments, while four more genes, Nono, Tprkb, Tspo, and Ttr passed all but one assessment and were included into the final set of marker genes to enhance robustness of normalisation against outliers. Using the geometric mean of expression of the genes to normalise Nanostring hybridization experiments we reliably identified age-related increases in the expression of Casein kinase 1δ and 1ϵ, and Sfpq, while the expression of the glucose transporter Glut2 decreased. The age-related changes were verified by real-time PCR and Western blot analysis. As conclusion, proper normalisation enhances the robustness of quantitative methods addressing age-related changes of a transcriptome.

  16. Aging increases the susceptibility of hepatic inflammation, liver fibrosis and aging in response to high-fat diet in mice.

    PubMed

    Kim, In Hee; Xu, Jun; Liu, Xiao; Koyama, Yukinori; Ma, Hsiao-Yen; Diggle, Karin; You, Young-Hyun; Schilling, Jan M; Jeste, Dilip; Sharma, Kumar; Brenner, David A; Kisseleva, Tatiana

    2016-08-01

    We aimed to investigate whether aging increases the susceptibility of hepatic and renal inflammation or fibrosis in response to high-fat diet (HFD) and explore the underlying genetic alterations. Middle (10 months old) and old (20 months old) aged, male C57BL/6N mice were fed either a low-fat diet (4 % fat) or HFD (60 % fat) for 4 months. Young (3 months old) aged mice were included as control group. HFD-induced liver and kidney injuries were analyzed by serum and urine assay, histologic staining, immunohistochemistry, and reverse-transcription real-time quantitative polymerase chain reaction. Total RNA sequencing with next-generation technology was done with RNA extracted from liver tissues. With HFD feeding, aged was associated with higher serum alanine aminotransferase levels, marked infiltration of hepatic macrophages, and increased expression of inflammatory cytokines (MCP1, TNF-α, IL-1β, IL-6, IL-12, IL-17A). Importantly, aged mice showed more advanced hepatic fibrosis and increased expression of fibrogenic markers (Col-I-α1, αSMA, TGF-β1, TGF-β2, TGFβRII, PDGF, PDGFRβII, TIMP1) in response to HFD. Aged mice fed on HFD also showed increased oxidative stress and TLR4 expression. In the total RNA seq and gene ontology analysis of liver, old-aged HFD group showed significant up-regulation of genes linked to innate immune response, immune response, defense response, inflammatory response compared to middle-aged HFD group. Meanwhile, aging and HFD feeding showed significant increase in glomerular size and mesangial area, higher urine albumin/creatinine ratio, and advanced renal inflammation or fibrosis. However, the difference of HFD-induced renal injury between old-aged group and middle-aged group was not significant. The susceptibility of hepatic fibrosis as well as hepatic inflammation in response to HFD was significantly increased with aging. In addition, aging was associated with glomerular alterations and increased renal inflammation or

  17. Low grade inflammation as a common pathogenetic denominator in age-related diseases: novel drug targets for anti-ageing strategies and successful ageing achievement.

    PubMed

    Candore, G; Caruso, C; Jirillo, E; Magrone, T; Vasto, S

    2010-01-01

    Nowadays, people are living much longer than they used to do, however they are not free from ageing. Ageing, an inexorable intrinsic process that affects all cells, tissues, organs and individuals, is a post-maturational process that, due to a diminished homeostasis and increased organism frailty, causes a reduction of the response to environmental stimuli and, in general, is associated to an increased predisposition to illness and death. However, the high incidence of death due to infectious, cardiovascular and cancer diseases underlies a common feature in these pathologies that is represented by dysregulation of both instructive and innate immunity. Several studies show that a low-grade systemic inflammation characterizes ageing and that inflammatory markers are significant predictors of mortality in old humans. This pro-inflammatory status of the elderly underlies biological mechanisms responsible for physical function decline and age-related diseases such as Alzheimer's disease and atherosclerosis are initiated or worsened by systemic inflammation. Understanding of the ageing process should have a prominent role in new strategies for extending the health old population. Accordingly, as extensively discussed in the review and in the accompanying related papers, investigating ageing pathophysiology, particularly disentangling age-related low grade inflammation, is likely to provide important clues about how to develop drugs that can slow or delay ageing.

  18. Age-related changes in ultra-triathlon performances

    PubMed Central

    2012-01-01

    Background The age-related decline in performance has been investigated in swimmers, runners and triathletes. No study has investigated the age-related performance decline in ultra-triathletes. The purpose of this study was to analyse the age-related declines in swimming, cycling, running and overall race time for both Triple Iron ultra-triathlon (11.4-km swimming, 540-km cycling and 126.6-km running) and Deca Iron ultra-triathlon (38-km swimming, 1,800-km cycling and 420-km running). Methods The age and performances of 423 male Triple Iron ultra-triathletes and 119 male Deca Iron ultra-triathletes were analysed from 1992 to 2010 using regression analyses and ANOVA. Results The mean age of the finishers was significantly higher for Deca Iron ultra-triathletes (41.3 ± 3.1 years) compared to a Triple Iron ultra-triathletes (38.5 ± 3.3 years) (P < 0.05). For both ultra-distances, the fastest overall race times were achieved between the ages of 25 and 44 years. Deca Iron ultra-triathletes achieved the same level of performance in swimming and cycling between 25 and 54 years of age. Conclusions The magnitudes of age-related declines in performance in the three disciplines of ultra-triathlon differ slightly between Triple and Deca Iron ultra-triathlon. Although the ages of Triple Iron ultra-triathletes were on average younger compared to Deca Iron ultra-triathletes, the fastest race times were achieved between 25 and 44 years for both distances. Further studies should investigate the motivation and training of ultra-triathletes to gain better insights in ultra-triathlon performance. PMID:23849327

  19. Age-Related Effects of Advanced Glycation End Products (Ages) in Bone Matrix on Osteoclastic Resorption.

    PubMed

    Yang, Xiao; Gandhi, Chintan; Rahman, Md Mizanur; Appleford, Mark; Sun, Lian-Wen; Wang, Xiaodu

    2015-12-01

    Advanced glycation end products (AGEs) accumulate in bone extracellular matrix as people age. Previous studies have shown controversial results regarding the role of in situ AGEs accumulation in osteoclastic resorption. To address this issue, this study cultured human osteoclast cells directly on human cadaveric bone slices from different age groups (young and elderly) to warrant its relevance to in vivo conditions. The cell culture was terminated on the 3rd, 7th, and 10th day, respectively, to assess temporal changes in the number of differentiated osteoclasts, the number and size of osteoclastic resorption pits, the amount of bone resorbed, as well as the amount of matrix AGEs released in the medium by resorption. In addition, the in situ concentration of matrix AGEs at each resorption pit was also estimated based on its AGEs autofluorescent intensity. The results indicated that (1) osteoclastic resorption activities were significantly correlated with the donor age, showing larger but shallower resorption pits on the elderly bone substrates than on the younger ones; (2) osteoclast resorption activities were not significantly dependent on the in situ AGEs concentration in bone matrix, and (3) a correlation was observed between osteoclast activities and the concentration of AGEs released by the resorption. These results suggest that osteoclasts tend to migrate away from initial anchoring sites on elderly bone substrate during resorption compared to younger bone substrates. However, such behavior is not directly related to the in situ concentration of AGEs in bone matrix at the resorption sites.

  20. Diminished Vision in Healthy Aging Is Associated with Increased Retinal L-Type Voltage Gated Calcium Channel Ion Influx

    PubMed Central

    Bissig, David; Goebel, Dennis; Berkowitz, Bruce A.

    2013-01-01

    Extensive evidence implicates an increase in hippocampal L-type voltage-gated calcium channel (L-VGCC) expression, and ion influx through these channels, in age-related cognitive declines. Here, we ask if this “calcium hypothesis" applies to the neuroretina: Is increased influx via L-VGCCs related to the well-documented but poorly-understood vision declines in healthy aging? In Long-Evans rats we find a significant age-related increase in ion flux through retinal L-VGCCs in vivo (manganese-enhanced MRI (MEMRI)) that are longitudinally linked with progressive vision declines (optokinetic tracking). Importantly, the degree of retinal Mn2+ uptake early in adulthood significantly predicted later visual contrast sensitivity declines. Furthermore, as in the aging hippocampus, retinal expression of a drug-insensitive L-VGCC isoform (α1D) increased – a pattern confirmed in vivo by an age-related decline in sensitivity to L-VGCC blockade. These data highlight mechanistic similarities between retinal and hippocampal aging, and raise the possibility of new treatment targets for minimizing vision loss during healthy aging. PMID:23457553

  1. Awareness, Knowledge, and Concern about Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Cimarolli, Verena R.; Laban-Baker, Allie; Hamilton, Wanda S.; Stuen, Cynthia

    2012-01-01

    Age-related macular degeneration (AMD)--a common eye disease causing vision loss--can be detected early through regular eye-health examinations, and measures can be taken to prevent visual decline. Getting eye examinations requires certain levels of awareness, knowledge, and concern related to AMD. However, little is known about AMD-related…

  2. Glycosaminoglycans in the Human Cornea: Age-Related Changes

    PubMed Central

    Pacella, Elena; Pacella, Fernanda; De Paolis, Giulio; Parisella, Francesca Romana; Turchetti, Paolo; Anello, Giulia; Cavallotti, Carlo

    2015-01-01

    AIM To investigate possible age-related changes in glycosaminoglycans (GAGs) in the human cornea. The substances today called GAGs were previously referred to as mucopolysaccharides. METHODS Samples of human cornea were taken from 12 younger (age 21 ± 1.2) and 12 older (age 72 ± 1.6) male subjects. Samples were weighed, homogenized, and used for biochemical and molecular analyses. All the quantitative results were statistically analyzed. RESULTS The human cornea appears to undergo age-related changes, as evidenced by our biochemical and molecular results. The total GAG and hyaluronic acid counts were significantly higher in the younger subjects than in the older subjects. The sulfated heavy GAGs, such as chondroitin, dermatan, keratan, and heparan sulfate, were lower in the younger subjects than in the older subjects. DISCUSSION GAGs of the human cornea undergo numerous age-related changes. Their quantity is significantly altered in the elderly in comparison with younger subjects. GAGs play an important role in age-related diseases of the human cornea. PMID:25674020

  3. Age-related differences in white matter integrity and cognitive function are related to APOE status

    PubMed Central

    Ryan, Lee; Walther, Katrin; Bendlin, Barbara B.; Lue, Lih-Fen; Walker, Douglas G.; Glisky, Elizabeth L.

    2010-01-01

    While an extensive literature is now available on age-related differences in white matter integrity measured by diffusion MRI, relatively little is known about the relationships between diffusion and cognitive functions in older adults. Even less is known about whether these relationships are influenced by the apolipoprotein (APOE) ε4 allele, despite growing evidence that ε4 increases cognitive impairment in older adults. The purpose of the present study was to examine these relationships in a group of community-dwelling cognitively normal older adults. Data were obtained from a sample of 126 individuals (ages 52–92) that included 32 ε4 heterozygotes, 6 ε4 homozygotes, and 88 non-carriers. Two measures of diffusion, the apparent diffusion coefficient (ADC) and fractional anisotropy (FA), were obtained from six brain regions – frontal white matter, lateral parietal white matter, the centrum semiovale, the genu and splenium of the corpus callosum, and the temporal stem white matter – and were used to predict composite scores of cognitive function in two domains, executive function and memory function. Results indicated that ADC and FA differed with increasing age in all six brain regions, and these differences were significantly greater for ε4 carriers compared to noncarriers. Importantly, after controlling for age, diffusion measures predicted cognitive function in a region-specific way that was also influenced by ε4 status. Regardless of APOE status, frontal ADC and FA independently predicted executive function scores for all participants, while temporal lobe ADC additionally predicted executive function for ε4 carriers, but not noncarriers. Memory scores were predicted by temporal lobe ADC but not frontal diffusion for all participants, and this relationship was significantly stronger in ε4 carriers compared to noncarriers. Taken together, age and temporal lobe ADC accounted for a striking 53% of the variance in memory scores within the ε4 carrier

  4. Two age-related accumulation profiles of toxic metals.

    PubMed

    Yasuda, Hiroshi; Yoshida, Kazuya; Yasuda, Yuichi; Tsutsui, Toyoharu

    2012-07-01

    In order to investigate the body burden levels of toxic metals in Japanese, five toxic metal concentrations in scalp hair samples from 28,424 subjects from infant to elderly were determined with inductively coupled plasma mass spectrometry (ICP-MS). The geometric mean of hair mercury concentrations showed a high-significant age-correlated increase (r = 0.341, p < 0.0001) with a peak at the 6th decade of life and then decreased with further aging in both sexes. The mean mercury concentrations in male adults were significantly higher than those in female (p < 0.001), indicating the gender difference (male > female) in mercury accumulation. Arsenic also showed a similar accumulation profile with age dependency and gender difference in adult subjects. In contrast, cadmium, lead and aluminium exhibited another type of accumulation profile: the highest burden level was observed in infants aged 0-3 years old for every element in both sexes. In addition, cadmium was found to have a character accumulating in aged females, with significant age-dependency (r = 0.134, p < 0.0001) and gender difference (female > male). These findings suggest that toxic metals are classified into two families on the basis of their accumulation profiles, and that the three elements of mercury, arsenic and cadmium which accumulate age-dependently in adults, may play a role in aging process and higher burden with them may lead to acceleration of aging.

  5. Observations related to chronologic and gynecologic age in pregnant adolescents.

    PubMed Central

    Felice, M. E.; James, M.; Shragg, P.; Hollingsworth, D. R.

    1984-01-01

    A low chronologic age (less than or equal to 15 years) and low gynecologic age (less than or equal to 2 years) have been considered factors that increase medical complications among adolescent pregnant women. Gynecologic age (GA) is defined in this study as age in years at conception minus age at menarche. Two hundred twelve consecutive pregnant teenagers were followed prospectively in the Teen OB Clinic at the University of California, San Diego Medical Center, between August 1978 and July 1981. The clinic population consisted of 37.3 percent Whites, 35.8 percent Hispanics, 20.8 percent Blacks, and 6.1 percent other (mostly Indochinese). Sixty-eight percent of the patients were funded by MediCal. The patient population was divided by chronological age (CA) at conception into those 15 years or less or 16 years or older. A low chronological age was found to be a significant risk factor for premature rupture of membranes. Teenagers with a low gynecologic age (less than or equal to 2) had a lower mean pre-pregnancy weight and body mass index (Kg/M2) than teenagers with a higher gynecologic age. In this study, we did not find that a low CA or GA was correlated with a higher frequency of pregnancy-induced hypertension, prenatal medical problems, obstetrical problems at labor or delivery, or an excessive number of low-birthweight infants. PMID:6523906

  6. Nutritional Considerations for Healthy Aging and Reduction in Age-Related Chronic Disease.

    PubMed

    Shlisky, Julie; Bloom, David E; Beaudreault, Amy R; Tucker, Katherine L; Keller, Heather H; Freund-Levi, Yvonne; Fielding, Roger A; Cheng, Feon W; Jensen, Gordon L; Wu, Dayong; Meydani, Simin N

    2017-01-01

    A projected doubling in the global population of people aged ≥60 y by the year 2050 has major health and economic implications, especially in developing regions. Burdens of unhealthy aging associated with chronic noncommunicable and other age-related diseases may be largely preventable with lifestyle modification, including diet. However, as adults age they become at risk of "nutritional frailty," which can compromise their ability to meet nutritional requirements at a time when specific nutrient needs may be high. This review highlights the role of nutrition science in promoting healthy aging and in improving the prognosis in cases of age-related diseases. It serves to identify key knowledge gaps and implementation challenges to support adequate nutrition for healthy aging, including applicability of metrics used in body-composition and diet adequacy for older adults and mechanisms to reduce nutritional frailty and to promote diet resilience. This review also discusses management recommendations for several leading chronic conditions common in aging populations, including cognitive decline and dementia, sarcopenia, and compromised immunity to infectious disease. The role of health systems in incorporating nutrition care routinely for those aged ≥60 y and living independently and current actions to address nutritional status before hospitalization and the development of disease are discussed.

  7. Exploring the power of yeast to model aging and age-related neurodegenerative disorders.

    PubMed

    Oliveira, Ana V; Vilaça, Rita; Santos, Cláudia N; Costa, Vítor; Menezes, Regina

    2017-02-01

    Aging is a multifactorial process determined by molecular, cellular and systemic factors and it is well established that advancing age is a leading risk factor for several neurodegenerative diseases. In fact, the close association of aging and neurodegenerative disorders has placed aging as the greatest social and economic challenge of the 21st century, and age-related diseases have also become a key priority for countries worldwide. The growing need to better understand both aging and neurodegenerative processes has led to the development of simple eukaryotic models amenable for mechanistic studies. Saccharomyces cerevisiae has proven to be an unprecedented experimental model to study the fundamental aspects of aging and to decipher the intricacies of neurodegenerative disorders greatly because the molecular mechanisms underlying these processes are evolutionarily conserved from yeast to human. Moreover, yeast offers several methodological advantages allowing a rapid and relatively easy way of establishing gene-protein-function associations. Here we review different aging theories, common cellular pathways driving aging and neurodegenerative diseases and discuss the major contributions of yeast to the state-of-art knowledge in both research fields.

  8. Discover the network mechanisms underlying the connections between aging and age-related diseases

    PubMed Central

    Yang, Jialiang; Huang, Tao; Song, Won-min; Petralia, Francesca; Mobbs, Charles V.; Zhang, Bin; Zhao, Yong; Schadt, Eric E.; Zhu, Jun; Tu, Zhidong

    2016-01-01

    Although our knowledge of aging has greatly expanded in the past decades, it remains elusive why and how aging contributes to the development of age-related diseases (ARDs). In particular, a global mechanistic understanding of the connections between aging and ARDs is yet to be established. We rely on a network modelling named “GeroNet” to study the connections between aging and more than a hundred diseases. By evaluating topological connections between aging genes and disease genes in over three thousand subnetworks corresponding to various biological processes, we show that aging has stronger connections with ARD genes compared to non-ARD genes in subnetworks corresponding to “response to decreased oxygen levels”, “insulin signalling pathway”, “cell cycle”, etc. Based on subnetwork connectivity, we can correctly “predict” if a disease is age-related and prioritize the biological processes that are involved in connecting to multiple ARDs. Using Alzheimer’s disease (AD) as an example, GeroNet identifies meaningful genes that may play key roles in connecting aging and ARDs. The top modules identified by GeroNet in AD significantly overlap with modules identified from a large scale AD brain gene expression experiment, supporting that GeroNet indeed reveals the underlying biological processes involved in the disease. PMID:27582315

  9. Relational learning and transitive expression in aging and amnesia.

    PubMed

    Ryan, Jennifer D; D'Angelo, Maria C; Kamino, Daphne; Ostreicher, Melanie; Moses, Sandra N; Rosenbaum, R Shayna

    2016-02-01

    Aging has been associated with a decline in relational memory, which is critically supported by the hippocampus. By adapting the transitivity paradigm (Bunsey and Eichenbaum (1996) Nature 379:255-257), which traditionally has been used in nonhuman animal research, this work examined the extent to which aging is accompanied by deficits in relational learning and flexible expression of relational information. Older adults' performance was additionally contrasted with that of amnesic case DA to understand the critical contributions of the medial temporal lobe, and specifically, the hippocampus, which endures structural and functional changes in healthy aging. Participants were required to select the correct choice item (B versus Y) based on the presented sample item (e.g., A). Pairwise relations must be learned (A->B, B->C, C->D) so that ultimately, the correct relations can be inferred when presented with a novel probe item (A->C?Z?). Participants completed four conditions of transitivity that varied in terms of the degree to which the stimuli and the relations among them were known pre-experimentally. Younger adults, older adults, and DA performed similarly when the condition employed all pre-experimentally known, semantic, relations. Older adults and DA were less accurate than younger adults when all to-be-learned relations were arbitrary. However, accuracy improved for older adults when they could use pre-experimentally known pairwise relations to express understanding of arbitrary relations as indexed through inference judgments. DA could not learn arbitrary relations nor use existing knowledge to support novel inferences. These results suggest that while aging has often been associated with an emerging decline in hippocampal function, prior knowledge can be used to support novel inferences. However, in case DA, significant damage to the hippocampus likely impaired his ability to learn novel relations, while additional damage to ventromedial prefrontal and

  10. Ageism, age relations, and garment industry work in Montreal.

    PubMed

    McMullin, J A; Marshall, V W

    2001-02-01

    This study examined the complexities of age relations at work. Garment workers believed that their fate was linked to ageism and that their work experience was discounted by management. Managers wanted to be rid of older workers because they commanded higher wages than younger workers. The issue was cost reduction, and age was implicated unintendedly. Still, managers seemed to use stereotypical images to discourage older workers and they did not organize work routines to facilitate the adaptation of them. Instead, they subcontracted the easy jobs, relying on the experience of the older employees for difficult work while not adapting the workplace. Theoretically, the authors argue that ageism and age discrimination can best be understood through a recognition of the importance of structured age relations and human agency.

  11. A "concrete view" of aging: event related potentials reveal age-related changes in basic integrative processes in language.

    PubMed

    Huang, Hsu-Wen; Meyer, Aaron M; Federmeier, Kara D

    2012-01-01

    Normal aging is accompanied by changes in both structural and functional cerebral organization. Although verbal knowledge seems to be relatively stable across the lifespan, there are age-related changes in the rapid use of that knowledge during on-line language processing. In particular, aging has been linked to reduce effectiveness in preparing for upcoming words and building an integrated sentence-level representation. The current study assessed whether such age-related changes extend even to much simpler language units, such as modification relations between a centrally presented adjective and a lateralized noun. Adjectives were used to elicit concrete and abstract meanings of the same, polysemous lexical items (e.g., "green book" vs. "interesting book"). Consistent with findings that lexical information is preserved with age, older adults, like younger adults, exhibited concreteness effects at the adjectives, with more negative responses to concrete adjectives over posterior (300-500 ms; N400) and frontal (300-900 ms) channels. However, at the noun, younger adults exhibited concreteness-based predictability effects linked to left hemisphere processing and imagery effects linked to right hemisphere processing, contingent on whether the adjectives and nouns formed a cohesive conceptual unit. In contrast, older adults showed neither effect, suggesting that they were less able to rapidly link the adjective-noun meaning to form an integrated conceptual representation. Age-related changes in language processing may thus be more pervasive than previously realized.

  12. Terrorism-related trauma in Africa, an increasing problem.

    PubMed

    Alfa-Wali, Maryam; Sritharan, Kaji; Mehes, Mira; Abdullah, Fizan; Rasheed, Shahnawaz

    2015-06-01

    Global terrorist activities have increased significantly over the past decade. The impact of terrorism-related trauma on the health of individuals in low- and middle-income countries is under-reported. Trauma management in African countries in particular is uncoordinated, with little or no infrastructure to cater for emergency surgical needs. This article highlights the need for education, training and research to mitigate the problems related to terrorism and surgical public health.

  13. High throughput screening technology and the small molecules modulating aging related signals.

    PubMed

    Mo, Chunfen; Zhang, Wei; Liu, Luhong; Wang, Ling; Xiao, Hengyi

    2012-03-01

    Aging and its related diseases are severe issues in modern society. Many efforts have been made to understand the mechanisms of aging and to find the ways to prevent age-related diseases. Identifying the compounds targeting aging-related signals is a challenging work because there are so many proteins and signals involved. Recently, alone with the progresses in high throughput screening (HTS) technology, increasing numbers of small molecules targeting aging-related pathologic processes have been identified. In this review, we introduce the basic workflow, classification and assay strategies of HTS technology, and sort out known small molecules identified via HTS technology by their roles in aging related diseases, such as neural degenerative diseases, diabetes and tumors. Given the fact that application of HTS on aging research is still at an early stage, we also summarize the cellular mechanisms about aging process, paralleled with the compounds which can modulate the functions of proteins important for aging signals. Finally, we briefly discuss some advanced HTS technologies for their potent applications on the discovery of anti-aging compounds. The main purpose of this review is to provide updated and useful information to those who are interested in pharmacology and HTS technology, but not familiar with aging biology, or vice versa.

  14. Common cell biologic and biochemical changes in aging and age-related diseases of the eye: Toward new therapeutic approaches to age-related ocular diseases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reviews of information about age related macular degeneration (AMD), cataract, and glaucoma make it apparent that while each eye tissue has its own characteristic metabolism, structure and function, there are common perturbations to homeostasis that are associated with age-related dysfunction. The c...

  15. Food restriction increases long-term memory persistence in adult or aged mice.

    PubMed

    Talhati, F; Patti, C L; Zanin, K A; Lopes-Silva, L B; Ceccon, L M B; Hollais, A W; Bizerra, C S; Santos, R; Tufik, S; Frussa-Filho, R

    2014-04-03

    Food restriction (FR) seems to be the unique experimental manipulation that leads to a remarkable increase in lifespan in rodents. Evidences have suggested that FR can enhance memory in distinct animal models mainly during aging. However, only few studies systemically evaluated the effects FR on memory formation in both adult (3-month-old) and aged (18-24-month-old) mice. Thus, the aim of the present study was to investigate the effects of acute (12h) or repeated (12h/day for 2days) FR protocols on learning and memory of adult and aged mice evaluated in the plus-maze discriminative avoidance task (PM-DAT), an animal model that concurrently (but independently) evaluates learning and memory, anxiety and locomotion. We also investigated the possible role of FR-induced stress by the corticosterone concentration in adult mice. Male mice were kept at home cage with food ad libitum (CTRL-control condition) or subjected to FR during the dark phase of the cycle for 12h/day or 12h/2days. The FR protocols were applied before training, immediately after it or before testing. Our results demonstrated that only FR for 2days enhanced memory persistence when applied before training in adults and before testing in aged mice. Conversely, FR for 2days impaired consolidation and exerted no effects on retrieval irrespective of age. These effects do not seem to be related to corticosterone concentration. Collectively, these results indicate that FR for 2days can promote promnestic effects not only in aged mice but also in adults.

  16. 2-Nonenal newly found in human body odor tends to increase with aging.

    PubMed

    Haze, S; Gozu, Y; Nakamura, S; Kohno, Y; Sawano, K; Ohta, H; Yamazaki, K

    2001-04-01

    Human body odor consists of various kinds of odor components. Here, we have investigated the changes in body odor associated with aging. The body odor of subjects between the ages of 26 and 75 was analyzed by headspace gas chromatography/mass spectrometry. 2-Nonenal, an unsaturated aldehyde with an unpleasant greasy and grassy odor, was detected only in older subjects (40 y or older). Furthermore, analysis of skin surface lipids revealed that omega7 unsaturated fatty acids and lipid peroxides also increased with aging and that there were positive correlations between the amount of 2-nonenal in body odor and the amount of omega7 unsaturated fatty acids or lipid peroxides in skin surface lipids. 2-Nonenal was generated only when omega7 unsaturated fatty acids were degraded by degradation tests in which some main components of skin surface lipids were oxidatively decomposed using lipid peroxides as initiator of an oxidative chain reaction. The results indicate that 2-nonenal is generated by the oxidative degradation of omega7 unsaturated fatty acids, and suggest that 2-nonenal may be involved in the age-related change of body odor.

  17. The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice

    SciTech Connect

    Hamrick, Mark W.; Herberg, Samuel; Arounleut, Phonepasong; He, Hong-Zhi; Shiver, Austin; Qi, Rui-Qun; Zhou, Li; Isales, Carlos M.; and others

    2010-09-24

    Research highlights: {yields} Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. {yields} We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. {yields} Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. {yields} Recombinant leptin therapy may therefore be a novel approach for treating age-related muscle atrophy. -- Abstract: Age-associated loss of muscle mass, or sarcopenia, contributes directly to frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs in mouse skeletal muscle, and many of these miRNAs are now reported to be associated specifically with age-related muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant leptin, to determine whether leptin therapy could improve muscle mass and alter the miRNA expression profile of aging skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37 miRNAs was altered in muscles of leptin-treated mice. In particular, leptin treatment increased the expression of miR-31 and miR-223, miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific miRNAs, and that nutrient-related

  18. Caffeine increases food intake while reducing anxiety-related behaviors.

    PubMed

    Sweeney, Patrick; Levack, Russell; Watters, Jared; Xu, Zhenping; Yang, Yunlei

    2016-06-01

    The objective of this study was to determine the effects of different doses of caffeine on appetite and anxiety-related behavior. Additionally, we sought to determine if withdrawal from chronic caffeine administration promotes anxiety. In this study, we utilized rodent open field testing and feeding behavior assays to determine the effects of caffeine on feeding and anxiety-related behavior (n = 8 mice; 4-8 weeks old). We also measured 2 h and 24 h food intake and body-weight during daily administration of caffeine (n = 12 mice; 4-8 weeks old). To test for caffeine withdrawal induced anxiety, anxiety-related behavior in rodents was quantified following withdrawal from four consecutive days of caffeine administration (n = 12 mice; 4-8 weeks old). We find that acute caffeine administration increases food intake in a dose-dependent manner with lower doses of caffeine more significantly increasing food intake than higher doses. Acute caffeine administration also reduced anxiety-related behaviors in mice without significantly altering locomotor activity. However, we did not observe any differences in 24 h food intake or body weight following chronic caffeine administration and there were no observable differences in anxiety-related behaviors during caffeine withdrawal. In conclusion, we find that caffeine can both increase appetite and decrease anxiety-related behaviors in a dose dependent fashion. Given the complex relationship between appetite and anxiety, the present study provides additional insights into potential caffeine-based pharmacological mechanisms governing appetite and anxiety disorders, such as bulimia nervosa.

  19. Age-Related and Sex-Related Differences in Hand and Pinch Grip Strength in Adults

    ERIC Educational Resources Information Center

    Puh, Urska

    2010-01-01

    The purpose of the study was to quantify age-related changes in hand grip strength and three types of pinch grip strength (key pinch, tip pinch, and palmar pinch) among male and female participants. The study included 199 healthy participants (100 females, 99 males) aged 20-79 years, who were divided into four age groups. The Baseline Hydraulic…

  20. Age-Related Neurochemical Changes in the Vestibular Nuclei

    PubMed Central

    Smith, Paul F.

    2016-01-01

    There is evidence that the normal aging process is associated with impaired vestibulo-ocular reflexes (VOR) and vestibulo-spinal reflexes, causing reduced visual acuity and postural instability. Nonetheless, the available evidence is not entirely consistent, especially with respect to the VOR. Some recent studies have reported that VOR gain can be intact even above 80 years of age. Similarly, although there is evidence for age-related hair cell loss and neuronal loss in Scarpa’s ganglion and the vestibular nucleus complex (VNC), it is not entirely consistent. Whatever structural and functional changes occur in the VNC as a result of aging, either to cause vestibular impairment or to compensate for it, neurochemical changes must underlie them. However, the neurochemical changes that occur in the VNC with aging are poorly understood because the available literature is very limited. This review summarizes and critically evaluates the available evidence relating to the noradrenaline, serotonin, dopamine, glutamate, GABA, glycine, and nitric oxide neurotransmitter systems in the aging VNC. It is concluded that, at present, it is difficult, if not impossible, to relate the neurochemical changes observed to the function of specific VNC neurons and whether the observed changes are the cause of a functional deficit in the VNC or an effect of it. A better understanding of the neurochemical changes that occur during aging may be important for the development of potential drug treatments for age-related vestibular disorders. However, this will require the use of more sophisticated methodology such as in vivo microdialysis with single neuron recording and perhaps new technologies such as optogenetics. PMID:26973593

  1. Fundus autofluorescence in exudative age-related macular degeneration.

    PubMed

    Peng, Q; Dong, Y; Zhao, P Q

    2013-12-02

    The aim of this study was to investigate the characteristics of fundus autofluorescence (FAF) in patients with wet (exudative) age-related macular degeneration (AMD). Color fundus photographs, fundus fluorescein angiograms, indocyanine green angiograms, and FAF images were obtained from 61 patients (72 eyes) with exudative AMD. The FAF results for different patterns of exudative AMD were compared to those revealed by other fundus images. Of the 72 eyes evaluated, which were classified into three patterns based on the results of fundus fluorescein angiography, 68 had abnormal FAF. Forty-six eyes (63.9%) had classic wet AMD with abnormal FAF. Among these, 10 exhibited a slightly decreased FAF with near-normal or background FAF signal at the center of the lesion area; 36 demonstrated not only decreased FAF at the center of the lesion but also an increased FAF signal toward the lesion edge. Sixteen eyes (22.2%) had occult wet AMD, of which 12 exhibited heterogeneous fluorescence at the lesion site; 4 yielded normal FAF images. Ten eyes (13.9%) had a mixed pattern of wet AMD with abnormal FAF. FAF imaging suggested that the areas of blood and exudates decreased; however, fluorescence angiography revealed that lesions with hyperfluorescence had background or slightly increased FAF. These results showed that various patterns of wet AMD exhibit different autofluorescence characteristics. These represent the functional and metabolic features of retinal pigment epithelial cells. Therefore, FAF can be used to monitor disease development and evaluate the severity and prognosis of AMD.

  2. Learning and Aging Related Changes in Intrinsic Neuronal Excitability

    PubMed Central

    Oh, M. Matthew; Oliveira, Fernando A.; Disterhoft, John F.

    2010-01-01

    A goal of many laboratories that study aging is to find a key cellular change(s) that can be manipulated and restored to a young-like state, and thus, reverse the age-related cognitive deficits. We have chosen to focus our efforts on the alteration of intrinsic excitability (as reflected by the postburst afterhyperpolarization, AHP) during the learning process in hippocampal pyramidal neurons. We have consistently found that the postburst AHP is significantly reduced in hippocampal pyramidal neurons from young adults that have successfully learned a hippocampus-dependent task. In the context of aging, the baseline intrinsic excitability of hippocampal neurons is decreased and therefore cognitive learning is impaired. In aging animals that are able to learn, neuron changes in excitability similar to those seen in young neurons during learning occur. Our challenge, then, is to understand how and why excitability changes occur in neurons from aging brains and cause age-associated learning impairments. After understanding the changes, we should be able to formulate strategies for reversing them, thus making old neurons function more as they did when they were young. Such a reversal should rescue the age-related cognitive deficits. PMID:20552042

  3. Age-Related Psychophysical Changes and Low Vision

    PubMed Central

    Dagnelie, Gislin

    2013-01-01

    When considering the burden of visual impairment on aging individuals and society at large, it is important to bear in mind that vision changes are a natural aspect of aging. In this article, we consider vision changes that are part of normal aging, the prevalence of abnormal vision changes caused by disorders of the visual system, and the anticipated incidence and impact of visual impairment as the US population ages. We then discuss the services available to reduce the impact of vision loss, and the extent to which those services can and should be improved, not only to be better prepared for the anticipated increase in low vision over the coming decades, but also to increase the awareness of interactions between visual impairment and comorbidities that are common among the elderly. Finally, we consider how to promote improved quality, availability, and acceptance of low vision care to lessen the impact of visual impairment on individuals, and its burden on society. PMID:24335074

  4. Primary and secondary haemostasis changes related to aging.

    PubMed

    Sepúlveda, Cesar; Palomo, Iván; Fuentes, Eduardo

    2015-09-01

    Life expectancy has increased in many countries as a result the world's population is aging. The projections indicate that the proportion of the elderly in a few decades will increase significantly. Aging carries with it a series of physiological changes; one of them is an imbalance in the hemostatic system. Thus the levels or activity of various proteins involved, such as most coagulation factors, natural anticoagulants and the fibrinolytic system are altered so that the hemostatic balance leans toward thrombosis. Also, platelet activity suggests a state of abnormal activation (P-selectin, beta thromboglobulin and platelet factor). In this review we will systematically examine the alterations in the hemostatic components that occur during aging. Therefore, understanding these hemostatic changes could contribute to developing strategies for the proper management of health in old age.

  5. Age-related similarities and differences in monitoring spatial cognition.

    PubMed

    Ariel, Robert; Moffat, Scott D

    2017-03-31

    Spatial cognitive performance is impaired in later adulthood but it is unclear whether the metacognitive processes involved in monitoring spatial cognitive performance are also compromised. Inaccurate monitoring could affect whether people choose to engage in tasks that require spatial thinking and also the strategies they use in spatial domains such as navigation. The current experiment examined potential age differences in monitoring spatial cognitive performance in a variety of spatial domains including visual-spatial working memory, spatial orientation, spatial visualization, navigation, and place learning. Younger and older adults completed a 2D mental rotation test, 3D mental rotation test, paper folding test, spatial memory span test, two virtual navigation tasks, and a cognitive mapping test. Participants also made metacognitive judgments of performance (confidence judgments, judgments of learning, or navigation time estimates) on each trial for all spatial tasks. Preference for allocentric or egocentric navigation strategies was also measured. Overall, performance was poorer and confidence in performance was lower for older adults than younger adults. In most spatial domains, the absolute and relative accuracy of metacognitive judgments was equivalent for both age groups. However, age differences in monitoring accuracy (specifically relative accuracy) emerged in spatial tasks involving navigation. Confidence in navigating for a target location also mediated age differences in allocentric navigation strategy use. These findings suggest that with the possible exception of navigation monitoring, spatial cognition may be spared from age-related decline even though spatial cognition itself is impaired in older age.

  6. Oxidative stress and epigenetic regulation in ageing and age-related diseases.

    PubMed

    Cencioni, Chiara; Spallotta, Francesco; Martelli, Fabio; Valente, Sergio; Mai, Antonello; Zeiher, Andreas M; Gaetano, Carlo

    2013-08-28

    Recent statistics indicate that the human population is ageing rapidly. Healthy, but also diseased, elderly people are increasing. This trend is particularly evident in Western countries, where healthier living conditions and better cures are available. To understand the process leading to age-associated alterations is, therefore, of the highest relevance for the development of new treatments for age-associated diseases, such as cancer, diabetes, Alzheimer and cardiovascular accidents. Mechanistically, it is well accepted that the accumulation of intracellular damage determined by reactive oxygen species (ROS) might orchestrate the progressive loss of control over biological homeostasis and the functional impairment typical of aged tissues. Here, we review how epigenetics takes part in the control of stress stimuli and the mechanisms of ageing physiology and physiopathology. Alteration of epigenetic enzyme activity, histone modifications and DNA-methylation is, in fact, typically associated with the ageing process. Specifically, ageing presents peculiar epigenetic markers that, taken altogether, form the still ill-defined "ageing epigenome". The comprehension of mechanisms and pathways leading to epigenetic modifications associated with ageing may help the development of anti-ageing therapies.

  7. Age-related changes in the fracture resistance of male Fischer F344 rat bone.

    PubMed

    Uppuganti, Sasidhar; Granke, Mathilde; Makowski, Alexander J; Does, Mark D; Nyman, Jeffry S

    2016-02-01

    In addition to the loss in bone volume that occurs with age, there is a decline in material properties. To test new therapies or diagnostic tools that target such properties as material strength and toughness, a pre-clinical model of aging would be useful in which changes in bone are similar to those that occur with aging in humans. Toward that end, we hypothesized that similar to human bone, the estimated toughness and material strength of cortical bone at the apparent-level decreases with age in the male Fischer F344 rat. In addition, we tested whether the known decline in trabecular architecture in rats translated to an age-related decrease in vertebra (VB) strength and whether non-X-ray techniques could quantify tissue changes at micron and sub-micron length scales. Bones were harvested from 6-, 12-, and 24-month (mo.) old rats (n=12 per age). Despite a loss in trabecular bone with age, VB compressive strength was similar among the age groups. Similarly, whole-bone strength (peak force) in bending was maintained (femur) or increased (radius) with aging. There was though an age-related decrease in post-yield toughness (radius) and bending strength (femur). The ability to resist crack initiation was actually higher for the 12-mo. and 24-mo. than for 6-mo. rats (notch femur), but the estimated work to propagate the crack was less for the aged bone. For the femur diaphysis region, porosity increased while bound water decreased with age. For the radius diaphysis, there was an age-related increase in non-enzymatic and mature enzymatic collagen crosslinks. Raman spectroscopy analysis of embedded cross-sections of the tibia mid-shaft detected an increase in carbonate subsitution with advanced aging for both inner and outer tissue.

  8. Effects of a native parasitic plant on an exotic invader decrease with increasing host age

    PubMed Central

    Li, Junmin; Yang, Beifen; Yan, Qiaodi; Zhang, Jing; Yan, Min; Li, Maihe

    2015-01-01

    Understanding changes in the interactions between parasitic plants and their hosts in relation to ontogenetic changes in the hosts is crucial for successful use of parasitic plants as biological controls. We investigated growth, photosynthesis and chemical defences in different-aged Bidens pilosa plants in response to infection by Cuscuta australis. We were particularly interested in whether plant responses to parasite infection change with changes in the host plant age. Compared with the non-infected B. pilosa, parasite infection reduced total host biomass and net photosynthetic rates, but these deleterious effects decreased with increasing host age. Parasite infection reduced the concentrations of total phenolics, total flavonoids and saponins in the younger B. pilosa but not in the older B. pilosa. Compared with the relatively older and larger plants, younger and smaller plants suffered from more severe damage and are likely less to recover from the infection, suggesting that C. australis is only a viable biocontrol agent for younger B. pilosa plants. PMID:25838325

  9. Investigations Into Age-related Changes in the Human Mandible().

    PubMed

    Parr, Nicolette M; Passalacqua, Nicholas V; Skorpinski, Katie

    2017-03-02

    While changes in mandibular shape over time are not widely recognized by skeletal biologists, mandibular remodeling and associated changes in gross morphology may result from a number of causes related to mechanical stress such as antemortem tooth loss, changes in bite force, or alterations of masticatory performance. This study investigated the relationship between age-related changes and antemortem tooth loss in adult humans via dry bone measurements. This study examined 10 standard mandibular measurements as well as individual antemortem tooth loss scores using the Eichner Index from a total of 319 female and male individuals with ages ranging from 16 to 99 years. Results indicate that few mandibular measurements exhibited age-related changes, and most were affected by antemortem tooth loss.

  10. Age-related macular degeneration: current treatment and future options.

    PubMed

    Moutray, Tanya; Chakravarthy, Usha

    2011-09-01

    Age-related macular degeneration is the leading cause of visual impairment among older adults in the developed world. Epidemiological studies have revealed a number of genetic, ocular and environmental risk factors for this condition, which can be addressed by disease reduction strategies. We discuss the various treatment options for dry and exudative age-related macular degeneration available and explain how the recommended treatment depends on the exact type, location and extent of the degeneration. Currently, vascular endothelial growth factor (VEGF) inhibition therapy is the best available treatment for exudative age-related macular degeneration but is limited by the need for repeated intravitreal injections. The current treatment regime is being refined through research on optimal treatment frequency and duration and type of anti-VEGF drug. Different modes of drug delivery are being developed and in the future other methods of VEGF inhibition may be used.

  11. Polyphenols decreased liver NADPH oxidase activity, increased muscle mitochondrial biogenesis and decreased gastrocnemius age-dependent autophagy in aged rats.

    PubMed

    Laurent, Caroline; Chabi, Beatrice; Fouret, Gilles; Py, Guillaume; Sairafi, Badie; Elong, Cecile; Gaillet, Sylvie; Cristol, Jean Paul; Coudray, Charles; Feillet-Coudray, Christine

    2012-09-01

    This study explored major systems of reactive oxygen species (ROS) production and their consequences on oxidative stress, mitochondriogenesis and muscle metabolism in aged rats, and evaluated the efficiency of 30-day oral supplementation with a moderate dose of a red grape polyphenol extract (RGPE) on these parameters. In the liver of aged rats, NADPH oxidase activity was increased and mitochondrial respiratory chain complex activities were altered, while xanthine oxidase activity remained unchanged. In muscles, only mitochondrial activity was modified with aging. The oral intake of RGPE decreased liver NADPH oxidase activity in the aged rats without affecting global oxidative stress, suggesting that NADPH oxidase was probably not the dominant detrimental source of production of O(2)·(-) in the liver. Interestingly, RGPE supplementation increased mitochondrial biogenesis and improved antioxidant status in the gastrocnemius of aged rats, while it had no significant effect in soleus. RGPE supplementation also decreased age-dependent autophagy in gastrocnemius of aged rats. These results extended existing findings on the beneficial effects of RGPE on mitochondriogenesis and muscle metabolism in aged rats.

  12. Association of age-related macular degeneration and reticular macular disease with cardiovascular disease.

    PubMed

    Rastogi, Neelesh; Smith, R Theodore

    2016-01-01

    Age-related macular degeneration is the leading cause of adult blindness in the developed world. Thus, major endeavors to understand the risk factors and pathogenesis of this disease have been undertaken. Reticular macular disease is a proposed subtype of age-related macular degeneration correlating histologically with subretinal drusenoid deposits located between the retinal pigment epithelium and the inner segment ellipsoid zone. Reticular lesions are more prevalent in females and in older age groups and are associated with a higher mortality rate. Risk factors for developing age-related macular degeneration include hypertension, smoking, and angina. Several genes related to increased risk for age-related macular degeneration and reticular macular disease are also associated with cardiovascular disease. Better understanding of the clinical and genetic risk factors for age-related macular degeneration and reticular macular disease has led to the hypothesis that these eye diseases are systemic. A systemic origin may help to explain why reticular disease is diagnosed more frequently in females as males suffer cardiovascular mortality at an earlier age, before the age of diagnosis of reticular macular disease and age-related macular degeneration.

  13. Protect Your Eyes: Age-Related Macular Degeneration (AMD) Facts and Prevention Tips

    MedlinePlus

    PROTECT YOUR EYES Age-Related Macular Degeneration ( AMD ) FACTS & PREVENTION TIPS A LEADING CAUSE OF VISION LOSS IN THE U.S . AMD is a ... Black 2% Other 89% White As the population ages, the number of cases is expected to increase ...

  14. Age-related changes in the central auditory system.

    PubMed

    Ouda, Ladislav; Profant, Oliver; Syka, Josef

    2015-07-01

    Aging is accompanied by the deterioration of hearing that complicates our understanding of speech, especially in noisy environments. This deficit is partially caused by the loss of hair cells as well as by the dysfunction of the stria vascularis. However, the central part of the auditory system is also affected by processes accompanying aging that may run independently of those affecting peripheral receptors. Here, we review major changes occurring in the central part of the auditory system during aging. Most of the information that is focused on age-related changes in the central auditory system of experimental animals arises from experiments using immunocytochemical targeting on changes in the glutamic-acid-decarboxylase, parvalbumin, calbindin and calretinin. These data are accompanied by information about age-related changes in the number of neurons as well as about changes in the behavior of experimental animals. Aging is in principle accompanied by atrophy of the gray as well as white matter, resulting in the enlargement of the cerebrospinal fluid space. The human auditory cortex suffers not only from atrophy but also from changes in the content of some metabolites in the aged brain, as shown by magnetic resonance spectroscopy. In addition to this, functional magnetic resonance imaging reveals differences between activation of the central auditory system in the young and old brain. Altogether, the information reviewed in this article speaks in favor of specific age-related changes in the central auditory system that occur mostly independently of the changes in the inner ear and that form the basis of the central presbycusis.

  15. 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.

  16. Age-related decline in emotional prosody discrimination: acoustic correlates.

    PubMed

    Mitchell, Rachel L C; Kingston, Rachel A

    2014-01-01

    It is now accepted that older adults have difficulty recognizing prosodic emotion cues, but it is not clear at what processing stage this ability breaks down. We manipulated the acoustic characteristics of tones in pitch, amplitude, and duration discrimination tasks to assess whether impaired basic auditory perception coexisted with our previously demonstrated age-related prosodic emotion perception impairment. It was found that pitch perception was particularly impaired in older adults, and that it displayed the strongest correlation with prosodic emotion discrimination. We conclude that an important cause of age-related impairment in prosodic emotion comprehension exists at the fundamental sensory level of processing.

  17. Age-related degradation of Westinghouse 480-volt circuit breakers

    SciTech Connect

    Subudhi, M.; Shier, W.; MacDougall, E. )

    1990-07-01

    An aging assessment of Westinghouse DS-series low-voltage air circuit breakers was performed as part of the Nuclear Plant Aging Research (NPAR) program. The objectives of this study are to characterize age-related degradation within the breaker assembly and to identify maintenance practices to mitigate their effect. Since this study has been promulgated by the failures of the reactor trip breakers at the McGuire Nuclear Station in July 1987, results relating to the welds in the breaker pole lever welds are also discussed. The design and operation of DS-206 and DS-416 breakers were reviewed. Failure data from various national data bases were analyzed to identify the predominant failure modes, causes, and mechanisms. Additional operating experiences from one nuclear station and two industrial breaker-service companies were obtained to develop aging trends of various subcomponents. The responses of the utilities to the NRC Bulletin 88-01, which discusses the center pole lever welds, were analyzed to assess the final resolution of failures of welds in the reactor trips. Maintenance recommendations, made by the manufacturer to mitigate age-related degradation were reviewed, and recommendations for improving the monitoring of age-related degradation are discussed. As described in Volume 2 of this NUREG, the results from a test program to assess degradation in breaker parts through mechanical cycling are also included. The testing has characterized the cracking of center-pole lever welds, identified monitoring techniques to determine aging in breakers, and provided information to augment existing maintenance programs. Recommendations to improve breaker reliability using effective maintenance, testing, and inspection programs are suggested. 13 refs., 21 figs., 8 tabs.

  18. Age trajectories of physiological indices in relation to healthy life course.

    PubMed

    Arbeev, Konstantin G; Ukraintseva, Svetlana V; Akushevich, Igor; Kulminski, Alexander M; Arbeeva, Liubov S; Akushevich, Lucy; Culminskaya, Irina V; Yashin, Anatoliy I

    2011-03-01

    We analysed relationship between the risk of onset of "unhealthy life" (defined as the onset of cancer, cardiovascular diseases, or diabetes) and longitudinal changes in body mass index, diastolic blood pressure, hematocrit, pulse pressure, pulse rate, and serum cholesterol in the Framingham Heart Study (Original Cohort) using the stochastic process model of human mortality and aging. The analyses demonstrate how decline in resistance to stresses and adaptive capacity accompanying human aging can be evaluated from longitudinal data. We showed how these components of the aging process, as well as deviation of the trajectories of physiological indices from those minimising the risk at respective ages, can lead to an increase in the risk of onset of unhealthy life with age. The results indicate the presence of substantial gender difference in aging related decline in stress resistance and adaptive capacity, which can contribute to differences in the shape of the sex-specific patterns of incidence rates of aging related diseases.

  19. Hippocampus age-related microstructural changes in schizophrenia: a case-control mean diffusivity study.

    PubMed

    Chiapponi, Chiara; Piras, Fabrizio; Fagioli, Sabrina; Girardi, Paolo; Caltagirone, Carlo; Spalletta, Gianfranco

    2014-08-01

    Macrostructural-volumetric abnormalities of the hippocampus have been described in schizophrenia. Here, we characterized age-related changes of hippocampal mean diffusivity as an index of microstructural damage by carrying out a neuroimaging study in 85 patients with a DSM-IV-TR diagnosis of schizophrenia and 85 age- and gender-matched healthy controls. We performed analyses of covariance, with diagnosis as fixed factor, mean diffusivity as dependent variable and age as covariate. Patients showed an early increase in mean diffusivity in the right and left hippocampus that increased with age. Thus, microstructural hippocampal changes associated with schizophrenia cannot be confined to a specific time window.

  20. Aging-related dysregulation of dopamine and angiotensin receptor interaction.

    PubMed

    Villar-Cheda, Begoña; Dominguez-Meijide, Antonio; Valenzuela, Rita; Granado, Noelia; Moratalla, Rosario; Labandeira-Garcia, Jose L

    2014-07-01

    It is not known whether the aging-related decrease in dopaminergic function leads to the aging-related higher vulnerability of dopaminergic neurons and risk for Parkinson's disease. The renin-angiotensin system (RAS) plays a major role in the inflammatory response, neuronal oxidative stress, and dopaminergic vulnerability via type 1 (AT1) receptors. In the present study, we observed a counterregulatory interaction between dopamine and angiotensin receptors. We observed overexpression of AT1 receptors in the striatum and substantia nigra of young adult dopamine D1 and D2 receptor-deficient mice and young dopamine-depleted rats, together with compensatory overexpression of AT2 receptors or compensatory downregulation of angiotensinogen and/or angiotensin. In aged rats, we observed downregulation of dopamine and dopamine receptors and overexpression of AT1 receptors in aged rats, without compensatory changes observed in young animals. L-Dopa therapy inhibited RAS overactivity in young dopamine-depleted rats, but was ineffective in aged rats. The results suggest that dopamine may play an important role in modulating oxidative stress and inflammation in the substantia nigra and striatum via the RAS, which is impaired by aging.

  1. Age-related changes in human posture control: Motor coordination tests

    NASA Technical Reports Server (NTRS)

    Peterka, R. J.; Black, F. O.

    1989-01-01

    Postural responses to support surface displacements were measured in 214 normal human subjects ranging in age from 7 to 81 years. Motor tests measured leg muscle Electromyography (EMG) latencies, body sway, and the amplitude and timing of changes in center of pressure displacements in response to sudden forward and backward horizontal translations of the support surface upon which the subjects stood. There were small increases in both EMG latencies and the time to reach the peak amplitude of center of pressure responses with increasing age. The amplitude of center of pressure responses showed little change with age if the amplitude measures were normalized by a factor related to subject height. In general, postural responses to sudden translations showed minimal changes with age, and all age related trends which were identified were small relative to the variability within the population.

  2. Age-related Changes in the Fracture Resistance of Male Fischer F344 Rat Bone

    PubMed Central

    Uppuganti, Sasidhar; Granke, Mathilde; Makowski, Alexander J.; Does, Mark D.; Nyman, Jeffry S.

    2015-01-01

    In addition to the loss in bone volume that occurs with age, there is a decline in material properties. To test new therapies or diagnostic tools that target such properties as material strength and toughness, a pre-clinical model of aging would be useful in which changes in bone are similar to those that occur with aging in humans. Toward that end, we hypothesized that similar to human bone, the estimated toughness and material strength of cortical bone at the apparent-level decreases with age in the male Fischer F344 rat. In addition, we tested whether the known decline in trabecular architecture in rats translated to an age-related decrease in vertebra (VB) strength and whether non-X-ray techniques could quantify tissue changes at micron and sub-micron length scales. Bones were harvested from 6-, 12-, and 24-month (mo.) old rats (n=12 per age). Despite a loss in trabecular bone with age, VB compressive strength was similar among the age groups. Similarly, whole-bone strength (peak force) in bending was maintained (femur) or increased (radius) with aging. There was though an age-related decrease in post-yield toughness (radius) and bending strength (femur). The ability to resist crack initiation was actually higher for the 12-mo. and 24-mo. than for 6-mo. rats (notch femur), but the estimated work to propagate the crack was less for the aged bone. For the femur diaphysis region, porosity increased while bound water decreased with age. For the radius diaphysis, there was an age-related increase in non-enzymatic and mature enzymatic collagen crosslinks. Both Raman spectroscopy and reference point indentation detected differences in tissue properties with age, though the trends did not necessarily match observations from human tissue. PMID:26610688

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

    PubMed Central

    Fama, Rosemary; Sullivan, Edith V.

    2015-01-01

    The thalamus, with its cortical, subcortical, and cerebellar connections, is a critical node in networks supporting cognitive functions known to decline in normal aging, including component processes of memory and executive functions of attention and information processing. The macrostructure, microstructure, and neural connectivity of the thalamus changes across the adult lifespan. Structural and functional magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) have demonstrated, regional thalamic volume shrinkage and microstructural degradation, with anterior regions generally more compromised than posterior regions. The integrity of selective thalamic nuclei and projections decline with advancing age, particularly those in thalamofrontal, thalamoparietal, and thalamolimbic networks. This review presents studies that assess the relations between age and aging and the structure, function, and connectivity of the thalamus and associated neural networks and focuses on their relations with processes of attention, speed of information processing, and working and episodic memory. PMID:25862940

  4. Age and work environment characteristics in relation to sleep: Additive, interactive and curvilinear effects.

    PubMed

    Parkes, Katharine R

    2016-05-01

    Although additive combinations of age and work environment characteristics have been found to predict sleep impairment, possible age x work environment interactions have been largely disregarded. The present study examined linear and curvilinear interactions of age with work environment measures in relation to sleep quality and duration. Survey data were collected from offshore day-shift personnel (N = 901). Main effects and interactions of the age terms with work environment measures (job demand, control, and social support, physical environment and strenuous work) were evaluated. Sleep duration was predicted by a curvilinear interaction, age(2) x job demand (p < .005), and by the age x social support interaction (p < .002); sleep quality was predicted by age x job demand (p < .002). Job control and physical environment showed significant additive effects. At a time when older employees are encouraged to remain in the workforce, the findings serve to increase understanding of how ageing and work demands jointly contribute to sleep impairment.

  5. Aging-associated formaldehyde-induced norepinephrine deficiency contributes to age-related memory decline.

    PubMed

    Mei, Yufei; Jiang, Chun; Wan, You; Lv, Jihui; Jia, Jianping; Wang, Xiaomin; Yang, Xu; Tong, Zhiqian

    2015-08-01

    A norepinephrine (NE) deficiency has been observed in aged rats and in patients with Alzheimer's disease and is thought to cause cognitive disorder. Which endogenous factor induces NE depletion, however, is largely unknown. In this study, we investigated the effects of aging-associated formaldehyde (FA) on the inactivation of NE in vitro and in vivo, and on memory behaviors in rodents. The results showed that age-related DNA demethylation led to hippocampal FA accumulation, and when this occurred, the hippocampal NE content was reduced in healthy male rats of different ages. Furthermore, biochemical analysis revealed that FA rapidly inactivated NE in vitro and that an intrahippocampal injection of FA markedly reduced hippocampal NE levels in healthy adult rats. Unexpectedly, an injection of FA (at a pathological level) or 6-hydroxydopamine (6-OHDA, a NE depletor) can mimic age-related NE deficiency, long-term potentiation (LTP) impairments, and spatial memory deficits in healthy adult rats. Conversely, an injection of NE reversed age-related deficits in both LTP and memory in aged rats. In agreement with the above results, the senescence-accelerated prone 8 (SAMP8) mice also exhibited a severe deficit in LTP and memory associated with a more severe NE deficiency and FA accumulation, when compared with the age-matched, senescence-resistant 1 (SAMR1) mice. Injection of resveratrol (a natural FA scavenger) or NE into SAMP8 mice reversed FA accumulation and NE deficiency and restored the magnitude of LTP and memory. Collectively, these findings suggest that accumulated FA is a critical endogenous factor for aging-associated NE depletion and cognitive decline.

  6. Heterogeneity of variation of relative risk by age at exposure in the Japanese atomic bomb survivors.

    PubMed

    Little, Mark P

    2009-08-01

    General reductions in cancer relative risk with increasing age at exposure are observed in the Japanese atomic bomb survivors and in other groups. However, there has been little evidence of heterogeneity in such trends by cancer type within the Japanese cohort, nor for cancer-type variations in other factors (sex, attained age) that modify relative risk. A recent report on the Japanese atomic bomb survivors published by Preston et al. in 2007 suggests that solid cancer relative risk exhibits a U-shaped relationship with age at exposure, and is initially decreasing and then increasing at older exposure ages. In this report, we reanalyse the latest Japanese atomic bomb survivor solid cancer mortality and incidence data analysed by Preston and co-workers, stratifying by cancer subtype where possible, the stratification being both in relation to the baseline and the radiation-associated excess. We find highly statistically significant (P < 0.001) variations of relative risk by cancer type, and statistically significant variations by cancer type in the adjustments for sex (P = 0.010) and age at exposure (P = 0.013) to the relative risk. There is no statistically significant (P > 0.2) variation by cancer type in the adjustment of relative risk for attained age. Although, for all incident solid cancers, there is marginally statistically significant (P = 0.033) variation of relative risk with a quadratic log-linear function of age at exposure, there is much weaker variation in the relative risk of solid cancer mortality (P > 0.1). However, the manner in which relative risk varies with age at exposure is qualitatively similar for incidence and mortality, so one should not make too much of these differences between the two datasets. Stratification by solid cancer type slightly weakens the evidence for quadratic variation in relative risk by age at exposure (P = 0.060).

  7. Age-related changes in metabolic properties of equine skeletal muscle associated with muscle plasticity.

    PubMed

    Kim, Jeong-su; Hinchcliff, Kenneth W; Yamaguchi, Mamoru; Beard, Laurie A; Markert, Chad D; Devor, Steven T

    2005-05-01

    The purpose of the present study was to determine the age-related changes in myosin heavy chain (MHC) composition and muscle oxidative and glycolytic capacity in 18 horses ranging in age from two to 30 years. Muscle samples were collected by excisional biopsy of the semimebranosus muscle. MHC expression and the key enzymatic activities were measured. There was no significant correlation between horse age and the proportions of type-IIA and type-IIX MHC isoforms. The percentage of type-I MHC isoforms decreased with advancing age. Muscle citrate synthase activity decreased, whereas lactate dehydrogenase activity increased with increasing age. Muscle 3-OH acyl CoA dehydrogenase activity did not change with ageing. The results suggest that, similar to humans, the oxidative capacity of equine skeletal muscle decreases with age. The age-related changes in muscle metabolic properties appear to be consistent with an age-related transition in MHC isoforms of equine skeletal muscle that shifts toward more glycolytic isoforms with age.

  8. Age-related associative deficits and the isolation effect.

    PubMed

    Badham, Stephen P; Maylor, Elizabeth A

    2013-01-01

    If all but one of the items in a list are similar (e.g., all black except one red), memory for the different item is enhanced (the isolation effect). Older adults generally show similar or smaller isolation effects compared to young adults, which has been attributed to age-related deficits in associative memory whereby older adults are less able to associate an isolated stimulus to its isolating feature. Experiment 1 examined the isolation effect for isolation based on spatial position, modality and color; in Experiment 2, the criterion for isolation was the associative relation between stimuli. The results consistently showed no differences between young and older participants in the magnitude of the isolation effect. Whilst age deficits in associative memory may act to reduce the isolation effect in older adults, age deficits in self-initiated processing and inhibitory functionality may counteract this reduction by enhancing the isolation effect in older adults.

  9. Age-related macular degeneration: Evidence of a major gene

    SciTech Connect

    Bhatt, S.; Warren, C.; Yang, H.

    1994-09-01

    Age-related macular degeneration is a major cause of blindness in developing countries. It remains a very poorly understood disorder. Although environmental and genetic factors have been implicated in its pathogenesis, none have been firmly implicated. The purpose of this study was to use pedigree analysis to evaluate the possible role of a major gene as a determinant of familial aggregation. Information was collected regarding occupation, smoking, sun exposure, associated medical problems and family history. 50 probands with age-related macular degeneration (ARMD) and 39 age, race and sex-matched controls were included in the study. In the ARMD group 15/50 (30%) of probands reported a positive family history; 22 out of 222 first degree relatives over age 60 were reported to be affected. In the control groups, none of the 138 first degree relatives over age 50 had a history of ARMD. This difference is statistically significant (p = 0.0003), indicating that genetic factors may play an important role in the pathogenesis of ARMD. In the ARMD group more siblings as compared to parents (16/127 vs. 5/82) were affected. 5/50 (10%) of the ARMD probands also gave a history of a second degree relative affected with ARMD, compared to none known among the relatives of controls. Data from 50 pedigrees were analyzed by complex segregation analysis under a class A regressive logistic model using the REGD program implemented in the SAGE package. Preliminary results allow rejection of a polygenic model and suggest there is a major gene for ARMD in these families. The inheritance model most compatible with the observed familial aggregation is autosomal recessive. In conclusion, these results are suggestive of a major gene effect in the etiology of ARMD. Identification of a major gene effect is a first step to further pursue linkage analysis and to search for the gene(s) involved in the causation of ARMD.

  10. Mitochondrial function and dysfunction in the cell: its relevance to aging and aging-related disease.

    PubMed

    Nicholls, David G

    2002-11-01

    Mitochondria plays a complex multi-factorial role in the cell. In addition to their primary role in ATP generation, the organelles sequester calcium and both generate and detoxify reactive oxygen species. All these functions are intimately inter-linked through the central bioenergetic parameter of the proton electrochemical gradient across the inner mitochondrial membrane. Subtle changes in respiratory chain capacity, substrate supply, glutathione levels, cytoplasmic calcium and membrane potential occur in aging and in conditions predisposing towards neurodegenerative disease. These interactions are incompletely understood and in this review I present an overview of some of the current research in this area, and its possible relevance to aging and aging-related disease.

  11. A review of the equine age-related changes in the immune system: comparisons between human and equine aging, with focus on lung-specific immune-aging.

    PubMed

    Hansen, S; Baptiste, K E; Fjeldborg, J; Horohov, D W

    2015-03-01

    The equine aging process involves many changes to the immune system that may be related to genetics, the level of nutrition, the environment and/or an underlying subclinical disease. Geriatric horses defined as horses above the age of 20, exhibit a decline in body condition, muscle tone and general well-being. It is not known whether these changes contribute to decreased immune function or are the result of declining immune function. Geriatric years are characterized by increased susceptibility to infections and a reduced antibody response to vaccination as a result of changes in the immune system. Humans and horses share many of these age-related changes, with only a few differences. Thus, inflamm-aging and immunosenescence are well-described phenomena in both human and equine research, particularly in relation to the peripheral blood and especially the T-cell compartment. However, the lung is faced with unique challenges because of its constant interaction with the external environment and thus may not share similarities to peripheral blood when considering age-related changes in immune function. Indeed, recent studies have shown discrepancies in cytokine mRNA and protein expression between the peripheral blood and bronchoalveolar lavage immune cells. These results provide important evidence that age-related immune changes or 'dys-functions' are organ-specific.

  12. Compromised respiratory adaptation and thermoregulation in aging and age-related diseases.

    PubMed

    Chan, Sic L; Wei, Zelan; Chigurupati, Srinivasulu; Tu, Weihong

    2010-01-01

    Mitochondrial dysfunction and reactive oxygen species (ROS) production are at the heart of the aging process and are thought to underpin age-related diseases. Mitochondria are not only the primary energy-generating system but also the dominant cellular source of metabolically derived ROS. Recent studies unravel the existence of mechanisms that serve to modulate the balance between energy metabolism and ROS production. Among these is the regulation of proton conductance across the inner mitochondrial membrane that affects the efficiency of respiration and heat production. The field of mitochondrial respiration research has provided important insight into the role of altered energy balance in obesity and diabetes. The notion that respiration and oxidative capacity are mechanistically linked is making significant headway into the field of aging and age-related diseases. Here we review the regulation of cellular energy and ROS balance in biological systems and survey some of the recent relevant studies that suggest that respiratory adaptation and thermodynamics are important in aging and age-related diseases.

  13. Stereotactic radiotherapy in neovascular age-related macular degeneration

    PubMed Central

    Ranjbar, Mahdy; Kurz, Maximilian; Holzhey, Annekatrin; Melchert, Corinna; Rades, Dirk; Grisanti, Salvatore

    2016-01-01

    Abstract Stereotactic radiotherapy (SRT) is a new approach to treat neovascular age-related macular degeneration (nAMD). The INTREPID trial suggested that SRT could reduce the frequency of regular intravitreal injections (IVIs) with antivascular endothelial growth factor drugs, which are necessary to control disease activity. However, the efficacy of SRT in nAMD and resulting morphological changes have not been validated under real-life circumstances, an issue, which we would like to address in this retrospective analysis. Patients who met the INTREPID criteria for best responders were eligible for SRT. A total of 32 eyes of 32 patients were treated. Thereafter, patients were examined monthly for 12 months and received pro re nata IVI of aflibercept or ranibizumab. Outcome measures were: mean number of injections, best-corrected visual acuity, and morphological changes of the outer retina-choroid complex as well as patient safety. Mean number of IVI decreased by almost 50% during the 12 months after SRT compared to the year before, whereas visual acuity increased by one line (logMAR). Morphological evaluation showed that most changes affect outer retinal layers. Stereotactic radiotherapy significantly reduced IVI retreatment in nAMD patients under real-life circumstances. Therefore, SRT might be the first step to stop visual loss as a result of IVI undertreatment, which is a major risk. PMID:28033280

  14. The Relative Age Effect in Elite Sport: The French Case

    ERIC Educational Resources Information Center

    Delorme, Nicolas; Boiche, Julie; Raspaud, Michel

    2009-01-01

    The relative age effect (RAE) is considered a common phenomenon in elite sport. However, it has not been examined systematically in previous research, and the mechanisms likely to generate or to limit such an effect are little understood. This paper investigates the prevalence of the RAE in French professional championship-level players, taking…

  15. [Impact of thymic function in age-related immune deterioration].

    PubMed

    Ferrando-Martínez, Sara; de la Fuente, Mónica; Guerrero, Juan Miguel; Leal, Manuel; Muñoz-Fernández, M Ángeles

    2013-01-01

    Age-related biological deterioration also includes immune system deterioration and, in consequence, a rise in the incidence and prevalence of infections and cancers, as well as low responses to vaccination strategies. Out of all immune cell subsets, T-lymphocytes seem to be involved in most of the age-related defects. Since T-lymphocytes mature during their passage through the thymus, and the thymus shows an age-related process of atrophy, thymic regression has been proposed as the triggering event of this immune deterioration in elderly people. Historically, it has been accepted that the young thymus sets the T-lymphocyte repertoire during the childhood, whereupon atrophy begins until the elderly thymus is a non-functional evolutionary trace. However, a rising body of knowledge points toward the thymus functioning during adulthood. In the elderly, higher thymic function is associated with a younger immune system, while thymic function failure is associated with all-cause mortality. Therefore, any new strategy focused on the improvement of the elderly quality of life, especially those trying to influence the immune system, should take into account, together with peripheral homeostasis, thymus function as a key element in slowing down age-related decline.

  16. Age-Related Health Stereotypes and Illusory Correlation

    ERIC Educational Resources Information Center

    Madey, Scott F.; Chasteen, Alison L.

    2004-01-01

    This experiment investigated how age-related health stereotypes affect people's judgments of younger and older patients' medical compliance. Previous research has shown that stereotypes of young adults include healthy components, but stereotypes of older adults include both healthy and unhealthy components (Hummert, 1990). We predicted that…

  17. The Experience of Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Wong, Elaine Y. H.; Guymer, Robyn H.; Hassell, Jennifer B.; Keeffe, Jill E.

    2004-01-01

    This qualitative article describes the impact of age-related macular degeneration (ARMD) among 15 participants: how a person makes sense of ARMD, the effect of ARMD on the person's quality of life, the psychological disturbances associated with the limitations of ARMD, and the influence of ARMD on social interactions. Such in-depth appreciation of…

  18. Treatment of dry age-related macular degeneration with dobesilate

    PubMed Central

    Cuevas, P; Outeiriño, L A; Angulo, J; Giménez-Gallego, G

    2012-01-01

    The authors present anatomical and functional evidences of dry age-macular degeneration improvement, after intravitreal treatment with dobesilate. Main outcomes measures were normalisation of retinal structure and function, assessed by optical coherence tomography, fundus-monitored microperimetry, electrophysiology and visual acuity. The effect might be related to the normalisation of the outer retinal architecture. PMID:22729337

  19. Language of the aging brain: Event-related potential studies of comprehension in older adults

    PubMed Central

    Wlotko, Edward W.; Lee, Chia-Lin; Federmeier, Kara D.

    2010-01-01

    Normal aging brings increased richness in knowledge and experience as well as declines in cognitive abilities. Event-related brain potential (ERP) studies of language comprehension corroborate findings showing that the structure and organization of semantic knowledge remains relatively stable with age. Highlighting the advantages of the temporal and functional specificity of ERPs, this survey focuses on age-related changes in higher-level processes required for the successful comprehension of meaning representations built from multiple words. Older adults rely on different neural pathways and cognitive processes during normal, everyday comprehension, including a shift away from the predictive use of sentential context, differential recruitment of neural resources, and reduced engagement of controlled processing. Within age groups, however, there are important individual differences that, for example, differentiate a subset of older adults whose processing patterns more closely resemble that of young adults, providing a window into cognitive skills and abilities that may mediate or moderate age-related declines. PMID:20823949

  20. Dynamical network model for age-related health deficits and mortality

    NASA Astrophysics Data System (ADS)

    Taneja, Swadhin; Mitnitski, Arnold B.; Rockwood, Kenneth; Rutenberg, Andrew D.

    2016-02-01

    How long people live depends on their health, and how it changes with age. Individual health can be tracked by the accumulation of age-related health deficits. The fraction of age-related deficits is a simple quantitative measure of human aging. This quantitative frailty index (F ) is as good as chronological age in predicting mortality. In this paper, we use a dynamical network model of deficits to explore the effects of interactions between deficits, deficit damage and repair processes, and the connection between the F and mortality. With our model, we qualitatively reproduce Gompertz's law of increasing human mortality with age, the broadening of the F distribution with age, the characteristic nonlinear increase of the F with age, and the increased mortality of high-frailty individuals. No explicit time-dependence in damage or repair rates is needed in our model. Instead, implicit time-dependence arises through deficit interactions—so that the average deficit damage rates increase, and deficit repair rates decrease, with age. We use a simple mortality criterion, where mortality occurs when the most connected node is damaged.

  1. Tocotrienol rich fraction reverses age-related deficits in spatial learning and memory in aged rats.

    PubMed

    Taridi, Nursiati Mohamad; Abd Rani, Nazirah; Abd Latiff, Azian; Ngah, Wan Zurinah Wan; Mazlan, Musalmah

    2014-09-01

    Little is known about the effect of vitamin E on brain function. Therefore, in this study we evaluated the effect of tocotrienol rich fraction (TRF) on behavioral impairment and oxidative stress in aged rats. Thirty-six male Wistar rats (young: 3-months-old; aged: 21-months-old) were treated with either the control (olive oil) or TRF (200 mg/kg) for 3 months. Behavioral studies were performed using the open field test and Morris water maze (MWM) task. Blood was taken for assessment of DNA damage, plasma malondialdehyde (MDA) and vitamin E, and erythrocyte antioxidant enzyme activity. Brains were also collected to measure vitamin E levels. Results showed that aged rats exhibited reduced exploratory activity, enhanced anxiety and decreased spatial learning and memory compared with young rats. DNA damage and plasma MDA were increased, and vitamin E levels in plasma and brain were reduced in aged rats. Aged rats supplemented with TRF showed a markedly reduced level of anxiety, improved spatial learning and memory, reduced amount and severity of DNA damage, a reduced level of MDA, and increased levels of antioxidant enzyme activity and plasma/brain vitamin E compared with age-matched controls. In conclusion, TRF supplementation reverses spatial learning and memory decline and decreases oxidative stress in aged rats.

  2. The Correlation of Age and Postoperative Visual Acuity for Age-Related Cataract

    PubMed Central

    Li, Xiaochun; Cao, Xiaoguang; Hou, Xianru; Bao, Yongzhen

    2016-01-01

    Purpose. Clinically, what is the best time for age-related cataract (ARC) patients to receive surgeries and get the most benefits is important. We explored the relationship between age and presenting postoperative visual acuity (POVA) in patients from rural China. Methods. Three Lifeline Express Hospital Eye-Train missions of Peking University People's Hospital were chosen. At the first day after surgery, 3452 ARC eyes with the presenting POVA ≥ 6/60 were enrolled. The relationship between age and POVA was analyzed statistically. Results. In these three missions, there were more female patients than males; the ratio of females to males was 1.71. The average age of females was older than males. Overall, the percentages of patients with good visual outcomes (≥6/18) were significantly decreased with aging. Different regions had variations, but the trends were the same. There was weak linear correlation between age and POVA. The correlations of females were stronger than males in Yuncheng and Sanmenxia and weaker than males in Zhoukou. Conclusion. The good visual outcomes of presenting POVA were significantly decreased with aging and there were weak linear correlations between age and POVA in rural China. The linear correlation might be influenced by the difference of gender and region. PMID:26881225

  3. Annual age-grouping and athlete development: a meta-analytical review of relative age effects in sport.

    PubMed

    Cobley, Stephen; Baker, Joseph; Wattie, Nick; McKenna, Jim

    2009-01-01

    Annual age-grouping is a common organizational strategy in sport. However, such a strategy appears to promote relative age effects (RAEs). RAEs refer both to the immediate participation and long-term attainment constraints in sport, occurring as a result of chronological age and associated physical (e.g. height) differences as well as selection practices in annual age-grouped cohorts. This article represents the first meta-analytical review of RAEs, aimed to collectively determine (i) the overall prevalence and strength of RAEs across and within sports, and (ii) identify moderator variables. A total of 38 studies, spanning 1984-2007, containing 253 independent samples across 14 sports and 16 countries were re-examined and included in a single analysis using odds ratios and random effects procedures for combining study estimates. Overall results identified consistent prevalence of RAEs, but with small effect sizes. Effect size increased linearly with relative age differences. Follow-up analyses identified age category, skill level and sport context as moderators of RAE magnitude. Sports context involving adolescent (aged 15-18 years) males, at the representative (i.e. regional and national) level in highly popular sports appear most at risk to RAE inequalities. Researchers need to understand the mechanisms by which RAEs magnify and subside, as well as confirm whether RAEs exist in female and more culturally diverse contexts. To reduce and eliminate this social inequality from influencing athletes' experiences, especially within developmental periods, direct policy, organizational and practitioner intervention is required.

  4. DIETARY CARBOHYDRATE AND PROGRESSION OF AGE-RELATED MACULAR DEGENERATION, A PROSPECTIVE STUDY FROM THE AGE-RELATED EYE DISEASE STUDY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background Cross-sectional studies indicate that diets that provide a higher dietary glycemic index (dGI) are associated with increased risk of age-related macular degeneration (AMD). No prospective studies have addressed this issue. Methods dGI was calculated as the weighted average of GIs from foo...

  5. The Potential of Chitosan and Its Derivatives in Prevention and Treatment of Age-Related Diseases

    PubMed Central

    Kerch, Garry

    2015-01-01

    Age-related, diet-related and protein conformational diseases, such as atherosclerosis, diabetes mellitus, cancer, hypercholesterolemia, cardiovascular and neurodegenerative diseases are common in the elderly population. The potential of chitosan, chitooligosaccharides and their derivatives in prevention and treatment of age-related dysfunctions is reviewed and discussed in this paper. The influence of oxidative stress, low density lipoprotein oxidation, increase of tissue stiffness, protein conformational changes, aging-associated chronic inflammation and their pathobiological significance have been considered. The chitosan-based functional food also has been reviewed. PMID:25871293

  6. Sociological effects on vocal aging: Age related F0 effects in two languages

    NASA Astrophysics Data System (ADS)

    Nagao, Kyoko

    2005-04-01

    Listeners can estimate the age of a speaker fairly accurately from their speech (Ptacek and Sander, 1966). It is generally considered that this perception is based on physiologically determined aspects of the speech. However, the degree to which it is due to conventional sociolinguistic aspects of speech is unknown. The current study examines the degree to which fundamental frequency (F0) changes due to advanced aging across two language groups of speakers. It also examines the degree to which the speakers associate these changes with aging in a voice disguising task. Thirty native speakers each of English and Japanese, taken from three age groups, read a target phrase embedded in a carrier sentence in their native language. Each speaker also read the sentence pretending to be 20-years younger or 20-years older than their own age. Preliminary analysis of eighteen Japanese speakers indicates that the mean and maximum F0 values increase when the speakers pretended to be younger than when they pretended to be older. Some previous studies on age perception, however, suggested that F0 has minor effects on listeners' age estimation. The acoustic results will also be discussed in conjunction with the results of the listeners' age estimation of the speakers.

  7. Oxidative stress, innate immunity, and age-related macular degeneration.

    PubMed

    Shaw, Peter X; Stiles, Travis; Douglas, Christopher; Ho, Daisy; Fan, Wei; Du, Hongjun; Xiao, Xu

    Age-related macular degeneration (AMD) is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD is characterized by the appearance of soft drusen, as well as pigmentary changes in the retinal pigment epithelium (RPE). These soft, confluent drusen can progress into two forms of advanced AMD: geographic atrophy (GA, or dry AMD) or choroidal neovascularization (CNV, or wet AMD). Both forms of AMD result in a similar clinical progression in terms of loss of central vision. The exact mechanism for developing early AMD, as well as triggers responsible for progressing to advanced stage of disease, is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as causes of AMD progression. Multiple genes and/or single nucleotide polymorphisms (SNPs) have been found associated with AMD, including various genes involved in the complement pathway, lipid metabolism and extracellular matrix (ECM) remodeling. Of the known genetic contributors to disease risk, the CFH Y402H and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress plays a critical role in many aging diseases including cardiovascular disease, cancer, Alzheimer's disease and AMD. Due to the exposure to sunlight and high oxygen concentration, the oxidative stress burden is higher in the eye than other tissues, which can be further complicated by additional oxidative stressors such as smoking. Increasingly, evidence is accumulating suggesting that functional abnormalities of the innate immune system incurred via high risk genotypes may be contributing to the pathogenesis of AMD by altering the inflammatory homeostasis in the eye, specifically in the handling of oxidation products. As the eye in non-pathological instances maintains a low level of inflammation despite the presence of a relative abundance of potentially inflammatory molecules, we have

  8. Oxidative stress, innate immunity, and age-related macular degeneration

    PubMed Central

    Shaw, Peter X.; Stiles, Travis; Douglas, Christopher; Ho, Daisy; Fan, Wei; Du, Hongjun; Xiao, Xu

    2016-01-01

    Age-related macular degeneration (AMD) is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD is characterized by the appearance of soft drusen, as well as pigmentary changes in the retinal pigment epithelium (RPE). These soft, confluent drusen can progress into two forms of advanced AMD: geographic atrophy (GA, or dry AMD) or choroidal neovascularization (CNV, or wet AMD). Both forms of AMD result in a similar clinical progression in terms of loss of central vision. The exact mechanism for developing early AMD, as well as triggers responsible for progressing to advanced stage of disease, is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as causes of AMD progression. Multiple genes and/or single nucleotide polymorphisms (SNPs) have been found associated with AMD, including various genes involved in the complement pathway, lipid metabolism and extracellular matrix (ECM) remodeling. Of the known genetic contributors to disease risk, the CFH Y402H and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress plays a critical role in many aging diseases including cardiovascular disease, cancer, Alzheimer’s disease and AMD. Due to the exposure to sunlight and high oxygen concentration, the oxidative stress burden is higher in the eye than other tissues, which can be further complicated by additional oxidative stressors such as smoking. Increasingly, evidence is accumulating suggesting that functional abnormalities of the innate immune system incurred via high risk genotypes may be contributing to the pathogenesis of AMD by altering the inflammatory homeostasis in the eye, specifically in the handling of oxidation products. As the eye in non-pathological instances maintains a low level of inflammation despite the presence of a relative abundance of potentially inflammatory molecules, we have

  9. AGING-RELATED CARBARYL EFFECTS IN BROWN NORWAY RATS

    EPA Science Inventory

    The rapid increase in older adults in the population highlights the importance ofunderstanding the role of aging in susceptibility to environmental contaminants. Aspart of a larger research program on life-stage susceptibility, this experiment determined the effect of the carbama...

  10. Retrospective investigation of captive red wolf reproductive success in relation to age and inbreeding.

    PubMed

    Lockyear, K M; Waddell, W T; Goodrowe, K L; MacDonald, S E

    2009-05-01

    The critically endangered red wolf (Canis rufus) has been subject to a strictly managed captive breeding program for three decades. A retrospective demographic analysis of the captive population was performed based on data from the red wolf studbook. Data analyses revealed a decrease in the effective population size relative to the total population size, and changes in age structure and inbreeding coefficients over time. To varying degrees, the probability of successful breeding and litter sizes declined in association with increasing dam age and sire inbreeding coefficients. Neonate survival also declined with increasing dam age. Recent changes in strategies regarding breed-pair recommendations have resulted in moderate increases in reproductive success.

  11. Strawberry or blueberry supplementation may protect against increased oxidative stress vulnerability from both irradiation and aging

    NASA Astrophysics Data System (ADS)

    Joseph, J. A.; Shukitt-Hale, B.; Carey, A.; Rabin, B. M.

    In several studies we have now shown that there are some interesting parallels between aging and the effects of heavy particle irradiation (56Fe) in a rat model. Interestingly this research also has shown that, much as has been seen in aged animals, dietary supplementation with high antioxidant-strawberry (SB) or blueberry (BB) extracts (2% of the diet) reversed many of the age-related changes. Similarly, supplementing the diets of young rats with SBs or BBs (2% of diet as in the aged animals) for 8 weeks prior to being exposed to 56Fe (1 GeV/n), using the AGS or NSRL at Brookhaven National Laboratory, prevented the deleterious effects of the radiation exposure on the motor, cognitive and neuronal parameters described above. In the present experiment we examined whether striatal tissue obtained from BB- or SB-supplemented or control-fed, irradiated or non-radiated, young rats would show differential sensitivity (as assessed via decrements in mAChR stimulation of dopamine release) to hydrogen peroxide, a reactive oxygen species (ROS) generating agent. The results indicated that, just as we had seen previously with respect to radiation protection in the parameters described above, the tissue from the SB or BB-supplemented irradiated or non-radiated animals showed increased mAChR-stimulated DA release from the striatal tissue following hydrogen peroxide exposure compared to that seen in non-supplemented irradiated or non-radiated animals (e.g., DA rels. p moles/mg protein, rad + H202 non-supplemented = 90, SB = 260, BB = 360). These results show that aging and irradiation may produce similar decrements in dopamine release and that, much as we have seen previously with age, radiation enhances the vulnerability to oxidative stressors, but these are reduced with SB or BB supplementation. They are discussed in-terms of protection against the effects of exposure to heavy particles and aging via nutritional supplementation with foods that are high in antioxidant activity

  12. Age-related ultrasonic properties of breast tissue in vivo.

    PubMed

    Katz-Hanani, Ilana; Rothstein, Tamara; Gaitini, Diana; Gallimidi, Zahava; Azhari, Haim

    2014-09-01

    The aim of the current work was to quantify the ultrasonic properties of the whole breast in vivo as a function of age. Forty-four women were scanned using a computerized ultrasonic scanner developed in our laboratory. Raster scans in two orthogonal views, mediolateral and craniocaudal, were obtained using the ultrasonic through-transmission method. By combining the information from the two views, we estimated two acoustic properties: speed of sound and attenuation coefficient. On the basis of the results, both the attenuation coefficient and the speed of sound follow a three-phase age-related pattern. During the first phase, which corresponds to ages 20 to 35 y, both properties decrease with time and then remain roughly unchanged until about 55 y. During the third phase corresponding to ages >55 y, values decrease again with time. The mean speed of sound decreases from 1504 ± 35 m/s at <30 y to 1452 ± 9 m/s at >60 y (p < 0.01), and the attenuation coefficient decreases from 1.27 ± 0.32 to 0.96 ± 0.13 dB/cm/MHz (p < 0.03), respectively. In conclusion, both the ultrasonic speed of sound and the attenuation coefficient of breast tissue are age related. Both parameters decrease during life, markedly during the first and third phases. These changes may be attributed to anatomic and physiologic changes associated with reproductivity and menopause.

  13. Mood, Memory and Movement: An Age-Related Neurodegenerative Complex?

    PubMed Central

    Granholm, Ann-Charlotte; Boger, Heather; Emborg, Marina E.

    2009-01-01

    The following review was constructed as a concept paper based on a recent workshop on neurodegenerative disease sponsored by the National Institute on Aging (NIA), the American Geriatric Society (AGS), and the John A. Hartford Foundation. The meeting was entitled “Thinking, moving and feeling: Common underlying mechanisms? 4th Annual Bedside-to-Bench Conference” and had the purpose to connect current basic and clinical findings on common brain-related alterations occurring with aging such as depression, movement disorders, and cognitive decline. Many prominent researchers expressed their opinion on aging and it was revealed that age-related brain dysfunction of any kind seems to share several risk factors and/or pathways. But can something be done to actively achieve “successful aging”? In this review, based largely on the workshop and current literature, we have summarized some of the current theories for depression, movement and cognitive impairment with aging, as well as potential preventive measures. We have also summarized the emerging need for relevant animal models and how these could be developed and utilized. PMID:20021382

  14. Wet age related macular degeneration management and follow-up.

    PubMed

    Alexandru, Malciolu Radu; Alexandra, Nica Maria

    2016-01-01

    Age-related macular degeneration (AMD) is referred to as the leading cause of irreversible visual loss in developed countries, with a profound effect on the quality of life. The neovascular form of AMD is characterized by the formation of subretinal choroidal neovascularization, leading to sudden and severe visual loss. Research has identified the vascular endothelial growth factor (VEGF) as an important pathophysiological component in neovascular AMD and its intraocular inhibition as one of the most efficient therapies in medicine. The introduction of anti-VEGF as a standard treatment in wet AMD has led to a great improvement in the prognosis of patients, allowing recovery and maintenance of visual function in the vast majority of cases. However, the therapeutic benefit is accompanied by a difficulty in maintaining the treatment schedule due to the increase in the amount of patients, stress of monthly assessments, as well as the associated economic burden. Therefore, treatment strategies have evolved from fixed monthly dosing, to individualized regimens, aiming for comparable results, with fewer injections. One such protocol is called "pro re nata", or "treat and observe". Patients are given a loading dose of 3 monthly injections, followed by an as-needed decision to treat, based on the worsening of visual acuity, clinical evidence of the disease activity on fundoscopy, or OCT evidence of retinal thickening in the presence of intra or subretinal fluid. A different regimen is called "treat and extend", in which the interval between injections is gradually increased, once the disease stabilization is achieved. This paper aims to review the currently available anti-VEGF agents--bevacizumab, ranibizumab, aflibercept, and the aforementioned treatment strategies.

  15. Nitric oxide availability is increased in contracting skeletal muscle from aged mice, but does not differentially decrease muscle superoxide.

    PubMed

    Pearson, T; McArdle, A; Jackson, M J

    2015-01-01

    Reactive oxygen and nitrogen species have been implicated in the loss of skeletal muscle mass and function that occurs during aging. Nitric oxide (NO) and superoxide are generated by skeletal muscle and where these are generated in proximity their chemical reaction to form peroxynitrite can compete with the superoxide dismutation to hydrogen peroxide. Changes in NO availability may therefore theoretically modify superoxide and peroxynitrite activities in tissues, but published data are contradictory regarding aging effects on muscle NO availability. We hypothesised that an age-related increase in NO generation might increase peroxynitrite generation in muscles from old mice, leading to an increased nitration of muscle proteins and decreased superoxide availability. This was examined using fluorescent probes and an isolated fiber preparation to examine NO content and superoxide in the cytosol and mitochondria of muscle fibers from adult and old mice both at rest and following contractile activity. We also examined the 3-nitrotyrosine (3-NT) and peroxiredoxin 5 (Prx5) content of muscles from mice as markers of peroxynitrite activity. Data indicate that a substantial age-related increase in NO levels occurred in muscle fibers during contractile activity and this was associated with an increase in muscle eNOS. Muscle proteins from old mice also showed an increased 3-NT content. Inhibition of NOS indicated that NO decreased superoxide bioavailability in muscle mitochondria, although this effect was not age related. Thus increased NO in muscles of old mice was associated with an increased 3-NT content that may potentially contribute to age-related degenerative changes in skeletal muscle.

  16. Age and gender related differences in aortic blood flow

    NASA Astrophysics Data System (ADS)

    Enevoldsen, Marie Sand; Pedersen, Mads Møller; Hemmsen, Martin Christian; Lönn, Lars; Henneberg, Kaj-Åge; Jensen, Jørgen Arendt

    2012-03-01

    The abdominal aorta (AA) is predisposed to development of abdominal aneurysms (AAA), a focal dilatation with fatal consequences if left untreated. The blood flow patterns is thought to play an important role in the development of AAA. The purpose of this work is to investigate the blood flow patterns within a group of healthy volunteers (six females, eight males) aged 23 to 76 years to identify changes and differences related to age and gender. The healthy volunteers were categorized by gender (male/female) and age (below/above 35 years). Subject-specific flow and geometry data were acquired using the research interface on a Profocus ultrasound scanner (B-K Medical, Herlev, Denmark; segmentation of 3D magnetic resonance angiography (Magnetom Trio, Siemens Healthcare, Erlangen, Germany). The largest average diameter was among the elderly males (19.7 (+/- 1.33) mm) and smallest among the young females (12.4 (+/- 0.605) mm). The highest peak systolic velocity was in the young female group (1.02 (+/- 0.336) m/s) and lowest in the elderly male group (0.836 (+/- 0.127) m/s). A geometrical change with age was observed as the AA becomes more bended with age. This also affects the blood flow velocity patterns, which are markedly different from young to elderly. Thus, changes in blood flow patterns in the AA related to age and gender are observed. Further investigations are needed to determine the relation between changes in blood flow patterns and AAA development.

  17. The aging correlation (RH + t): Relative humidity (%) + temperature (deg C)

    NASA Technical Reports Server (NTRS)

    Cuddihy, E. F.

    1986-01-01

    An aging correlation between corrosion lifetime, and relative humidity RH (%) and temperature t (C) has been reported in the literature. This aging correlation is a semi-log plot of corrosion lifetime on the log scale versus the interesting summation term RH(%) + t(C) on the linear scale. This empirical correlation was derived from observation of experimental data trends and has been referred to as an experimental law. Using electrical resistivity data of polyvinyl butyral (PVB) measured as a function of relative humidity and temperature, it was found that the electrical resistivity could be expressed as a function of the term RH(%) t(C). Thus, if corrosion is related to leakage current through an organic insulator, which, in turn, is a function of RH and t, then some partial theoretical validity for the correlation is indicated. This article describes the derivation of the term RH(%) t(C) from PVB electrical resistivity data.

  18. Lipids, Lipoproteins, and Age-Related Macular Degeneration

    PubMed Central

    Ebrahimi, Katayoon B.; Handa, James T.

    2011-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly. While excellent treatment has emerged for neovascular disease, treatment for early AMD is lacking due to an incomplete understanding of the early molecular events. A prominent age-related change is the accumulation of neutral lipid in normal Bruch's membrane (BrM) throughout adulthood and also disease-related BrM accumulations called basal deposits and drusen. AMD lesion formation has thus been conceptualized as sharing mechanisms with atherosclerotic plaque formation, where low-density lipoprotein (LDL) retention within the arterial wall initiates a cascade of pathologic events. However, we do not yet understand how lipoproteins contribute to AMD. This paper explores how systemic and local production of lipoproteins might contribute to the pathogenesis of AMD. PMID:21822496

  19. Age-related macular degeneration: Complement in action.

    PubMed

    van Lookeren Campagne, Menno; Strauss, Erich C; Yaspan, Brian L

    2016-06-01

    The complement system plays a key role in host-defense against common pathogens but must be tightly controlled to avoid inflammation and tissue damage. Polymorphisms in genes encoding two important negative regulators of the alternative complement pathway, complement factor H (CFH) and complement factor I (CFI), are associated with the risk for Age-Related Macular Degeneration (AMD), a leading cause of vision impairment in the ageing population. In this review, we will discuss the genetic basis of AMD and the potential impact of complement de-regulation on disease pathogenesis. Finally, we will highlight recent therapeutic approaches aimed at controlling complement activation in patients with AMD.

  20. Increased Lung Weights in Drug-related Fatalities.

    PubMed

    Chen, Heather I-Hsuan; deJong, Joyce

    2017-03-20

    This study is of autopsy data for potential validation as to whether increased weights of the lungs support toxic effects of drugs as the cause of death. This retrospective study compared data from 133 deaths resulting from the toxic effects of drugs with previously reported normal lung weights (Toxicol Mech Methods, 22, 2012, 159; Am J Forensic Med Pathol 33, 2012, 368). The lung weights and their standard errors were used in a two-sample independent t-test comparing the average drug-related death weight to the average control weights. To account for multiple comparisons, a Bonferroni-adjusted alpha level of 0.0125 was used. We are 98.75% confident that the mean right lung weight for female drug-related deaths is between 227 and 377 g greater than the mean right lung weight for female non-drug-related deaths. We are 98.75% confident that the mean right lung weight for male drug-related deaths is between 245 and 378 g greater than the mean right lung weight for male non-drug-related deaths.

  1. Near-infrared light increases ATP, extends lifespan and improves mobility in aged Drosophila melanogaster

    PubMed Central

    Begum, Rana; Calaza, Karin; Kam, Jaimie Hoh; Salt, Thomas E.; Hogg, Chris; Jeffery, Glen

    2015-01-01

    Ageing is an irreversible cellular decline partly driven by failing mitochondrial integrity. Mitochondria accumulate DNA mutations and reduce ATP production necessary for cellular metabolism. This is associated with inflammation. Near-infrared exposure increases retinal ATP in old mice via cytochrome c oxidase absorption and reduces inflammation. Here, we expose fruitflies daily to 670 nm radiation, revealing elevated ATP and reduced inflammation with age. Critically, there was a significant increase in average lifespan: 100–175% more flies survived into old age following 670 nm exposure and these had significantly improved mobility. This may be a simple route to extending lifespan and improving function in old age. PMID:25788488

  2. Near-infrared light increases ATP, extends lifespan and improves mobility in aged Drosophila melanogaster.

    PubMed

    Begum, Rana; Calaza, Karin; Kam, Jaimie Hoh; Salt, Thomas E; Hogg, Chris; Jeffery, Glen

    2015-03-01

    Ageing is an irreversible cellular decline partly driven by failing mitochondrial integrity. Mitochondria accumulate DNA mutations and reduce ATP production necessary for cellular metabolism. This is associated with inflammation. Near-infrared exposure increases retinal ATP in old mice via cytochrome c oxidase absorption and reduces inflammation. Here, we expose fruitflies daily to 670 nm radiation, revealing elevated ATP and reduced inflammation with age. Critically, there was a significant increase in average lifespan: 100-175% more flies survived into old age following 670 nm exposure and these had significantly improved mobility. This may be a simple route to extending lifespan and improving function in old age.

  3. Accelerated tissue aging and increased oxidative stress in broiler chickens fed allopurinol.

    PubMed

    Klandorf, H; Rathore, D S; Iqbal, M; Shi, X; Van Dyke, K

    2001-06-01

    Uric acid has been hypothesized as being one of the more important antioxidants in limiting the accumulation of glycosylated endproducts in birds. Study 1 was designed to quantitatively manipulate the plasma concentrations of uric acid using hemin and allopurinol while study 2 determined their effects on skin pentosidine, the shear force value of Pectoralis major muscle, plasma glucose, body weight and chemiluminescence monitored oxidative stress in broiler chickens. Hemin was hypothesized to raise uric acid concentrations thereby lowering oxidative stress whereas allopurinol was hypothesized to lower uric acid concentrations and raise measures of oxidative stress. In study 1 feeding allopurinol (10 mg/kg body weight) to 8-week-old broiler chicks (n=50) for 10 days decreased plasma uric acid by 57%. However, hemin (10 mg/kg body weight) increased uric acid concentrations 20%. In study 2, 12-week-old broiler chicks (n=90) were randomly assigned to either an ad libitum (AL) diet or a diet restricted (DR) group. Each group was further divided into three treatments (control, allopurinol or hemin fed). Unexpectedly, hemin did not significantly effect uric acid concentrations but increased (P<0.05) measures of chemiluminescence dependent oxidative stress in both the DR and AL birds probably due to the ability of iron to generate oxygen radicals. Allopurinol lowered concentrations of uric acid and increased (P<0.05) the oxidative stress in the AL birds at week 22, reduced (P<0.05) body weight in both the AL and DR fed birds at 16 and 22 weeks of age, and markedly increased (P<0.001) shear force values of the pectoralis major muscle. Skin pentosidine levels increased (P<0.05) in AL birds fed allopurinol or hemin fed birds, but not in the diet restricted birds at 22 weeks. The significance of these studies is that concentrations of plasma uric acid can be related to measures of oxidative stress, which can be linked to tissue aging.

  4. Age-related lesions in the cerebrum in middle-aged female cynomolgus monkeys.

    PubMed

    Kodama, Rinya; Yang, Xiuying; Saski, Yuji; Iwashige, Shuichiro; Tanigawa, Yohei; Yoshikawa, Tsuyoshi; Nagaoka, Takaharu; Kamimura, Yasuhiro; Maeda, Horishi

    2010-02-01

    Alzheimer's disease (AD) in humans is a progressive neurogenic disease that can be linked with such characteristic pathological findings in the cerebrum as senile plaques (SPs), neurofibrillary tangles (NFTs), cerebral amyloid angiopathy (CAA), and neuronal loss. In the present study, the authors investigated the age-related morphological changes in 12 middle-aged and 12 young cynomolgus monkeys. Low numbers of neurons and astrocytes in the hippocampal region in cynomolgus monkeys accompanied ageing, and there was a high number of microglial cells; however, no clearly neurotoxic abnormalities due to beta-amyloid were noted before the age of 20 years. The onset of SPs and CAA in the cerebrum in cynomolgus monkeys can occur before the age of 20 years. SPs were almost all categorized as diffuse plaques (DPs); they did not have amyloid cores and were unaccompanied by neuritic degeneration. In cynomolgus monkeys, SPs (DPs) occur before the appearance of CAA. From the above, it was concluded that cynomolgus monkeys showed pathological changes due to ageing similar to those related to Alzheimer's disease in humans, even before they were 20 years old.

  5. Neurophysiological correlates of aging-related muscle weakness

    PubMed Central

    Cunningham, David A.; Bonnett, Corin; Gohar, Dina; Bayram, Mehmed; Wyant, Alexandria; Varnerin, Nicole; Mamone, Bernadett; Siemionow, Vlodek; Hou, Juliet; Machado, Andre; Yue, Guang H.

    2013-01-01

    Muscle weakness associated with aging implicates central neural degeneration. However, role of the primary motor cortex (M1) is poorly understood, despite evidence that gains in strength in younger adults are associated with its adaptations. We investigated whether weakness of biceps brachii in aging analogously relates to processes in M1. We enrolled 20 young (22.6 ± 0.87 yr) and 28 old (74.79 ± 1.37 yr) right-handed participants. Using transcranial magnetic stimulation, representation of biceps in M1 was identified. We examined the effect of age and sex on strength of left elbow flexion, voluntary activation of biceps, corticospinal excitability and output, and short-interval intracortical and interhemispheric inhibition. Interhemispheric inhibition was significantly exaggerated in the old (P = 0.047), while strength tended to be lower (P = 0.075). Overall, women were weaker (P < 0.001). Processes of M1 related to strength or voluntary activation of biceps, but only in older adults. Corticospinal excitability was lower in weaker individuals (r = 0.38), and corticospinal output, intracortical inhibition and interhemispheric inhibition were reduced too in individuals who poorly activated biceps (r = 0.43, 0.54 and 0.38). Lower intracortical inhibition may reflect compensation for reduced corticospinal excitability, allowing weaker older adults to spread activity in M1 to recruit synergists and attempt to sustain motor output. Exaggerated interhemispheric inhibition, however, conflicts with previous evidence, potentially related to greater callosal damage in our older sample, our choice of proximal vs. distal muscle and differing influence of measurement of inhibition in rest vs. active states of muscle. Overall, age-specific relation of M1 to strength and muscle activation emphasizes that its adaptations only emerge when necessitated, as in a weakening neuromuscular system in aging. PMID:24027104

  6. Age-related cognitive decline during normal aging: the complex effect of education.

    PubMed

    Ardila, A; Ostrosky-Solis, F; Rosselli, M; Gómez, C

    2000-08-01

    The purpose of this study was to further analyze the effects of education on cognitive decline during normal aging. An 806-subject sample was taken from five different Mexican regions. Participants ranged in age from 16 to 85 years. Subjects were grouped into four educational levels: illiterate, 1-4, 5-9, and 10 or more years of education, and four age ranges: 16-30, 31-50, 51-65, and 66-85 years. A brief neuropsychological test battery (NEUROPSI), standardized and normalized in Spanish, was administered. The NEUROPSI test battery includes assessment of orientation, attention, memory, language, visuoperceptual abilities, motor skills, and executive functions. In general, test scores were strongly associated with level of educational, and differences among age groups were smaller than differences among education groups. However, there was an interaction between age and education such as that among illiterate individuals scores of participants 31-50 years old were higher than scores of participants 16-30 years old for over 50% of the tests. Different patterns of interaction among educational groups were distinguished. It was concluded that: (a) The course of life-span changes in cognition are affected by education. Among individuals with a low level of education, best neuropsychological test performance is observed at an older age than among higher-educated subjects; and (b) there is not a single relationship between age-related cognitive decline and education, but different patterns may be found, depending upon the specific cognitive domain.

  7. Ozone depletion, related UVB changes and increased skin cancer incidence

    NASA Astrophysics Data System (ADS)

    Kane, R. P.

    1998-03-01

    Stratospheric ozone at middle latitudes shows a seasonal variation of about +/-20%, a quasi-biennial oscillation of 1-10% range and a long-term variation in which the level was almost steady up to about 1979 and declined thereafter to the present day by about 10%. These variations are expected to be reflected in solar UVB observed at the ground, but in an opposite direction. Thus UVB should have had a long-term increase of about 10-20%, which should cause an increase in skin cancer incidence of about 20-40%. Skin cancer incidence has increased all over the world, e.g. about 90% in USA during 1974-1990. It is popularly believed that this increase in skin cancer incidence is related to the recent ozone depletion. This seems to be incorrect, for two reasons. Firstly, the observed skin cancer increase is too large (90%) compared with the expected value (40%) from ozone depletion. Secondly, cancer does not develop immediately after exposure to solar UVB. The sunburns may occur within hours; but cancer development and detection may take years, even decades. Hence the observed skin cancer increase since 1974 (no data available for earlier periods) must have occurred due to exposure to solar UVB in the 1950s and 1960s, when there was no ozone depletion. Thus, the skin cancer increase must be attributed to harmful solar UVB levels existing even in the 1960s, accentuated later not by ozone depletion (which started only much later, by 1979) but by other causes, such as a longer human life span, better screening, increasing tendencies of sunbathing at beaches, etc., in affluent societies. On the other hand, the recent ozone depletion and the associated UVB increases will certainly take their toll; only that the effects will not be noticed now but years or decades from now. The concern for the future expressed in the Montreal Protocol for reducing ozone depletion by controlling CFC production is certainly justified, especially because increased UVB is harmful to animal and

  8. NADPH oxidases: key modulators in aging and age-related cardiovascular diseases?

    PubMed Central

    Sahoo, Sanghamitra; Meijles, Daniel N.; Pagano, Patrick J.

    2016-01-01

    Reactive oxygen species (ROS) and oxidative stress have long been linked to aging and diseases prominent in the elderly such as hypertension, atherosclerosis, diabetes and atrial fibrillation (AF). NADPH oxidases (Nox) are a major source of ROS in the vasculature and are key players in mediating redox signalling under physiological and pathophysiological conditions. In this review, we focus on the Nox-mediated ROS signalling pathways involved in the regulation of ‘longevity genes’ and recapitulate their role in age-associated vascular changes and in the development of age-related cardiovascular diseases (CVDs). This review is predicated on burgeoning knowledge that Nox-derived ROS propagate tightly regulated yet varied signalling pathways, which, at the cellular level, may lead to diminished repair, the aging process and predisposition to CVDs. In addition, we briefly describe emerging Nox therapies and their potential in improving the health of the elderly population. PMID:26814203

  9. Dietary compound score and risk of age-related macular degeneration in the Age-Related Eye Disease Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Purpose: Because foods provide many nutrients, which may interact with each other to modify risk for multifactorial diseases such as age-related macular degeneration (AMD), we sought to develop a composite scoring system to summarize the combined effect of multiple dietary nutrients on AMD risk. Th...

  10. Treatment with dexamethasone and vitamin D3 attenuates neuroinflammatory age-related changes in rat hippocampus.

    PubMed

    Moore, Michelle; Piazza, Alessia; Nolan, Yvonne; Lynch, Marina A

    2007-10-01

    Among the changes which occur in the brain with age is an increase in hippocampal concentration of proinflammatory cytokines like interleukin-1beta (IL-1beta) and an increase in IL-1beta-induced signaling. Here we demonstrate that the increase in IL-1beta concentration is accompanied by an increase in expression of IL-1 type I receptor (IL-1RI) and an age-related increase in microglial activation, as shown by increased expression of the cell surface marker, major histocompatibility complex II (MHCII) and increased MHCII staining. The evidence indicates that these age-related changes were abrogated in hippocampus of aged rats treated with dexamethasone and vitamin D3. Similarly, the age-related increases in activation of the stress-activated protein kinase, c-Jun N-terminal kinase (JNK), as well as caspase-3 and PARP were all attenuated in hippocampal tissue prepared from rats that received dexamethasone and vitamin D3. The data indicate that dexamethasone and vitamin D3 ameliorated the age-related increase in IFNgamma and suggest that IFNgamma may be the trigger leading to microglial activation, since it increases MHCII mRNA and IL-1beta release from cultured glia. In parallel with its ability to decrease microglial activation in vivo, we report that treatment of cultured glia with dexamethasone and vitamin D3 blocked the lipopolysaccharide increased MHCII mRNA and IL-1beta concentration, while the IL-1beta-induced increases in activation of JNK and caspase 3 in cultured neurons were also reversed by treatment with dexamethasone and vitamin D3. The data suggest that the antiinflammatory effect of dexamethasone and vitamin D3 derives from their ability to downreguate microglial activation.

  11. Middle-aged rats orally supplemented with gel-encapsulated catechin favorably increases blood cytosolic NADPH levels.

    PubMed

    Cueno, Marni E; Tamura, Muneaki; Ochiai, Kuniyasu

    2015-04-15

    Green tea catechins are primarily known to function as free radical scavengers and have several beneficial uses. Orally supplemented catechin (OSC) was previously shown to increase mitochondrial heme and catalase levels in rat heart blood, however, its effect in the cytosol has not been elucidated. Here, we determined the effects of OSC in the rat heart blood cytosol. We used middle-aged (40 week-old) and young (4 week-old) rats throughout the study. We isolated blood cytosol, verified its purity, and determined heme, hydrogen peroxide (H2O2) levels, catalase (CAT) activities, gp91(phox) amounts, NADP and NAD pools, sirtuin 1 (SIRT1) and glutathione reductase (GR) activities, and free fatty acids (FFA). We established that OSC is associated with decreased heme-dependent H2O2 amounts while increasing heme-independent CAT activity. Moreover, we found that OSC-related decrease in NAD(+) amounts among middle-aged rats is associated to increased NADPH levels and SIRT1 activity. In contrast, we associated OSC-related decrease in NAD(+) amounts among young rats to decreased NADPH levels and increased SIRT1 activity. This highlights a major difference between catechin-treated middle-aged and young rats. Furthermore, we observed that cytosolic FFA and GR levels were significantly increased only among OSC-treated middle-aged rats which we hypothesize are related to increased NADPH levels. This insinuates that OSC treatment allows higher catechin amounts to enter the bloodstream of middle-aged rats. We propose that this would favorably increase NADPH amounts and lead to the simultaneous decrease in NADPH-related pro-oxidant activity and increase in NADPH-related biomolecules and anti-oxidant activities.

  12. Exercising self-control increases relative left frontal cortical activation.

    PubMed

    Schmeichel, Brandon J; Crowell, Adrienne; Harmon-Jones, Eddie

    2016-02-01

    Self-control refers to the capacity to override or alter a predominant response tendency. The current experiment tested the hypothesis that exercising self-control temporarily increases approach motivation, as revealed by patterns of electrical activity in the prefrontal cortex. Participants completed a writing task that did vs did not require them to exercise self-control. Then they viewed pictures known to evoke positive, negative or neutral affect. We assessed electroencephalographic (EEG) activity while participants viewed the pictures, and participants reported their trait levels of behavioral inhibition system (BIS) and behavioral activation system (BAS) sensitivity at the end of the study. We found that exercising (vs not exercising) self-control increased relative left frontal cortical activity during picture viewing, particularly among individuals with relatively higher BAS than BIS, and particularly during positive picture viewing. A similar but weaker pattern emerged during negative picture viewing. The results suggest that exercising self-control temporarily increases approach motivation, which may help to explain the aftereffects of self-control (i.e. ego depletion).

  13. Age-Related Changes in Performance and Recovery Kinetics in Masters Athletes: A Narrative Review.

    PubMed

    Borges, Nattai; Reaburn, Peter; Driller, Matthew; Argus, Christos

    2016-01-01

    Despite increasing participation rates in masters sport and extensive research examining age-related changes in performance, little is known about the effect of age on recovery kinetics in masters athletes. This narrative review focuses on the relationship between aging and sport participation, and the effect on both performance and recovery following an exercise bout. Current research suggests the effect of age on performance and recovery may be smaller than originally suggested and that increasing sedentary lifestyles appear to play a larger role in any observed decrements in performance and recovery in masters athletes. Currently, it appears that performance decrements are inevitable with age. However, performance capacities can be maintained through systematic physical training. Moreover, the limited current research suggests there may be an age effect on recovery kinetics following an exercise bout, although further research is required to understand the acute and chronic recovery processes in the masters athlete.

  14. Age-related disruption of autophagy in dermal fibroblasts modulates extracellular matrix components

    SciTech Connect

    Tashiro, Kanae; Shishido, Mayumi; Fujimoto, Keiko; Hirota, Yuko; Yo, Kazuyuki; Gomi, Takamasa; Tanaka, Yoshitaka

    2014-01-03

    Highlights: •Autophagosomes accumulate in aged dermal fibroblasts. •Autophagic degradation is impaired in aged dermal fibroblasts. •Autophagy disruption affects extracellular matrix components in dermal fibroblasts. -- Abstract: Autophagy is an intracellular degradative system that is believed to be involved in the aging process. The contribution of autophagy to age-related changes in the human skin is unclear. In this study, we examined the relationship between autophagy and skin aging. Transmission electron microscopy and immunofluorescence microscopy analyses of skin tissue and cultured dermal fibroblasts derived from women of different ages revealed an increase in the number of nascent double-membrane autophagosomes with age. Western blot analysis showed that the amount of LC3-II, a form associated with autophagic vacuolar membranes, was significantly increased in aged dermal fibroblasts compared with that in young dermal fibroblasts. Aged dermal fibroblasts were minimally affected by inhibition of autophagic activity. Although lipofuscin autofluorescence was elevated in aged dermal fibroblasts, the expression of Beclin-1 and Atg5—genes essential for autophagosome formation—was similar between young and aged dermal fibroblasts, suggesting that the increase of autophagosomes in aged dermal fibroblasts was due to impaired autophagic flux rather than an increase in autophagosome formation. Treatment of young dermal fibroblasts with lysosomal protease inhibitors, which mimic the condition of aged dermal fibroblasts with reduced autophagic activity, altered the fibroblast content of type I procollagen, hyaluronan and elastin, and caused a breakdown of collagen fibrils. Collectively, these findings suggest that the autophagy pathway is impaired in aged dermal fibroblasts, which leads to deterioration of dermal integrity and skin fragility.

  15. Mild eccentric exercise increases Hsp72 content in skeletal muscles from adult and late middle-aged rats.

    PubMed

    Lewis, Evan J H; Ramsook, Andrew H; Locke, Marius; Amara, Catherine E

    2013-09-01

    The loss of muscle mass with age or sarcopenia contributes to increased morbidity and mortality. Thus, preventing muscle loss with age is important for maintaining health. Hsp72, the inducible member of the Hsp70 family, is known to provide protection to skeletal muscle and can be increased by exercise. However, ability to increase Hsp72 by exercise is intensity-dependent and appears to diminish with advanced age. Thus, other exercise modalities capable of increasing HSP content and potentially preventing the age related loss of muscle need to be explored. The purpose of this study was to determine if the stress from one bout of mild eccentric exercise was sufficient to elicit an increase in Hsp72 content in the vastus intermedius (VI) and white gastrocnemius (WG) muscles, and if the Hsp72 response differed between adult and late middle-aged rats. To do this, 30 adult (6 months) and late middle-aged (24 months) F344BN rats were randomly divided into three groups (n = 6/group): control (C), level exercise (16 m x min(-1)) and eccentric exercise (16 m x min(-1), 16 degree decline). Exercised animals were sacrificed immediately post-exercise or after 48 hours. Hematoxylin and Eosin staining was used to assess muscle damage, while Western Blotting was used to measure muscle Hsp72 content. A nested ANOVA with Tukey post hoc analysis was performed to determine significant difference (p < 0.05) between groups. Hsp72 content was increased in the VI for both adult and late middle-aged rats 48 hours after eccentric exercise when compared to level and control groups but no differences between age groups was observed. Hsp72 was not detected in the WG following any type of exercise. In conclusion, mild eccentric exercise can increase Hsp72 content in the rat VI muscle and this response is maintained into late middle-age.

  16. Age-related degeneration of the egg-laying system promotes matricidal hatching in Caenorhabditis elegans.

    PubMed

    Pickett, Christopher L; Kornfeld, Kerry

    2013-08-01

    The identification and characterization of age-related degenerative changes is a critical goal because it can elucidate mechanisms of aging biology and contribute to understanding interventions that promote longevity. Here, we document a novel, age-related degenerative change in C. elegans hermaphrodites, an important model system for the genetic analysis of longevity. Matricidal hatching--intra-uterine hatching of progeny that causes maternal death--displayed an age-related increase in frequency and affected ~70% of mated, wild-type hermaphrodites. The timing and incidence of matricidal hatching were largely independent of the levels of early and total progeny production and the duration of male exposure. Thus, matricidal hatching appears to reflect intrinsic age-related degeneration of the egg-laying system rather than use-dependent damage accumulation. Consistent with this model, mutations that extend longevity by causing dietary restriction significantly delayed matricidal hatching, indicating age-related degeneration of the egg-laying system is controlled by nutrient availability. To identify the underlying tissue defect, we analyzed serotonin signaling that triggers vulval muscle contractions. Mated hermaphrodites displayed an age-related decline in the ability to lay eggs in response to exogenous serotonin, indicating that vulval muscles and/or a further downstream function that is necessary for egg laying degenerate in an age-related manner. By characterizing a new, age-related degenerative event displayed by C. elegans hermaphrodites, these studies contribute to understanding a frequent cause of death in mated hermaphrodites and establish a model of age-related reproductive complications that may be relevant to the birthing process in other animals such as humans.

  17. Age-related differences in arithmetic strategy sequential effects.

    PubMed

    Lemaire, Patrick

    2016-03-01

    In this article, I review a series of new findings concerning how age-related changes in strategic variations are modulated by sequential effects. Sequential effects refer to how strategy selection and strategy execution on current problems are influenced by which strategy is used on immediately preceding problems. Two sequential effects during strategy selection (i.e., strategy revisions and strategy perseverations) and during strategy execution (i.e., strategy switch costs and modulations of poorer strategy effects) are presented. I also discuss how these effects change with age during adulthood. These phenomena are important, as they shed light on arithmetic processes and how these processes change with age during adulthood. In particular, they speak to the role of executive control while participants select and execute arithmetic strategies. Finally, I discuss the implications of sequential effects for theories of strategies and of arithmetic.

  18. Relative ages of lava flows at Alba Patera, Mars

    NASA Technical Reports Server (NTRS)

    Schneeberger, Dale M.; Pieri, David C.

    1987-01-01

    Many large lava flows on the flanks of Alba Patera are astonishing in their volume and length. As a suite, these flows suggest tremendously voluminous and sustained eruptions, and provide dimensional boundary conditions typically a factor of 100 larger than terrestrial flows. One of the most striking features associated with Alba Patera is the large, radially oriented lava flows that exhibit a variety of flow morphologies. These include sheet flows, tube fed and tube channel flows, and undifferentiated flows. Three groups of flows were studied; flows on the northwest flank, southeast flank, and the intracaldera region. The lava flows discussed probably were erupted as a group during the same major volcanic episode as suggested by the data presented. Absolute ages are poorly constrained for both the individual flows and shield, due in part to disagreement as to which absolute age curve is representative for Mars. A relative age sequence is implied but lacks precision due to the closeness of the size frequency curves.

  19. Relations of age and personality dimensions to cognitive ability factors.

    PubMed

    Costa, P T; Fozard, J L; McCrae, R R; Bosśe, R

    1976-11-01

    The relation between three cognitive ability factors - Information Processing Ability (IPA), Manual Dexterity (MD), and Pattern Analysis Capability (PAC) - and three personality dimensions - Anxiety, Extraversion, and Openness to Experience - were examined in three age groups. Subjects were 969 male volunteers ranging in age from 25 to 82. Subjects high in anixety scored lower on all three cognitive factors; subjects open to experience scored higher on IPA and PAC; and introverted subjects scored higher on PAC. Most of these effects remained when the education and socio-economic status were held constant in covariance analyses. Older subjects performed less well than younger ones on MD and PAC, but not on IPA. While personality has some influence on cognitive performance, the declines with age in performance on some cognitive tasks are not mediated by personality.

  20. Age-related differences in stepping performance during step cycle-related removal of vision.

    PubMed

    Chapman, G J; Hollands, M A

    2006-10-01

    The aim of the present study was to investigate whether there are age-related changes in the ability of individuals to use vision to plan (feedforward control) and guide (on-line control) foot placement during locomotion. This aim was achieved by constraining the availability of vision and comparing the effects on the stepping performances of older and young adults during a precision stepping task. We experimentally controlled the availability of visual information such that: (1) vision was only available during each stance phase of the targeting limb, (2) vision was only available during each swing phase of the targeting limb or (3) vision was always available. Our visual manipulations had relatively little effect on younger adults' stepping performance as demonstrated by their missing the target on less than 10% of occasions. However, there were clear visual condition-related differences in older adults' stepping performance. When vision was only available during the stance phase of the targeting limb, older adults demonstrated significantly larger foot placement error and associated task failure rate (23%) than trials in which vision was always available (10%). There was an even greater increase in older adults' foot placement error and task failure rate (42%) during trials in which vision was only available in the swing phase than the other visual conditions. These findings suggest that older adults need vision at particular times during the step cycle, to effectively pre-plan future stepping movements. We discuss the evidence that these age-related changes in performance reflect decline in visual and visuomotor CNS pathways.

  1. Ageing, longevity, exceptional longevity and related genetic and non genetics markers: panel statement.

    PubMed

    Avery, Peter; Barzilai, Nir; Benetos, Athanase; Bilianou, Helen; Capri, Miriam; Caruso, Calogero; Franceschi, Claudio; Katsiki, Niki; Mikhailidis, Dimitri P; Panotopoulos, George; Sikora, Ewa; Tzanetakou, Irene P; Kolovou, Genovefa

    2014-01-01

    In May 2012, a group of scientists and clinicians met in Athens (Greece) to consider the relevance of ageing, longevity, exceptional longevity and related genetic and non genetic markers. During this meeting, we firstly reviewed recent epidemiological and clinical studies on ageing, longevity and exceptional longevity, briefly analyzed the ageing theories and discussed successful and unsuccessful ageing also taking into account the evolutionary perspective. Secondly, we considered the three phenotypes based on the definition of ageing, longevity and exceptional longevity and the associated biomarkers. Third, we discussed proposed treatments suitable to counteract or slow down ageing. Finally, this panel produced a consensus statement to highlight the importance of ageing, longevity and exceptional longevity, since this is a rapidly increasing phenotype worldwide. We acknowledge that not all experts in this field may completely agree with this statement.

  2. Advanced glycation end products (AGEs) increase human mesangial foam cell formation by increasing Golgi SCAP glycosylation in vitro.

    PubMed

    Yuan, Yang; Zhao, Lei; Chen, Yaxi; Moorhead, John F; Varghese, Zac; Powis, Stephen H; Minogue, Shane; Sun, Zilin; Ruan, Xiong Z

    2011-07-01

    Advanced glycation end products (AGEs) is one of the causative factors of diabetic nephropathy, which is associated with lipid accumulation in glomeruli. This study was designed to investigate whether N(ε)-(carboxymethyl) lysine (CML; a member of the AGEs family) increases lipid accumulation by impairing the function of sterol-regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) in human mesangial cells (HMCs). Intracellular cholesterol content was assessed by Oil Red O staining and quantitative assay. The expression of molecules controlling cholesterol homeostasis was examined using real-time quantitative RT-PCR and Western blotting. The activity of Golgi-processing enzymes was determined using enzyme-based methods, and the translocation of SCAP from the endoplasmic reticulum (ER) to the Golgi was detected by confocal microscopy. CML increased cholesterol accumulation in HMCs. Exposure to CML increased expression and abnormal translocation of SCAP from the ER to the Golgi even in the presence of a high concentration of LDL. The increased SCAP translocation carried more SREBP-2 to the Golgi for activation by proteolytic cleavages, enhancing transcription of 3-hydroxy-3-methylclutaryl-CoA reductase and the LDL receptor. CML increased Golgi mannosidase activity, which may enhance glycosylation of SCAP. This prolonged the half-life and enhanced recycling of SCAP between the ER and the Golgi. The effects of CML were blocked by inhibitors of Golgi mannosidases. AGEs (CML) increased lipid synthesis and uptake, thereby causing foam cell formation via increasing transcription and protein glycosylation of SCAP in HMCs. These data imply that inhibitors of Golgi-processing enzymes might have a potential renoprotective role in prevention of mesangial foam cell formation.

  3. Age class, longevity and growth rate relationships: protracted growth increases in old trees in the eastern United States.

    PubMed

    Johnson, Sarah E; Abrams, Marc D

    2009-11-01

    This study uses data from the International Tree-Ring Data Bank website and tree cores collected in the field to explore growth rate (basal area increment, BAI) relationships across age classes (from young to old) for eight tree species in the eastern US. These species represent a variety of ecological traits and include those in the genera Populus, Quercus, Pinus, Tsuga and Nyssa. We found that most trees in all age classes and species exhibit an increasing BAI throughout their lives. This is particularly unusual for trees in the older age classes that we expected to have declining growth in the later years, as predicted by physiological growth models. There exists an inverse relationship between growth rate and increasing age class. The oldest trees within each species have consistently slow growth throughout their lives, implying an inverse relationship between growth rate and longevity. Younger trees (< 60 years of age) within each species are consistently growing faster than the older trees when they are of the same age resulting from a higher proportion of fast-growing trees in these young age classes. Slow, but increasing, BAI in the oldest trees in recent decades is a continuation of their growth pattern established in previous centuries. The fact that they have not shown a decreasing growth rate in their old age contradicts physiological growth models and may be related to the stimulatory effects of global change phenomenon (climate and land-use history).

  4. Age-related oxidative stress compromises endosomal proteostasis.

    PubMed

    Cannizzo, Elvira S; Clement, Cristina C; Morozova, Kateryna; Valdor, Rut; Kaushik, Susmita; Almeida, Larissa N; Follo, Carlo; Sahu, Ranjit; Cuervo, Ana Maria; Macian, Fernando; Santambrogio, Laura

    2012-07-26

    A hallmark of aging is an imbalance between production and clearance of reactive oxygen species and increased levels of oxidatively damaged biomolecules. Herein, we demonstrate that splenic and nodal antigen-presenting cells purified from aging mice accumulate oxidatively modified proteins with side-chain carbonylation, advanced glycation end products, and lipid peroxidation. Furthermore, we show that the endosomal accumulation of oxidatively modified proteins interferes with the efficient processing of exogenous antigens and degradation of macroautophagy-delivered proteins. In support of a causative role for oxidized products in the inefficient immune response, a decrease in oxidative stress improved the adaptive immune response to immunizing antigens. These findings underscore a previously unrecognized negative effect of age-dependent changes in cellular proteostasis on the immune response.

  5. Age-Related Frontal Hyperactivation Observed across Different Working Memory Tasks: An fMRI Study

    PubMed Central

    Fakhri, Mohammad; Sikaroodi, Hajir; Maleki, Farid; Ali Oghabian, Mohammad; Ghanaati, Hosein

    2012-01-01

    Purpose: To evaluate patterns of activation, convergence and divergence of three functional magnetic resonance imaging (fMRI) Working Memory (WM) tasks in two different age groups. We want to understand potential impact of task and subjects’ age on WM activations as well as most important areas with regard to WM functions. Materials and methods: Thirty-five healthy volunteers completed visual, verbal, and novel auditory WM tasks. The subjects were selected from age extremes to depict possible impact of normal aging. The General Linear Model was used to report significant activations and the effect of age group. Contrasts revealed differences in activation between tasks, and Combined Task Analysis was performed to determine common regions of activation across tasks. Results: Most of the observed differences between the tasks were seen in areas that were responsible for feature processing. Frontal regions were mainstay activation areas, regardless of the utilized stimulus. We found an age-related reduction in activity of visual (in visually-presented tasks) and auditory (in auditory task) cortices but an age-related increase in prefrontal cortex for all tasks. Conclusion: Regardless of the type of the task stimuli, frontal regions are the most important activation areas in WM processing. These areas are also main targets of age-related changes with regard to activation patterns. Our results also indicate that prefrontal overactivity in working memory might be a compensatory effort to mask age-related decline in sensory processing. PMID:22885811

  6. Nitroxide pharmaceutical development for age-related degeneration and disease

    PubMed Central

    Zarling, Jacob A.; Brunt, Vienna E.; Vallerga, Anne K.; Li, Weixing; Tao, Albert; Zarling, David A.; Minson, Christopher T.

    2015-01-01

    Nitroxide small molecule agents are in development as preventative or therapeutic pharmaceutical drugs for age-related macular degeneration (AMD) and cardiovascular disease, which are two major diseases of aging. These aging diseases are associated with patient genetics, smoking, diet, oxidative stress, and chronic inflammation. Nitroxide drugs preventing aging-, smoking-, high sugar or high fat diet-, or radiation- and other environmental-induced pathophysiological conditions in aging disease are reviewed. Tempol (TP), Tempol Hydroxylamine (TP-H), and TP-H prodrug (OT-551) are evaluated in (1) non-smokers versus smokers with cutaneous microvascular dysfunction, rapidly reversed by cutaneous TP; (2) elderly cancer patients at risk for radiation-induced skin burns or hair loss, prevented by topical TP; and (3) elderly smoker or non-smoker AMD patients at risk for vision loss, prevented by daily eye drops of OT-551. The human data indicates safety and efficacy for these nitroxide drugs. Both TP and TP-H topically penetrate and function in skin or mucosa, protecting and treating radiation burns and hair loss or smoking-induced cutaneous vascular dysfunction. TP and TP-H do not penetrate the cornea, while OT-551 does effectively penetrate and travels to the back of the eye, preserving visual acuity and preserving normal and low light luminance in dry AMD smokers and non-smoker patients. Topical, oral, or injectable drug formulations are discussed. PMID:26594225

  7. Oxidative modification of proteins: age-related changes.

    PubMed

    Chakravarti, Bulbul; Chakravarti, Deb N

    2007-01-01

    Aging is a complex biological phenomenon which involves progressive loss of different physiological functions of various tissues of living organisms. It is the inevitable fate of life and is a major risk factor for death and different pathological disorders. Based on a wide variety of studies performed in humans as well as in various animal models and microbial systems, reactive oxygen species (ROS) are believed to play a key role in the aging process. The production of ROS is influenced by cellular metabolic activities as well as environmental factors. ROS can react with all major biological macromolecules such as carbohydrates, nucleic acids, lipids, and proteins. Since, in general, proteins are the key molecules that play the ultimate role in various structural and functional aspects of living organisms, this review will focus on the age-related oxidative modifications of proteins as well as on mechanism for removal or repair of the oxidized proteins. The topics covered include protein oxidation as a marker of oxidative stress, experimental evidence indicating the role of ROS in protein oxidation, protein carbonyl content, enzymatic degradation of oxidized proteins, and effects of caloric restriction on protein oxidation in the context of aging. Finally, we will discuss different strategies which have been or can be undertaken to slow down the oxidative damage of proteins and the aging process.

  8. Breed- and age-related differences in canine mammary tumors

    PubMed Central

    Kim, Hyun-Woo; Lim, Ha-Young; Shin, Jong-Il; Seung, Byung-Joon; Ju, Jung-Hyung; Sur, Jung-Hyang

    2016-01-01

    Triple-negative breast cancer is a type of breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). It is an important and clinically relevant condition as it has a poor prognosis and is difficult to treat. Basal-like triple-negative cancer is highly prevalent in both African-Americans and adolescents. We therefore examined whether such a cancer likewise occurs in specific breeds and age groups in dogs, focusing on basal-like triple-negative cancer in particular. In this study, 181 samples from dogs with malignant mammary carcinoma from the 5 most common breeds and 2 age groups in Korea were analyzed. Histological classification and molecular subtyping, including assessment of immunohistochemical findings, were carried out. Twenty-five of 28 (89.3%) triple-negative carcinomas were identified as basal-like triple-negative carcinomas. Analysis of associations of classified factors revealed that the shih tzu breed (9/25, 36.0%) and advanced-age (19/25, 76.0%) groups were characterized by higher prevalence of basal-like triple-negative tumors with diverse histological types and of a higher grade. These results suggest that breed- and age-related differences can be identified in canine mammary carcinoma and, notably, in the shih tzu breed and at older ages. Further investigation of these distinguishing characteristics of the shih tzu breed is warranted. PMID:27127342

  9. Breed- and age-related differences in canine mammary tumors.

    PubMed

    Kim, Hyun-Woo; Lim, Ha-Young; Shin, Jong-Il; Seung, Byung-Joon; Ju, Jung-Hyung; Sur, Jung-Hyang

    2016-04-01

    Triple-negative breast cancer is a type of breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). It is an important and clinically relevant condition as it has a poor prognosis and is difficult to treat. Basal-like triple-negative cancer is highly prevalent in both African-Americans and adolescents. We therefore examined whether such a cancer likewise occurs in specific breeds and age groups in dogs, focusing on basal-like triple-negative cancer in particular. In this study, 181 samples from dogs with malignant mammary carcinoma from the 5 most common breeds and 2 age groups in Korea were analyzed. Histological classification and molecular subtyping, including assessment of immunohistochemical findings, were carried out. Twenty-five of 28 (89.3%) triple-negative carcinomas were identified as basal-like triple-negative carcinomas. Analysis of associations of classified factors revealed that the shih tzu breed (9/25, 36.0%) and advanced-age (19/25, 76.0%) groups were characterized by higher prevalence of basal-like triple-negative tumors with diverse histological types and of a higher grade. These results suggest that breed- and age-related differences can be identified in canine mammary carcinoma and, notably, in the shih tzu breed and at older ages. Further investigation of these distinguishing characteristics of the shih tzu breed is warranted.

  10. Nitroxide pharmaceutical development for age-related degeneration and disease.

    PubMed

    Zarling, Jacob A; Brunt, Vienna E; Vallerga, Anne K; Li, Weixing; Tao, Albert; Zarling, David A; Minson, Christopher T

    2015-01-01

    Nitroxide small molecule agents are in development as preventative or therapeutic pharmaceutical drugs for age-related macular degeneration (AMD) and cardiovascular disease, which are two major diseases of aging. These aging diseases are associated with patient genetics, smoking, diet, oxidative stress, and chronic inflammation. Nitroxide drugs preventing aging-, smoking-, high sugar or high fat diet-, or radiation- and other environmental-induced pathophysiological conditions in aging disease are reviewed. Tempol (TP), Tempol Hydroxylamine (TP-H), and TP-H prodrug (OT-551) are evaluated in (1) non-smokers versus smokers with cutaneous microvascular dysfunction, rapidly reversed by cutaneous TP; (2) elderly cancer patients at risk for radiation-induced skin burns or hair loss, prevented by topical TP; and (3) elderly smoker or non-smoker AMD patients at risk for vision loss, prevented by daily eye drops of OT-551. The human data indicates safety and efficacy for these nitroxide drugs. Both TP and TP-H topically penetrate and function in skin or mucosa, protecting and treating radiation burns and hair loss or smoking-induced cutaneous vascular dysfunction. TP and TP-H do not penetrate the cornea, while OT-551 does effectively penetrate and travels to the back of the eye, preserving visual acuity and preserving normal and low light luminance in dry AMD smokers and non-smoker patients. Topical, oral, or injectable drug formulations are discussed.

  11. THE AGE OF ELLIPTICALS AND THE COLOR-MAGNITUDE RELATION

    SciTech Connect

    Schombert, James; Rakos, Karl E-mail: karl.rakos@chello.at

    2009-07-10

    Using new narrowband color observations of early-type galaxies in clusters, we reconstruct the color-magnitude relation (CMR) with a higher degree of accuracy than previous work. We then use the spectroscopically determined ages and metallicities from three samples, combined with multimetallicity spectral energy distribution models, to compare predicted colors for galaxies with young ages (less than 8 Gyr) with the known CMR. We find that the CMR cannot by reproduced by the spectroscopically determined ages and metallicities in any of the samples despite the high internal accuracies to the spectroscopic indices. In contrast, using only the (Fe) index to determine [Fe/H], and assuming a mean age of 12 Gyr for a galaxy's stellar population, we derive colors that exactly match not only the color zero point of the CMR but also its slope. We consider the source of young age estimates, the H{beta} index, and examine the conflict between red continuum colors and large H{beta} values in galaxy spectra. We conclude that our current understanding of stellar populations is insufficient to correctly interpret H{beta} values.

  12. Increased anxiety-related behaviour in Hint1 knockout mice.

    PubMed

    Varadarajulu, Jeeva; Lebar, Maria; Krishnamoorthy, Gurumoorthy; Habelt, Sonja; Lu, Jia; Bernard Weinstein, I; Li, Haiyang; Holsboer, Florian; Turck, Christoph W; Touma, Chadi

    2011-07-07

    Several reports have implicated a role for the histidine triad nucleotide-binding protein-1 (Hint1) in psychiatric disorders. We have studied the emotional behaviour of male Hint1 knockout (Hint1 KO) mice in a battery of tests and performed biochemical analyses on brain tissue. The behavioural analysis revealed that Hint1 KO mice exhibit an increased emotionality phenotype compared to wildtype (WT) mice, while no significant differences in locomotion or general exploratory activity were noted. In the elevated plus-maze (EPM) test, the Hint1 KO animals entered the open arms of the apparatus less often than WT littermates. Similarly, in the dark-light box test, Hint1 KO mice spent less time in the lit compartment and the number of entries were reduced, which further confirmed an increased anxiety-related behaviour. Moreover, the Hint1 KO animals showed significantly more struggling and less floating behaviour in the forced swim test (FST), indicating an increased emotional arousal in aversive situations. Hint1 is known as a protein kinase C (PKC) interacting protein. Western blot analysis showed that PKCγ expression was elevated in Hint1 KO compared to WT mice. Interestingly, PKCγ mRNA levels of the two groups did not show a significant difference, implying a post-transcriptional PKCγ regulation. In addition, PKC enzymatic activity was increased in Hint1 KO compared to WT mice. In summary, our results indicate a role for Hint1 and PKCγ in modulating anxiety-related and stress-coping behaviour in mice.

  13. Exploring age-related brain degeneration in meditation practitioners.

    PubMed

    Luders, Eileen

    2014-01-01

    A growing body of research suggests that meditation practices are associated with substantial psychological as well as physiological benefits. In searching for the biological mechanisms underlying the beneficial impact of meditation, studies have revealed practice-induced alterations of neurotransmitters, brain activity, and cognitive abilities, just to name a few. These findings not only imply a close link between meditation and brain structure, but also suggest possible modulating effects of meditation on age-related brain atrophy. Given that normal aging is associated with significant loss of brain tissue, meditation-induced growth and/or preservation might manifest as a seemingly reduced brain age in meditators (i.e., cerebral measures characteristic of younger brains). Surprisingly, there are only three published studies that have addressed the question of whether meditation diminishes age-related brain degeneration. This paper reviews these three studies with respect to the brain attributes studied, the analytical strategies applied, and the findings revealed. The review concludes with an elaborate discussion on the significance of existing studies, implications and directions for future studies, as well as the overall relevance of this field of research.

  14. Age-related memory impairments due to reduced blood glucose responses to epinephrine.

    PubMed

    Morris, Ken A; Chang, Qing; Mohler, Eric G; Gold, Paul E

    2010-12-01

    Increases in blood glucose levels are an important component of the mechanisms by which epinephrine enhances memory formation. The present experiments addressed the hypothesis that a dysfunction in the blood glucose response to circulating epinephrine contributes to age-related memory impairments. Doses of epinephrine and glucagon that significantly increased blood glucose levels in young adult rats were far less effective at doing so in 2-year-old rats. In young rats, epinephrine and glucose were about equally effective in enhancing memory and in prolonging post-training release of acetylcholine in the hippocampus. However, glucose was more effective than epinephrine in enhancing both memory and acetylcholine release in aged rats. These results suggest that an uncoupling between circulating epinephrine and glucose levels in old rats may lead to an age-related reduction in the provision of glucose to the brain during training. This in turn may contribute to age-related changes in memory and neural plasticity.

  15. Paternal aging and increased risk of congenital disease, psychiatric disorders, and cancer

    PubMed Central

    Conti, Simon L; Eisenberg, Michael L

    2016-01-01

    As couples are increasingly delaying parenthood, the effect of the aging men and women on reproductive outcomes has been an area of increased interest. Advanced paternal age has been shown to independently affect the entire spectrum of male fertility as assessed by reductions in sperm quality and fertilization (both assisted and unassisted). Moreover, epidemiological data suggest that paternal age can lead to higher rates of adverse birth outcomes and congenital anomalies. Mounting evidence also suggests increased risk of specific pediatric and adult disease states ranging from cancer to behavioral traits. While disease states associated with advancing paternal age have been well described, consensus recommendations for neonatal screening have not been as widely implemented as have been with advanced maternal age. PMID:26975491

  16. Age-related changes in haematology and serum chemistry of Weiser-Maples guineapigs (Cavia porcellus).

    PubMed

    Kitagaki, M; Yamaguchi, M; Nakamura, M; Sakurada, K; Suwa, T; Sasa, H

    2005-07-01

    Age-related changes in haematology and serum chemistry values were examined in male and female Weiser-Maples guineapigs (Cavia porcellus). Haematological changes that significantly (P<0.01) correlated with ageing were increased white blood cell and neutrophil counts in both sexes, decreased lymphocyte counts in both sexes, decreased reticulocyte and platelet counts in males, and decreased basophil counts in females. For serum chemistry, increases in total protein, triglycerides, blood urea nitrogen and creatinine were seen in both sexes, along with increases in total cholesterol in males and sodium in females. Decreased alkaline phosphatase in both sexes and decreased chloride in males were significantly (P<0.01) associated with age. These age-related changes are compared with the published literature.

  17. Age-related Dysregulation of Inflammation and Innate Immunity: Lessons Learned from Rodent Models

    PubMed Central

    Brubaker, Aleah L.; Palmer, Jessica L.; Kovacs, Elizabeth J.

    2011-01-01

    In the elderly patient population, it has become increasingly evident that immune dysregulation is a contributing factor to age-related pathologies and their associated morbidity and mortality. In particular, elderly subjects are plagued by poor responses to infectious challenge and immunization and are at heightened risk for the development of autoimmune, neuroinflammatory and tumor-associated pathologies. Rodent models of aging and age-related disorders have been utilized to better describe how innate immune cell dysfunction contributes to these clinical scenarios. As the elderly population continues to increase in size, use of these aging rodent models to study immune dysregulation may translate into increased healthy living years for these individuals. PMID:22396887

  18. 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

  19. Idiom understanding in adulthood: examining age-related differences.

    PubMed

    Hung, Pei-Fang; Nippold, Marilyn A

    2014-03-01

    Idioms are figurative expressions such as hold your horses, kick the bucket, and lend me a hand, which commonly occur in everyday spoken and written language. Hence, the understanding of these expressions is essential for daily communication. In this study, we examined idiom understanding in healthy adults in their 20s, 40s, 60s and 80s (n=30 per group) to determine if performance would show an age-related decline. Participants judged their own familiarity with a set of 20 idioms, explained the meaning of each, described a situation in which the idiom could be used, and selected the appropriate interpretation from a set of choices. There was no evidence of an age-related decline on any tasks. Rather, the 60s group reported greater familiarity and offered better explanations than did the 20s group. Moreover, greater familiarity with idioms was associated with better understanding in adults.

  20. Versatile Functions of Caveolin-1 in Aging-related Diseases

    PubMed Central

    Nguyen, Kim Cuc Thi

    2017-01-01

    Caveolin-1 (Cav-1) is a trans-membrane protein that is a major component of the caveolae structure on the plasma membrane. Cav-1 is involved in the regulation of various cellular processes, including cell growth, differentiation, endocytosis, and in particular it has been implied in cellular senescence. Here we review current knowledge about Cav-1 in cellular signaling and discuss the role of Cav-1 in aging-related diseases. PMID:28184336

  1. Complement pathway biomarkers and age-related macular degeneration

    PubMed Central

    Gemenetzi, M; Lotery, A J

    2016-01-01

    In the age-related macular degeneration (AMD) ‘inflammation model', local inflammation plus complement activation contributes to the pathogenesis and progression of the disease. Multiple genetic associations have now been established correlating the risk of development or progression of AMD. Stratifying patients by their AMD genetic profile may facilitate future AMD therapeutic trials resulting in meaningful clinical trial end points with smaller sample sizes and study duration. PMID:26493033

  2. Vitreomacular traction and age-related macular degeneration.

    PubMed

    Green-Simms, Amy E; Bakri, Sophie J

    2011-05-01

    The interaction between the vitreous and the internal limiting membrane of the retina is important in the pathoetiology of numerous ocular disease processes. Recent studies have focused on the vitreo-retinal interface in the context of age-related macular degeneration (AMD), linking vitreo-retinal adhesion to exudative AMD in particular. This review summarizes our knowledge of vitreous anatomy and recent investigations regarding vitreomacular adhesion and AMD.

  3. Supervised Recognition of Age-Related Spanish Temporal Phrases

    NASA Astrophysics Data System (ADS)

    Galicia-Haro, Sofia N.; Gelbukh, Alexander F.

    This paper reports research on temporal expressions shaped by a common temporal expression for a period of years modified by an adverb of time. From a Spanish corpus we found that some of those phrases are age-related expressions. To determine automatically the temporal phrases with such meaning we analyzed a bigger sample obtained from the Internet. We analyzed these examples to define the relevant features to support a learning method. We present some preliminary results when a decision tree is applied.

  4. Smoking and age-related macular degeneration: review and update.

    PubMed

    Velilla, Sara; García-Medina, José Javier; García-Layana, Alfredo; Dolz-Marco, Rosa; Pons-Vázquez, Sheila; Pinazo-Durán, M Dolores; Gómez-Ulla, Francisco; Arévalo, J Fernando; Díaz-Llopis, Manuel; Gallego-Pinazo, Roberto

    2013-01-01

    Age-related macular degeneration (AMD) is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health.

  5. Smoking and Age-Related Macular Degeneration: Review and Update

    PubMed Central

    Velilla, Sara; García-Medina, José Javier; García-Layana, Alfredo; Pons-Vázquez, Sheila; Pinazo-Durán, M. Dolores; Gómez-Ulla, Francisco; Arévalo, J. Fernando; Díaz-Llopis, Manuel; Gallego-Pinazo, Roberto

    2013-01-01

    Age-related macular degeneration (AMD) is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health. PMID:24368940

  6. Early detection of age related macular degeneration: current status.

    PubMed

    Schwartz, Roy; Loewenstein, Anat

    2015-01-01

    Early diagnosis and treatment of choroidal neovascularization (CNV), a main cause of severe vision loss in age related macular degeneration (AMD), is crucial in order to preserve vision and the quality of life of patients. This review summarizes current literature on the subject of early detection of CNV, both in the clinic setting and mainly in the patient's home. New technologies are evolving to allow for earlier detection and thus vision preservation in AMD patients.

  7. On the Increasing Fragility of Human Teeth with Age: ADeep-Ultraviolet Resonance Raman Study

    SciTech Connect

    Ager III, J.W.; Nalla, R.K.; Balooch, G.; Kim, G.; Pugach, M.; Habelitz, S.; Marshall, G.W.; Kinney, J.H.; Ritchie, R.O.

    2006-07-14

    Ultraviolet resonance Raman spectroscopy (UVRRS) using 244nm excitation was used to investigate the impact of aging on humandentin. The intensity of a spectroscopic feature from the peptide bondsin the collagen increases with tissue age, similar to a finding reportedpreviously for human cortical bone.

  8. DNA damage and repair in telomeres: relation to aging.

    PubMed Central

    Kruk, P A; Rampino, N J; Bohr, V A

    1995-01-01

    We have established a method for the detection of DNA damage and its repair in human telomeres, the natural ends of chromosomes which are necessary for replication and critical for chromosomal stability. We find that ultraviolet light-induced pyrimidine dimers in telomeric DNA are repaired less efficiently than endogenous genes but more efficiently than inactive, noncoding regions. We have also measured telomeric length, telomeric DNA damage, and its repair in relation to the progression of aging. Telomeres are shorter in fibroblasts from an old donor compared to fibroblasts from a young donor, shortest in cells from a patient with the progeroid disorder Werner syndrome, and relatively long in fibroblasts from a patient with Alzheimer disease. Telomeric DNA repair efficiency is lower in cells from an old donor than in cells from a young donor, normal in Alzheimer cells, and slightly lower in Werner cells. It is possible that this decline in telomeric repair with aging is of functional significance to an age-related decline in genomic stability. Images Fig. 1 Fig. 2 PMID:7816828

  9. Impact of age related macular degeneration on quality of life

    PubMed Central

    Hassell, J B; Lamoureux, E L; Keeffe, J E

    2006-01-01

    Aims To describe the impact of age related macular degeneration (AMD) on quality of life and explore the association with vision, health, and demographic variables. Methods Adult participants diagnosed with AMD and with impaired vision (visual acuity <6/12) were assessed with the Impact of Vision Impairment (IVI) questionnaire. Participants rated the extent that vision restricted participation in activities affecting quality of life and completed the Short Form General Health Survey (SF‐12) and a sociodemographic questionnaire. Results The mean age of the 106 participants (66% female) was 83.6 years (range 64–98). One quarter had mild vision impairment, (VA<6/12–6/18) and 75% had moderate or severely impaired vision. Participants reported from at least “a little” concern on 23 of the 32 IVI items including reading, emotional health, mobility, and participation in relevant activities. Those with mild and moderate vision impairment were similarly affected but significantly different from those with severe vision loss (p<0.05). Distance vision was associated with IVI scores but not age, sex, or duration of vision loss. Conclusion AMD affects many quality of life related activities and not just those related to reading. Referral to low vision care services should be considered for people with mild vision loss and worse. PMID:16622089

  10. Increased susceptibility of aging gastric mucosa to injury: the mechanisms and clinical implications.

    PubMed

    Tarnawski, Andrzej S; Ahluwalia, Amrita; Jones, Michael K

    2014-04-28

    This review updates the current views on aging gastric mucosa and the mechanisms of its increased susceptibility to injury. Experimental and clinical studies indicate that gastric mucosa of aging individuals-"aging gastropathy"-has prominent structural and functional abnormalities vs young gastric mucosa. Some of these abnormalities include a partial atrophy of gastric glands, impaired mucosal defense (reduced bicarbonate and prostaglandin generation, decreased sensory innervation), increased susceptibility to injury by a variety of damaging agents such as ethanol, aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), impaired healing of injury and reduced therapeutic efficacy of ulcer-healing drugs. Detailed analysis of the above changes indicates that the following events occur in aging gastric mucosa: reduced mucosal blood flow and impaired oxygen delivery cause hypoxia, which leads to activation of the early growth response-1 (egr-1) transcription factor. Activation of egr-1, in turn, upregulates the dual specificity phosphatase, phosphatase and tensin homologue deleted on chromosome ten (PTEN) resulting in activation of pro-apoptotic caspase-3 and caspase-9 and reduced expression of the anti-apoptosis protein, survivin. The imbalance between pro- and anti-apoptosis mediators results in increased apoptosis and increased susceptibility to injury. This paradigm has human relevance since increased expression of PTEN and reduced expression of survivin were demonstrated in gastric mucosa of aging individuals. Other potential mechanisms operating in aging gastric mucosa include reduced telomerase activity, increase in replicative cellular senescence, and reduced expression of vascular endothelial growth factor and importin-α-a nuclear transport protein essential for transport of transcription factors to nucleus. Aging gastropathy is an important and clinically relevant issue because of: (1) an aging world population due to prolonged life span; (2) older

  11. Imaging geographic atrophy in age-related macular degeneration.

    PubMed

    Göbel, Arno P; Fleckenstein, Monika; Schmitz-Valckenberg, Steffen; Brinkmann, Christian K; Holz, Frank G

    2011-01-01

    Advances in retinal imaging technology have largely contributed to the understanding of the natural history, prognostic markers and disease mechanisms of geographic atrophy (GA) due to age-related macular degeneration. There is still no therapy available to halt or slow the disease process. In order to evaluate potential therapeutic effects in interventional trials, there is a need for precise quantification of the GA progression rate. Fundus autofluorescence imaging allows for accurate identification and segmentation of atrophic areas and currently represents the gold standard for evaluating progressive GA enlargement. By means of high-resolution spectral-domain optical coherence tomography, distinct microstructural alterations related to GA can be visualized.

  12. Age-related changes to the production of linguistic prosody

    NASA Astrophysics Data System (ADS)

    Barnes, Daniel R.

    The production of speech prosody (the rhythm, pausing, and intonation associated with natural speech) is critical to effective communication. The current study investigated the impact of age-related changes to physiology and cognition in relation to the production of two types of linguistic prosody: lexical stress and the disambiguation of syntactically ambiguous utterances. Analyses of the acoustic correlates of stress: speech intensity (or sound-pressure level; SPL), fundamental frequency (F0), key word/phrase duration, and pause duration revealed that both young and older adults effectively use these acoustic features to signal linguistic prosody, although the relative weighting of cues differed by group. Differences in F0 were attributed to age-related physiological changes in the laryngeal subsystem, while group differences in duration measures were attributed to relative task complexity and the cognitive-linguistic load of these respective tasks. The current study provides normative acoustic data for older adults which informs interpretation of clinical findings as well as research pertaining to dysprosody as the result of disease processes.

  13. Transient Elastography-Based Liver Stiffness Age-Dependently Increases in Children

    PubMed Central

    Tokuhara, Daisuke; Cho, Yuki; Shintaku, Haruo

    2016-01-01

    Background and Aims Pediatric use of liver transient elastography (TE) is attractive for its non-invasiveness, but reference values have not been established. We aimed to determine reference values for TE in children. Methods In pediatric patients (1 to 18 years), TE (FibroScan®) with an M probe was used for both liver stiffness measurement (LSM) and measurement of hepatic fat deposition by using a controlled attenuation parameter (CAP). The patients were divided into three relevant age groups: preschoolers (1 to 5 years), elementary school children (6 to 11 years), and adolescents (12 to 18 years). Overweight or obese patients or those with known liver disease, elevated serum liver enzymes, or hepatic echogenic abnormality were excluded from the study. Results Among 139 children, 123 (88.5%; 62 male; median age, 11.7 years; age range, 1.3 to 17.2 years) were successfully subjected to M-probe TE without anesthesia. Median LSM increased with age: it was 3.4 kPa (2.3 to 4.6 kPa, 5th to 95th percentiles) at ages 1 to 5 years; 3.8 (2.5 to 6.1) kPa at ages 6 to 11; and 4.1 (3.3 to 7.9) kPa at ages 12 to 18 (P = 0.001). Median CAP was not age dependent: it was 183 (112 to 242) for ages 1 to 18 years. Conclusions M-probe TE is suitable in a wide age range of children from age 1 year up. In children without evidence of liver disease, LSM has an age-dependent increase, whereas CAP does not differ between ages 1 and 18. PMID:27861607

  14. Age-related decline of precision and binding in visual working memory.

    PubMed

    Peich, Muy-Cheng; Husain, Masud; Bays, Paul M

    2013-09-01

    Working memory declines with normal aging, but the nature of this impairment is debated. Studies based on detecting changes to