Science.gov

Sample records for age-related functional decline

  1. 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

  2. Early Age-Related Functional Connectivity Decline in High-Order Cognitive Networks

    PubMed Central

    Siman-Tov, Tali; Bosak, Noam; Sprecher, Elliot; Paz, Rotem; Eran, Ayelet; Aharon-Peretz, Judith; Kahn, Itamar

    2017-01-01

    As the world ages, it becomes urgent to unravel the mechanisms underlying brain aging and find ways of intervening with them. While for decades cognitive aging has been related to localized brain changes, growing attention is now being paid to alterations in distributed brain networks. Functional connectivity magnetic resonance imaging (fcMRI) has become a particularly useful tool to explore large-scale brain networks; yet, the temporal course of connectivity lifetime changes has not been established. Here, an extensive cross-sectional sample (21–85 years old, N = 887) from a public fcMRI database was used to characterize adult lifespan connectivity dynamics within and between seven brain networks: the default mode, salience, dorsal attention, fronto-parietal control, auditory, visual and motor networks. The entire cohort was divided into young (21–40 years, mean ± SD: 25.5 ± 4.8, n = 543); middle-aged (41–60 years, 50.6 ± 5.4, n = 238); and old (61 years and above, 69.0 ± 6.3, n = 106) subgroups. Correlation matrices as well as a mixed model analysis of covariance indicated that within high-order cognitive networks a considerable connectivity decline is already evident by middle adulthood. In contrast, a motor network shows increased connectivity in middle adulthood and a subsequent decline. Additionally, alterations in inter-network interactions are noticeable primarily in the transition between young and middle adulthood. These results provide evidence that aging-related neural changes start early in adult life. PMID:28119599

  3. Hypothalamic ΔFosB prevents age-related metabolic decline and functions via SNS

    PubMed Central

    Nagano, Kenichi; Rowe, Glenn C.; Gori, Francesca; Baron, Roland

    2017-01-01

    The ventral hypothalamus (VHT) integrates several physiological cues to maintain glucose homeostasis and energy balance. Aging is associated with increased glucose intolerance but the underlying mechanisms responsible for age-related metabolic decline, including neuronal signaling in the VHT, remain elusive. We have shown that mice with VHT-targeted overexpression of ΔFosB, a splice variant of the AP1 transcription factor FosB, exhibit increased energy expenditure, leading to decreased adiposity. Here, we show that VHT-targeted overexpression of ΔFosB also improves glucose tolerance, increases insulin sensitivity in target organs and thereby suppresses insulin secretion. These effects are also observed by the overexpression of dominant negative JunD, demonstrating that they occur via AP1 antagonism within the VHT. Furthermore, the improved glucose tolerance and insulin sensitivity persisted in aged animals overexpressing ΔFosB in the VHT. These beneficial effects on glucose metabolism were abolished by peripheral sympathectomy and α-adrenergic, but not β-adrenergic, blockade. Taken together, our results show that antagonizing AP1 transcription activity in the VHT leads to a marked improvement in whole body glucose homeostasis via activation of the SNS, conferring protection against age-related impairment in glucose metabolism. These findings may open novel avenues for therapeutic intervention in diabetes and age-related glucose intolerance. PMID:28121620

  4. Dietary anthocyanin intake and age-related decline in lung function: longitudinal findings from the VA Normative Aging Study123

    PubMed Central

    Mehta, Amar J; Cassidy, Aedín; Litonjua, Augusto A; Sparrow, David; Vokonas, Pantel; Schwartz, Joel

    2016-01-01

    Background: It is unknown whether habitual intake of dietary flavonoids, known for their antioxidative and anti-inflammatory properties, affects longitudinal change in lung function. Objective: We investigated whether different flavonoid subclasses present in the habitual diet were associated with beneficial changes in lung function over time in the elderly. Design: This longitudinal analysis included 839 participants from the VA (Veterans Affairs) Normative Aging Study whose lung function [forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)] was measured at 2 and up to 5 visits between 1992 and 2008 (n = 2623 measurements). Yearly average intake of major flavonoid subclasses (anthocyanins, flavanones, flavan-3-ols, flavonols, flavones, and polymers) was calculated from food-frequency questionnaires at each visit. We estimated adjusted differences in annual change in lung function associated with each flavonoid subclass, categorized into quartiles, in linear mixed-effects regression models after adjustment for lifestyle and dietary confounders. Results: Strong inverse associations were found between anthocyanin intake and age-related decline in lung function. Independent of dietary and nondietary risk factors, slower rates of FEV1 and FVC decline by 23.6 (95% CI: 16.6, 30.7) and 37.3 (95% CI: 27.8, 46.8) mL/y, respectively, were observed in participants in the fourth quartile of intake compared with participants in the first quartile (P-trend < 0.0001). The protective associations observed for anthocyanin intake were present in both current/former and never smokers. Compared with no or very low intakes, an intake of ≥2 servings of anthocyanin-rich blueberries/wk was associated with slower decline in FEV1 and FVC by 22.5 (95% CI: 10.8, 34.2) and 37.9 (95% CI: 22.1, 53.7) mL/y, respectively. To a lesser extent, higher flavan-3-ol intake was also associated with slower lung function decline. Conclusions: An attenuation of age-related lung function

  5. Grape Powder Improves Age-Related Decline in Mitochondrial and Kidney Functions in Fischer 344 Rats

    PubMed Central

    Ali, Quaisar

    2016-01-01

    We examined the effects and mechanism of grape powder- (GP-) mediated improvement, if any, on aging kidney function. Adult (3-month) and aged (21-month) Fischer 344 rats were treated without (controls) and with GP (1.5% in drinking water) and kidney parameters were measured. Control aged rats showed higher levels of proteinuria and urinary kidney injury molecule-1 (KIM-1), which decreased with GP treatment in these rats. Renal protein carbonyls (protein oxidation) and gp91phox-NADPH oxidase levels were high in control aged rats, suggesting oxidative stress burden in these rats. GP treatment in aged rats restored these parameters to the levels of adult rats. Moreover, glomerular filtration rate and sodium excretion were low in control aged rats suggesting compromised kidney function, which improved with GP treatment in aged rats. Interestingly, low renal mitochondrial respiration and ATP levels in control aged rats were associated with reduced levels of mitochondrial biogenesis marker MtTFA. Also, Nrf2 proteins levels were reduced in control aged rats. GP treatment increased levels of MtTFA and Nrf2 in aged rats. These results suggest that GP by potentially regulating Nrf2 improves aging mitochondrial and kidney functions. PMID:27528887

  6. Common SIRT1 variants modify the effect of abdominal adipose tissue on aging-related lung function decline.

    PubMed

    Curjuric, Ivan; Imboden, Medea; Bridevaux, Pierre-Olivier; Gerbase, Margaret W; Haun, Margot; Keidel, Dirk; Kumar, Ashish; Pons, Marco; Rochat, Thierry; Schikowski, Tamara; Schindler, Christian; von Eckardstein, Arnold; Kronenberg, Florian; Probst-Hensch, Nicole M

    2016-06-01

    Lung function is an independent predictor of mortality and serves as an aging marker in never smokers. The protein sirtuin-1 of gene SIRT1 has profound anti-inflammatory effects and regulates metabolic pathways. Its suggested longevity effects on lower organisms remain poorly studied in humans. In 1132 never smokers of the population-based SAPALDIA cohort, we investigated associations between single nucleotide polymorphisms (SNPs; rs730821, rs10997868, rs10823116) of SIRT1 and aging-related lung function decline over 11 years in terms of change in forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and forced expiratory flow between 25 and 75 % of FVC (FEF25-75) using multiple linear regression models. Interactions between the SIRT1 SNPs and adiposity parameters (body mass index (BMI), its change and weight gain) were tested by including multiplicative interaction terms into the models. SIRT1 polymorphisms exhibited no main effects, but modified the association between obesity measures and FEV1/FVC and FEF25-75 decline (p = 0.009-0.046). Per risk allele, FEV1/FVC decline was accelerated up to -0.5 % (95 % CI -1.0 to 0 %) and -0.7 % (-1.3 to -0.2 %) over interquartile range increases in BMI (2.4 kg/m(2)) or weight (6.5 kg), respectively. For FEF25-75 decline, corresponding estimates were -57 mL/s (-117 to 4 mL/s) and -76 mL/s (-1429 to -9 mL/s). Interactions were not present in participants with genetically lowered C-reactive protein concentrations. Genetic variation in SIRT1 might therefore affect lung function and human longevity by modifying subclinical inflammation arising from abdominal adipose tissue.

  7. An olive oil-derived antioxidant mixture ameliorates the age-related decline of skeletal muscle function.

    PubMed

    Pierno, Sabata; Tricarico, Domenico; Liantonio, Antonella; Mele, Antonietta; Digennaro, Claudio; Rolland, Jean-François; Bianco, Gianpatrizio; Villanova, Luciano; Merendino, Alessandro; Camerino, Giulia Maria; De Luca, Annamaria; Desaphy, Jean-François; Camerino, Diana Conte

    2014-02-01

    Age-related skeletal muscle decline is characterized by the modification of sarcolemma ion channels important to sustain fiber excitability and to prevent metabolic dysfunction. Also, calcium homeostasis and contractile function are impaired. In the aim to understand whether these modifications are related to oxidative damage and can be reverted by antioxidant treatment, we examined the effects of in vivo treatment with an waste water polyphenolic mixture (LACHI MIX HT) supplied by LACHIFARMA S.r.l. Italy containing hydroxytirosol (HT), gallic acid, and homovanillic acid on the skeletal muscles of 27-month-old rats. After 6-week treatment, we found an improvement of chloride ClC-1 channel conductance, pivotal for membrane electrical stability, and of ATP-dependent potassium channel activity, important in coupling excitability with fiber metabolism. Both of them were analyzed using electrophysiological techniques. The treatment also restored the resting cytosolic calcium concentration, the sarcoplasmic reticulum calcium release, and the mechanical threshold for contraction, an index of excitation-contraction coupling mechanism. Muscle weight and blood creatine kinase levels were preserved in LACHI MIX HT-treated aged rats. The antioxidant activity of LACHI MIX HT was confirmed by the reduction of malondialdehyde levels in the brain of the LACHI MIX HT-treated aged rats. In comparison, the administration of purified HT was less effective on all the parameters studied. Although muscle function was not completely recovered, the present study provides evidence of the beneficial effects of LACHI MIX HT, a natural compound, to ameliorate skeletal muscle functional decline due to aging-associated oxidative stress.

  8. Functional magnetic resonance imaging in aging and dementia: detection of age-related cognitive changes and prediction of cognitive decline.

    PubMed

    Woodard, John L; Sugarman, Michael A

    2012-01-01

    Functional magnetic resonance imaging (fMRI) allows for dynamic observation of the neural substrates of cognitive processing, which makes it a valuable tool for studying brain changes that may occur with both normal and pathological aging. fMRI studies have revealed that older adults frequently exhibit a greater magnitude and extent activation of the blood-oxygen-level-dependent signal compared to younger adults. This additional activation may reflect compensatory recruitment associated with functional and structural deterioration of neural resources. Increased activation has also been associated with several risk factors for Alzheimer's disease (AD), including the apolipoprotein ε4 allele. Longitudinal studies have also demonstrated that fMRI may have predictive utility in determining which individuals are at the greatest risk of developing cognitive decline. This chapter will review the results of a number of task-activated fMRI studies of older adults, focusing on both healthy aging and neuropathology associated with AD. We also discuss models that account for cognitive aging processes, including the hemispheric asymmetry reduction in older adults (HAROLD) and scaffolding theory of aging and cognition (STAC) models. Finally, we discuss methodological issues commonly associated with fMRI research in older adults.

  9. Age-related decline in Kv3.1b expression in the mouse auditory brainstem correlates with functional deficits in the medial olivocochlear efferent system.

    PubMed

    Zettel, Martha L; Zhu, Xiaoxia; O'Neill, William E; Frisina, Robert D

    2007-06-01

    Kv3.1b channel protein is widely distributed in the mammalian auditory brainstem, but studies have focused mainly on regions critical for temporal processing, including the medial nucleus of the trapezoid body (MNTB) and anteroventral cochlear nucleus (AVCN). Because temporal processing declines with age, this study was undertaken to determine if the expression of Kv3.1b likewise declines, and if changes are specific to these nuclei. Immunocytochemistry using an anti-Kv3.1b antibody was performed, and the relative optical density of cells and neuropil was determined from CBA/CaJ mice of four age groups. Declines in expression in AVCN, MNTB, and lateral superior olive (35, 26, and 23%) were found, but changes were limited to neuropil. Interestingly, cellular optical density declines were found in superior paraolivary nucleus, ventral nucleus of the trapezoid body, and lateral nucleus of the trapezoid body (24, 29, and 26%), which comprise the medial olivocochlear (MOC) feedback system. All declines occurred by middle age (15 months old). No age-related changes were found in the remaining regions of cochlear nucleus or in the inferior colliculus. Contralateral suppression of distortion-product otoacoustic emission amplitudes of age-matched littermates also declined by middle age, suggesting a correlation between Kv3.1 expression and MOC function. In search of more direct evidence for such a correlation, Kv3.1b knockout mice were examined. Knockouts show poor MOC function as compared to +/+ and +/- genotypes. Thus, Kv3.1b expression declines in MOC neurons by middle age, and these changes appear to correlate with functional declines in efferent activity in both middle-aged CBA mice and Kv3.1b knockout mice.

  10. 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

  11. The potential effects of meditation on age-related cognitive decline: a systematic review

    PubMed Central

    Gard, Tim; Hölzel, Britta K.; Lazar, Sara W.

    2014-01-01

    With a rapidly aging society it becomes increasingly important to counter normal age-related decline in cognitive functioning. Growing evidence suggests that cognitive training programs may have the potential to counteract this decline. On the basis of a growing body of research that shows that meditation has positive effects on cognition in younger and middle-aged adults, meditation may be able to offset normal age-related cognitive decline or even enhance cognitive function in older adults. In this paper, we review studies investigating the effects of meditation on age-related cognitive decline. We searched the Web of Science (1900 to present), PsycINFO (1597 to present), MEDLINE (1950 to present), and CABI (1910 to present) to identify original studies investigating the effects of meditation on cognition and cognitive decline in the context of aging. Twelve studies were included in the review, six of which were randomized controlled trials. Studies involved a wide variety of meditation techniques and reported preliminary positive effects on attention, memory, executive function, processing speed, and general cognition. However, most studies had a high risk of bias and small sample sizes. Reported dropout rates were low and compliance rates high. We conclude that meditation interventions for older adults are feasible, and preliminary evidence suggests that meditation can offset age-related cognitive decline. PMID:24571182

  12. The potential effects of meditation on age-related cognitive decline: a systematic review.

    PubMed

    Gard, Tim; Hölzel, Britta K; Lazar, Sara W

    2014-01-01

    With a rapidly aging society it becomes increasingly important to counter normal age-related decline in cognitive functioning. Growing evidence suggests that cognitive training programs may have the potential to counteract this decline. On the basis of a growing body of research that shows that meditation has positive effects on cognition in younger and middle-aged adults, meditation may be able to offset normal age-related cognitive decline or even enhance cognitive function in older adults. In this paper, we review studies investigating the effects of meditation on age-related cognitive decline. We searched the Web of Science (1900 to present), PsycINFO (1597 to present), MEDLINE (1950 to present), and CABI (1910 to present) to identify original studies investigating the effects of meditation on cognition and cognitive decline in the context of aging. Twelve studies were included in the review, six of which were randomized controlled trials. Studies involved a wide variety of meditation techniques and reported preliminary positive effects on attention, memory, executive function, processing speed, and general cognition. However, most studies had a high risk of bias and small sample sizes. Reported dropout rates were low and compliance rates high. We conclude that meditation interventions for older adults are feasible, and preliminary evidence suggests that meditation can offset age-related cognitive decline.

  13. 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.

  14. Recent Advances in Berry Supplementation and Age-Related Cognitive Decline

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To summarize recent findings and current concepts in the beneficial effects of berry consumption on brain function during aging. Berryfruit supplementation has continued to demonstrate efficacy in reversing age-related cognitive decline in animal studies. In terms of the mechanisms behind the effe...

  15. 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.

  16. 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…

  17. Preventing age-related decline of gut compartmentalization limits microbiota dysbiosis and extends lifespan

    PubMed Central

    Li, Hongjie; Qi, Yanyan; Jasper, Heinrich

    2016-01-01

    Summary Compartmentalization of the gastrointestinal (GI) tract of metazoans is critical for health. GI compartments contain specific microbiota, and microbiota dysbiosis is associated with intestinal dysfunction. Dysbiosis develops in aging intestines, yet how this relates to changes in GI compartmentalization remains unclear. The Drosophila GI tract is an accessible model to address this question. Here we show that the stomach-like copper cell region (CCR) in the middle midgut controls distribution and composition of the microbiota. We find that chronic activation of JAK/Stat signaling in the aging gut induces a metaplasia of the gastric epithelium, CCR decline, and subsequent commensal dysbiosis and epithelial dysplasia along the GI tract. Accordingly, inhibition of JAK/Stat signaling in the CCR specifically prevents age-related metaplasia, commensal dysbiosis and functional decline in old guts, and extends lifespan. Our results establish a mechanism by which age-related chronic inflammation causes the decline of intestinal compartmentalization and microbiota dysbiosis, limiting lifespan. PMID:26867182

  18. Preventing Age-Related Decline of Gut Compartmentalization Limits Microbiota Dysbiosis and Extends Lifespan.

    PubMed

    Li, Hongjie; Qi, Yanyan; Jasper, Heinrich

    2016-02-10

    Compartmentalization of the gastrointestinal (GI) tract of metazoans is critical for health. GI compartments contain specific microbiota, and microbiota dysbiosis is associated with intestinal dysfunction. Dysbiosis develops in aging intestines, yet how this relates to changes in GI compartmentalization remains unclear. The Drosophila GI tract is an accessible model to address this question. Here we show that the stomach-like copper cell region (CCR) in the middle midgut controls distribution and composition of the microbiota. We find that chronic activation of JAK/Stat signaling in the aging gut induces a metaplasia of the gastric epithelium, CCR decline, and subsequent commensal dysbiosis and epithelial dysplasia along the GI tract. Accordingly, inhibition of JAK/Stat signaling in the CCR specifically prevents age-related metaplasia, commensal dysbiosis and functional decline in old guts, and extends lifespan. Our results establish a mechanism by which age-related chronic inflammation causes the decline of intestinal compartmentalization and microbiota dysbiosis, limiting lifespan.

  19. Ability of university-level education to prevent age-related decline in emotional intelligence.

    PubMed

    Cabello, Rosario; Navarro Bravo, Beatriz; Latorre, José Miguel; Fernández-Berrocal, Pablo

    2014-01-01

    Numerous studies have suggested that educational history, as a proxy measure of active cognitive reserve, protects against age-related cognitive decline and risk of dementia. Whether educational history also protects against age-related decline in emotional intelligence (EI) is unclear. The present study examined ability EI in 310 healthy adults ranging in age from 18 to 76 years using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). We found that older people had lower scores than younger people for total EI and for the EI branches of perceiving, facilitating, and understanding emotions, whereas age was not associated with the EI branch of managing emotions. We also found that educational history protects against this age-related EI decline by mediating the relationship between age and EI. In particular, the EI scores of older adults with a university education were higher than those of older adults with primary or secondary education, and similar to those of younger adults of any education level. These findings suggest that the cognitive reserve hypothesis, which states that individual differences in cognitive processes as a function of lifetime intellectual activities explain differential susceptibility to functional impairment in the presence of age-related changes and brain pathology, applies also to EI, and that education can help preserve cognitive-emotional structures during aging.

  20. Cognition enhancers in age-related cognitive decline.

    PubMed

    Riedel, W J; Jolles, J

    1996-04-01

    A review of recently published studies on the effect of cognition enhancers in non-demented human study participants is presented. The heterogeneity of the therapeutic target, age-associated cognitive decline, can be improved by separately treating groups in whom age-extrinsic factors may underlie cognitive pathology. Standardisation of cognitive assessments is necessary, since many different tests are applied to answer the same question. Modelling cognitive dysfunction, either by pharmacological or nonpharmacological means, in humans is highly recommended since it allows hypotheses to be tested in a clearly operationalised way. Predictive validity of the currently applied models for the clinical situation remains a problem, however. The scopolamine (hyoscine) model has, to a reasonable extent, predictive validity for the cholinergic agents. The results of 67 single-dose studies and 30 multiple-dose studies are summarised. All single-dose studies and 14 multiple-dose studies were carried out in young or elderly human volunteers. In 45 of 81 volunteer studies, models of cognitive dysfunction were employed. The scopolamine model was the most used (n = 21); the other studies induced cognitive dysfunction by means of benzodiazepines (8), hypoxia (7), alcohol (5) and sleep-deprivation (4). The remaining 16 multiple-dose studies were clinical trials of a duration varying between 2 weeks and 1 year (average duration was 14 weeks). In these trials, the effects of cognition enhancers were assessed in elderly people in whom impairment of memory, psychomotor performance or cognitive function was determined. These included age-associated memory impairment (AAMI) and age-associated cognitive decline (AACD). There were many studies in which the cognition enhancing properties of substances in humans were reliably demonstrated. The cognition enhancing properties of substances that are widely used, such as caffeine, nicotine and vitamins, may already be active against AACD. New

  1. Glutamatergic regulation prevents hippocampal-dependent age-related cognitive decline through dendritic spine clustering

    PubMed Central

    Pereira, Ana C.; Lambert, Hilary K.; Grossman, Yael S.; Dumitriu, Dani; Waldman, Rachel; Jannetty, Sophia K.; Calakos, Katina; Janssen, William G.; McEwen, Bruce S.; Morrison, John H.

    2014-01-01

    The dementia of Alzheimer’s disease (AD) results primarily from degeneration of neurons that furnish glutamatergic corticocortical connections that subserve cognition. Although neuron death is minimal in the absence of AD, age-related cognitive decline does occur in animals as well as humans, and it decreases quality of life for elderly people. Age-related cognitive decline has been linked to synapse loss and/or alterations of synaptic proteins that impair function in regions such as the hippocampus and prefrontal cortex. These synaptic alterations are likely reversible, such that maintenance of synaptic health in the face of aging is a critically important therapeutic goal. Here, we show that riluzole can protect against some of the synaptic alterations in hippocampus that are linked to age-related memory loss in rats. Riluzole increases glutamate uptake through glial transporters and is thought to decrease glutamate spillover to extrasynaptic NMDA receptors while increasing synaptic glutamatergic activity. Treated aged rats were protected against age-related cognitive decline displayed in nontreated aged animals. Memory performance correlated with density of thin spines on apical dendrites in CA1, although not with mushroom spines. Furthermore, riluzole-treated rats had an increase in clustering of thin spines that correlated with memory performance and was specific to the apical, but not the basilar, dendrites of CA1. Clustering of synaptic inputs is thought to allow nonlinear summation of synaptic strength. These findings further elucidate neuroplastic changes in glutamatergic circuits with aging and advance therapeutic development to prevent and treat age-related cognitive decline. PMID:25512503

  2. Age-related decline in motor behavior and striatal dopamine transporter in cynomolgus monkeys.

    PubMed

    Yue, Feng; Zeng, Sien; Wu, Di; Yi, Deqiao; Alex Zhang, Y; Chan, Piu

    2012-08-01

    Advanced human aging is associated with progressive declines of motor function and a risk factor for Parkinson's disease, which mainly involves central nigrostriatal dopaminergic system. The present study investigated age-related changes in motor behaviors and alterations of the number of nigrostriatal dopaminergic terminals in non-human primates. A total of 30 cynomolgus monkeys (Macaca fascicularis) of age 3.5-15.5 years were studied. Motor behaviors including upper limb movement time and the amount of overall home cage activity were quantitatively assessed using a modified movement assessment panel and a newly developed webcam-based monitoring system. The function of the dopaminergic system was semi-quantitatively measured by (99m)Tc-TRODAT-1 uptake rates, a dopamine transporter (DAT) specific radiopharmaceutical with SPECT imaging. The results showed a significant decline in motor behaviors associated with aging which were significantly correlated with age-related decreases of (99m)Tc-TRODAT-1 uptake. A further partial correlation analysis independent of age indicated that age contributed to the relationship between striatal DAT levels and motor behaviors. Our results indicate that normal aging-related dopamine physiology influences certain aspects of motor behaviors and suggest that aging-associated dysfunction in the nigrostriatal dopaminergic system may be an important factor contributing to the decline of motor behaviors in aging cynomolgus monkeys.

  3. Dizziness and Imbalance in the Elderly: Age-related Decline in the Vestibular System

    PubMed Central

    Iwasaki, Shinichi; Yamasoba, Tatsuya

    2015-01-01

    Dizziness and imbalance are amongst the most common complaints in older people, and are a growing public health concern since they put older people at a significantly higher risk of falling. Although the causes of dizziness in older people are multifactorial, peripheral vestibular dysfunction is one of the most frequent causes. Benign paroxysmal positional vertigo is the most frequent form of vestibular dysfunction in the elderly, followed by Meniere’s disease. Every factor associated with the maintenance of postural stability deteriorates during aging. Age-related deterioration of peripheral vestibular function has been demonstrated through quantitative measurements of the vestibulo-ocular reflex with rotational testing and of the vestibulo-collic reflex with testing of vestibular evoked myogenic potentials. Age-related decline of vestibular function has been shown to correlate with the age-related decrease in the number of vestibular hair cells and neurons. The mechanism of age-related cellular loss in the vestibular endorgan is unclear, but it is thought that genetic predisposition and cumulative effect of oxidative stress may both play an important role. Since the causes of dizziness in older people are multi-factorial, management of this disease should be customized according to the etiologies of each individual. Vestibular rehabilitation is found to be effective in treating both unilateral and bilateral vestibular dysfunction. Various prosthetic devices have also been developed to improve postural balance in older people. Although there have been no medical treatments improving age-related vestibular dysfunction, new medical treatments such as mitochondrial antioxidants or caloric restriction, which have been effective in preventing age-related hearing loss, should be ienvestigated in the future. PMID:25657851

  4. Blueberry-enriched diet ameliorates age-related declines in NMDA receptor-dependent LTP

    PubMed Central

    Bickford, Paula C.; Browning, Michael D.

    2008-01-01

    NMDA receptor-dependent long-term potentiation (LTP) in the hippocampus is widely accepted as a cellular substrate for memory formation. Age-related declines in the expression of both NMDAR-dependent LTP and NMDAR subunit proteins in the CA1 region of the hippocampus have been well characterized and likely underlie age-related memory impairment. In the current study, we examined NMDAR-dependent LTP in young Fischer 344 rats (4 months old) and aged rats (24 months old) given either a control diet or a diet supplemented with blueberry extract for 6–8 weeks. NMDAR-dependent LTP was evoked by high-frequency stimulation (HFS) in the presence of nifedipine, to eliminate voltage-gated calcium channel LTP. Field excitatory postsynaptic potentials (fEPSPs) were increased by 57% 1 h after HFS in young animals, but this potentiation was reduced to 31% in aged animals. Supplementation of the diet with blueberry extract elevated LTP (63%) in aged animals to levels seen in young. The normalization of LTP may be due to the blueberry diet preventing a decline in synaptic strength, as measured by the slope of the fEPSP for a given fiber potential. The blueberry diet did not prevent age-related declines in NMDAR protein expression. However, phosphorylation of a key tyrosine residue on the NR2B subunit, important for increasing NMDAR function, was enhanced by the diet, suggesting that an increase in NMDAR function might overcome the loss in protein. This report provides evidence that dietary alterations later in life may prevent or postpone the cognitive declines associated with aging. PMID:19424850

  5. [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.

  6. Enriched childhood experiences moderate age-related motor and cognitive decline

    PubMed Central

    Metzler, Megan J.; Saucier, Deborah M.; Metz, Gerlinde A.

    2012-01-01

    Aging is associated with deterioration of skilled manual movement. Specifically, aging corresponds with increased reaction time, greater movement duration, segmentation of movement, increased movement variability, and reduced ability to adapt to external forces and inhibit previously learned sequences. Moreover, it is thought that decreased lateralization of neural function in older adults may point to increased neural recruitment as a compensatory response to deterioration of key frontal and intra-hemispheric networks, particularly of callosal structures. However, factors that mediate age-related motor decline are not well understood. Here we show that music training in childhood is associated with reduced age-related decline of bimanual and unimanual motor skills in a MIDI keyboard motor learning task. Compared to older adults without music training, older adults with more than a year of music training demonstrated proficient bimanual and unimanual movement, evidenced by enhanced speed and decreased movement errors. Further, this group demonstrated significantly better implicit learning in the weather prediction task, a non-motor task. The performance of older adults with music training in those tasks was comparable to young adults. Older adults, however, displayed greater verbal ability compared to young adults irrespective of a past history of music training. Our results indicate that music training early in life may reduce age-associated decline of neural motor and cognitive networks. PMID:23423702

  7. Are ancient proteins responsible for the age-related decline in health and fitness?

    PubMed

    Truscott, Roger John Willis

    2010-02-01

    There are a number of sites in the body where proteins are present for decades and sometimes for all of our lives. Over a period of many years, such proteins are subject to two types of modifications. The first results from the intrinsic instability of certain amino acid residues and leads to deamidation, racemization, and truncation. The second type can be traced to relentless covalent modification of such ancient proteins by reactive biochemicals produced during cellular metabolism.The accumulation of both types of posttranslational modifications over time may have important consequences for the properties of tissues that contain such proteins. It is proposed that the age-related decline in function of organs such as the eye, heart, brain, and lung, as well as skeletal components, comes about, in part, from the posttranslational modification of these long-lived proteins. Examples are provided in which this may be an important factor in the etiology of age-related conditions. As the properties of these proteins alter inexorably over time, the molecular changes contribute to a gradual decline in the function of individual organs and also tissues such as joints. This cumulative degeneration of old proteins at multiple sites in the body may also constrain the ultimate life span of the individual. The human lens may be particularly useful for discovering which reactive metabolites in the body are of most importance for posttranslational modification of long-lived proteins.

  8. Higher mortality and impaired elimination of bacteria in aged mice after intracerebral infection with E. coli are associated with an age-related decline of microglia and macrophage functions.

    PubMed

    Schütze, Sandra; Ribes, Sandra; Kaufmann, Annika; Manig, Anja; Scheffel, Jörg; Redlich, Sandra; Bunkowski, Stephanie; Hanisch, Uwe-Karsten; Brück, Wolfgang; Nau, Roland

    2014-12-30

    Incidence and mortality of bacterial meningitis are strongly increased in aged compared to younger adults demanding new strategies to improve prevention and therapy of bacterial central nervous system (CNS) infections the elderly. Here, we established a geriatric mouse model for an intracerebral E. coli infection which reflects the clinical situation in aged patients: After intracerebral challenge with E. coli K1, aged mice showed a higher mortality, a faster development of clinical symptoms, and a more pronounced weight loss. Elimination of bacteria and systemic inflammatory response were impaired in aged mice, however, the number of infiltrating leukocytes and microglial cells in the CNS of aged and young mice did not differ substantially. In vitro, primary microglial cells and peritoneal macrophages from aged mice phagocytosed less E. coli and released less NO and cyto-/chemokines compared to cells from young mice both without activation and after stimulation by agonists of TLR 2, 4, and 9. Our results suggest that the age-related decline of microglia and macrophage functions plays an essential role for the higher susceptibility of aged mice to intracerebral infections. Strategies to improve the phagocytic potential of aged microglial cells and macrophages appear promising for prevention and treatment of CNS infections in elderly patients.

  9. Mechanisms of Age-Related Decline in Memory Search across the Adult Life Span

    ERIC Educational Resources Information Center

    Hills, Thomas T.; Mata, Rui; Wilke, Andreas; Samanez-Larkin, Gregory R.

    2013-01-01

    Three alternative mechanisms for age-related decline in memory search have been proposed, which result from either reduced processing speed (global slowing hypothesis), overpersistence on categories (cluster-switching hypothesis), or the inability to maintain focus on local cues related to a decline in working memory (cue-maintenance hypothesis).…

  10. Age-related declines in car following performance under simulated fog conditions

    PubMed Central

    Ni, Rui; Kang, Julie J.; Andersen, George J.

    2010-01-01

    The present study examined age-related differences in car following performance when contrast of the driving scene was reduced by simulated fog. Older (mean age of 72.6) and younger (mean age of 21.1) drivers were presented with a car following scenario in a simulator in which a lead vehicle (LV) varied speed according to a sum of three sine wave functions. Drivers were shown an initial following distance of 18m and were asked to maintain headway distance by controlling speed to match changes in LV speed. Five simulated fog conditions were examined ranging from a no fog condition (contrast of 0.55) to a high fog condition (contrast of 0.03). Average LV speed varied across trials (40, 60, or 80 km/h). The results indicated age-related declines in car following performance for both headway distance and RMS (root mean square) error in matching speed. The greatest decline occurred at moderate speeds under the highest fog density condition, with older drivers maintaining a headway distance that was 21% closer than younger drivers. At higher speeds older drivers maintained a greater headway distance than younger drivers. These results suggest that older drivers may be at greater risk for a collision under high fog density and moderate speeds. PMID:20380908

  11. Age-related declines in car following performance under simulated fog conditions.

    PubMed

    Ni, Rui; Kang, Julie J; Andersen, George J

    2010-05-01

    The present study examined age-related differences in car following performance when contrast of the driving scene was reduced by simulated fog. Older (mean age of 72.6) and younger (mean age of 21.1) drivers were presented with a car following scenario in a simulator in which a lead vehicle (LV) varied speed according to a sum of three sine wave functions. Drivers were shown an initial following distance of 18 m and were asked to maintain headway distance by controlling speed to match changes in LV speed. Five simulated fog conditions were examined ranging from a no fog condition (contrast of 0.55) to a high fog condition (contrast of 0.03). Average LV speed varied across trials (40, 60, or 80 km/h). The results indicated age-related declines in car following performance for both headway distance and RMS (root mean square) error in matching speed. The greatest decline occurred at moderate speeds under the highest fog density condition, with older drivers maintaining a headway distance that was 21% closer than younger drivers. At higher speeds older drivers maintained a greater headway distance than younger drivers. These results suggest that older drivers may be at greater risk for a collision under high fog density and moderate speeds.

  12. Prevention of Age-Related Cognitive Decline: Which Strategies, When, and for Whom?

    PubMed

    Shatenstein, Bryna; Barberger-Gateau, Pascale; Mecocci, Patrizia

    2015-01-01

    Brain aging is characterized by the progressive and gradual accumulation of detrimental changes in structure and function, which increase risk of age-related cognitive decline and dementia. This devastating chronic condition generates a huge social and economic burden and accounts for 11.2% of years of disability. The increase in lifespan has contributed to the increase in dementia prevalence; however, there is currently no curative treatment for most causes of dementias. This paper reviews evidence-based strategies to build, enhance, and preserve cognition over the lifespan by examining approaches that work best, proposing when in the life course they should be implemented, and in which population group(s). Recent work shows a tendency to decreased age-specific prevalence and incidence of cognitive problems and dementia among people born later in the first half of the 20th century, citing higher educational levels, improvements in lifestyle, and better handling of vascular risk factors. This implies that we can target modifiable environmental, lifestyle, and health risk factors to modify the trajectory of cognitive decline before the onset of irreversible dementia. Because building cognitive reserve and prevention of cognitive decline are of critical importance, interventions are needed at every stage of the life course to foster cognitive stimulation, and enable healthy eating habits and physical activity throughout the lifespan. Preventive interventions to decrease and delay cognitive decline and its consequences in old age will also require collaboration and action on the part of policy-makers at the political and social level.

  13. Neurogenesis in a rat model of age-related cognitive decline.

    PubMed

    Bizon, J L; Lee, H J; Gallagher, M

    2004-08-01

    Age-related decrements in hippocampal neurogenesis have been suggested as a basis for learning impairment during aging. In the current study, a rodent model of age-related cognitive decline was used to evaluate neurogenesis in relation to hippocampal function. New hippocampal cell survival was assessed approximately 1 month after a series of intraperitoneal injections of 5-bromo-2'-deoxyuridine (BrdU). Correlational analyses between individual measures of BrdU-positive cells and performance on the Morris water maze task provided no indication that this measure of neurogenesis was more preserved in aged rats with intact cognitive abilities. On the contrary, among aged rats, higher numbers of BrdU-positive cells in the granule cell layer were associated with a greater degree of impairment on the learning task. Double-labelling studies confirmed that the majority of the BrdU+ cells were of the neuronal phenotype; the proportion of differentiated neurons was not different across a broad range of cognitive abilities. These data demonstrate that aged rats that maintain cognitive function do so despite pronounced reductions in hippocampal neurogenesis. In addition, these findings suggest the interesting possibility that impaired hippocampal function is associated with greater survival of newly generated hippocampal neurons at advanced ages.

  14. Epigenetic alterations in the suprachiasmatic nucleus and hippocampus contribute to age-related cognitive decline

    PubMed Central

    Deibel, Scott H.; Zelinski, Erin L.; Keeley, Robin J.; Kovalchuk, Olga; McDonald, Robert J.

    2015-01-01

    Circadian rhythm dysfunction and cognitive decline, specifically memory loss, frequently accompany natural aging. Circadian rhythms and memory are intertwined, as circadian rhythms influence memory formation and recall in young and old rodents. Although, the precise relationship between circadian rhythms and memory is still largely unknown, it is hypothesized that circadian rhythm disruption, which occurs during aging, contributes to age-associated cognitive decline, specifically memory loss. While there are a variety of mechanisms that could mediate this effect, changes in the epigenome that occur during aging has been proposed as a potential candidate. Interestingly, epigenetic mechanisms, such as DNA methylation and sirtuin1 (SIRT1) are necessary for both circadian rhythms and memory. During aging, similar alterations of epigenetic mechanisms occur in the suprachiasmatic nucleus (SCN) and hippocampus, which are necessary for circadian rhythm generation and memory, respectively. Recently, circadian rhythms have been linked to epigenetic function in the hippocampus, as some of these epigenetic mechanisms oscillate in the hippocampus and are disrupted by clock gene deletion. The current paper will review how circadian rhythms and memory change with age, and will suggest how epigenetic changes in these processes might contribute to age-related cognitive decline. PMID:26252151

  15. Genetic architecture of age-related cognitive decline in African Americans

    PubMed Central

    Raj, Towfique; Chibnik, Lori B.; McCabe, Cristin; Wong, Andus; Replogle, Joseph M.; Yu, Lei; Gao, Sujuan; Unverzagt, Frederick W.; Stranger, Barbara; Murrell, Jill; Barnes, Lisa; Hendrie, Hugh C.; Foroud, Tatiana; Krichevsky, Anna; Bennett, David A.; Hall, Kathleen S.; Evans, Denis A.

    2016-01-01

    Objective: To identify genetic risk factors associated with susceptibility to age-related cognitive decline in African Americans (AAs). Methods: We performed a genome-wide association study (GWAS) and an admixture-mapping scan in 3,964 older AAs from 5 longitudinal cohorts; for each participant, we calculated a slope of an individual's global cognitive change from neuropsychological evaluations. We also performed a pathway-based analysis of the age-related cognitive decline GWAS. Results: We found no evidence to support the existence of a genomic region which has a strongly different contribution to age-related cognitive decline in African and European genomes. Known Alzheimer disease (AD) susceptibility variants in the ABCA7 and MS4A loci do influence this trait in AAs. Of interest, our pathway-based analyses returned statistically significant results highlighting a shared risk from lipid/metabolism and protein tyrosine signaling pathways between cognitive decline and AD, but the role of inflammatory pathways is polarized, being limited to AD susceptibility. Conclusions: The genetic architecture of aging-related cognitive in AA individuals is largely similar to that of individuals of European descent. In both populations, we note a surprising lack of enrichment for immune pathways in the genetic risk for cognitive decline, despite strong enrichment of these pathways among genetic risk factors for AD. PMID:28078323

  16. Age-related decline in associative learning in healthy Chinese adults.

    PubMed

    Lee, Annie; Archer, Jo; Wong, Caroline Kai Yun; Chen, Shen-Hsing Annabel; Qiu, Anqi

    2013-01-01

    Paired associates learning (PAL) has been widely used in aging-related research, suggesting an age-related decline in associative learning. However, there are several cognitive processes (attention, spatial and recognition memory, strategy, and associative learning) involved in PAL. It is unclear which component contributes to the decline in PAL performance associated with age effects. The present study determines whether age effects on associative learning are independent of other cognitive processes involved in PAL. Using a validated computerized cognitive program (CANTAB), we examined cognitive performance of associative learning, spatial and recognition memory, attention and strategy use in 184 Singaporean Chinese adults aged from 21 to 80 years old. Linear regression revealed significant age-related decline in associative learning, spatial and recognition memory, and the level of strategy use. This age-related decline in associative learning remains even after adjusting for attention, spatial and recognition memory, and strategy use. These results show that age effects on associative learning are independent of other cognitive processes involved in PAL.

  17. A Subset of Men With Age-Related Decline in Testosterone Have Gonadotroph Autoantibodies

    PubMed Central

    Ricciuti, Adriana; Travison, Thomas G.; Di Dalmazi, Giulia; Talor, Monica V.; DeVincentiis, Ludovica; Manley, Robert W.; Bhasin, Shalender; Caturegli, Patrizio

    2016-01-01

    Context: Age-related decline in serum testosterone (T) is being increasingly diagnosed. In most men, it associates with low or inappropriately normal gonadotropin levels, which suggests a hypothalamic-pituitary etiology. Autoantibodies against adenohypophyseal cells have been associated with pituitary dysfunction; however, the prevalence of pituitary autoimmunity in this age-related T decline has not been assessed. Objectives: This is a proof-of-concept study with the objective of determining the prevalence of antibodies to gonadotrophs in older men with age-related low T and compare it with healthy young and older eugonadal men. Study Design: This is a cross-sectional case-control study of 182 men. Cases included 100 older men (≥65 years) with age-related low T levels; the control groups were composed of 50 young and 32 older healthy eugonadal men. Serum antibodies against the anterior pituitary gland were measured using a two-step approach: 1) single indirect immunofluorescence (ie, participant serum only) to determine the pattern of cytosolic staining; and 2) double indirect immunofluorescence (ie, participant serum plus a commercial adenohypophyseal hormone antibody) to identify the anterior pituitary cell type recognized by the patient's antibodies). Results: In participants with positive antipituitary antibodies, the granular cytosolic pattern (highly predictive of pituitary autoimmunity) was only seen in older men with age-related low T (4%) and none in control groups (0%, P = .001). Double indirect immunofluorescence confirmed that pituitary antibodies were exclusively directed against the gonadotrophs. Conclusion: A subset of older men with age-related low T levels have specific antibodies against the gonadotrophs. Whether these antibodies are pathogenic and contributory to the age-related decline in T remains to be established. PMID:26963952

  18. Alzheimer’s Disease and Age-Related Memory Decline (Preclinical)

    PubMed Central

    Terry, Alvin V.; Callahan, Patrick M.; Hall, Brandon; Webster, Scott J.

    2011-01-01

    An unfortunate result of the rapid rise in geriatric populations worldwide is the increasing prevalence of age-related cognitive disorders such as Alzheimer’s disease (AD). AD is a devastating neurodegenerative illness that is characterized by a profound impairment of cognitive function, marked physical disability, and an enormous economic burden on the afflicted individual, caregivers, and society in general. The rise in elderly populations is also resulting in an increase in individuals with related (potentially treatable) conditions such as “Mild Cognitive Impairment” (MCI) which is characterized by a less severe (but abnormal) level of cognitive impairment and a high-risk for developing dementia. Even in the absence of a diagnosable disorder of cognition (e.g., AD, MCI), the perception of increased forgetfulness and declining mental function is a clear source of apprehension in the elderly. This is a valid concern given that even a modest impairment of cognitive function is likely to be associated with significant disability in a rapidly evolving, technology-based society. Unfortunately, the currently available therapies designed to improve cognition (i.e., for AD and other forms of dementia) are limited by modest efficacy, adverse side effects, and their effects on cognitive function are not sustained over time. Accordingly, it is incumbent on the scientific community to develop safer and more effective therapies that improve and/or sustain cognitive function in the elderly allowing them to remain mentally active and productive for as long as possible. As diagnostic criteria for memory disorders evolve, the demand for pro-cognitive therapeutic agents is likely to surpass AD and dementia to include MCI and potentially even less severe forms of memory decline. The purpose of this review is to provide an overview of the contemporary therapeutic targets and preclinical pharmacologic approaches (with representative drug examples) designed to enhance memory

  19. 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.

  20. 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 arrays of visual objects have identified two possible components to age-related decline: a reduction in the number of items that can be stored, or a deficit in maintaining the associations (bindings) between individual object features. However, some investigations have reported intact binding with aging, and specific deficits arising only in Alzheimer's disease. Here, using a recently developed continuous measure of recall fidelity, we tested the precision with which adults of different ages could reproduce from memory the orientation and color of a probed array item. The results reveal a further component of cognitive decline: an age-related decrease in the resolution with which visual information can be maintained in working memory. This increase in recall variability with age was strongest under conditions of greater memory load. Moreover, analysis of the distribution of errors revealed that older participants were more likely to incorrectly report one of the unprobed items in memory, consistent with an age-related increase in misbinding. These results indicate a systematic decline with age in working memory resources that can be recruited to store visual information. The paradigm presented here provides a sensitive index of both memory resolution and feature binding, with the potential for assessing their modulation by interventions. The findings have implications for understanding the mechanisms underpinning working memory deficits in both health and disease.

  1. An age-related decline in striatal taurine is correlated with a loss of dopaminergic markers.

    PubMed

    Dawson, R; Pelleymounter, M A; Cullen, M J; Gollub, M; Liu, S

    1999-02-01

    Taurine is present in high concentration in the mammalian brain and is known to decline with aging. The present studies examined the relationship between the loss of striatal neurotransmitters and spatial learning ability in aged male Long-Evans rats. The effects of intrahippocampal infusions of neurotrophic factors-nerve growth factor (NGF) and brain-derived neurotrophic factor-were also examined for their ability to ameliorate the age-related decline in brain amino acid content. Taurine content was found to be significantly reduced in the striatum of aged rats (26 months old) that were impaired in spatial learning performance when compared to young unimpaired rats (5 months old). Aged rats that were behaviorally unimpaired had more modest reductions in taurine. Striatal dopamine content was also significantly reduced in aged learning-impaired rats. There was a significant (p < 0.001) correlation (r=0.61) between the striatal content of taurine and dopamine, but no such correlation was found for other striatal transmitters (glutamate, serotonin, norepinephrine). Treatment with neurotrophins had little effect on the age-related decline in striatal amino acids, although NGF treatment did improve spatial learning. These studies suggest (1) a link between age-related declines in striatal dopamine and taurine and (2) that NGF-induced improvement in spatial learning is not related to mechanisms involving changes in taurine or glutamate content.

  2. Compensatory responses to age-related decline in odor quality acuity: cholinergic neuromodulation and olfactory enrichment.

    PubMed

    Mandairon, Nathalie; Peace, Shane T; Boudadi, Karim; Boxhorn, Christine E; Narla, Venkata Anupama; Suffis, Sara D; Cleland, Thomas A

    2011-12-01

    The perceptual differentiation of odors can be measured behaviorally using generalization gradients. The steepness of these gradients defines a form of olfactory acuity for odor quality that depends on neural circuitry within the olfactory bulb and is regulated by cholinergic activity therein as well as by associative learning. Using this system as a reduced model for age-related cognitive decline, we show that aged mice, while maintaining almost the same baseline behavioral performance as younger mice, are insensitive to the effects of acutely elevated acetylcholine, which sharpens generalization gradients in young adult mice. Moreover, older mice exhibit evidence of chronically elevated acetylcholine levels in the olfactory bulb, suggesting that their insensitivity to further elevated levels of acetylcholine may arise because the maximum capacity of the system to respond to acetylcholine has already been reached. We propose a model in which an underlying, age-related, progressive deficit is mitigated by a compensatory cholinergic feedback loop that acts to retard the behavioral effects of what would otherwise be a substantial age-related decline in olfactory plasticity. We also treated mice with 10-day regimens of olfactory environmental enrichment and/or repeated systemic injections of the acetylcholinesterase inhibitor physostigmine. Each treatment alone sharpened odor quality acuity, but administering both treatments together had no greater effect than either alone. Age was not a significant main effect in this study, suggesting that some capacity for acetylcholine-dependent plasticity is still present in aged mice despite their sharply reduced ability to respond to acute increases in acetylcholine levels. These results suggest a dynamical framework for understanding age-related decline in neural circuit processing in which the direct effects of aging can be mitigated, at least temporarily, by systemic compensatory responses. In particular, a decline in

  3. Resting-state networks associated with cognitive processing show more age-related decline than those associated with emotional processing.

    PubMed

    Nashiro, Kaoru; Sakaki, Michiko; Braskie, Meredith N; Mather, Mara

    2017-03-11

    Correlations in activity across disparate brain regions during rest reveal functional networks in the brain. Although previous studies largely agree that there is an age-related decline in the "default mode network," how age affects other resting-state networks, such as emotion-related networks, is still controversial. Here we used a dual-regression approach to investigate age-related alterations in resting-state networks. The results revealed age-related disruptions in functional connectivity in all 5 identified cognitive networks, namely the default mode network, cognitive-auditory, cognitive-speech (or speech-related somatosensory), and right and left frontoparietal networks, whereas such age effects were not observed in the 3 identified emotion networks. In addition, we observed age-related decline in functional connectivity in 3 visual and 3 motor/visuospatial networks. Older adults showed greater functional connectivity in regions outside 4 out of the 5 identified cognitive networks, consistent with the dedifferentiation effect previously observed in task-based functional magnetic resonance imaging studies. Both reduced within-network connectivity and increased out-of-network connectivity were correlated with poor cognitive performance, providing potential biomarkers for cognitive aging.

  4. Age-related decline in cognitive control: the role of fluid intelligence and processing speed

    PubMed Central

    2014-01-01

    Background Research on cognitive control suggests an age-related decline in proactive control abilities whereas reactive control seems to remain intact. However, the reason of the differential age effect on cognitive control efficiency is still unclear. This study investigated the potential influence of fluid intelligence and processing speed on the selective age-related decline in proactive control. Eighty young and 80 healthy older adults were included in this study. The participants were submitted to a working memory recognition paradigm, assessing proactive and reactive cognitive control by manipulating the interference level across items. Results Repeated measures ANOVAs and hierarchical linear regressions indicated that the ability to appropriately use cognitive control processes during aging seems to be at least partially affected by the amount of available cognitive resources (assessed by fluid intelligence and processing speed abilities). Conclusions This study highlights the potential role of cognitive resources on the selective age-related decline in proactive control, suggesting the importance of a more exhaustive approach considering the confounding variables during cognitive control assessment. PMID:24401034

  5. 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

  6. Experience-Based Mitigation of Age-Related Performance Declines: Evidence From Air Traffic Control

    PubMed Central

    Nunes, Ashley; Kramer, Arthur F.

    2010-01-01

    Previous research has found age-related deficits in a variety of cognitive processes. However, some studies have demonstrated age-related sparing on tasks where individuals have substantial experience, often attained over many decades. Here, the authors examined whether decades of experience in a fast-paced demanding profession, air traffic control (ATC), would enable older controllers to perform at high levels of proficiency. The authors also investigated whether older controllers would show diminished age-related decrements on domain-relevant cognitive abilities. Both young and old controllers and noncontrollers performed a battery of cognitive and ATC tasks. Results indicate that although high levels of experience can reduce the magnitude of age-related decline on the component processes that underlie complex task performance, this sparing is limited in scope. More important, however, the authors observed experience-based sparing on simulated ATC tasks, with the sparing being most evident on the more complex air traffic control tasks. These results suggest that given substantial experience, older adults may be quite capable of performing at high levels of proficiency on fast-paced demanding real-world tasks. The implications of these findings for global skilled labor shortages are discussed. PMID:19309213

  7. Use of a robotic device to measure age-related decline in finger proprioception.

    PubMed

    Ingemanson, Morgan L; Rowe, Justin B; Chan, Vicky; Wolbrecht, Eric T; Cramer, Steven C; Reinkensmeyer, David J

    2016-01-01

    Age-related changes in proprioception are known to affect postural stability, yet the extent to which such changes affect the finger joints is poorly understood despite the importance of finger proprioception in the control of skilled hand movement. We quantified age-related changes in finger proprioception in 37 healthy young, middle-aged, and older adults using two robot-based tasks wherein participants' index and middle fingers were moved by an exoskeletal robot. The first task assessed finger position sense by asking participants to indicate when their index and middle fingers were directly overlapped during a passive crisscross movement; the second task assessed finger movement detection by asking participants to indicate the onset of passive finger movement. When these tasks were completed without vision, finger position sense errors were 48 % larger in older adults compared to young participants (p < 0.05); proprioceptive reaction time was 78 % longer in older adults compared to young adults (p < 0.01). When visual feedback was provided in addition to proprioception, these age-related differences were no longer apparent. No difference between dominant and non-dominant hand performance was found for either proprioception task. These findings demonstrate that finger proprioception is impaired in older adults, and visual feedback can be used to compensate for this deficit. The findings also support the feasibility and utility of the FINGER robot as a sensitive tool for detecting age-related decline in proprioception.

  8. Accelerated age-related cognitive decline and neurodegeneration, caused by deficient DNA repair.

    PubMed

    Borgesius, Nils Z; de Waard, Monique C; van der Pluijm, Ingrid; Omrani, Azar; Zondag, Gerben C M; van der Horst, Gijsbertus T J; Melton, David W; Hoeijmakers, Jan H J; Jaarsma, Dick; Elgersma, Ype

    2011-08-31

    Age-related cognitive decline and neurodegenerative diseases are a growing challenge for our societies with their aging populations. Accumulation of DNA damage has been proposed to contribute to these impairments, but direct proof that DNA damage results in impaired neuronal plasticity and memory is lacking. Here we take advantage of Ercc1(Δ/-) mutant mice, which are impaired in DNA nucleotide excision repair, interstrand crosslink repair, and double-strand break repair. We show that these mice exhibit an age-dependent decrease in neuronal plasticity and progressive neuronal pathology, suggestive of neurodegenerative processes. A similar phenotype is observed in mice where the mutation is restricted to excitatory forebrain neurons. Moreover, these neuron-specific mutants develop a learning impairment. Together, these results suggest a causal relationship between unrepaired, accumulating DNA damage, and age-dependent cognitive decline and neurodegeneration. Hence, accumulated DNA damage could therefore be an important factor in the onset and progression of age-related cognitive decline and neurodegenerative diseases.

  9. Mechanisms of Age-Related Decline in Memory Search Across the Adult Life Span

    PubMed Central

    Hills, Thomas T.; Mata, Rui; Wilke, Andreas; Samanez-Larkin, Gregory R.

    2013-01-01

    Three alternative mechanisms for age-related decline in memory search have been proposed, which result from either reduced processing speed (global slowing hypothesis), overpersistence on categories (cluster-switching hypothesis), or the inability to maintain focus on local cues related to a decline in working memory (cue-maintenance hypothesis). We investigated these 3 hypotheses by formally modeling the semantic recall patterns of 185 adults between 27 to 99 years of age in the animal fluency task (Thurstone, 1938). The results indicate that people switch between global frequency-based retrieval cues and local item-based retrieval cues to navigate their semantic memory. Contrary to the global slowing hypothesis that predicts no qualitative differences in dynamic search processes and the cluster-switching hypothesis that predicts reduced switching between retrieval cues, the results indicate that as people age, they tend to switch more often between local and global cues per item recalled, supporting the cue-maintenance hypothesis. Additional support for the cue-maintenance hypothesis is provided by a negative correlation between switching and digit span scores and between switching and total items recalled, which suggests that cognitive control may be involved in cue maintenance and the effective search of memory. Overall, the results are consistent with age-related decline in memory search being a consequence of reduced cognitive control, consistent with models suggesting that working memory is related to goal perseveration and the ability to inhibit distracting information. PMID:23586941

  10. Motor Skills Enhance Procedural Memory Formation and Protect against Age-Related Decline

    PubMed Central

    Müller, Nils C. J.; Genzel, Lisa; Konrad, Boris N.; Pawlowski, Marcel; Neville, David; Fernández, Guillén; Steiger, Axel

    2016-01-01

    The ability to consolidate procedural memories declines with increasing age. Prior knowledge enhances learning and memory consolidation of novel but related information in various domains. Here, we present evidence that prior motor experience–in our case piano skills–increases procedural learning and has a protective effect against age-related decline for the consolidation of novel but related manual movements. In our main experiment, we tested 128 participants with a sequential finger-tapping motor task during two sessions 24 hours apart. We observed enhanced online learning speed and offline memory consolidation for piano players. Enhanced memory consolidation was driven by a strong effect in older participants, whereas younger participants did not benefit significantly from prior piano experience. In a follow up independent control experiment, this compensatory effect of piano experience was not visible after a brief offline period of 30 minutes, hence requiring an extended consolidation window potentially involving sleep. Through a further control experiment, we rejected the possibility that the decreased effect in younger participants was caused by training saturation. We discuss our results in the context of the neurobiological schema approach and suggest that prior experience has the potential to rescue memory consolidation from age-related cognitive decline. PMID:27333186

  11. Education and Age-Related Cognitive Decline: The Contribution of Mental Workload.

    ERIC Educational Resources Information Center

    Bosma, H.; van Boxtel, M. P. J.; Ponds, R. W. H. M.; Houx, P. J. H.; Jolles, J.

    2003-01-01

    Longitudinal data from a Dutch study of 708 older adults showed that persons with low educational attainment experienced more decline in information processing speed, memory, and cognitive function. About 42% of the variance was explained by low stimulus or challenge in work. Decline was independent of crystallized intelligence. (Contains 24…

  12. Age-Related Decline in Cardiorespiratory Fitness among Career Firefighters: Modification by Physical Activity and Adiposity.

    PubMed

    Baur, Dorothee M; Christophi, Costas A; Cook, E Francis; Kales, Stefanos N

    2012-01-01

    Firefighting is a very hazardous occupation, and strenuous fire duties require high levels of physical fitness. In the general adult population, cardiorespiratory fitness (CRF) declines with aging. We sought to investigate the effect of increasing age on CRF in male career firefighters as well as the modifying effects of physical activity and adiposity. We cross-sectionally examined 804 male career firefighters from two Midwestern states. CRF was determined from symptom-limited maximal treadmill exercise testing in metabolic equivalents (METS) following the Bruce protocol. Physical activity self-reports were extracted from responses to a health and lifestyle questionnaire. We found as expected that CRF declines with advancing age; however, the decline is greatly attenuated among leaner firefighters who report more physical activity. Furthermore, in a linear regression model including age, BMI, and variables describing physical activity behaviors, we could predict CRF (R(2) = 0.6286). The total weekly duration of aerobic exercise as well as the duration of weight lifting sessions both had significant impacts on age-related decline. We conclude that firefighters are more likely to maintain the high levels of CRF needed to safely perform their duties if they engage in frequent exercise and maintain healthy weights.

  13. Age-Related Declines in Early Sensory Memory: Identification of Rapid Auditory and Visual Stimulus Sequences

    PubMed Central

    Fogerty, Daniel; Humes, Larry E.; Busey, Thomas A.

    2016-01-01

    Age-related temporal-processing declines of rapidly presented sequences may involve contributions of sensory memory. This study investigated recall for rapidly presented auditory (vowel) and visual (letter) sequences presented at six different stimulus onset asynchronies (SOA) that spanned threshold SOAs for sequence identification. Younger, middle-aged, and older adults participated in all tasks. Results were investigated at both equivalent performance levels (i.e., SOA threshold) and at identical physical stimulus values (i.e., SOAs). For four-item sequences, results demonstrated best performance for the first and last items in the auditory sequences, but only the first item for visual sequences. For two-item sequences, adults identified the second vowel or letter significantly better than the first. Overall, when temporal-order performance was equated for each individual by testing at SOA thresholds, recall accuracy for each position across the age groups was highly similar. These results suggest that modality-specific processing declines of older adults primarily determine temporal-order performance for rapid sequences. However, there is some evidence for a second amodal processing decline in older adults related to early sensory memory for final items in a sequence. This selective deficit was observed particularly for longer sequence lengths and was not accounted for by temporal masking. PMID:27199737

  14. 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.

  15. Age-related declines in immune response in a wild mammal are unrelated to immune cell telomere length

    PubMed Central

    Waring, Laura; McDonald, Robbie A.; Delahay, Richard; Young, Andrew

    2016-01-01

    Senescence has been hypothesized to arise in part from age-related declines in immune performance, but the patterns and drivers of within-individual age-related changes in immunity remain virtually unexplored in natural populations. Here, using a long-term epidemiological study of wild European badgers (Meles meles), we (i) present evidence of a within-individual age-related decline in the response of a key immune-signalling cytokine, interferon-gamma (IFNγ), to ex vivo lymphocyte stimulation, and (ii) investigate three putative drivers of individual variation in the rate of this decline (sex, disease and immune cell telomere length; ICTL). That the within-individual rate of age-related decline markedly exceeded that at the population level suggests that individuals with weaker IFNγ responses are selectively lost from this population. IFNγ responses appeared to decrease with the progression of bovine tuberculosis infection (independent of age) and were weaker among males than females. However, neither sex nor disease influenced the rate of age-related decline in IFNγ response. Similarly, while ICTL also declines with age, variation in ICTL predicted neither among- nor within-individual variation in IFNγ response. Our findings provide evidence of within-individual age-related declines in immune performance in a wild mammal and highlight the likely complexity of the mechanisms that generate them. PMID:26888036

  16. Age-related declines in immune response in a wild mammal are unrelated to immune cell telomere length.

    PubMed

    Beirne, Christopher; Waring, Laura; McDonald, Robbie A; Delahay, Richard; Young, Andrew

    2016-02-24

    Senescence has been hypothesized to arise in part from age-related declines in immune performance, but the patterns and drivers of within-individual age-related changes in immunity remain virtually unexplored in natural populations. Here, using a long-term epidemiological study of wild European badgers (Meles meles), we (i) present evidence of a within-individual age-related decline in the response of a key immune-signalling cytokine, interferon-gamma (IFNγ), to ex vivo lymphocyte stimulation, and (ii) investigate three putative drivers of individual variation in the rate of this decline (sex, disease and immune cell telomere length; ICTL). That the within-individual rate of age-related decline markedly exceeded that at the population level suggests that individuals with weaker IFNγ responses are selectively lost from this population. IFNγ responses appeared to decrease with the progression of bovine tuberculosis infection (independent of age) and were weaker among males than females. However, neither sex nor disease influenced the rate of age-related decline in IFNγ response. Similarly, while ICTL also declines with age, variation in ICTL predicted neither among- nor within-individual variation in IFNγ response. Our findings provide evidence of within-individual age-related declines in immune performance in a wild mammal and highlight the likely complexity of the mechanisms that generate them.

  17. Age-related decline in olympic triathlon performance: effect of locomotion mode.

    PubMed

    Bernard, Thierry; Sultana, Frédéric; Lepers, Romuald; Hausswirth, Christophe; Brisswalter, Jeanick

    2010-01-01

    This study describes the decline in performance with age during Olympic triathlon Age Groups World Championships among the different locomotion modes. Mean performance of top 10 performers were analyzed for each group of age using the exponential model proposed by Baker, Tang, and Turner (2003, Experimental Aging Research, 29, 47-65). Comparison in performance decline was done between locomotion modes. Decline in performance in triathlon as a function of age follows an exponential model. A significant interaction effect between age and locomotion mode was observed on performance values. In swimming, a significant decrease was observed close to 5% per year after 45 years. Decline in performance was less pronounced in cycling until 60 years. Analysis of the effect of age in the different locomotion modes of a triathlon could provide information for maintaining quality of life with aging.

  18. 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.

  19. Age-Related Declines in the Fidelity of Newly Acquired Category Representations

    ERIC Educational Resources Information Center

    Davis, Tyler; Love, Bradley C.; Maddox, W. Todd

    2012-01-01

    We present a theory suggesting that the ability to build category representations that reflect the nuances of category structures in the environment depends upon clustering mechanisms instantiated in an MTL-PFC-based circuit. Because function in this circuit declines with age, we predict that the ability to build category representations will be…

  20. Lifelong strength training mitigates the age-related decline in efferent drive.

    PubMed

    Unhjem, Runar; Nygård, Mona; van den Hoven, Lene T; Sidhu, Simranjit K; Hoff, Jan; Wang, Eivind

    that strength training may be particularly beneficial for counteracting age-related loss of neuromuscular function.

  1. Age-related decline in oligodendrogenesis retards white matter repair in mice

    PubMed Central

    Miyamoto, Nobukazu; Pham, Loc-Duyen D.; Hayakawa, Kazuhide; Matsuzaki, Toshinori; Seo, Ji Hae; Magnain, Caroline; Ayata, Cenk; Kim, Kyu-Won; Boas, David; Lo, Eng H.; Arai, Ken

    2013-01-01

    Background/Purpose Aging is one of the major risk factors for white matter injury in cerebrovascular disease. However, the effects of age on the mechanisms of injury/repair in white matter remain to be fully elucidated. Here, we ask if compared to young brains, white matter regions in older brains may be more vulnerable in part due to decreased rates of compensatory oligodendrogenesis after injury. Methods A mouse model of prolonged cerebral hypoperfusion was prepared by bilateral common carotid artery stenosis in 2-month and 8-month old mice. Matching in vitro studies were performed by subjecting oligodendrocyte precursor cells (OPCs) to sub-lethal 7-day CoCl2 treatment to induce chemical hypoxic stress. Results Baseline myelin density in the corpus callosum was similar in 2-month and 8-month old mice. But after induction of prolonged cerebral hypoperfusion, older mice showed more severe white matter injury together with worse deficits in working memory. The numbers of newborn oligodendrocytes and their precursors were increased by cerebral hypoperfusion in young mice, whereas these endogenous responses were significantly dampened in older mice. Defects in CREB signaling may be involved because activating CREB with the type-III phosphodiesterase inhibitor cilostazol in older mice restored the differentiation of OPCs, alleviated myelin loss and improved cognitive dysfunction during cerebral hypoperfusion. Cell culture systems confirmed that cilostazol promoted the differentiation of OPCs. Conclusions An age-related decline in CREB-mediated oligodendrogenesis may compromise endogenous white matter repair mechanisms, and therefore, drugs that activate CREB signaling provide a potential therapeutic approach for treating white matter injury in aging brains. PMID:23881957

  2. The Rate of Age-Related Olfactory Decline Among the General Population of Older U.S. Adults

    PubMed Central

    Wroblewski, Kristen E.; Kern, David W.; Schumm, L. Philip; McClintock, Martha K.

    2015-01-01

    Background. Age-related olfactory loss (presbyosmia) is a prevalent sensory impairment with a large public health impact. In cross-sectional analyses, we found striking health disparities in olfactory function among older U.S. adults. Here, we report a 5-year follow-up to determine the magnitude of within-person olfactory decline. Methods. The National Social Life, Health, and Aging Project (NSHAP) interviewed a probability sample of home-dwelling older U.S. adults (57–85 years) in 2005–2006 (Wave 1) and reinterviewed them in 2010–2011 (Wave 2), assessing demographics, social life, and health, including olfaction. Odor identification was measured with a 5-item version of the Sniffin’ Sticks (0–5 correct). Fourteen hundred and thirty-six respondents provided olfaction data in both waves. Multivariate linear and logistic regression were used to model the association between change in olfactory performance and demographic, health, and psychosocial factors. Results. Odor identification declined most rapidly among older individuals (0.25 additional errors per 5 years for each decade of age, p < .001) and in men (0.17 additional errors per 5 years compared to women, p = .005). Among those with perfect scores in Wave 1, African Americans declined more rapidly than Whites (p = .04). Neither socioeconomic status, health conditions, cognition, mental health, alcohol use nor smoking was associated with change in olfaction (p > .05, all). Conclusions. The rate of olfactory decline increases with age and is greater among men than women despite adjusting for differences in psychosocial and health conditions, indicating physiologic factors as drivers. African Americans are more likely to experience initial olfactory decline, consistent with an earlier onset of aging among this subgroup. PMID:26253908

  3. Experience-Based Mitigation of Age-Related Performance Declines: Evidence from Air Traffic Control

    ERIC Educational Resources Information Center

    Nunes, Ashley; Kramer, Arthur F.

    2009-01-01

    Previous research has found age-related deficits in a variety of cognitive processes. However, some studies have demonstrated age-related sparing on tasks where individuals have substantial experience, often attained over many decades. Here, the authors examined whether decades of experience in a fast-paced demanding profession, air traffic…

  4. Musical training orchestrates coordinated neuroplasticity in auditory brainstem and cortex to counteract age-related declines in categorical vowel perception.

    PubMed

    Bidelman, Gavin M; Alain, Claude

    2015-01-21

    Musicianship in early life is associated with pervasive changes in brain function and enhanced speech-language skills. Whether these neuroplastic benefits extend to older individuals more susceptible to cognitive decline, and for whom plasticity is weaker, has yet to be established. Here, we show that musical training offsets declines in auditory brain processing that accompanying normal aging in humans, preserving robust speech recognition late into life. We recorded both brainstem and cortical neuroelectric responses in older adults with and without modest musical training as they classified speech sounds along an acoustic-phonetic continuum. Results reveal higher temporal precision in speech-evoked responses at multiple levels of the auditory system in older musicians who were also better at differentiating phonetic categories. Older musicians also showed a closer correspondence between neural activity and perceptual performance. This suggests that musicianship strengthens brain-behavior coupling in the aging auditory system. Last, "neurometric" functions derived from unsupervised classification of neural activity established that early cortical responses could accurately predict listeners' psychometric speech identification and, more critically, that neurometric profiles were organized more categorically in older musicians. We propose that musicianship offsets age-related declines in speech listening by refining the hierarchical interplay between subcortical/cortical auditory brain representations, allowing more behaviorally relevant information carried within the neural code, and supplying more faithful templates to the brain mechanisms subserving phonetic computations. Our findings imply that robust neuroplasticity conferred by musical training is not restricted by age and may serve as an effective means to bolster speech listening skills that decline across the lifespan.

  5. Greater Age-Related Decline in Markers of Physical, Mental and Cognitive Health among Israeli Older Adults Exposed to Lifetime Cumulative Adversity

    PubMed Central

    Shrira, Amit

    2013-01-01

    Objectives This longitudinal investigation addressed whether and how lifetime cumulative adversity and depressive symptoms moderated age-related decline in markers of physical, mental and cognitive health. Method 1,248 older adults (mean age = 62 at Wave 1) who completed the first two waves of the Israeli component of the Survey of Health, Ageing and Retirement in Europe (SHARE-Israel) reported on exposure to potentially traumatic life events, depressive symptoms, and three outcomes – disability, quality of life and cognitive markers. Results Age was related to greater functional decline in outcome measures across the two waves (i.e., increase in disability and decrease in quality of life and cognitive functioning). This age-related decline became stronger as lifetime adversity increased. A three-way interaction showed that the greatest age-related functional decline in outcome measures was especially salient among those with high level of lifetime adversity and high level of depressive symptoms. Conclusion Lifetime cumulative adversity is associated with a more noticeable process of age-related dysfunction across various markers of health. Although the majority of older adults are resilient to lifetime adversity, prevention and intervention programs should be aimed at mitigating the pronounced senescence observed when adversity accumulated to a large degree, and especially when it is accompanied with high level of distress. PMID:24328416

  6. Are delta-aminolevulinate dehydratase inhibition and metal concentrations additional factors for the age-related cognitive decline?

    PubMed

    Baierle, Marília; Charão, Mariele F; Göethel, Gabriela; Barth, Anelise; Fracasso, Rafael; Bubols, Guilherme; Sauer, Elisa; Campanharo, Sarah C; Rocha, Rafael C C; Saint'Pierre, Tatiana D; Bordignon, Suelen; Zibetti, Murilo; Trentini, Clarissa M; Avila, Daiana S; Gioda, Adriana; Garcia, Solange C

    2014-10-17

    Aging is often accompanied by cognitive impairments and influenced by oxidative status and chemical imbalances. Thus, this study was conducted to examine whether age-related cognitive deficit is associated with oxidative damage, especially with inhibition of the enzyme delta-aminolevulinate dehydratase (ALA-D), as well as to verify the influence of some metals in the enzyme activity and cognitive performance. Blood ALA-D activity, essential (Fe, Zn, Cu, Se) and non-essential metals (Pb, Cd, Hg, As, Cr, Ni, V) were measured in 50 elderly and 20 healthy young subjects. Cognitive function was assessed by tests from Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery and other. The elderly group presented decreased ALA-D activity compared to the young group. The index of ALA-D reactivation was similar to both study groups, but negatively associated with metals. The mean levels of essential metals were within the reference values, while the most toxic metals were above them in both groups. Cognitive function impairments were observed in elderly group and were associated with decreased ALA-D activity, with lower levels of Se and higher levels of toxic metals (Hg and V). Results suggest that the reduced ALA-D activity in elderly can be an additional factor involved in cognitive decline, since its inhibition throughout life could lead to accumulation of the neurotoxic compound ALA. Toxic metals were found to contribute to cognitive decline and also to influence ALA-D reactivation.

  7. Are Delta-Aminolevulinate Dehydratase Inhibition and Metal Concentrations Additional Factors for the Age-Related Cognitive Decline?

    PubMed Central

    Baierle, Marília; Charão, Mariele F.; Göethel, Gabriela; Barth, Anelise; Fracasso, Rafael; Bubols, Guilherme; Sauer, Elisa; Campanharo, Sarah C.; Rocha, Rafael C. C.; Saint’Pierre, Tatiana D.; Bordignon, Suelen; Zibetti, Murilo; Trentini, Clarissa M.; Ávila, Daiana S.; Gioda, Adriana; Garcia, Solange C.

    2014-01-01

    Aging is often accompanied by cognitive impairments and influenced by oxidative status and chemical imbalances. Thus, this study was conducted to examine whether age-related cognitive deficit is associated with oxidative damage, especially with inhibition of the enzyme delta-aminolevulinate dehydratase (ALA-D), as well as to verify the influence of some metals in the enzyme activity and cognitive performance. Blood ALA-D activity, essential (Fe, Zn, Cu, Se) and non-essential metals (Pb, Cd, Hg, As, Cr, Ni, V) were measured in 50 elderly and 20 healthy young subjects. Cognitive function was assessed by tests from Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) battery and other. The elderly group presented decreased ALA-D activity compared to the young group. The index of ALA-D reactivation was similar to both study groups, but negatively associated with metals. The mean levels of essential metals were within the reference values, while the most toxic metals were above them in both groups. Cognitive function impairments were observed in elderly group and were associated with decreased ALA-D activity, with lower levels of Se and higher levels of toxic metals (Hg and V). Results suggest that the reduced ALA-D activity in elderly can be an additional factor involved in cognitive decline, since its inhibition throughout life could lead to accumulation of the neurotoxic compound ALA. Toxic metals were found to contribute to cognitive decline and also to influence ALA-D reactivation. PMID:25329536

  8. Processing Speed, Inhibitory Control, and Working Memory: Three Important Factors to Account for Age-Related Cognitive Decline

    ERIC Educational Resources Information Center

    Pereiro Rozas, Arturo X.; Juncos-Rabadan, Onesimo; Gonzalez, Maria Soledad Rodriguez

    2008-01-01

    Processing speed, inhibitory control and working memory have been identified as the main possible culprits of age-related cognitive decline. This article describes a study of their interrelationships and dependence on age, including exploration of whether any of them mediates between age and the others. We carried out a LISREL analysis of the…

  9. Age-related decline in verbal learning is moderated by demographic factors, working memory capacity, and presence of amnestic mild cognitive impairment.

    PubMed

    Constantinidou, Fofi; Zaganas, Ioannis; Papastefanakis, Emmanouil; Kasselimis, Dimitrios; Nidos, Andreas; Simos, Panagiotis G

    2014-09-01

    Age-related memory changes are highly varied and heterogeneous. The study examined the rate of decline in verbal episodic memory as a function of education level, auditory attention span and verbal working memory capacity, and diagnosis of amnestic mild cognitive impairment (a-MCI). Data were available on a community sample of 653 adults aged 17-86 years and 70 patients with a-MCI recruited from eight broad geographic areas in Greece and Cyprus. Measures of auditory attention span and working memory capacity (digits forward and backward) and verbal episodic memory (Auditory Verbal Learning Test [AVLT]) were used. Moderated mediation regressions on data from the community sample did not reveal significant effects of education level on the rate of age-related decline in AVLT indices. The presence of a-MCI was a significant moderator of the direct effect of Age on both immediate and delayed episodic memory indices. The rate of age-related decline in verbal episodic memory is normally mediated by working memory capacity. Moreover, in persons who display poor episodic memory capacity (a-MCI group), age-related memory decline is expected to advance more rapidly for those who also display relatively poor verbal working memory capacity.

  10. Foreign language training as cognitive therapy for age-related cognitive decline: a hypothesis for future research.

    PubMed

    Antoniou, Mark; Gunasekera, Geshri M; Wong, Patrick C M

    2013-12-01

    Over the next fifty years, the number of older adults is set to reach record levels. Protecting older adults from the age-related effects of cognitive decline is one of the greatest challenges of the next few decades as it places increasing pressure on families, health systems, and economies on a global scale. The disease-state of age-related cognitive decline-Alzheimer's disease and other dementias-hijacks our consciousness and intellectual autonomy. However, there is evidence that cognitively stimulating activities protect against the adverse effects of cognitive decline. Similarly, bilingualism is also considered to be a safeguard. We propose that foreign language learning programs aimed at older populations are an optimal solution for building cognitive reserve because language learning engages an extensive brain network that is known to overlap with the regions negatively affected by the aging process. It is recommended that future research should test this potentially fruitful hypothesis.

  11. Investigation of age-related decline of microfibril-associated glycoprotein-1 in human skin through immunohistochemistry study.

    PubMed

    Zheng, Qian; Chen, Siming; Chen, Ying; Lyga, John; Wyborski, Russell; Santhanam, Uma

    2013-01-01

    During aging, the reduction of elastic and collagen fibers in dermis can lead to skin atrophy, fragility, and aged appearance, such as increased facial wrinkling and sagging. Microfibril-associated glycoprotein-1 (MAGP-1) is an extracellular matrix protein critical for elastic fiber assembly. It integrates and stabilizes the microfibril and elastin matrix network that helps the skin to endure mechanical stretch and recoil. However, the observation of MAGP-1 during skin aging and its function in the dermis has not been established. To better understand age-related changes in the dermis, we investigated MAGP-1 during skin aging and photoaging, using a combination of in vitro and in vivo studies. Gene expression by microarray was performed using human skin biopsies from young and aged female donors. In addition, immunofluorescence analysis on the MAGP-1 protein was performed in dermal fibroblast cultures and in human skin biopsies. Specific antibodies against MAGP-1 and fibrillin-1 were used to examine protein expression and extracellular matrix structure in the dermis via biopsies from donors of multiple age groups. A reduction of the MAGP-1 gene and protein levels were observed in human skin with increasing age and photoexposure, indicating a loss of the functional MAGP-1 fiber network and a lack of structural support in the dermis. Loss of MAGP-1 around the hair follicle/pore areas was also observed, suggesting a possible correlation between MAGP-1 loss and enlarged pores in aged skin. Our findings demonstrate that a critical "pre-elasticity" component, MAGP-1, declines with aging and photoaging. Such changes may contribute to age-related loss of dermal integrity and perifollicular structural support, which may lead to skin fragility, sagging, and enlarged pores.

  12. Foreign language training as cognitive therapy for age-related cognitive decline: A hypothesis for future research

    PubMed Central

    Antoniou, Mark; Gunasekera, Geshri; Wong, Patrick C. M.

    2014-01-01

    Over the next fifty years, the number of older adults is set to reach record levels. Protecting older adults from the age-related effects of cognitive decline is one of the greatest challenges of the next few decades as it places increasing pressure on families, health systems, and economies on a global scale. The disease-state of age-related cognitive decline—Alzheimer's disease and other dementias—hijacks our consciousness and intellectual autonomy. However, there is evidence that cognitively stimulating activities protect against the adverse effects of cognitive decline. Similarly, bilingualism is also considered to be a safeguard. We propose that foreign language learning programs aimed at older populations are an optimal solution for building cognitive reserve because language learning engages an extensive brain network that is known to overlap with the regions negatively affected by the aging process. It is recommended that future research should test this potentially fruitful hypothesis. PMID:24051310

  13. Endurance running program reverses the age related declines in peak oxygen consumption

    SciTech Connect

    Cartee, G.D.; Farrar, R.P.

    1986-03-01

    This study was designed to determine whether aging per se produces a decline in peak oxygen consumption (peak VO/sub 2/) or whether that decline may be due to the documented reduction in spontaneous activity. Male F344 rats, at the initial ages of 4 and 18 mos. of age, were divided into trained and untrained groups (YUT, YT, OUT, and OT). The trained groups ran up to 60 min/day 5 days/wk at a speed of 20m/min for 6 mos. The OUT rats demonstrated a 12% decline in peak VO/sub 2/ when compared to YUT rats. The OT rats had the same peak VO/sub 2/ as the YUT, but a 13% lower peak VO/sub 2/ than the YT. Representative enzymes of the TCA cycle, B oxidation, and electron transport system from gastrocnemius homogenates all declined in the OUT compared to YUT (14 to 24%). /sup 14/C-palmitate oxidation declined 45% in the OUT gastrocnemius compared to YUT. The carnitine values of the OUT were not significantly lower than the YUT and could not account for the large depression in palmitate oxidation. In contrast to the peak VO/sub 2/ which increased in OT only up to YUT values, the oxidative capacity of the skeletal muscle of OT was increased above the YUT group values equal to those of YT.

  14. Age-Related Differences and Heterogeneity in Executive Functions: Analysis of NAB Executive Functions Module Scores.

    PubMed

    Buczylowska, Dorota; Petermann, Franz

    2016-05-01

    Normative data from the German adaptation of the Neuropsychological Assessment Battery were used to examine age-related differences in 6 executive function tasks. A multivariate analysis of variance was employed to investigate the differences in performance in 484 participants aged 18-99 years. The coefficient of variation was calculated to compare the heterogeneity of scores between 10 age groups. Analyses showed an increase in the dispersion of scores with age, varying from 7% to 289%, in all subtests. Furthermore, age-dependent heterogeneity appeared to be associated with age-dependent decline because the subtests with the greatest increase in dispersion (i.e., Mazes, Planning, and Categories) also exhibited the greatest decrease in mean scores. In contrast, scores for the subtests Letter Fluency, Word Generation, and Judgment had the lowest increase in dispersion with the lowest decrease in mean scores. Consequently, the results presented here show a pattern of age-related differences in executive functioning that is consistent with the concept of crystallized and fluid intelligence.

  15. Glutamate cysteine ligase and the age-related decline in cellular glutathione: The therapeutic potential of γ-glutamylcysteine.

    PubMed

    Ferguson, Gavin; Bridge, Wallace

    2016-03-01

    A consistent underlying index of aging is a decline in the cellular levels of the tripeptide glutathione (GSH). GSH is an essential thiol antioxidant produced in the cytosol of all cells and plays a key role in protecting against oxidative stress by neutralising free radicals and reactive oxygen species (ROS). The decline in GSH has been associated with changes in the expression and activity of the rate-limiting enzyme glutamate cysteine ligase (GCL), which produces the intermediate dipeptide γ-glutamylcysteine (γ-GC). The molecular mechanisms that affect these age-related changes remain unclear due to the complexity of GCL regulation. Impairment of the transcriptional activity of Nrf2 has been demonstrated to contribute to GCL dysregulation in aged rats. However, considering the complex nature of GCL regulation, relatively little research has been conducted to investigate the age-associated post-transcriptional controls of the enzyme. Defining these unknown mechanisms may inform our understanding of the aetiology of many age-related diseases and assist in formulating appropriate therapeutic strategies. This review focuses on the suitability of treatment with exogenous γ-GC to raise GSH levels by circumventing the age-related dysregulation of the rate-limiting step of GSH, providing promise for future research for the treatment of chronic oxidative stress-related diseases.

  16. Sex-dependent modulation of age-related cognitive decline by the L-type calcium channel gene Cacna1c (Cav 1.2).

    PubMed

    Zanos, Panos; Bhat, Shambhu; Terrillion, Chantelle E; Smith, Robert J; Tonelli, Leonardo H; Gould, Todd D

    2015-10-01

    Increased calcium influx through L-type voltage-gated calcium channels has been implicated in the neuronal dysfunction underlying age-related memory declines. The present study aimed to test the specific role of Cacna1c (which encodes Cav 1.2) in modulating age-related memory dysfunction. Short-term, spatial and contextual/emotional memory was evaluated in young and aged, wild-type as well as mice with one functional copy of Cacna1c (haploinsufficient), using the novel object recognition, Y-maze and passive avoidance tasks, respectively. Hippocampal expression of Cacna1c mRNA was measured by quantitative polymerase chain reaction. Ageing was associated with object recognition and contextual/emotional memory deficits, and a significant increase in hippocampal Cacna1c mRNA expression. Cacna1c haploinsufficiency was associated with decreased Cacna1c mRNA expression in both young and old animals. However, haploinsufficient mice did not manifest an age-related increase in expression of this gene. Behaviourally, Cacna1c haploinsufficiency prevented object recognition deficits during ageing in both male and female mice. A significant correlation between higher Cacna1c levels and decreased object recognition performance was observed in both sexes. Also, a sex-dependent protective role of decreased Cacna1c levels in contextual/emotional memory loss has been observed, specifically in male mice. These data provide evidence for an association between increased hippocampal Cacna1c expression and age-related cognitive decline. Additionally, they indicate an interaction between the Cacna1c gene and sex in the modulation of age-related contextual memory declines.

  17. Imaging mass spectrometry demonstrates age-related decline in human adipose plasticity

    PubMed Central

    Fazeli, Pouneh K.; Kim, Soomin; Lun, Mingyue; Zuflacht, Jonah P.; Milian, Jessica; Lee, Hang; Francois-Saint-Cyr, Hugues; Horreard, Francois; Larson, David; Rosen, Evan D.; Lee, Richard T.; Lechene, Claude P.; Steinhauser, Matthew L.

    2017-01-01

    Quantification of stable isotope tracers has revealed the dynamic state of living tissues. A new form of imaging mass spectrometry quantifies isotope ratios in domains much smaller than a cubic micron, enabling measurement of cell turnover and metabolism with stable isotope tracers at the single-cell level with a methodology we refer to as multi-isotope imaging mass spectrometry. In a first-in-human study, we utilize stable isotope tracers of DNA synthesis and de novo lipogenesis to prospectively measure cell birth and adipocyte lipid turnover. In a study of healthy adults, we elucidate an age-dependent decline in new adipocyte generation and adipocyte lipid turnover. A linear regression model suggests that the aging effect could be mediated by a decline in insulin-like growth factor-1 (IGF-1). This study therefore establishes a method for measurement of cell turnover and metabolism in humans with subcellular resolution while implicating the growth hormone/IGF-1 axis in adipose tissue aging. PMID:28289709

  18. Edited magnetic resonance spectroscopy detects an age-related decline in brain GABA levels.

    PubMed

    Gao, Fei; Edden, Richard A E; Li, Muwei; Puts, Nicolaas A J; Wang, Guangbin; Liu, Cheng; Zhao, Bin; Wang, Huiquan; Bai, Xue; Zhao, Chen; Wang, Xin; Barker, Peter B

    2013-09-01

    Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain. Although measurements of GABA levels in vivo in the human brain using edited proton magnetic resonance spectroscopy ((1)H-MRS) have been established for some time, it is has not been established how regional GABA levels vary with age in the normal human brain. In this study, 49 healthy men and 51 healthy women aged between 20 and 76 years were recruited and J-difference edited spectra were recorded at 3T to determine the effect of age on GABA levels, and to investigate whether there are regional and gender differences in GABA in mesial frontal and parietal regions. Because the signal detected at 3.02 ppm using these experimental parameters is also expected to contain contributions from both macromolecules (MM) and homocarnosine, in this study the signal is labeled GABA+ rather than GABA. Significant negative correlations were observed between age and GABA+ in both regions studied (GABA+/Cr: frontal region, r=-0.68, p<0.001, parietal region, r=-0.54, p<0.001; GABA+/NAA: frontal region, r=-0.58, p<0.001, parietal region, r=-0.49, p<0.001). The decrease in GABA+ with age in the frontal region was more rapid in women than men. Evidence of a measureable decline in GABA is important in considering the neurochemical basis of the cognitive decline that is associated with normal aging.

  19. Does lifelong training temper age-related decline in sport performance? Interpreting differences between cross-sectional and longitudinal data.

    PubMed

    Young, Bradley W; Weir, Patricia L; Starkes, Janet L; Medic, Nikola

    2008-01-01

    In the face of remarkable aging trends in North American society, organized sport/physical activity is an important vehicle for promoting physical health, and a domain in which long-term participation might mitigate pessimistic trends for age decline. This investigation examined patterns of age-related decline in performance for 45 Masters runners who rigorously trained continuously for at least a decade. Longitudinal data for age and performance were collected for 200 m, 1500 m, and 10 km events retrospectively across participants' careers. Cross-sectional (CS) data representing normal patterns of aging were derived from online archives. Longitudinal data reflected within-participant training effects whereas CS data did not. Second-order regression analyses were performed separately for each data type and quadratic beta coefficients, indicative of accelerated age decline, were compared for CS and longitudinal samples on a within-event basis. Results showed evidence of accelerated decline with advancing age for both samples, although rates for longitudinal samples were moderated for the 200 m and 1500 m events. Findings for the long-distance event were anomalous. Results provide evidence for moderated age-decline in physical performance measures for individuals who sustain engagement in organized sport for lengthy periods. Discussion focuses on methodological considerations for advancing future research that contrasts CS and longitudinal samples, and the importance of encouraging sport involvement opportunities to aging individuals.

  20. Edited Magnetic Resonance Spectroscopy Detects an Age-Related Decline in Nonhuman Primate Brain GABA Levels

    PubMed Central

    Killiany, Ronald J.

    2016-01-01

    Recent research had shown a correlation between aging and decreasing Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the brain. However, how GABA level varies with age in the medial portion of the brain has not yet been studied. The purpose of this study was to investigate the GABA level variation with age focusing on the posterior cingulate cortex, which is the “core hub” of the default mode network. In this study, 14 monkeys between 4 and 21 years were recruited, and MEGA-PRESS MRS was performed to measure GABA levels, in order to explore a potential link between aging and GABA. Our results showed that a correlation between age and GABA+/Creatine ratio was at the edge of significance (r = −0.523, p = 0.081). There was also a near-significant trend between gray matter/white matter ratio and the GABA+/Creatine ratio (r = −0.518, p = 0.0848). Meanwhile, the correlation between age and grey matter showed no significance (r = −0.028, p = 0.93). Therefore, age and gray matter/white matter ratio account for different part of R-squared (adjusted R-squared = 0.5187) as independent variables for predicting GABA levels. Adjusted R-squared is about 0.5 for two independent variables. These findings suggest that there is internal neurochemical variation of GABA levels in the nonhuman primates associated with normal aging and structural brain decline. PMID:27660760

  1. Video games as a means to reduce age-related cognitive decline: attitudes, compliance, and effectiveness.

    PubMed

    Boot, Walter R; Champion, Michael; Blakely, Daniel P; Wright, Timothy; Souders, Dustin J; Charness, Neil

    2013-01-01

    Recent research has demonstrated broad benefits of video game play to perceptual and cognitive abilities. These broad improvements suggest that video game-based cognitive interventions may be ideal to combat the many perceptual and cognitive declines associated with advancing age. Furthermore, game interventions have the potential to induce higher rates of intervention compliance compared to other cognitive interventions as they are assumed to be inherently enjoyable and motivating. We explored these issues in an intervention that tested the ability of an action game and a "brain fitness" game to improve a variety of abilities. Cognitive abilities did not significantly improve, suggesting caution when recommending video game interventions as a means to reduce the effects of cognitive aging. However, the game expected to produce the largest benefit based on previous literature (an action game) induced the lowest intervention compliance. We explain this low compliance by participants' ratings of the action game as less enjoyable and by their prediction that training would have few meaningful benefits. Despite null cognitive results, data provide valuable insights into the types of video games older adults are willing to play and why.

  2. 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

  3. Is It Possible to Delay or Prevent Age-Related Cognitive Decline?

    PubMed Central

    2016-01-01

    Already in the 90s, Khachaturian stated that postponing dementia onset by five years would decrease the prevalence of the late onset dementia by 50%. After two decades of lack of success in dementia drug discovery and development, and knowing that worldwide, currently 36 million patients have been diagnosed with Alzheimer's disease, a number that will double by 2030 and triple by 2050, the World Health Organization and the Alzheimer's Disease International declared that prevention of cognitive decline was a 'public health priority.' Numerous longitudinal studies and meta-analyses were conducted to analyze the risk and protective factors for dementia. Among the 93 identified risk factors, seven major modifiable ones should be considered: low education, sedentary lifestyle, midlife obesity, midlife smoking, hypertension, diabetes, and midlife depression. Three other important modifiable risk factors should also be added to this list: midlife hypercholesterolemia, late life atrial fibrillation, and chronic kidney disease. After their identification, numerous authors attempted to establish dementia risk scores; however, the proposed values were not convincing. Identifying the possible interventions, able to either postpone or delay dementia has been an important challenge. Observational studies focused on a single life-style intervention increased the global optimism concerning these possibilities. However, a recent extensive literature review of the randomized control trials (RCTs) conducted before 2014 yielded negative results. The first results of RCTs of multimodal interventions (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, Multidomain Alzheimer Prevention Study, and Prediva) brought more optimism. Lastly, interventions targeting compounds of beta amyloid started in 2012 and no results have yet been published. PMID:27688858

  4. Parkinson's disease accelerates age-related decline in haptic perception by altering somatosensory integration.

    PubMed

    Konczak, Jürgen; Sciutti, Alessandra; Avanzino, Laura; Squeri, Valentina; Gori, Monica; Masia, Lorenzo; Abbruzzese, Giovanni; Sandini, Giulio

    2012-11-01

    This study investigated how Parkinson's disease alters haptic perception and the underlying mechanisms of somatosensory and sensorimotor integration. Changes in haptic sensitivity and acuity (the abilities to detect and to discriminate between haptic stimuli) due to Parkinson's disease were systematically quantified and contrasted to the performance of healthy older and young adults. Using a robotic force environment, virtual contours of various curvatures were presented. Participants explored these contours with their hands and indicated verbally whether they could detect or discriminate between two contours. To understand what aspects of sensory or sensorimotor integration are altered by ageing and disease, we manipulated the sensorimotor aspect of the task: the robot either guided the hand along the contour or the participant actively moved the hand. Active exploration relies on multimodal sensory and sensorimotor integration, while passive guidance only requires sensory integration of proprioceptive and tactile information. The main findings of the study are as follows: first, a decline in haptic precision can already be observed in adults before the age of 70 years. Parkinson's disease may lead to an additional decrease in haptic sensitivity well beyond the levels typically seen in middle-aged and older adults. Second, the haptic deficit in Parkinson's disease is general in nature. It becomes manifest as a decrease in sensitivity and acuity (i.e. a smaller perceivable range and a diminished ability to discriminate between two perceivable haptic stimuli). Third, thresholds during both active and passive exploration are elevated, but not significantly different from each other. That is, active exploration did not enhance the haptic deficit when compared to passive hand motion. This implies that Parkinson's disease affects early stages of somatosensory integration that ultimately have an impact on processes of sensorimotor integration. Our results suggest that

  5. Stuck in default mode: inefficient cross-frequency synchronization may lead to age-related short-term memory decline.

    PubMed

    Pinal, Diego; Zurrón, Montserrat; Díaz, Fernando; Sauseng, Paul

    2015-04-01

    Aging-related decline in short-term memory capacity seems to be caused by deficient balancing of task-related and resting state brain networks activity; however, the exact neural mechanism underlying this deficit remains elusive. Here, we studied brain oscillatory activity in healthy young and old adults during visual information maintenance in a delayed match-to-sample task. Particular emphasis was on long range phase:amplitude coupling of frontal alpha (8-12 Hz) and posterior fast oscillatory activity (>30 Hz). It is argued that through posterior fast oscillatory activity nesting into the excitatory or the inhibitory phase of frontal alpha wave, long-range networks can be efficiently coupled or decoupled, respectively. On the basis of this mechanism, we show that healthy, elderly participants exhibit a lack of synchronization in task-relevant networks while maintaining synchronized regions of the resting state network. Lacking disconnection of this resting state network is predictive of aging-related short-term memory decline. These results support the idea of inefficient orchestration of competing brain networks in the aging human brain and identify the neural mechanism responsible for this control breakdown.

  6. Like cognitive function, decision making across the life span shows profound age-related changes

    PubMed Central

    Tymula, Agnieszka; Rosenberg Belmaker, Lior A.; Ruderman, Lital; Glimcher, Paul W.; Levy, Ifat

    2013-01-01

    It has long been known that human cognitive function improves through young adulthood and then declines across the later life span. Here we examined how decision-making function changes across the life span by measuring risk and ambiguity attitudes in the gain and loss domains, as well as choice consistency, in an urban cohort ranging in age from 12 to 90 y. We identified several important age-related patterns in decision making under uncertainty: First, we found that healthy elders between the ages of 65 and 90 were strikingly inconsistent in their choices compared with younger subjects. Just as elders show profound declines in cognitive function, they also show profound declines in choice rationality compared with their younger peers. Second, we found that the widely documented phenomenon of ambiguity aversion is specific to the gain domain and does not occur in the loss domain, except for a slight effect in older adults. Finally, extending an earlier report by our group, we found that risk attitudes across the life span show an inverted U-shaped function; both elders and adolescents are more risk-averse than their midlife counterparts. Taken together, these characterizations of decision-making function across the life span in this urban cohort strengthen the conclusions of previous reports suggesting a profound impact of aging on cognitive function in this domain. PMID:24082105

  7. Cortical grey matter content is associated with both age and bimanual performance, but is not observed to mediate age-related behavioural decline.

    PubMed

    van Ruitenbeek, Peter; Serbruyns, Leen; Solesio-Jofre, Elena; Meesen, Raf; Cuypers, Koen; Swinnen, Stephan P

    2017-01-01

    Declines in both cortical grey matter and bimanual coordination performance are evident in healthy ageing. However, the relationship between ageing, bimanual performance, and grey matter loss remains unclear, particularly across the whole adult lifespan. Therefore, participants (N = 93, range 20-80 years) performed a complex Bimanual Tracking Task, and structural brain images were obtained using magnetic resonance imaging. Analyses revealed that age correlated negatively with task performance. Voxel-based morphometry analysis revealed that age was associated with grey matter declines in task-relevant cortical areas and that grey matter in these areas was negatively associated with task performance. However, no evidence for a mediating effect of grey matter in age-related bimanual performance decline was observed. We propose a new hypothesis that functional compensation may account for the observed absence of mediation, which is in line with the observed pattern of increased inter-individual variance in performance with age.

  8. Gender differences in age-related decline in glomerular filtration rates in healthy people and chronic kidney disease patients

    PubMed Central

    2010-01-01

    Background Since men with chronic kidney disease (CKD) progress faster than women, an accurate assessment of CKD progression rates should be based on gender differences in age-related decline of glomerular filtration rate (GFR) in healthy individuals. Methods A Chinese sample population from a stratified, multistage, and clustered CKD screening study was classified into healthy, at-risk, and CKD groups. The gender differences in estimated GFR (eGFR) and age-related eGFR decline were calculated for each group after controlling for blood pressure, fasting glucose levels, serum lipids levels, education level, and smoking status. After referencing to the healthy group, gender-specific multivariate-adjusted rates of decline in eGFR and differences in the rates of decline were calculated for both CKD and at-risk groups. Results The healthy, at-risk, and CKD groups consisted of 4569, 7434, and 1573 people, respectively. In all the 3 groups, the multivariate-adjusted eGFRs in men were lower than the corresponding eGFRs in women. In addition, in the healthy and at-risk groups, the rates of decline in eGFR in men were lower than the corresponding rates of decline in women (healthy group: 0.51 mL·min-1·1.73 m-2·yr-1 vs. 0.74 mL·min-1·1.73 m-2·yr-1 and at-risk group: 0.60 mL·min-1·1.73 m-2·yr-1 vs. 0.73 mL·min-1·1.73 m-2·yr-1). However, in the CKD group, the rates of decline in eGFR in men were similar to those in women (0.96 mL·min-1·1.73 m-2·yr-1 vs. 0.91 mL·min-1·1.73 m-2·yr-1). However, after referencing to the healthy group, the rates of decline in eGFR in men in the at-risk and CKD groups were greater faster than the corresponding rates in women (at-risk group: 0.10 mL·min-1·1.73 m-2·yr-1 vs. -0.03 mL·min-1·1.73 m-2·yr-1 and CKD group: 0.44 mL·min-1·1.73 m-2·yr-1 vs. 0.15 mL·min-1·1.73 m-2·yr-1). Conclusion To accurately assess gender differences in CKD progression rates, gender differences in age-related decline in GFR should be considered

  9. Age-related decline in thermal adaptation capacities: an evoked potentials study.

    PubMed

    Kemp, Jennifer; Després, Olivier; Pebayle, Thierry; Dufour, André

    2014-06-01

    Aging is associated with changes in thermosensitivity and decreases in the functionality of the autonomic thermoregulation. The underlying mechanisms are, however, not fully understood. Elderly subjects may undergo functional changes in the integration process of the thermal sensory system, especially in their thermal adaptation capacities. To verify this hypothesis, we compared thermal evoked responses in younger and older subjects exposed to thermoneutral (27 °C) and warm (30 °C) environments. In the warm environment, the amplitudes of thermal evoked potentials (EPs) were significantly lower in older than in younger subjects, whereas in the thermoneutral environment, the EP amplitudes were similar in both groups. These findings suggest that thermal adaptation capacities are reduced in elderly individuals, due to a dysfunction of C-fibers with aging, particularly expressed by lowered adaptation capacities to temperature variations.

  10. Age-related declines in exploratory behavior and markers of hippocampal plasticity are attenuated by prenatal choline supplementation in rats.

    PubMed

    Glenn, Melissa J; Kirby, Elizabeth D; Gibson, Erin M; Wong-Goodrich, Sarah J; Mellott, Tiffany J; Blusztajn, Jan K; Williams, Christina L

    2008-10-27

    Supplemental choline in the maternal diet produces a lasting enhancement in memory in offspring that resists age-related decline and is accompanied by neuroanatomical, neurophysiological and neurochemical changes in the hippocampus. The present study was designed to examine: 1) if prenatal choline supplementation alters behaviors that contribute to risk or resilience in cognitive aging, and 2) whether, at old age (25 months), prenatally choline-supplemented rats show evidence of preserved hippocampal plasticity. A longitudinal design was used to look at exploration of an open field, with and without objects, at 1 and 24 months of age in male and female rats whose mothers were fed a diet supplemented with choline (SUP; 5 mg/kg choline chloride) or not supplemented (CON; 1.1 mg/kg choline chloride) on embryonic days 12-17. Aging caused a significant decline in open field exploration that was more pronounced in males but interest in novel objects was maintained in both sexes. Prenatal choline supplementation attenuated, but did not prevent age-related decline in exploration in males and increased object exploration in young females. Following behavioral assessment, rats were euthanized to assess markers of hippocampal plasticity. Aged SUP males and females had more newly proliferated cells in the hippocampal dentate gyrus and protein levels of vascular endothelial growth factor (VEGF) and neurotrophin-3 (NT-3) were significantly elevated in female SUP rats in comparison to all other groups. Taken together, these findings provide the first evidence that prenatal choline supplementation causes changes in exploratory behaviors over the lifespan and preserves some features of hippocampal plasticity that can be seen even at 2 years of age.

  11. Age-related decline in prostacyclin synthesis by human aortic endothelial cells. Qualitative and quantitative analysis.

    PubMed Central

    Tokunaga, O.; Yamada, T.; Fan, J. L.; Watanabe, T.

    1991-01-01

    To investigate the functional alteration of human aortic endothelial cells with aging, prostacyclin synthesis was qualitatively and quantitatively examined. The endothelial cells of human aortas and umbilical veins or inferior vena cavae were immunohistochemically examined and found positive for prostacyclin, but the intensity of aortic endothelial cells from older subjects was low. In addition to the endothelial cells, smooth muscle cells in the thickened intima, not the media, of the aorta were also immunoreactive. Endothelial cells were successfully cultured from human aortas obtained from infants through aged subjects and were subdivided into three groups: young, middle, and old. Prostacyclin synthesis by endothelial cells from all types of blood vessels was extremely great at the primary culture, but decreased abruptly in the following subcultures. Among the aortic endothelial cells, the young group synthesized the largest amount of prostacyclin in a conventional culture condition, with synthesis progressively decreasing in the older groups. The in vitro prostacyclin biosynthesis was supported by the qualitative analysis on the tissue sections. These results indicate that prostacyclin synthesis of the aortic endothelial cells decreases with age, but intimal smooth muscle cells potentially have a back-up mechanism and substitute this synthesis to some extent. The decreased synthesis of prostacyclin with age may play an important role in the development and advancement of thrombosis and atherosclerosis. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:1707240

  12. Effects of a computer-based cognitive exercise program on age-related cognitive decline.

    PubMed

    Bozoki, Andrea; Radovanovic, Mirjana; Winn, Brian; Heeter, Carrie; Anthony, James C

    2013-01-01

    We developed a 'senior friendly' suite of online 'games for learning' with interactive calibration for increasing difficulty, and evaluated the feasibility of a randomized clinical trial to test the hypothesis that seniors aged 60-80 can improve key aspects of cognitive ability with the aid of such games. Sixty community-dwelling senior volunteers were randomized to either an online game suite designed to train multiple cognitive abilities, or to a control arm with online activities that simulated the look and feel of the games but with low level interactivity and no calibration of difficulty. Study assessment included measures of recruitment, retention and play-time. Cognitive change was measured with a computerized assessment battery administered just before and within two weeks after completion of the six-week intervention. Impediments to feasibility included: limited access to in-home high-speed internet, large variations in the amount of time devoted to game play, and a reluctance to pursue more challenging levels. Overall analysis was negative for assessed performance (transference effects) even though subjects improved on the games themselves. Post hoc analyses suggest that some types of games may have more value than others, but these effects would need to be replicated in a study designed for that purpose. We conclude that a six-week, moderate-intensity computer game-based cognitive intervention can be implemented with high-functioning seniors, but the effect size is relatively small. Our findings are consistent with Owen et al. (2010), but there are open questions about whether more structured, longer duration or more intensive 'games for learning' interventions might yield more substantial cognitive improvement in seniors.

  13. The age-related performance decline in Ironman triathlon starts earlier in swimming than in cycling and running.

    PubMed

    Käch, Ilja; Rüst, Christoph A; Nikolaidis, Pantelis T; Rosemann, Thomas; Knechtle, Beat

    2017-02-21

    In Ironman triathlon, the number of overall male and female finishers increased in the last 30 years, while an improvement in performance has been reported. Studies concluding these numbers only analysed the top ten athletes per age group instead of all finishers, therefore a selection bias might have occurred. The aim of the present study was to investigate participation, performance and the age-related performance decline of all pro and age group triathletes ranked in all Ironman triathlons held worldwide between 2002 and 2015. Split and overall race times of 329,066 (80%) male and 81,815 (20%) female athletes competing in 253 different Ironman triathlon races were analysed. The number of finishers increased in all age groups with exception of women in age group 75-79 years. In pro athletes, performance improved in all disciplines. In age group athletes, performance improved in younger age groups for running (18-24 to 40-44 years) and older age groups for swimming (50-54 to 65-69 years) and cycling (35-39 to 55-59 years), while it impaired in younger age groups for swimming (18-24 to 45-49 years) and cycling (18-24 to 30-34), and older age groups in running (45-49 to 70-74 years). The age-related performance decline started in women in age group 25-29 years in swimming and in age group 30-34 years in cycling, running and overall race time, whereas it started in men in age group 25-29 years in swimming and in age group 35-39 years in cycling, running and overall race time. For athletes and coaches, performance improved in younger age groups for running and older age groups for swimming and cycling and the age-related decline in performance started earlier in swimming than in cycling and running. In summary, women should start competing in Ironman triathlon before the age of 30 years and men before the age of 35 years to achieve their personal best Ironman race time.

  14. Age-related decline in the responsiveness of motor cortex to plastic forces reverses with levodopa or cerebellar stimulation.

    PubMed

    Kishore, Asha; Popa, Traian; James, Praveen; Yahia-Cherif, Lydia; Backer, Febina; Varughese Chacko, Lijo; Govind, Preetha; Pradeep, Salini; Meunier, Sabine

    2014-11-01

    The plasticity of motor cortex is integral for motor memory and skills acquisition but it declines with aging. Forty healthy volunteers, across 6 decades, were tested to examine the (a) age-dependency of motor cortex responsiveness to plasticity induction, as measured from the response to paired associative stimulation (PAS) and the (b) effect of aging on the cerebellar modulation of motor cortex response to PAS. We examined if reduced dopaminergic transmission was involved in the age-related decline of response to PAS by retesting 10 of the older subjects after a single dose of levodopa. There was a substantial decline in the motor cortex response to PAS with aging, which was restored by levodopa in the older subjects. The cerebellar modulation of motor cortex response to PAS was less vulnerable to aging and a single session of cerebellar inhibition reinstated the cortical responsiveness in older subjects. Both levodopa and cerebellar inhibition can be tested for their ability to enhance motor skills acquisition and motor performance in the elderly individuals.

  15. Age-related hearing loss: prevention of threshold declines, cell loss and apoptosis in spiral ganglion neurons

    PubMed Central

    Zhu, Xiaoxia; Walton, Joseph P.

    2016-01-01

    Age-related hearing loss (ARHL) -presbycusis - is the most prevalent neurodegenerative disease and number one communication disorder of our aged population; and affects hundreds of millions of people worldwide. Its prevalence is close to that of cardiovascular disease and arthritis, and can be a precursor to dementia. The auditory perceptual dysfunction is well understood, but knowledge of the biological bases of ARHL is still somewhat lacking. Surprisingly, there are no FDA-approved drugs for treatment. Based on our previous studies of human subjects, where we discovered relations between serum aldosterone levels and the severity of ARHL, we treated middle age mice with aldosterone, which normally declines with age in all mammals. We found that hearing thresholds and suprathreshold responses significantly improved in the aldosterone-treated mice compared to the non-treatment group. In terms of cellular and molecular mechanisms underlying this therapeutic effect, additional experiments revealed that spiral ganglion cell survival was significantly improved, mineralocorticoid receptors were upregulated via post-translational protein modifications, and age-related intrinsic and extrinsic apoptotic pathways were blocked by the aldosterone therapy. Taken together, these novel findings pave the way for translational drug development towards the first medication to prevent the progression of ARHL. PMID:27667674

  16. Age-related hearing loss: prevention of threshold declines, cell loss and apoptosis in spiral ganglion neurons.

    PubMed

    Frisina, Robert D; Ding, Bo; Zhu, Xiaoxia; Walton, Joseph P

    2016-09-23

    Age-related hearing loss (ARHL) -presbycusis - is the most prevalent neurodegenerative disease and number one communication disorder of our aged population; and affects hundreds of millions of people worldwide. Its prevalence is close to that of cardiovascular disease and arthritis, and can be a precursor to dementia. The auditory perceptual dysfunction is well understood, but knowledge of the biological bases of ARHL is still somewhat lacking. Surprisingly, there are no FDA-approved drugs for treatment. Based on our previous studies of human subjects, where we discovered relations between serum aldosterone levels and the severity of ARHL, we treated middle age mice with aldosterone, which normally declines with age in all mammals. We found that hearing thresholds and suprathreshold responses significantly improved in the aldosterone-treated mice compared to the non-treatment group. In terms of cellular and molecular mechanisms underlying this therapeutic effect, additional experiments revealed that spiral ganglion cell survival was significantly improved, mineralocorticoid receptors were upregulated via post-translational protein modifications, and age-related intrinsic and extrinsic apoptotic pathways were blocked by the aldosterone therapy. Taken together, these novel findings pave the way for translational drug development towards the first medication to prevent the progression of ARHL.

  17. Age-related neuromuscular function during drop jumps.

    PubMed

    Hoffrén, M; Ishikawa, M; Komi, P V

    2007-10-01

    Muscle- and movement-specific fascicle-tendon interaction affects the performance of the neuromuscular system. This interaction is unknown among elderly and consequently contributes to the lack of understanding the age-related problems on neuromuscular control. The present experiment studied the age specificity of fascicle-tendon interaction of the gastrocnemius medialis (GM) muscle in drop jump (DJ) exercises. Twelve young and thirteen elderly subjects performed maximal squat jumps and DJs with maximal rebound effort on a sledge apparatus. Ankle and knee joint angles, reaction force, and electromyography (EMG) from the soleus (Sol), GM, and tibialis anterior (TA) muscles were measured together with the GM fascicle length by ultrasonography. The results showed that the measured ankle joint stiffness (AJS) during the braking phase correlated positively with the rebound speed in both age groups and that both parameters were significantly lower in the elderly than in young subjects. In both groups, the AJS correlated positively with averaged EMG (aEMG) in Sol during the braking phase and was further associated with GM activation (r = 0.55, P < 0.01) and TA coactivation (TA/GM r = -0.4 P < 0.05) in the elderly subjects. In addition, compared with the young subjects, the elderly subjects showed significantly lower GM aEMG in the braking phase and higher aEMG in the push-off phase, indicating less utilization of tendinous tissue (TT) elasticity. These different activation patterns are in line with the mechanical behavior of GM showing significantly less fascicle shortening and relative TT stretching in the braking phase in the elderly than in the young subjects. These results suggest that age-specific muscle activation patterns as well as mechanical behaviors exist during DJs.

  18. Age-Related Decline of Neutrophilic Inflammation Is Associated with Better Postoperative Prognosis in Non-eosinophilic Nasal Polyps

    PubMed Central

    Kim, Dae Woo; Kim, Dong-Kyu; Jo, Ara; Jin, Hong Ryul; Eun, Kyoung Mi; Mo, Ji-Hun; Cho, Seong H.

    2016-01-01

    Background Innate and adaptive immune responses change with increasing age and affect the course of diseases. Previous study investigated immunologic alteration in Western nasal polyps (NP) which is mostly eosinophilic. However, there are no reports regarding age-related immune changes of non-eosinophilic NP (NE-NP) which is a predominant subtype in Asian population. Methods A total of 153 subjects, including 20 with control, 63 with chronic rhinosinusitis (CRS) without NP (CRSsNP), and 70 with CRS with NP were enrolled. Age-related changes in computed tomography (CT), cytokines and clinical information were investigated. Tissue samples were analyzed for protein levels of IL-5, IL-17A, IL-23, interferon (IFN)-γ, CCL-11, and CXCL-8, using Luminex immunoassay and for mRNA expression levels of interleukin (IL)-5, IL-17A, IL-23p19, IFN-γ, CCL-11, CXCL-1, CXCL-2, CXCL-8, and CXCR2 by quantitative RT-PCR. Immunohistochemistry (IHC) was performed for the number of inflammatory cells. Results We observed that Lund-Mackay CT scores decreased with age in NE-NP. The number of human neutrophil elastase-positive cells and myeloperoxidase gene expression decreased in older patients with NE-NP, but not in control subjects, CRSsNP, and E-NP. Neutrophil-associated cytokines including IL-17A and IL-23, were negatively correlated with age in NE-NP at the protein and mRNA levels. Additionally, the expression of CXCR2, a receptor for CXCL-1 and CXCL-2, was decreased with age in NE-NP. However, there were no age-related changes in blood neutrophil count, and neutrophil-recruiting chemokines such as CXCL-1, CXCL-2, and CXCL-8. Elderly NE-NP patients showed better endoscopic scores at 12 months after surgery compared with the non-elderly. Conclusion Age-related decline in neutrophil inflammation may favorably affect postoperative results in elderly patients with NE-NP. PMID:26849431

  19. 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

  20. Rapid iterative negative geotaxis (RING): a new method for assessing age-related locomotor decline in Drosophila.

    PubMed

    Gargano, Julia Warner; Martin, Ian; Bhandari, Poonam; Grotewiel, Michael S

    2005-05-01

    Age-related behavioral declines are common manifestations of aging in animals. Negative geotaxis, an innate escape response during which flies ascend the wall of a cylinder after being tapped to its bottom, is one of the behaviors that senesces in Drosophila. Many laboratories, including ours, have used a variety of negative geotaxis assays based on the performance of single flies. To circumvent limitations of single-fly assays, we developed a new method for assessing negative geotaxis called rapid iterative negative geotaxis (RING). In RING assays, digital photography is used to document negative geotaxis in multiple groups of animals simultaneously. We show that performance in RING assays is not influenced by the density of flies being tested, the time of day, or repeated testing. We used the RING assay to demonstrate that negative geotaxis declines with the age of animals as previously shown in single fly studies and that senescence of negative geotaxis is sensitive to genetic background. Finally, we used RING assays to show that long-lived Indy and chico mutants exhibit delayed senescence of negative geotaxis. Our results demonstrate that RING is a powerful method for assessing negative geotaxis that should facilitate the search for manipulations that influence behavioral aging in Drosophila.

  1. Neural stem cell deforestation as the main force driving the age-related decline in adult hippocampal neurogenesis.

    PubMed

    Encinas, Juan M; Sierra, Amanda

    2012-02-14

    Newborn neurons derived from radial glia-like stem cells located in the dentate gyrus integrate into the adult hippocampal circuitry and participate in memory formation, spatial learning, pattern separation, fear conditioning, and anxiety. This process takes place throughout the life span of mammals, including humans; however, it follows a sharp declining curve. New neurons are generated abundantly during youth but very scarcely in the aged brain. The absolute number of newly generated neurons, or neurogenic output, is determined at different levels along the neurogenic cascade: the activation of quiescent stem cells; the mitotic potential of proliferating precursors; and the survival of neuronal fate-committed precursors. A continuous depletion of the hippocampal neural stem cell pool has been recently proposed as the main force underlying the age-related decline of neurogenesis, in contrast to the previous view of population of neural stem cells whose number remains constant but loses its ability to bear fruit. Nevertheless, the diminished neurogenic output may be reflecting other phenomena such as decreased mitotic capability of proliferating progenitors, decreased survival or changes in differentiation. We describe herein the most important events in determining the amount of neurogenesis in the dentate gyrus and examine the literature to understand the effects of age throughout the cascade.

  2. Genetic background influences age-related decline in visual and nonvisual retinal responses, circadian rhythms, and sleep☆

    PubMed Central

    Banks, Gareth; Heise, Ines; Starbuck, Becky; Osborne, Tamzin; Wisby, Laura; Potter, Paul; Jackson, Ian J.; Foster, Russell G.; Peirson, Stuart N.; Nolan, Patrick M.

    2015-01-01

    The circadian system is entrained to the environmental light/dark cycle via retinal photoreceptors and regulates numerous aspects of physiology and behavior, including sleep. These processes are all key factors in healthy aging showing a gradual decline with age. Despite their importance, the exact mechanisms underlying this decline are yet to be fully understood. One of the most effective tools we have to understand the genetic factors underlying these processes are genetically inbred mouse strains. The most commonly used reference mouse strain is C57BL/6J, but recently, resources such as the International Knockout Mouse Consortium have started producing large numbers of mouse mutant lines on a pure genetic background, C57BL/6N. Considering the substantial genetic diversity between mouse strains we expect there to be phenotypic differences, including differential effects of aging, in these and other strains. Such differences need to be characterized not only to establish how different mouse strains may model the aging process but also to understand how genetic background might modify age-related phenotypes. To ascertain the effects of aging on sleep/wake behavior, circadian rhythms, and light input and whether these effects are mouse strain-dependent, we have screened C57BL/6J, C57BL/6N, C3H-HeH, and C3H-Pde6b+ mouse strains at 5 ages throughout their life span. Our data show that sleep, circadian, and light input parameters are all disrupted by the aging process. Moreover, we have cataloged a number of strain-specific aging effects, including the rate of cataract development, decline in the pupillary light response, and changes in sleep fragmentation and the proportion of time spent asleep. PMID:25179226

  3. Age-related structural and functional changes of low back muscles.

    PubMed

    Hiepe, Patrick; Gussew, Alexander; Rzanny, Reinhard; Kurz, Eduard; Anders, Christoph; Walther, Mario; Scholle, Hans-Christoph; Reichenbach, Jürgen R

    2015-05-01

    During aging declining maximum force capacity with more or less unchanged fatigability is observed with the underlying mechanisms still not fully understood. Therefore, we compared morphology and function of skeletal muscles between different age groups. Changes in high-energy phosphate turnover (PCr, Pi and pH) and muscle functional MRI (mfMRI) parameters, including proton transverse relaxation time (T2), diffusion (D) and vascular volume fraction (f), were investigated in moderately exercised low back muscles of young and late-middle-aged healthy subjects with (31)P-MR spectroscopy, T2- and diffusion-weighted MRI at 3T. In addition, T1-weighted MRI data were acquired to determine muscle cross-sectional areas (CSA) and to assess fat infiltration into muscle tissue. Except for pH, both age groups showed similar load-induced MR changes and rates of perceived exertion (RPE), which indicates comparable behavior of muscle activation at moderate loads. Changes of mfMRI parameters were significantly associated with RPE in both cohorts. Age-related differences were observed, with lower pH and higher Pi/ATP ratios as well as lower D and f values in the late-middle-aged subjects. These findings are ascribed to age-related changes of fiber type composition, fiber size and vascularity. Interestingly, post exercise f was negatively associated with fat infiltration with the latter being significantly higher in late-middle-aged subjects. CSA of low back muscles remained unchanged, while CSA of inner back muscle as well as mean T2 at rest were associated with maximum force capacity. Overall, applying the proposed MR approach provides evidence of age-related changes in several muscle tissue characteristics and gives new insights into the physiological processes that take place during aging.

  4. Functional decline in old age

    PubMed Central

    Hébert, R

    1997-01-01

    Functional decline is a common condition, occurring each year in nearly 12% of Canadians 75 years of age and older. The model of functional health proposed by the World Health Organization (WHO) represents a useful theoretical framework and is the basis for the SMAF (Système de measure de l'autonomie fonctionelle or Functional Autonomy Measurement System), an instrument that measures functional autonomy. The functional decline syndrome, in which functional autonomy is diminished or lost, may present as an acute condition, i.e., a medical emergency for which the patient must be admitted to a geriatric assessment unit. The subacute form is a more insidious condition in which the patient requires comprehensive assessment and a rehabilitation program. A preventive approach based on screening of those at risk and early intervention should prevent or delay the appearance of functional decline or diminish its consequences. Effective strategies for the prevention of or rehabilitation from functional decline will help reduce the incidence of disabilities and the period of dependence near the end of life. These strategies are absolute prerequisites for controlling sociohealth expenses and, most importantly, for allowing people to live independently in old age. PMID:9347774

  5. [Age-related characteristics of structural support for ovarian function].

    PubMed

    Koval'skiĭ, G B

    1984-12-01

    Histoenzymological assay was used to investigate various structures of the ovaries of rats of two groups aged 3-4 and 12-14 months during estral cycle. The activity of 3 beta-, 17 beta- and 20 alpha-steroid dehydrogenases, glucose-6-phosphate dehydrogenase, NAD and NADP-diaphorases, esterase, acid and alkaline phosphatases was studied. It has been shown that transport alterations in the microcirculation including the hematofollicular barrier play, the leading part in age-dependent depression of reproductive and endocrine functions. Ageing rats demonstrated no linkage between endothelial, thecal and granular cells, which points to the injury of the histophysiological mechanisms of the follicular system integration.

  6. Neural correlates of age-related visual search decline: a combined ERP and sLORETA study.

    PubMed

    Lorenzo-López, Laura; Amenedo, Elena; Pascual-Marqui, Roberto D; Cadaveira, Fernando

    2008-06-01

    Differences in the neural systems underlying visual search processes for young (n=17, mean age 19.6+/-1.9) and older (n=22, mean age 68.5+/-6) subjects were investigated combining the Event-Related Potential (ERP) technique with standardized Low-Resolution brain Electromagnetic Tomography (sLORETA) analyses. Behavioral results showed an increase in mean reaction times (RTs) and a reduction in hit rates with age. The ERPs were significantly different between young and older subjects at the P3 component, showing longer latencies and lower amplitudes in older subjects. These ERP results suggest an age-related decline in the intensity and speed of visual processing during visual search that imply a reduction in attentional resources with normal aging. The sLORETA data revealed a significantly reduced neural differentiation in older subjects, who recruited bilateral prefrontal regions in a nonselective manner for the different search arrays. Finally, sLORETA between-group comparisons revealed that relative to young subjects, older subjects showed significantly reduced activity in anterior cingulate cortex as well as in numerous limbic and occipitotemporal regions contributing to visual search processes. These findings provide evidence that the neural circuit supporting this cognitive process is vulnerable to normal aging. All these attentional factors could contribute to poorer performance of older compared to young subjects in visual search tasks.

  7. Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study

    PubMed Central

    Lipnicki, Darren M.; Crawford, John D.; Thalamuthu, Anbupalam; Castro-Costa, Erico; Stephan, Blossom C. M.; Lipton, Richard B.; Katz, Mindy J.; Ritchie, Karen; Scali, Jacqueline; Ancelin, Marie-Laure; Scarmeas, Nikolaos; Yannakoulia, Mary; Dardiotis, Efthimios; Lam, Linda C. W.; Fung, Ada W. T.; Vaccaro, Roberta; Davin, Annalisa; Kim, Ki Woong; Han, Ji Won; Kim, Tae Hui; Cherbuin, Nicolas; Butterworth, Peter; Scazufca, Marcia; Kumagai, Shuzo; Chen, Sanmei; Narazaki, Kenji; Lobo, Antonio; Lopez-Anton, Raúl; Santabárbara, Javier; Sachdev, Perminder S.

    2017-01-01

    Background The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (APOE*4) carrier status were associated with decline. Methods and findings We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54–105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2–16 assessment waves (median = 3) and a follow-up duration of 2–15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval [CI] [-0.35, -0.16], p < 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI [-0.10, -0.03], p = 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (p = 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI [-0.28, -0.12], p < 0.001) than for whites (-0.09 SD/decade, 95% CI [-0.16, -0.02], p = 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0

  8. Over the Hill at 24: Persistent Age-Related Cognitive-Motor Decline in Reaction Times in an Ecologically Valid Video Game Task Begins in Early Adulthood

    PubMed Central

    Thompson, Joseph J.; Blair, Mark R.; Henrey, Andrew J.

    2014-01-01

    Typically studies of the effects of aging on cognitive-motor performance emphasize changes in elderly populations. Although some research is directly concerned with when age-related decline actually begins, studies are often based on relatively simple reaction time tasks, making it impossible to gauge the impact of experience in compensating for this decline in a real world task. The present study investigates age-related changes in cognitive motor performance through adolescence and adulthood in a complex real world task, the real-time strategy video game StarCraft 2. In this paper we analyze the influence of age on performance using a dataset of 3,305 players, aged 16-44, collected by Thompson, Blair, Chen & Henrey [1]. Using a piecewise regression analysis, we find that age-related slowing of within-game, self-initiated response times begins at 24 years of age. We find no evidence for the common belief expertise should attenuate domain-specific cognitive decline. Domain-specific response time declines appear to persist regardless of skill level. A second analysis of dual-task performance finds no evidence of a corresponding age-related decline. Finally, an exploratory analyses of other age-related differences suggests that older participants may have been compensating for a loss in response speed through the use of game mechanics that reduce cognitive load. PMID:24718593

  9. Over the hill at 24: persistent age-related cognitive-motor decline in reaction times in an ecologically valid video game task begins in early adulthood.

    PubMed

    Thompson, Joseph J; Blair, Mark R; Henrey, Andrew J

    2014-01-01

    Typically studies of the effects of aging on cognitive-motor performance emphasize changes in elderly populations. Although some research is directly concerned with when age-related decline actually begins, studies are often based on relatively simple reaction time tasks, making it impossible to gauge the impact of experience in compensating for this decline in a real world task. The present study investigates age-related changes in cognitive motor performance through adolescence and adulthood in a complex real world task, the real-time strategy video game StarCraft 2. In this paper we analyze the influence of age on performance using a dataset of 3,305 players, aged 16-44, collected by Thompson, Blair, Chen & Henrey [1]. Using a piecewise regression analysis, we find that age-related slowing of within-game, self-initiated response times begins at 24 years of age. We find no evidence for the common belief expertise should attenuate domain-specific cognitive decline. Domain-specific response time declines appear to persist regardless of skill level. A second analysis of dual-task performance finds no evidence of a corresponding age-related decline. Finally, an exploratory analyses of other age-related differences suggests that older participants may have been compensating for a loss in response speed through the use of game mechanics that reduce cognitive load.

  10. Hearing, Cognition, and Healthy Aging: Social and Public Health Implications of the Links between Age-Related Declines in Hearing and Cognition

    PubMed Central

    Pichora-Fuller, M. Kathleen; Mick, Paul; Reed, Marilyn

    2015-01-01

    Sensory input provides the signals used by the brain when listeners understand speech and participate in social activities with other people in a range of everyday situations. When sensory inputs are diminished, there can be short-term consequences to brain functioning, and long-term deprivation can affect brain neuroplasticity. Indeed, the association between hearing loss and cognitive declines in older adults is supported by experimental and epidemiologic evidence, although the causal mechanisms remain unknown. These interactions of auditory and cognitive aging play out in the challenges confronted by people with age-related hearing problems when understanding speech and engaging in social interactions. In the present article, we use the World Health Organization's International Classification of Functioning, Disability and Health and the Selective Optimization with Compensation models to highlight the importance of adopting a healthy aging perspective that focuses on facilitating active social participation by older adults. First, we examine epidemiologic evidence linking ARHL to cognitive declines and other health issues. Next, we examine how social factors influence and are influenced by auditory and cognitive aging and if they may provide a possible explanation for the association between ARHL and cognitive decline. Finally, we outline how audiologists could reposition hearing health care within the broader context of healthy aging. PMID:27516713

  11. Hearing, Cognition, and Healthy Aging: Social and Public Health Implications of the Links between Age-Related Declines in Hearing and Cognition.

    PubMed

    Pichora-Fuller, M Kathleen; Mick, Paul; Reed, Marilyn

    2015-08-01

    Sensory input provides the signals used by the brain when listeners understand speech and participate in social activities with other people in a range of everyday situations. When sensory inputs are diminished, there can be short-term consequences to brain functioning, and long-term deprivation can affect brain neuroplasticity. Indeed, the association between hearing loss and cognitive declines in older adults is supported by experimental and epidemiologic evidence, although the causal mechanisms remain unknown. These interactions of auditory and cognitive aging play out in the challenges confronted by people with age-related hearing problems when understanding speech and engaging in social interactions. In the present article, we use the World Health Organization's International Classification of Functioning, Disability and Health and the Selective Optimization with Compensation models to highlight the importance of adopting a healthy aging perspective that focuses on facilitating active social participation by older adults. First, we examine epidemiologic evidence linking ARHL to cognitive declines and other health issues. Next, we examine how social factors influence and are influenced by auditory and cognitive aging and if they may provide a possible explanation for the association between ARHL and cognitive decline. Finally, we outline how audiologists could reposition hearing health care within the broader context of healthy aging.

  12. Age-related changes of the functional architecture of the cortico-basal ganglia circuitry during motor task execution.

    PubMed

    Marchand, William R; Lee, James N; Suchy, Yana; Garn, Cheryl; Johnson, Susanna; Wood, Nicole; Chelune, Gordon

    2011-03-01

    Normal human aging is associated with declining motor control and function. It is thought that dysfunction of the cortico-basal ganglia circuitry may contribute to age-related sensorimotor impairment, however the underlying mechanisms are poorly characterized. The aim of this study was to enhance our understanding of age-related changes in the functional architecture of these circuits. Fifty-nine subjects, consisting of a young, middle and old group, were studied using functional MRI and a motor activation paradigm. Functional connectivity analyses and examination of correlations of connectivity strength with performance on the activation task as well as neurocognitive tasks completed outside of magnet were conducted. Results indicated that increasing age is associated with changes in the functional architecture of the cortico-basal ganglia circuitry. Connectivity strength increased between subcortical nuclei and cortical motor and sensory regions but no changes were found between subcortical components of the circuitry. Further, increased connectivity was correlated with poorer performance on a neurocognitive task independently of age. This result suggests that increased connectivity reflects a decline in brain function rather than a compensatory process. These findings advance our understanding of the normal aging process. Further, the methods employed will likely be useful for future studies aimed at disambiguating age-related versus illness progression changes associated with neuropsychiatric disorders that involve the cortico-basal ganglia circuitry.

  13. Age-related changes in the function of autophagy in rat kidneys.

    PubMed

    Cui, Jing; Bai, Xue-Yuan; Shi, Suozhu; Cui, Shaoyuan; Hong, Quan; Cai, Guangyan; Chen, Xiangmei

    2012-04-01

    Autophagy is a highly regulated intracellular process for the degradation of cytoplasmic components, especially protein aggregates and damaged organelles. It is essential for maintaining healthy cells. Impaired or deficient autophagy is believed to cause or contribute to aging and age-related disease. In this study, we investigated the effects of age on autophagy in the kidneys of 3-, 12-, and 24-month-old Fischer 344 rats. The results revealed that autophagy-related gene (Atg)7 was significantly downregulated in kidneys of increasing age. The protein expression level of the autophagy marker light chain 3/Atg8 exhibited a marked decline in aged kidneys. The levels of p62/SQSTM1 and polyubiquitin aggregates, representing the function of autophagy and proteasomal degradation, increased in older kidneys. The level of 8-hydroxydeoxyguanosine, a marker of mitochondrial DNA oxidative damage, was also increased in older kidneys. Analysis by transmission electron microscope demonstrated swelling and disintegration of cristae in the mitochondria of aged kidneys. These results suggest that autophagic function decreases with age in the kidneys of Fischer 344 rats, and autophagy may mediate the process of kidney aging, leading to the accumulation of damaged mitochondria.

  14. Age-Related Declines in General Cognitive Abilities of Balb/C Mice and General Activity Are Associated with Disparities in Working Memory, Body Weight, and General Activity

    ERIC Educational Resources Information Center

    Matzel, Louis D.; Grossman, Henya; Light, Kenneth; Townsend, David; Kolata, Stefan

    2008-01-01

    A defining characteristic of age-related cognitive decline is a deficit in general cognitive performance. Here we use a testing and analysis regimen that allows us to characterize the general learning abilities of young (3-5 mo old) and aged (19-21 mo old) male and female Balb/C mice. Animals' performance was assessed on a battery of seven diverse…

  15. [Functional decline in older people].

    PubMed

    Wada, Taizo

    2013-10-01

    World Health Organization(WHO) proposed to be used as an index of the health of elderly independence of functioning. Basic activities of daily living (BADL), such as bathing, dressing, toileting, transferring, continence, and feeding are well known as the functioning of the elderly. However, not only BADL, there are a variety of levels, such as the ability to play a social role, intellectual activities and instrumental activities of daily living (IADL), which are components of the Tokyo Metropolitan Institute of Gerontology Index of Competence(TMIG-IC). Functional decline in older people is associated with age, gender, depression, up and go test and manual dexterity. Smoking, body-mass index, and exercise patterns in midlife and late adulthood are predictors of subsequent disability.

  16. The Role of Inhibition in Age-related Off-Topic Verbosity: Not Access but Deletion and Restraint Functions

    PubMed Central

    Yin, Shufei; Peng, Huamao

    2016-01-01

    The speech of older adults is commonly described as verbose and off-topic, which is thought to influence their social communication. This study investigated the role of inhibition in age-related off-topic verbosity (OTV). Inhibition consists of three functions: access, deletion, and restraint. The access function is responsible for preventing irrelevant information from accessing the attention center (pre-mechanism of inhibition); The deletion function is responsible for deleting previously relevant but currently irrelevant information from working memory, and the restraint function is responsible for restraining strong but inappropriate responses (post-mechanisms of inhibition). A referential communication task was used to determine whether OTV was influenced by the pre-mechanism of inhibition. A self-involved event interview task was used to investigate the effect of the post-mechanisms of inhibition on OTV. Results showed that the OTV of the elderly participants was associated with an age-related decline in the post-mechanisms of inhibition, while the OTV exhibited by young adults was most likely due to deficits in the pre-mechanism function of inhibition. This research contributed to fill gaps in the existing knowledge about the potential relationship between specific functions of inhibition and age-related OTV. PMID:27199793

  17. 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.

  18. Age-Related Changes in Axonal and Mitochondrial Ultrastructure and Function in White Matter

    PubMed Central

    Stahon, Katharine E.; Bastian, Chinthasagar; Griffith, Shelby; Kidd, Grahame J.; Brunet, Sylvain

    2016-01-01

    The impact of aging on CNS white matter (WM) is of general interest because the global effects of aging on myelinated nerve fibers are more complex and profound than those in cortical gray matter. It is important to distinguish between axonal changes created by normal aging and those caused by neurodegenerative diseases, including multiple sclerosis, stroke, glaucoma, Alzheimer's disease, and traumatic brain injury. Using three-dimensional electron microscopy, we show that in mouse optic nerve, which is a pure and fully myelinated WM tract, aging axons are larger, have thicker myelin, and are characterized by longer and thicker mitochondria, which are associated with altered levels of mitochondrial shaping proteins. These structural alterations in aging mitochondria correlate with lower ATP levels and increased generation of nitric oxide, protein nitration, and lipid peroxidation. Moreover, mitochondria–smooth endoplasmic reticulum interactions are compromised due to decreased associations and decreased levels of calnexin and calreticulin, suggesting a disruption in Ca2+ homeostasis and defective unfolded protein responses in aging axons. Despite these age-related modifications, axon function is sustained in aging WM, which suggests that age-dependent changes do not lead to irreversible functional decline under normal conditions, as is observed in neurodegenerative diseases. SIGNIFICANCE STATEMENT Aging is a common risk factor for a number of neurodegenerative diseases, including stroke. Mitochondrial dysfunction and oxidative damage with age are hypothesized to increase risk for stroke. We compared axon–myelin–node–mitochondrion–smooth endoplasmic reticulum (SER) interactions in white matter obtained at 1 and 12 months. We show that aging axons have enlarged volume, thicker myelin, and elongated and thicker mitochondria. Furthermore, there are reduced SER connections to mitochondria that correlate with lower calnexin and calreticulin levels. Despite a

  19. 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

  20. Age-related declines in thirst and salt appetite responses in male Fischer 344×Brown Norway rats.

    PubMed

    Thunhorst, Robert L; Beltz, Terry; Johnson, Alan Kim

    2014-08-01

    The F344×BN strain is the first generational cross between Fischer 344 (F344) and Brown Norway (BN) rats. The F344×BN strain is widely used in aging studies as it is regarded as a model of "healthy" aging (Sprott, 1991). In the present work, male F344×BN rats aged 4mo (young, n=6) and 20mo (old, n=9) received a series of experimental challenges to body fluid homeostasis to determine their thirst and salt appetite responses. Corresponding urinary responses were measured in some of the studies. Following sodium depletion, old rats ingested less saline solution (0.3M NaCl) than young rats on a body weight basis, but both ages drank enough saline solution to completely repair the accrued sodium deficits. Following intracellular dehydration, old rats drank less water than young rats, again on a body weight basis, and were less able than young rats to drink amounts of water proportionate to the osmotic challenge. Compared with young rats, old rats drank less of both water and saline solution after combined food and fluid restriction, and also were refractory to the stimulatory effects of low doses of captopril on water drinking and sodium ingestion. Age differences in urinary water and sodium excretion could not account for the age differences in accumulated water and sodium balances. These results extend observations of diminished behavioral responses of aging animals to the F344×BN rat strain and support the idea that impairments in behavior contribute more to the waning ability of aging animals to respond to body fluid challenges than do declines in kidney function. In addition, the results suggest that behavioral defense of sodium homeostasis is less diminished with age in the F344×BN strain compared to other strains so far studied.

  1. Age-related decline of autocrine pituitary adenylate cyclase-activating polypeptide impairs angiogenic capacity of rat cerebromicrovascular endothelial cells.

    PubMed

    Banki, Eszter; Sosnowska, Danuta; Tucsek, Zsuzsanna; Gautam, Tripti; Toth, Peter; Tarantini, Stefano; Tamas, Andrea; Helyes, Zsuzsanna; Reglodi, Dora; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2015-06-01

    Aging impairs angiogenic capacity of cerebromicrovascular endothelial cells (CMVECs) promoting microvascular rarefaction, but the underlying mechanisms remain elusive. PACAP is an evolutionarily conserved neuropeptide secreted by endothelial cells and neurons, which confers important antiaging effects. To test the hypothesis that age-related changes in autocrine PACAP signaling contributes to dysregulation of endothelial angiogenic capacity, primary CMVECs were isolated from 3-month-old (young) and 24-month-old (aged) Fischer 344 x Brown Norway rats. In aged CMVECs, expression of PACAP was decreased, which was associated with impaired capacity to form capillary-like structures, impaired adhesiveness to collagen (assessed using electric cell-substrate impedance sensing [ECIS] technology), and increased apoptosis (caspase3 activity) when compared with young cells. Overexpression of PACAP in aged CMVECs resulted in increased formation of capillary-like structures, whereas it did not affect cell adhesion. Treatment with recombinant PACAP also significantly increased endothelial tube formation and inhibited apoptosis in aged CMVECs. In young CMVECs shRNA knockdown of autocrine PACAP expression significantly impaired tube formation capacity, mimicking the aging phenotype. Cellular and mitochondrial reactive oxygen species production (dihydroethidium and MitoSox fluorescence, respectively) were increased in aged CMVECs and were unaffected by PACAP. Collectively, PACAP exerts proangiogenic effects and age-related dysregulation of autocrine PACAP signaling may contribute to impaired angiogenic capacity of CMVECs in aging.

  2. Age-Related Decline of Autocrine Pituitary Adenylate Cyclase-Activating Polypeptide Impairs Angiogenic Capacity of Rat Cerebromicrovascular Endothelial Cells

    PubMed Central

    Banki, Eszter; Sosnowska, Danuta; Tucsek, Zsuzsanna; Gautam, Tripti; Toth, Peter; Tarantini, Stefano; Tamas, Andrea; Helyes, Zsuzsanna; Reglodi, Dora; Sonntag, William E.; Csiszar, Anna

    2015-01-01

    Aging impairs angiogenic capacity of cerebromicrovascular endothelial cells (CMVECs) promoting microvascular rarefaction, but the underlying mechanisms remain elusive. PACAP is an evolutionarily conserved neuropeptide secreted by endothelial cells and neurons, which confers important antiaging effects. To test the hypothesis that age-related changes in autocrine PACAP signaling contributes to dysregulation of endothelial angiogenic capacity, primary CMVECs were isolated from 3-month-old (young) and 24-month-old (aged) Fischer 344 x Brown Norway rats. In aged CMVECs, expression of PACAP was decreased, which was associated with impaired capacity to form capillary-like structures, impaired adhesiveness to collagen (assessed using electric cell-substrate impedance sensing [ECIS] technology), and increased apoptosis (caspase3 activity) when compared with young cells. Overexpression of PACAP in aged CMVECs resulted in increased formation of capillary-like structures, whereas it did not affect cell adhesion. Treatment with recombinant PACAP also significantly increased endothelial tube formation and inhibited apoptosis in aged CMVECs. In young CMVECs shRNA knockdown of autocrine PACAP expression significantly impaired tube formation capacity, mimicking the aging phenotype. Cellular and mitochondrial reactive oxygen species production (dihydroethidium and MitoSox fluorescence, respectively) were increased in aged CMVECs and were unaffected by PACAP. Collectively, PACAP exerts proangiogenic effects and age-related dysregulation of autocrine PACAP signaling may contribute to impaired angiogenic capacity of CMVECs in aging. PMID:25136000

  3. Looking for age-related growth decline in natural forests: unexpected biomass patterns from tree rings and simulated mortality

    USGS Publications Warehouse

    Foster, Jane R.; D'Amato, Anthony W.; Bradford, John B.

    2014-01-01

    Forest biomass growth is almost universally assumed to peak early in stand development, near canopy closure, after which it will plateau or decline. The chronosequence and plot remeasurement approaches used to establish the decline pattern suffer from limitations and coarse temporal detail. We combined annual tree ring measurements and mortality models to address two questions: first, how do assumptions about tree growth and mortality influence reconstructions of biomass growth? Second, under what circumstances does biomass production follow the model that peaks early, then declines? We integrated three stochastic mortality models with a census tree-ring data set from eight temperate forest types to reconstruct stand-level biomass increments (in Minnesota, USA). We compared growth patterns among mortality models, forest types and stands. Timing of peak biomass growth varied significantly among mortality models, peaking 20–30 years earlier when mortality was random with respect to tree growth and size, than when mortality favored slow-growing individuals. Random or u-shaped mortality (highest in small or large trees) produced peak growth 25–30 % higher than the surviving tree sample alone. Growth trends for even-aged, monospecific Pinus banksiana or Acer saccharum forests were similar to the early peak and decline expectation. However, we observed continually increasing biomass growth in older, low-productivity forests of Quercus rubra, Fraxinus nigra, and Thuja occidentalis. Tree-ring reconstructions estimated annual changes in live biomass growth and identified more diverse development patterns than previous methods. These detailed, long-term patterns of biomass development are crucial for detecting recent growth responses to global change and modeling future forest dynamics.

  4. Looking for age-related growth decline in natural forests: unexpected biomass patterns from tree rings and simulated mortality.

    PubMed

    Foster, Jane R; D'Amato, Anthony W; Bradford, John B

    2014-05-01

    Forest biomass growth is almost universally assumed to peak early in stand development, near canopy closure, after which it will plateau or decline. The chronosequence and plot remeasurement approaches used to establish the decline pattern suffer from limitations and coarse temporal detail. We combined annual tree ring measurements and mortality models to address two questions: first, how do assumptions about tree growth and mortality influence reconstructions of biomass growth? Second, under what circumstances does biomass production follow the model that peaks early, then declines? We integrated three stochastic mortality models with a census tree-ring data set from eight temperate forest types to reconstruct stand-level biomass increments (in Minnesota, USA). We compared growth patterns among mortality models, forest types and stands. Timing of peak biomass growth varied significantly among mortality models, peaking 20-30 years earlier when mortality was random with respect to tree growth and size, than when mortality favored slow-growing individuals. Random or u-shaped mortality (highest in small or large trees) produced peak growth 25-30% higher than the surviving tree sample alone. Growth trends for even-aged, monospecific Pinus banksiana or Acer saccharum forests were similar to the early peak and decline expectation. However, we observed continually increasing biomass growth in older, low-productivity forests of Quercus rubra, Fraxinus nigra, and Thuja occidentalis. Tree-ring reconstructions estimated annual changes in live biomass growth and identified more diverse development patterns than previous methods. These detailed, long-term patterns of biomass development are crucial for detecting recent growth responses to global change and modeling future forest dynamics.

  5. Use it or lose it? SES mitigates age-related decline in a recency/recognition task

    PubMed Central

    Czernochowski, Daniela; Fabiani, Monica; Friedman, David

    2008-01-01

    An important goal of aging research is to determine factors leading to individual differences that might compensate for some of the deleterious effects of aging on cognition. To determine whether socio-economic status (SES) plays a role in mitigating age-related decrements in the recollection of contextual details, we categorized older participants into low- and high-SES groups. Event-related potentials (ERPs) and behavioral data were recorded in a picture memory task involving recency and recognition judgments. Young, old-low and old-high SES groups did not differ in recognition performance. However, on recency judgments, old-low subjects performed at chance, whereas old-high subjects did not differ significantly from young adults. Consistent with their preserved recency performance, a long-duration frontal negativity was significantly larger for recency compared to recognition trials in the ERPs of the old-high SES group only. These data suggest that older adults with higher SES levels can use strategies to compensate for the adverse effects of aging in complex source memory tasks by recruiting additional neural resources apparently not required by the young. PMID:17280741

  6. Age-related decline of the cytochrome c oxidase subunit expression in the auditory cortex of the mimetic aging rat model associated with the common deletion.

    PubMed

    Zhong, Yi; Hu, Yujuan; Peng, Wei; Sun, Yu; Yang, Yang; Zhao, Xueyan; Huang, Xiang; Zhang, Honglian; Kong, Weijia

    2012-12-01

    The age-related deterioration in the central auditory system is well known to impair the abilities of sound localization and speech perception. However, the mechanisms involved in the age-related central auditory deficiency remain unclear. Previous studies have demonstrated that mitochondrial DNA (mtDNA) deletions accumulated with age in the auditory system. Also, a cytochrome c oxidase (CcO) deficiency has been proposed to be a causal factor in the age-related decline in mitochondrial respiratory activity. This study was designed to explore the changes of CcO activity and to investigate the possible relationship between the mtDNA common deletion (CD) and CcO activity as well as the mRNA expression of CcO subunits in the auditory cortex of D-galactose (D-gal)-induced mimetic aging rats at different ages. Moreover, we explored whether peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM) were involved in the changes of nuclear- and mitochondrial-encoded CcO subunits in the auditory cortex during aging. Our data demonstrated that d-gal-induced mimetic aging rats exhibited an accelerated accumulation of the CD and a gradual decline in the CcO activity in the auditory cortex during the aging process. The reduction in the CcO activity was correlated with the level of CD load in the auditory cortex. The mRNA expression of CcO subunit III was reduced significantly with age in the d-gal-induced mimetic aging rats. In contrast, the decline in the mRNA expression of subunits I and IV was relatively minor. Additionally, significant increases in the mRNA and protein levels of PGC-1α, NRF-1 and TFAM were observed in the auditory cortex of D-gal-induced mimetic aging rats with aging. These findings suggested that the accelerated accumulation of the CD in the auditory cortex may induce a substantial decline in CcO subunit III and lead to a significant decline in the Cc

  7. Age-Related Wayfinding Differences in Real Large-Scale Environments: Detrimental Motor Control Effects during Spatial Learning Are Mediated by Executive Decline?

    PubMed Central

    Taillade, Mathieu; Sauzéon, Hélène; Arvind Pala, Prashant; Déjos, Marie; Larrue, Florian; Gross, Christian; N’Kaoua, Bernard

    2013-01-01

    The aim of this study was to evaluate motor control activity (active vs. passive condition) with regards to wayfinding and spatial learning difficulties in large-scale spaces for older adults. We compared virtual reality (VR)-based wayfinding and spatial memory (survey and route knowledge) performances between 30 younger and 30 older adults. A significant effect of age was obtained on the wayfinding performances but not on the spatial memory performances. Specifically, the active condition deteriorated the survey measure in all of the participants and increased the age-related differences in the wayfinding performances. Importantly, the age-related differences in the wayfinding performances, after an active condition, were further mediated by the executive measures. All of the results relative to a detrimental effect of motor activity are discussed in terms of a dual task effect as well as executive decline associated with aging. PMID:23843992

  8. Early-life infection is a vulnerability factor for aging-related glial alterations and cognitive decline.

    PubMed

    Bilbo, Staci D

    2010-07-01

    There is significant individual variability in cognitive decline during aging, suggesting the existence of "vulnerability factors" for eventual deficits. Neuroinflammation may be one such factor; increased glial reactivity is a common outcome of aging, which in turn is associated with numerous neurodegenerative conditions. Early-life infection leads to cognitive impairment in conjunction with an inflammatory challenge in young adulthood, which led us to explore whether it might also accelerate the cognitive decline associated with aging. Rats were treated on postnatal day 4 with PBS or Escherichia coli, and then tested for learning and memory at 2 or 16months of age, using two fear-conditioning tasks (context pre-exposure and ambiguous cue), and a spatial water maze task. Neonatally-infected rats exhibited memory impairments in both the ambiguous cue fear-conditioning task and in the water maze, but only at 16months. There were no differences in anxiety between groups. Neonatally-infected rats also exhibited greater aging-induced increases in glial markers (CD11b and MHCII on microglia, and GFAP on astrocytes), as well as selective changes in NMDA receptor subunit expression within the hippocampus, but not in amygdala or parietal cortex compared to controls. Taken together, these data suggest that early-life infection leads to less successful cognitive aging, which may be linked to changes in glial reactivity.

  9. Higher serum cholesterol is associated with intensified age-related neural network decoupling and cognitive decline in early- to mid-life.

    PubMed

    Spielberg, Jeffrey M; Sadeh, Naomi; Leritz, Elizabeth C; McGlinchey, Regina E; Milberg, William P; Hayes, Jasmeet P; Salat, David H

    2017-03-31

    Mounting evidence indicates that serum cholesterol and other risk factors for cardiovascular disease intensify normative trajectories of age-related cognitive decline. However, the neural mechanisms by which this occurs remain largely unknown. To understand the impact of cholesterol on brain networks, we applied graph theory to resting-state fMRI in a large sample of early- to mid-life Veterans (N = 206, Meanage  = 32). A network emerged (centered on the banks of the superior temporal sulcus) that evidenced age-related decoupling (i.e., decreased network connectivity with age), but only in participants with clinically-elevated total cholesterol (≥180 mg/dL). Crucially, decoupling in this network corresponded to greater day-to-day disability and mediated age-related declines in psychomotor speed. Finally, examination of network organization revealed a pattern of age-related dedifferentiation for the banks of the superior temporal sulcus, again present only with higher cholesterol. More specifically, age was related to decreasing within-module communication (indexed by Within-Module Degree Z-Score) and increasing between-module communication (indexed by Participation Coefficient), but only in participants with clinically-elevated cholesterol. Follow-up analyses indicated that all findings were driven by low-density lipoprotein (LDL) levels, rather than high-density lipoprotein (HDL) or triglycerides, which is interesting as LDL levels have been linked to increased risk for cardiovascular disease, whereas HDL levels appear inversely related to such disease. These findings provide novel insight into the deleterious effects of cholesterol on brain health and suggest that cholesterol accelerates the impact of age on neural trajectories by disrupting connectivity in circuits implicated in integrative processes and behavioral control. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

  10. Central insulin-like growth factor-1 (IGF-1) restores whole-body insulin action in a model of age-related insulin resistance and IGF-1 decline.

    PubMed

    Huffman, Derek M; Farias Quipildor, Gabriela; Mao, Kai; Zhang, Xueying; Wan, Junxiang; Apontes, Pasha; Cohen, Pinchas; Barzilai, Nir

    2016-02-01

    Low insulin-like growth factor-1 (IGF-1) signaling is associated with improved longevity, but is paradoxically linked with several age-related diseases in humans. Insulin-like growth factor-1 has proven to be particularly beneficial to the brain, where it confers protection against features of neuronal and cognitive decline. While aging is characterized by central insulin resistance in the face of hyperinsulinemia, the somatotropic axis markedly declines in older humans. Thus, we hypothesized that increasing IGF-1 in the brain may prove to be a novel therapeutic alternative to overcome central insulin resistance and restore whole-body insulin action in aging. Utilizing hyperinsulinemic-euglycemic clamps, we show that old insulin-resistant rats with age-related declines in IGF-1 level demonstrate markedly improved whole-body insulin action, when treated with central IGF-1, as compared to central vehicle or insulin (P < 0.05). Furthermore, central IGF-1, but not insulin, suppressed hepatic glucose production and increased glucose disposal rates in aging rats (P < 0.05). Taken together, IGF-1 action in the brain and periphery provides a 'balance' between its beneficial and detrimental actions. Therefore, we propose that strategies aimed at 'tipping the balance' of IGF-1 action centrally are the optimal approach to achieve healthy aging and longevity in humans.

  11. Pupillary responses and memory-guided visual search reveal age-related and Alzheimer's-related memory decline.

    PubMed

    Dragan, Michelle C; Leonard, Timothy K; Lozano, Andres M; McAndrews, Mary Pat; Ng, Karen; Ryan, Jennifer D; Tang-Wai, David F; Wynn, Jordana S; Hoffman, Kari L

    2017-03-30

    Episodic memory - composed of memory for unique spatiotemporal experiences - is known to decline with aging, and even more severely in Alzheimer 's disease (AD). Memory for trial-unique objects in spatial scenes depends on the integrity of the hippocampus and interconnected structures that are among the first areas affected in AD. We reasoned that memory for objects-in-scenes would be impaired with aging, and that further impairments would be observed in AD. We asked younger adults, healthy older adults, older adults at-risk for developing cognitive impairments, and older adults with probable early AD to find changing items ('targets') within images of natural scenes, measuring repeated-trial changes in search efficiency and pupil diameter. Compared to younger adults, older adults took longer to detect target objects in repeated scenes, they required more fixations and those fixations were more dispersed. Whereas individuals with AD showed some benefit of memory in this task, they had substantially longer detection times, and more numerous, dispersed fixations on repeated scenes compared to age-matched older adults. Correspondingly, pupillary responses to novel and repeated scenes were diminished with aging and further in AD, and the memory-related changes were weaker with aging and absent in AD. Our results suggest that several nonverbal measures from memory-guided visual search tasks can index aging and Alzheimer's disease status, including pupillary dynamics. The task measurements are sensitive to the integrity of brain structures that are associated with Alzheimer's-related neurodegeneration, the task is well tolerated across a range of abilities, and thus, it may prove useful in early diagnostics and longitudinal tracking of memory decline.

  12. Age-Related Differences in Gait Kinematics, Kinetics, and Muscle Function: A Principal Component Analysis.

    PubMed

    Schloemer, Sarah A; Thompson, Julie A; Silder, Amy; Thelen, Darryl G; Siston, Robert A

    2017-03-01

    Age-related increased hip extensor recruitment during gait is a proposed compensation strategy for reduced ankle power generation and may indicate a distal-to-proximal shift in muscle function with age. Extending beyond joint level analyses, identifying age-related changes at the muscle level could capture more closely the underlying mechanisms responsible for movement. The purpose of this study was to characterize and compare muscle forces and induced accelerations during gait in healthy older adults with those of young adults. Simulations of one gait cycle for ten older (73.9 ± 5.3 years) and six young (21.0 ± 2.1 years) adults walking at their self-selected speed were analyzed. Muscle force and induced acceleration waveforms, along with kinematic, kinetic, and muscle activation waveforms, were compared between age-groups using principal component analysis. Simulations of healthy older adults had greater gluteus maximus force and vertical support contribution, but smaller iliacus force, psoas force, and psoas vertical support contribution. There were no age-group differences in distal muscle force, contribution, or ankle torque magnitudes. Later peak dorsiflexion and peak ankle angular velocity in older adults may have contributed to their greater ankle power absorption during stance. These findings reveal the complex interplay between age-related changes in neuromuscular control, kinematics, and muscle function during gait.

  13. Current evidence for the use of coffee and caffeine to prevent age-related cognitive decline and Alzheimer's disease.

    PubMed

    Carman, A J; Dacks, P A; Lane, R F; Shineman, D W; Fillit, H M

    2014-04-01

    Although nothing has been proven conclusively to protect against cognitive aging, Alzheimer's disease or related dementias, decades of research suggest that specific approaches including the consumption of coffee may be effective. While coffee and caffeine are known to enhance short-term memory and cognition, some limited research also suggests that long-term use may protect against cognitive decline or dementia. In vitro and pre-clinical animal models have identified plausible neuroprotective mechanisms of action of both caffeine and other bioactive components of coffee, though epidemiology has produced mixed results. Some studies suggest a protective association while others report no benefit. To our knowledge, no evidence has been gathered from randomized controlled trials. Although moderate consumption of caffeinated coffee is generally safe for healthy people, it may not be for everyone, since comorbidities and personal genetics influence potential benefits and risks. Future studies could include short-term clinical trials with biomarker outcomes to validate findings from pre-clinical models and improved epidemiological studies that incorporate more standardized methods of data collection and analysis. Given the enormous economic and emotional toll threatened by the current epidemic of Alzheimer's disease and other dementias, it is critically important to validate potential prevention strategies such as coffee and caffeine.

  14. The Role of RFamide-Related Peptide-3 in Age-Related Reproductive Decline in Female Rats

    PubMed Central

    Geraghty, Anna C.; Muroy, Sandra E.; Kriegsfeld, Lance J.; Bentley, George E.; Kaufer, Daniela

    2016-01-01

    Reproductive senescence, the point in time when females cease to show estrous cyclicity, is associated with endocrine changes in the hypothalamus, pituitary, and gonads. However, the mechanisms triggering this transition are not well understood. To gain a better understanding of the top-down control of the transition from reproductive competence to a state of reproductive senescence, we investigated middle-aged female rats exhibiting varying degrees of reproductive decline, including individuals with normal cycles, irregular cycles, and complete cessation of cycles. We identified hormonal changes in the brain that manifest before ovarian cycles exhibit any deterioration. We found that females exhibit an increase in RFamide-related peptide-3 (RFRP3) mRNA expression in the hypothalamus in middle age prior to changes in estrous cycle length. This increase is transient and followed by subsequent decreases in kisspeptin (KiSS1) and gonadotropin-releasing hormone (GnRH) mRNA expression. Expression of RFRP3 and its receptor also increased locally in the ovaries with advancing age. While it is well known that aging is associated with decreased GnRH release and downstream disruption of the hypothalamic–pituitary–gonadal (HPG) axis, herein, we provide evidence that reproductive senescence is likely triggered by alterations in a network of regulatory neuropeptides upstream of the GnRH system. PMID:27445974

  15. Age-related decline in task switching is linked to both global and tract-specific changes in white matter microstructure.

    PubMed

    Jolly, Todd A D; Cooper, Patrick S; Rennie, Jaime L; Levi, Christopher R; Lenroot, Rhoshel; Parsons, Mark W; Michie, Patricia T; Karayanidis, Frini

    2017-03-01

    Task-switching performance relies on a broadly distributed frontoparietal network and declines in older adults. In this study, they investigated whether this age-related decline in task switching performance was mediated by variability in global or regional white matter microstructural health. Seventy cognitively intact adults (43-87 years) completed a cued-trials task switching paradigm. Microstructural white matter measures were derived using diffusion tensor imaging (DTI) analyses on the diffusion-weighted imaging (DWI) sequence. Task switching performance decreased with increasing age and radial diffusivity (RaD), a measure of white matter microstructure that is sensitive to myelin structure. RaD mediated the relationship between age and task switching performance. However, the relationship between RaD and task switching performance remained significant when controlling for age and was stronger in the presence of cardiovascular risk factors. Variability in error and RT mixing cost were associated with RaD in global white matter and in frontoparietal white matter tracts, respectively. These findings suggest that age-related increase in mixing cost may result from both global and tract-specific disruption of cerebral white matter linked to the increased incidence of cardiovascular risks in older adults. Hum Brain Mapp 38:1588-1603, 2017. © 2016 Wiley Periodicals, Inc.

  16. Long-term moderate alcohol consumption does not exacerbate age-related cognitive decline in healthy, community-dwelling older adults

    PubMed Central

    Moussa, Malaak N.; Simpson, Sean L.; Mayhugh, Rhiannon E.; Grata, Michelle E.; Burdette, Jonathan H.; Porrino, Linda J.; Laurienti, Paul J.

    2015-01-01

    Recent census data has found that roughly 40% of adults 65 years and older not only consume alcohol but also drink more of it than previous generations. Older drinkers are more vulnerable than younger counterparts to the psychoactive effects of alcohol due to natural biological changes that occur with aging. This study was specifically designed to measure the effect of long-term moderate alcohol consumption on cognitive health in older adult drinkers. An extensive battery of validated tests commonly used in aging and substance use literature was used to measure performance in specific cognitive domains, including working memory and attention. An age (young, old) * alcohol consumption (light, moderate) factorial study design was used to evaluate the main effects of age and alcohol consumption on cognitive performance. The focus of the study was then limited to light and moderate older drinkers, and whether or not long-term moderate alcohol consumption exacerbated age-related cognitive decline. No evidence was found to support the idea that long-term moderate alcohol consumption in older adults exacerbates age-related cognitive decline. Findings were specific to healthy community dwelling social drinkers in older age and they should not be generalized to individuals with other consumption patterns, like heavy drinkers, binge drinkers or ex-drinkers. PMID:25601835

  17. Sex Differences in Age-Related Decline of Urinary Insulin-Like Growth Factor-Binding Protein-3 Levels in Adult Bonobos and Chimpanzees

    PubMed Central

    Behringer, Verena; Wudy, Stefan A.; Blum, Werner F.; Stevens, Jeroen M. G.; Remer, Thomas; Boesch, Christophe; Hohmann, Gottfried

    2016-01-01

    There is increasing interest in the characterization of normative senescence in humans. To assess to what extent aging patterns in humans are unique, comparative data from closely related species, such as non-human primates, can be very useful. Here, we use data from bonobos and chimpanzees, two closely related species that share a common ancestor with humans, to explore physiological markers that are indicative of aging processes. Many studies on aging in humans focus on the somatotropic axis, consisting of growth hormone (GH), insulin-like growth factors (IGFs), and IGF binding proteins (IGFBPs). In humans, IGFBP-3 levels decline steadily with increasing age. We used urinary IGFBP-3 levels as an alternative endocrine marker for IGF-I to identify the temporal pattern known to be related with age-related changes in cell proliferation, growth, and apoptosis. We measured urinary IGFBP-3 levels in samples from 71 bonobos and 102 chimpanzees. Focusing on samples from individuals aged 10 years or older, we found that urinary IGFBP-3 levels decline in both ape species with increasing age. However, in both species, females start with higher urinary IGFBP-3 levels than males, experience a steeper decline with increasing age, and converge with male levels around the age of 30–35 years. Our measurements of urinary IGFBP-3 levels indicate that bonobos and chimpanzees mirror human patterns of age-related decline in IGFBP-3 in older individuals (<10 years) of both sexes. Moreover, such as humans, both ape species show sex-specific differences in IGFBP-3 levels with females having higher levels than males, a result that correlates with sex differences in life expectancy. Using changes in urinary IGFBP-3 levels as a proxy for changes in GH and IGF-I levels that mark age-related changes in cell proliferation, this approach provides an opportunity to investigate trade-offs in life-history strategies in cross-sectional and in longitudinal studies, both in captivity and in

  18. Age-Related Impairment of Pancreatic Beta-Cell Function: Pathophysiological and Cellular Mechanisms

    PubMed Central

    De Tata, Vincenzo

    2014-01-01

    The incidence of type 2 diabetes significantly increases with age. The relevance of this association is dramatically magnified by the concomitant global aging of the population, but the underlying mechanisms remain to be fully elucidated. Here, some recent advances in this field are reviewed at the level of both the pathophysiology of glucose homeostasis and the cellular senescence of pancreatic islets. Overall, recent results highlight the crucial role of beta-cell dysfunction in the age-related impairment of pancreatic endocrine function and delineate the possibility of new original therapeutic interventions. PMID:25232350

  19. 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.

  20. Flavonoid Chrysin prevents age-related cognitive decline via attenuation of oxidative stress and modulation of BDNF levels in aged mouse brain.

    PubMed

    Souza, Leandro Cattelan; Antunes, Michelle Silva; Filho, Carlos Borges; Del Fabbro, Lucian; de Gomes, Marcelo Gomes; Goes, André Tiago Rossito; Donato, Franciele; Prigol, Marina; Boeira, Silvana Peterini; Jesse, Cristiano R

    2015-07-01

    In this study, the effect of Chrysin (5,7-dihydroxyflavone), an important member of the flavonoid family, on memory impairment, oxidative stress and BDNF reduction generated by aging in mice were investigated. Young and aged mice were treated daily per 60days with Chrysin (1 and 10mg/kg; per oral, p.o.) or veichle (10ml/kg; p.o.). Mice were trained and tested in Morris Water Maze task. After the behavioural test, the levels of reactive species (RS), the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), as well as the activity of Na(+), K(+)-ATPase and the levels of brain-derived neurotrophic factor (BDNF) were determined in the prefrontal cortex (PFC) and hippocampus (HC) of mice. Results demonstrated that the age-related memory decline was partially protected by Chrysin at a dose of 1mg/kg, and normalized at the dose of 10mg/kg (p<0.001). Treatment with Chrysin significantly attenuated the increase of RS levels and the inhibition of SOD, CAT and GPx activities of aged mice. Inhibition of Na(+), K(+)-ATPase activity in PFC and HP of aged mice was also attenuated by Chrysin treatment. Moreover, Chrysin marked mitigated the decrease of BDNF levels in the PFC and HC of aged mice. These results demonstrated that flavonoid Chrysin, an antioxidant compound, was able to prevent age-associated memory probably by their free radical scavenger action and modulation of BDNF production. Thus, this study indicates that Chrysin may represent a new pharmacological approach to alleviate the age-related declines during normal age, acting as an anti-aging agent.

  1. 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

  2. Relationship between macular pigment and visual function in subjects with early age-related macular degeneration

    PubMed Central

    Nolan, John M; Peto, Tunde; Stack, Jim; Leung, Irene; Corcoran, Laura; Beatty, Stephen

    2017-01-01

    Purpose To investigate the relationship between macular pigment (MP) and visual function in subjects with early age-related macular degeneration (AMD). Methods 121 subjects with early AMD enrolled as part of the Central Retinal Enrichment Supplementation Trial (CREST; ISRCTN13894787) were assessed using a range of psychophysical measures of visual function, including best corrected visual acuity (BCVA), letter contrast sensitivity (CS), mesopic and photopic CS, mesopic and photopic glare disability (GD), photostress recovery time (PRT), reading performance and subjective visual function, using the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). MP was measured using customised heterochromatic flicker photometry. Results Letter CS, mesopic and photopic CS, photopic GD and mean reading speed were each significantly (p<0.05) associated with MP across a range of retinal eccentricities, and these statistically significant relationships persisted after controlling for age, sex and cataract grade. BCVA, NEI VFQ-25 score, PRT and mesopic GD were unrelated to MP after controlling for age, sex and cataract grade (p>0.05, for all). Conclusions MP relates positively to many measures of visual function in unsupplemented subjects with early AMD. The CREST trial will investigate whether enrichment of MP influences visual function among those afflicted with this condition. Trial registration number ISRCTN13894787. PMID:27091854

  3. Long-term ginsenoside Rg1 supplementation improves age-related cognitive decline by promoting synaptic plasticity associated protein expression in C57BL/6J mice.

    PubMed

    Yang, Lumeng; Zhang, Jing; Zheng, Kunmu; Shen, Hui; Chen, Xiaochun

    2014-03-01

    In aging individuals, age-related cognitive decline is the most common cause of memory impairment. Among the remedies, ginsenoside Rg1, a major active component of ginseng, is often recommended for its antiaging effects. However, its role in improving cognitive decline during normal aging remains unknown and its molecular mechanism partially understood. This study employed a scheme of Rg1 supplementation for female C57BL/6J mice, which started at the age of 12 months and ended at 24 months, to investigate the effects of Rg1 supplementation on the cognitive performance. We found that Rg1 supplementation improved the performance of aged mice in behavior test and significantly upregulated the expression of synaptic plasticity-associated proteins in hippocampus, including synaptophysin, N-methyl-D-aspartate receptor subunit 1, postsynaptic density-95, and calcium/calmodulin-dependent protein kinase II alpha, via promoting mammalian target of rapamycin pathway activation. These data provide further support for Rg1 treatment of cognitive degeneration during aging.

  4. The interaction between gut microbiota and age-related changes in immune function and inflammation

    PubMed Central

    2013-01-01

    Intestinal microbiota and gut immune systems interact each other, maintaining a condition of homeostasis in the context of the intestinal habitat. However, both systems undergo modifications in elderly, thus accounting for a low grade inflammatory status which, in turn, may evolve toward more severe pathological conditions such as inflammatory bowel disease and colon rectal cancer. In addition, in western societies dietary habits may negatively influence the microbiota composition, also altering gut immune response which is per se impaired in elderly. In order to prevent the outcome of aged-related disease, supplementation of nutraceuticals able to correct abnormalities of both immune system and microbiota has become more frequent than in the past. In this respect, a better identification of components of the aged microbiota as well as a deeper analysis of gut mucosal immunity function should be pursued. PMID:23915308

  5. Improving function in age-related macular degeneration: design and methods of a randomized clinical trial.

    PubMed

    Rovner, Barry W; Casten, Robin J; Hegel, Mark T; Massof, Robert W; Leiby, Benjamin E; Tasman, William S

    2011-03-01

    Age-Related Macular Degeneration (AMD) is the leading cause of severe vision loss in older adults and impairs the ability to read, drive, and live independently and increases the risk for depression, falls, and earlier mortality. Although new medical treatments have improved AMD's prognosis, vision-related disability remains a major public health problem. Improving Function in AMD (IF-AMD) is a two-group randomized, parallel design, controlled clinical trial that compares the efficacy of Problem-Solving Therapy (PST) with Supportive Therapy (ST) (an attention control treatment) to improve vision function in 240 patients with AMD. PST and ST therapists deliver 6 one-hour respective treatment sessions to subjects in their homes over 2 months. Outcomes are assessed masked to treatment assignment at 3 months (main trial endpoint) and 6 months (maintenance effects). The primary outcome is targeted vision function (TVF), which refers to specific vision-dependent functional goals that subjects highly value but find difficult to achieve. TVF is an innovative outcome measure in that it is targeted and tailored to individual subjects yet is measured in a standardized way. This paper describes the research methods, theoretical and clinical aspects of the study treatments, and the measures used to evaluate functional and psychiatric outcomes in this population.

  6. Improving Function in Age-Related Macular Degeneration: Design and Methods of a Randomized Clinical Trial

    PubMed Central

    Rovner, Barry W.; Casten, Robin J.; Hegel, Mark T.; Massof, Robert W.; Leiby, Benjamin E.; Tasman, William S.

    2010-01-01

    Age-Related Macular Degeneration (AMD) is the leading cause of severe vision loss in older adults and impairs the ability to read, drive, and live independently and increases the risk for depression, falls, and earlier mortality. Although new medical treatments have improved AMD’s prognosis, vision-related disability remains a major public health problem. Improving Function in AMD (IF-AMD) is a two-group randomized, parallel design, controlled clinical trial that compares the efficacy of Problem-Solving Therapy (PST) with Supportive Therapy (ST) (an attention control treatment) to improve vision function in 240 patients with AMD. PST and ST therapists deliver 6 one-hour respective treatment sessions to subjects in their homes over 2 months. Outcomes are assessed masked to treatment assignment at 3 months (main trial endpoint) and 6 months (maintenance effects). The primary outcome is targeted vision function (TVF), which refers to specific vision-dependent functional goals that subjects highly value but find difficult to achieve. TVF is an innovative outcome measure in that it is targeted and tailored to individual subjects yet is measured in a standardized way. This paper describes the research methods, theoretical and clinical aspects of the study treatments, and the measures used to evaluate functional and psychiatric outcomes in this population. PMID:20974293

  7. Age-related dedifferentiation and compensatory changes in the functional network underlying face processing.

    PubMed

    Burianová, Hana; Lee, Yunjo; Grady, Cheryl L; Moscovitch, Morris

    2013-12-01

    Recent evidence has shown that older adults fail to show adaptation in the right fusiform gyrus (FG) to the same face presented repeatedly, despite accurate detection of the previously presented face. We used functional magnetic resonance imaging to investigate whether this phenomenon is associated with age-related reductions in face specificity in brain activity and whether older adults compensate for these face-processing deficiencies by increasing activity in other areas within the face-processing network, or outside this network. A comparison of brain activity across multiple stimulus categories showed that, unlike young adults who engaged a number of brain regions specific to face processing, older adults generalized these patterns of activity to objects and houses. Also, young adults showed functional connectivity between the right FG and its homologous region during face processing, whereas older adults did not engage the left FG but showed a functional connection between the right FG and left orbitofrontal cortex. Finally, this frontotemporal functional connection was activated more strongly in older adults who performed better on a face-matching task (done outside of the scanner), suggesting increased involvement of this functional link for successful face recognition with increasing age. These findings suggest that 2 neural mechanisms, dedifferentiation and compensatory neural recruitment, underlie age differences in face processing.

  8. Age-related loss of muscle mass and bone strength in mice is associated with a decline in physical activity and serum leptin.

    PubMed

    Hamrick, Mark W; Ding, Ke-Hong; Pennington, Catherine; Chao, Yuh J; Wu, Yii-Der; Howard, Boyd; Immel, David; Borlongan, Cesario; McNeil, Paul L; Bollag, Wendy B; Curl, Walton W; Yu, Jack; Isales, Carlos M

    2006-10-01

    The mechanisms underlying age-related loss of muscle and bone tissue are poorly understood but are thought to involve changes in sex hormone status, physical activity, and circulating levels of inflammatory cytokines. This study attempts to develop an animal model useful for evaluating these mechanisms in vivo. Male C57BL/6 mice were included for study at 3, 6, 12, 18, 24, and 29 months of age. Endocortical mineralizing surface, serum leptin, body weight, and percentage of body fat all increased between 6 and 12 months of age as activity level declined. Serum levels of the inflammatory marker IL-6 increased significantly after 12 months of age, following the observed increase in body weight and percent body fat. Hindlimb muscle mass declined significantly between 18 and 24 months of age, both absolutely and relative to total body mass, with a further decline ( approximately 15%) between 24 and 29 months. Loss of muscle mass after 18 months of age was accompanied by a significant increase in bone resorption, as indicated by serum pyridinoline cross-links, and a significant decrease in fat mass, serum leptin, bone strength, bone mineral density, and vertical cage activity. No significant changes in serum testosterone with aging were detected in the mice, as levels were essentially constant between 6 and 29 months. Our data show that mice lose a significant amount of muscle and bone tissue with age, and this loss of musculoskeletal tissue is accompanied by a drop in serum leptin and preceded by a significant decrease in physical activity.

  9. Acetyl-L-carnitine supplementation reverses the age-related decline in carnitine palmitoyltransferase 1 (CPT1) activity in interfibrillar mitochondria without changing the L-carnitine content in the rat heart.

    PubMed

    Gómez, Luis A; Heath, Shi-Hua D; Hagen, Tory M

    2012-01-01

    The aging heart displays a loss of bioenergetic reserve capacity partially mediated through lower fatty acid utilization. We investigated whether the age-related impairment of cardiac fatty acid catabolism occurs, at least partially, through diminished levels of L-carnitine, which would adversely affect carnitine palmitoyltransferase 1 (CPT1), the rate-limiting enzyme for fatty acyl-CoA uptake into mitochondria for β-oxidation. Old (24-28 mos) Fischer 344 rats were fed±acetyl-L-carnitine (ALCAR; 1.5% [w/v]) for up to four weeks prior to sacrifice and isolation of cardiac interfibrillar (IFM) and subsarcolemmal (SSM) mitochondria. IFM displayed a 28% (p<0.05) age-related loss of CPT1 activity, which correlated with a decline (41%, p<0.05) in palmitoyl-CoA-driven state 3 respiration. Interestingly, SSM had preserved enzyme function and efficiently utilized palmitate. Analysis of IFM CPT1 kinetics showed both diminished V(max) and K(m) (60% and 49% respectively, p<0.05) when palmitoyl-CoA was the substrate. However, no age-related changes in enzyme kinetics were evident with respect to L-carnitine. ALCAR supplementation restored CPT1 activity in heart IFM, but not apparently through remediation of L-carnitine levels. Rather, ALCAR influenced enzyme activity over time, potentially by modulating conditions in the aging heart that ultimately affect palmitoyl-CoA binding and CPT1 kinetics.

  10. Hyperhomocysteinemia disrupts retinal pigment epithelial structure and function with features of age-related macular degeneration

    PubMed Central

    Ibrahim, Ahmed S.; Mander, Suchreet; Hussein, Khaled A.; Elsherbiny, Nehal M.; Smith, Sylvia B.; Al-Shabrawey, Mohamed; Tawfik, Amany

    2016-01-01

    The disruption of retinal pigment epithelial (RPE) function and the degeneration of photoreceptors are cardinal features of age related macular degeneration (AMD); however there are still gaps in our understanding of underlying biological processes. Excess homocysteine (Hcy) has been reported to be elevated in plasma of patients with AMD. This study aimed to evaluate the direct effect of hyperhomocysteinemia (HHcy) on structure and function of RPE. Initial studies in a mouse model of HHcy, in which cystathionine-β-synthase (cbs) was deficient, revealed abnormal RPE cell morphology with features similar to that of AMD upon optical coherence tomography (OCT), fluorescein angiography (FA), histological, and electron microscopic examinations. These features include atrophy, vacuolization, hypopigmentation, thickened basal laminar membrane, hyporeflective lucency, choroidal neovascularization (CNV), and disturbed RPE–photoreceptor relationship. Furthermore, intravitreal injection of Hcy per se in normal wild type (WT) mice resulted in diffuse hyper-fluorescence, albumin leakage, and CNV in the area of RPE. In vitro experiments on ARPE-19 showed that Hcy dose-dependently reduced tight junction protein expression, increased FITC dextran leakage, decreased transcellular electrical resistance, and impaired phagocytic activity. Collectively, our results demonstrated unreported effects of excess Hcy levels on RPE structure and function that lead to the development of AMD-like features. PMID:26885895

  11. Age-related individual variability in memory performance is associated with amygdala-hippocampal circuit function and emotional pattern separation.

    PubMed

    Leal, Stephanie L; Noche, Jessica A; Murray, Elizabeth A; Yassa, Michael A

    2017-01-01

    While aging is generally associated with episodic memory decline, not all older adults exhibit memory loss. Furthermore, emotional memories are not subject to the same extent of forgetting and appear preserved in aging. We conducted high-resolution fMRI during a task involving pattern separation of emotional information in older adults with and without age-related memory impairment (characterized by performance on a word-list learning task: low performers: LP vs. high performers: HP). We found signals consistent with emotional pattern separation in hippocampal dentate (DG)/CA3 in HP but not in LP individuals, suggesting a deficit in emotional pattern separation. During false recognition, we found increased DG/CA3 activity in LP individuals, suggesting that hyperactivity may be associated with overgeneralization. We additionally observed a selective deficit in basolateral amygdala-lateral entorhinal cortex-DG/CA3 functional connectivity in LP individuals during pattern separation of negative information. During negative false recognition, LP individuals showed increased medial temporal lobe functional connectivity, consistent with overgeneralization. Overall, these results suggest a novel mechanistic account of individual differences in emotional memory alterations exhibited in aging.

  12. Age-related changes in the functional neuroanatomy of overt speech production.

    PubMed

    Sörös, Peter; Bose, Arpita; Sokoloff, Lisa Guttman; Graham, Simon J; Stuss, Donald T

    2011-08-01

    Alterations of existing neural networks during healthy aging, resulting in behavioral deficits and changes in brain activity, have been described for cognitive, motor, and sensory functions. To investigate age-related changes in the neural circuitry underlying overt non-lexical speech production, functional MRI was performed in 14 healthy younger (21-32 years) and 14 healthy older individuals (62-84 years). The experimental task involved the acoustically cued overt production of the vowel /a/ and the polysyllabic utterance /pataka/. In younger and older individuals, overt speech production was associated with the activation of a widespread articulo-phonological network, including the primary motor cortex, the supplementary motor area, the cingulate motor areas, and the posterior superior temporal cortex, similar in the /a/ and /pataka/ condition. An analysis of variance with the factors age and condition revealed a significant main effect of age. Irrespective of the experimental condition, significantly greater activation was found in the bilateral posterior superior temporal cortex, the posterior temporal plane, and the transverse temporal gyri in younger compared to older individuals. Significantly greater activation was found in the bilateral middle temporal gyri, medial frontal gyri, middle frontal gyri, and inferior frontal gyri in older vs. younger individuals. The analysis of variance did not reveal a significant main effect of condition and no significant interaction of age and condition. These results suggest a complex reorganization of neural networks dedicated to the production of speech during healthy aging.

  13. Age-related changes in the functional neuroanatomy of overt speech production

    PubMed Central

    Sörös, Peter; Bose, Arpita; Sokoloff, Lisa Guttman; Graham, Simon J.; Stuss, Donald T.

    2016-01-01

    Alterations of existing neural networks during healthy aging, resulting in behavioral deficits and changes in brain activity, have been described for cognitive, motor, and sensory functions. To investigate age-related changes in the neural circuitry underlying overt non-lexical speech production, functional MRI was performed in 14 healthy younger (21–32 years) and 14 healthy older individuals (62–84 years). The experimental task involved the acoustically cued overt production of the vowel /a/ and the polysyllabic utterance /pataka/. In younger and older individuals, overt speech production was associated with the activation of a widespread articulo-phonological network, including the primary motor cortex, the supplementary motor area, the cingulate motor areas, and the posterior superior temporal cortex, similar in the /a/ and /pataka/ condition. An analysis of variance with the factors age and condition revealed a significant main effect of age. Irrespective of the experimental condition, significantly greater activation was found in the bilateral posterior superior temporal cortex, the posterior temporal plane, and the transverse temporal gyri in younger compared to older individuals. Significantly greater activation was found in the bilateral middle temporal gyri, medial frontal gyri, middle frontal gyri, and inferior frontal gyri in older vs. younger individuals. The analysis of variance did not reveal a significant main effect of condition and no significant interaction of age and condition. These results suggest a complex reorganization of neural networks dedicated to the production of speech during healthy aging. PMID:19782435

  14. Late onset of dietary restriction reverses age-related decline of malate-aspartate shuttle enzymes in the liver and kidney of mice.

    PubMed

    Goyary, Danswrang; Sharma, Ramesh

    2008-02-01

    Dietary restriction (DR) influences several physiological processes, retards the incidences and severity of various age-related diseases and extends lifespan of various animal species. The effect of DR on the activities of malate-aspartate shuttle enzymes, viz. cytosolic and mitochondrial aspartate aminotransferase (c- and m-AsAT) and malate dehydrogenase (c- and m-MDH) was investigated in the liver and kidney of adult (5-months) and old (21-months) male mice. The results show that the activity (U/mg protein) of both c- and m-MDH and AsAT is decreased significantly in the liver and kidney of old mice compared to adult ones. However, DR in old mice reverses significantly the enzyme activities to a level closer to adult animals. Polyacrylamide gel electrophoresis (PAGE) and specific staining of c-AsAT, one of the selected isoenzymes of the shuttle, showed a similar pattern of activity expression as observed by activity measurements in both the tissues studied. Slot blot analysis of c-AsAT confirmed the lower protein content of this isoenzyme in old mice compared to adult ones and a higher level in old-dietary restricted mice. Thus, our results suggest that the late onset of DR in older mice reverses decline in malate-aspartate shuttle enzymes and that it may allow a better metabolic regulation in older animals.

  15. Age-related neurogenesis decline in the subventricular zone is associated with specific cell cycle regulation changes in activated neural stem cells

    PubMed Central

    Daynac, Mathieu; Morizur, Lise; Chicheportiche, Alexandra; Mouthon, Marc-André; Boussin, François D.

    2016-01-01

    Although neural stem cells (NSCs) sustain continuous neurogenesis throughout the adult lifespan of mammals, they progressively exhibit proliferation defects that contribute to a sharp reduction in subventricular neurogenesis during aging. However, little is known regarding the early age-related events in neurogenic niches. Using a fluorescence-activated cell sorting technique that allows for the prospective purification of the main neurogenic populations from the subventricular zone (SVZ), we demonstrated an early decline in adult neurogenesis with a dramatic loss of progenitor cells in 4 month-old young adult mice. Whereas the activated and quiescent NSC pools remained stable up to 12 months, the proliferative status of activated NSCs was already altered by 6 months, with an overall extension of the cell cycle resulting from a specific lengthening of G1. Whole genome analysis of activated NSCs from 2- and 6-month-old mice further revealed distinct transcriptomic and molecular signatures, as well as a modulation of the TGFβ signalling pathway. Our microarray study constitutes a cogent identification of new molecular players and signalling pathways regulating adult neurogenesis and its early modifications. PMID:26893147

  16. Age-related impairment of T cell-induced skeletal muscle precursor cell function

    PubMed Central

    Dumke, Breanna R.

    2011-01-01

    Sarcopenia is the age-associated loss of skeletal muscle mass and strength. Recent evidence suggests that an age-associated loss of muscle precursor cell (MPC) functionality contributes to sarcopenia. The objectives of the present study were to examine the influence of activated T cells on MPCs and determine whether an age-related defect in this signaling occurs. MPCs were collected from the gastrocnemius and plantaris of 3-mo-old (young) and 32-mo-old (old) animals. Splenic T cells were harvested using anti-CD3 Dynabead isolation. T cells were activated for 48 h with costimulation of 100 IU/ml interleukin-2 (IL-2) and 5 μg/ml of anti-CD28. Costimulation increased 5-bromo-2′-deoxyuridine incorporation of T cells from 13.4 ± 4.6% in control to 64.8 ± 6.0% in costimulated cells. Additionally, T cell cytokines increased proliferation on MPCs isolated from young muscle by 24.0 ± 5.7%, whereas there was no effect on MPCs isolated from aged muscle. T cell cytokines were also found to be a chemoattractant. T cells were able to promote migration of MPCs isolated from young muscle; however, MPCs isolated from aged muscle did not respond to the T cell-released chemokines. Conversely, whereas T cell-released cytokines did not affect myogenesis of MPCs isolated from young animals, there was a decrease in MPCs isolated from old animals. These data suggest that T cells may play a critical role in mediating MPC function. Furthermore, aging may alter T cell-induced MPC function. These findings have implications for developing strategies aimed at increasing MPC migration and proliferation leading to an improved regenerative capacity of aged skeletal muscle. PMID:21325640

  17. Functional Outcomes of the Low Vision Depression Prevention Trial in Age-Related Macular Degeneration

    PubMed Central

    Deemer, Ashley D.; Massof, Robert W.; Rovner, Barry W.; Casten, Robin J.; Piersol, Catherine V.

    2017-01-01

    Purpose To compare the efficacy of behavioral activation (BA) plus low vision rehabilitation with an occupational therapist (OT-LVR) with supportive therapy (ST) on visual function in patients with age-related macular degeneration (AMD). Methods Single-masked, attention-controlled, randomized clinical trial with AMD patients with subsyndromal depressive symptoms (n = 188). All subjects had two outpatient low vision rehabilitation optometry visits, then were randomized to in-home BA + OT-LVR or ST. Behavioral activation is a structured behavioral treatment aiming to increase adaptive behaviors and achieve valued goals. Supportive therapy is a nondirective, psychological treatment that provides emotional support and controls for attention. Functional vision was assessed with the activity inventory (AI) in which participants rate the difficulty level of goals and corresponding tasks. Participants were assessed at baseline and 4 months. Results Improvements in functional vision measures were seen in both the BA + OT-LVR and ST groups at the goal level (d = 0.71; d = 0.56 respectively). At the task level, BA + OT-LVR patients showed more improvement in reading, inside-the-home tasks and outside-the-home tasks, when compared to ST patients. The greatest effects were seen in the BA + OT-LVR group in subjects with a visual acuity ≥20/70 (d = 0.360 reading; d = 0.500 inside the home; d = 0.468 outside the home). Conclusions Based on the trends of the AI data, we suggest that BA + OT-LVR services, provided by an OT in the patient's home following conventional low vision optometry services, are more effective than conventional optometric low vision services alone for those with mild visual impairment. (ClinicalTrials.gov number, NCT00769015.) PMID:28273318

  18. Age-Related Effects of the Apolipoprotein E Gene on Brain Function.

    PubMed

    Matura, Silke; Prvulovic, David; Hartmann, Daniel; Scheibe, Monika; Sepanski, Beate; Butz, Marius; Oertel-Knöchel, Viola; Knöchel, Christian; Karakaya, Tarik; Fußer, Fabian; Hattingen, Elke; Pantel, Johannes

    2016-03-16

    The apolipoprotein E (ApoE) ɛ4 allele is a well-established genetic risk factor for sporadic Alzheimer's disease. Some evidence suggests a negative role of the ApoE ɛ4 allele for cognitive performance in late life, while beneficial effects on cognition have been shown in young age. We investigated age-related effects of the ApoE gene on brain function by assessing cognitive performance, as well as functional activation patterns during retrieval of Face-Name pairs in a group of young (n = 50; age 26.4±4.6 years, 25 ɛ4 carriers) and old (n = 40; age 66.1±7.0 years, 20 ɛ4 carriers) participants. A cross-sectional factorial design was used to examine the effects of age, ApoE genotype, and their interaction on both cognitive performance and the blood oxygenation level dependent (BOLD) brain response during retrieval of Face-Name pairs. While there were no genotype-related differences in cognitive performance, we found a significant interaction of age and ApoE genotype on task-related activation bilaterally in anterior cingulate gyrus and superior frontal gyrus, as well as left and right insula. Old age was associated with increased activity in ɛ4 carriers. The increased BOLD response in old ɛ4 carriers during retrieval could indicate a neurocognitive disadvantage associated with the ɛ4 allele with increasing age. Furthermore, recruitment of neuronal resources resulted in enhanced memory performance in young ɛ4 carriers, pointing to a better neurofunctional capacity associated with the ApoE4 genotype in young age.

  19. The Factor Structure and Age-Related Factorial Invariance of the Delis-Kaplan Executive Function System (D-KEFS)

    ERIC Educational Resources Information Center

    Latzman, Robert D.; Markon, Kristian E.

    2010-01-01

    There has been an increased interest in the structure of and relations among executive functions.The present study examined the factor structure as well as age-related factorial invariance of the Delis-Kaplan Executive Function System (D-KEFS), a widely used inventory aimed at assessing executive functions. Analyses were first conducted using data…

  20. Trade off situation between thymus and growth hormone: age-related decline of growth hormone is a cause of thymic involution but favorable for elongation of lifespan.

    PubMed

    Hirokawa, Katsuiku; Utsuyama, Masanori; Kikuchi, Yuko

    2016-02-01

    High level of growth hormone (GH) is necessary for the activation of thymic function to promote T cell differentiation in the early stage of animal life. In the later stage of the life, administration of GH promotes the development of immune system and rejuvenates declined immune function of elderly people. By contraries, GH deficiency is favorable for the longer lifespan, as hypo-pituitary dwarf mice such as Ames and Snell dwarf mice exhibit longer lifespan than control. Furthermore over-expression of heterologous or homologous GH in transgenic mice shortens the lifespan. Ecuadorians carrying mutations of GH receptor gene are short in height, but exhibited low frequency of malignancy and no cases of diabetes. These data indicate that GH is necessary for the development of thymus dependent immune system but GH deficiency is favorable for long life span and decreases occurrence of cancer and DM. This situation is a kind of trade off situation between the immune system and GH. Thus the early decline of high level of GH occurring shortly after the birth is a cause of early decline of thymic functions, but favorable for longer lifespan. This situation could be a kind of trade off situation between thymus and GH.

  1. Building a better hormone therapy? How understanding the rapid effects of sex steroid hormones could lead to new therapeutics for age-related memory decline.

    PubMed

    Frick, Karyn M

    2012-02-01

    A wealth of data collected in recent decades has demonstrated that ovarian sex-steroid hormones, particularly 17β-estradiol (E2), are important trophic factors that regulate the function of cognitive regions of the brain such as the hippocampus. The loss of hormone cycling at menopause is associated with cognitive decline and dementia in women, and the onset of memory decline in animal models. However, hormone therapy is not currently recommended to prevent or treat cognitive decline, in part because of its detrimental side effects. In this article, it is proposed that investigations of the rapid effects of E2 on hippocampal function be used to further the design of new drugs that mimic the beneficial effects of E2 on memory without the side effects of current therapies. A conceptual model is presented for elucidating the molecular and biochemical mechanisms through which sex-steroid hormones modulate memory, and a specific hypothesis is proposed to account for the rapid memory-enhancing effects of E2. Empirical support for this hypothesis is discussed as a means of stimulating the consideration of new directions for the development of hormone-based therapies to preserve memory function in menopausal women.

  2. Improving Function in Age-Related Macular Degeneration: A Randomized Clinical Trial

    PubMed Central

    Rovner, Barry W.; Casten, Robin J.; Hegel, Mark T.; Massof, Robert W.; Leiby, Benjamin E.; Ho, Allen C.; Tasman, William S.

    2013-01-01

    Purpose To compare the efficacy of Problem-Solving Therapy (PST) with Supportive Therapy (ST) to improve Targeted Vision Function in Age-Related Macular Degeneration (AMD). Design Single-masked, attention controlled randomized clinical trial with outcome assessments at 3 months (main trial endpoint) and 6 months (maintenance effects). Participants Patients with AMD (N = 241) attending retina practices. Interventions PST uses a structured problem-solving approach to reduce vision-related task difficulty. ST is a standardized attention control treatment. Main Outcome Measures Targeted Vision Function (TVF); National Eye Institute Vision Function Questionnaire - 25 plus Supplement (NEI VFQ); Activities Inventory (AI); and Vision-Related Quality of Life. Results There were no significant between-group differences in TVF scores at 3 months (p = 0.47) or 6 months (p = 0.62). For PST subjects, mean [standard deviation (SD)] TVF scores improved from 2.71 (0.52) at baseline to 2.18 (0.88) at 3 months (p = 0.001) and were 2.18 (0.95) at 6 months (change from 3 to 6 months, p = .74). For ST subjects, TVF scores improved from 2.73 (0.52) at baseline to 2.14 (0.96) at 3 months (p = 0.001) and were 2.15 (0.96) at 6 months (change from 3 to 6 months, p = .85). Similar proportions of PST and ST subjects had less difficulty performing a TVF goal at 3 months (77.4% vs. 78.6%, respectively; p = 0.83) and 6 months (76.2% vs. 79.1%, respectively; p = 0.61). There were no significant changes in the NEI VFQ or AI. Vision-related quality-of-life improved for PST relative to ST subjects at 3 months [F (4,192) = 2.46; p = 0.05] and 6 months [F (4,178) = 2.55; p = 0.05)]. PST subjects also developed more adaptive coping strategies than ST subjects. Conclusions We found that PST was not superior to ST at improving vision function in patients with AMD but PST improved their vision-related quality of life. Despite the benefits of anti-vascular endothelial growth factor (anti-VEGF) treatments

  3. High-Density Lipoprotein Function in Exudative Age-Related Macular Degeneration

    PubMed Central

    Pertl, Laura; Kern, Sabine; Weger, Martin; Hausberger, Silke; Trieb, Markus; Gasser-Steiner, Vanessa; Haas, Anton; Scharnagl, Hubert; Heinemann, Akos; Marsche, Gunther

    2016-01-01

    Purpose High-density lipoproteins (HDL) have long been implicated in the pathogenesis of age-related macular degeneration (AMD). However, conflicting results have been reported with regard to the associations of AMD with HDL-cholesterol levels. The present study is the first to assess HDL composition and metrics of HDL function in patients with exudative AMD and control patients. Methods Blood samples were collected from 29 patients with exudative AMD and 26 age-matched control patients. Major HDL associated apolipoproteins were determined in apoB-depleted serum by immunoturbidimetry or ELISA, HDL-associated lipids were quantified enzymatically. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function, including cholesterol efflux capacity, anti-oxidative and anti-inflammatory activities using apoB-depleted serum from study participants. Results In our study, we observed that the HDL associated acute phase protein serum amyloid A (SAA) was significantly increased in AMD patients (p<0.01), whereas all other assessed apolipoproteins including ApoA-I, apoA-II, apoC-II, apoC-III and apoE as well as major HDL associated lipids were not altered. HDL efflux capacity, anti-oxidative capacity and arylesterase activity were not different in AMD patients when compared with the control group. The ability of apoB-depleted serum to inhibit monocyte NF-κB expression was significantly improved in AMD patients (mean difference (MD) -5.6, p<0.01). Moreover, lipoprotein-associated phospholipase A2 activity, a marker of vascular inflammation, was decreased in AMD subjects (MD -24.1, p<0.01). Conclusions The investigated metrics of HDL composition and HDL function were not associated with exudative AMD in this study, despite an increased content of HDL associated SAA in AMD patients. Unexpectedly, anti-inflammatory activity of apoB-depleted serum was even increased in our study. Our data suggest that the investigated parameters of serum HDL

  4. Age-related changes in the bimanual advantage and in brain oscillatory activity during tapping movements suggest a decline in processing sensory reafference.

    PubMed

    Sallard, Etienne; Spierer, Lucas; Ludwig, Catherine; Deiber, Marie-Pierre; Barral, Jérôme

    2014-02-01

    Deficits in the processing of sensory reafferences have been suggested as accounting for age-related decline in motor coordination. Whether sensory reafferences are accurately processed can be assessed based on the bimanual advantage in tapping: because of tapping with an additional hand increases kinesthetic reafferences, bimanual tapping is characterized by a reduced inter-tap interval variability than unimanual tapping. A suppression of the bimanual advantage would thus indicate a deficit in sensory reafference. We tested whether elderly indeed show a reduced bimanual advantage by measuring unimanual (UM) and bimanual (BM) self-paced tapping performance in groups of young (n = 29) and old (n = 27) healthy adults. Electroencephalogram was recorded to assess the underlying patterns of oscillatory activity, a neurophysiological mechanism advanced to support the integration of sensory reafferences. Behaviorally, there was a significant interaction between the factors tapping condition and age group at the level of the inter-tap interval variability, driven by a lower variability in BM than UM tapping in the young, but not in the elderly group. This result indicates that in self-paced tapping, the bimanual advantage is absent in elderly. Electrophysiological results revealed an interaction between tapping condition and age group on low beta band (14-20 Hz) activity. Beta activity varied depending on the tapping condition in the elderly but not in the young group. Source estimations localized this effect within left superior parietal and left occipital areas. We interpret our results in terms of engagement of different mechanisms in the elderly depending on the tapping mode: a 'kinesthetic' mechanism for UM and a 'visual imagery' mechanism for BM tapping movement.

  5. Novel gene function revealed by mouse mutagenesis screens for models of age-related disease

    PubMed Central

    Potter, Paul K.; Bowl, Michael R.; Jeyarajan, Prashanthini; Wisby, Laura; Blease, Andrew; Goldsworthy, Michelle E.; Simon, Michelle M.; Greenaway, Simon; Michel, Vincent; Barnard, Alun; Aguilar, Carlos; Agnew, Thomas; Banks, Gareth; Blake, Andrew; Chessum, Lauren; Dorning, Joanne; Falcone, Sara; Goosey, Laurence; Harris, Shelley; Haynes, Andy; Heise, Ines; Hillier, Rosie; Hough, Tertius; Hoslin, Angela; Hutchison, Marie; King, Ruairidh; Kumar, Saumya; Lad, Heena V.; Law, Gemma; MacLaren, Robert E.; Morse, Susan; Nicol, Thomas; Parker, Andrew; Pickford, Karen; Sethi, Siddharth; Starbuck, Becky; Stelma, Femke; Cheeseman, Michael; Cross, Sally H.; Foster, Russell G.; Jackson, Ian J.; Peirson, Stuart N.; Thakker, Rajesh V.; Vincent, Tonia; Scudamore, Cheryl; Wells, Sara; El-Amraoui, Aziz; Petit, Christine; Acevedo-Arozena, Abraham; Nolan, Patrick M.; Cox, Roger; Mallon, Anne-Marie; Brown, Steve D. M.

    2016-01-01

    Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss. PMID:27534441

  6. Age-related variance in decisions under ambiguity is explained by changes in reasoning, executive functions, and decision-making under risk.

    PubMed

    Schiebener, Johannes; Brand, Matthias

    2016-03-22

    Previous literature has explained older individuals' disadvantageous decision-making under ambiguity in the Iowa Gambling Task (IGT) by reduced emotional warning signals preceding decisions. We argue that age-related reductions in IGT performance may also be explained by reductions in certain cognitive abilities (reasoning, executive functions). In 210 participants (18-86 years), we found that the age-related variance on IGT performance occurred only in the last 60 trials. The effect was mediated by cognitive abilities and their relation with decision-making performance under risk with explicit rules (Game of Dice Task). Thus, reductions in cognitive functions in older age may be associated with both a reduced ability to gain explicit insight into the rules of the ambiguous decision situation and with failure to choose the less risky options consequently after the rules have been understood explicitly. Previous literature may have underestimated the relevance of cognitive functions for age-related decline in decision-making performance under ambiguity.

  7. Age Related Differences of Executive Functioning Problems in Everyday Life of Children and Adolescents in the Autism Spectrum

    ERIC Educational Resources Information Center

    van den Bergh, Sanne F. W. M.; Scheeren, Anke M.; Begeer, Sander; Koot, Hans M.; Geurts, Hilde M.

    2014-01-01

    Numerous studies investigated executive functioning (EF) problems in people with autism spectrum disorders (ASD) using laboratory EF tasks. As laboratory task performances often differ from real life observations, the current study focused on EF in everyday life of 118 children and adolescents with ASD (6-18 years). We investigated age-related and…

  8. Executive Functioning and Processing Speed in Age-Related Differences in Memory: Contribution of a Coding Task

    ERIC Educational Resources Information Center

    Baudouin, Alexia; Clarys, David; Vanneste, Sandrine; Isingrini, Michel

    2009-01-01

    The aim of the present study was to examine executive dysfunctioning and decreased processing speed as potential mediators of age-related differences in episodic memory. We compared the performances of young and elderly adults in a free-recall task. Participants were also given tests to measure executive functions and perceptual processing speed…

  9. Assessment of Age-Related Differences in Functional Capacity Using the Virtual Reality Functional Capacity Assessment Tool (VRFCAT)

    PubMed Central

    Atkins, A.S.; Stroescu, I.; Spagnola, N.B.; Davis, V.G.; Patterson, T.D.; Narasimhan, M.; Harvey, P.D.; Keefe, R.S.E.

    2015-01-01

    Clinical trials for primary prevention and early intervention in preclinical AD require measures of functional capacity with improved sensitivity to deficits in healthier, non-demented individuals. To this end, the Virtual Reality Functional Capacity Assessment Tool (VRFCAT) was developed as a direct performance-based assessment of functional capacity that is sensitive to changes in function across multiple populations. Using a realistic virtual reality environment, the VRFCAT assesses a subject's ability to complete instrumental activities associated with a shopping trip. The present investigation represents an initial evaluation of the VRFCAT as a potential co-primary measure of functional capacity in healthy aging and preclinical MCI/AD by examining test-retest reliability and associations with cognitive performance in healthy young and older adults. The VRFCAT was compared and contrasted with the UPSA-2-VIM, a traditional performance-based assessment utilizing physical props. Results demonstrated strong age-related differences in performance on each VRFCAT outcome measure, including total completion time, total errors, and total forced progressions. VRFCAT performance showed strong correlations with cognitive performance across both age groups. VRFCAT Total Time demonstrated good test-retest reliability (ICC=.80 in young adults; ICC=.64 in older adults) and insignificant practice effects, indicating the measure is suitable for repeated testing in healthy populations. Taken together, these results provide preliminary support for the VRFCAT as a potential measure of functionally relevant change in primary prevention and preclinical AD/MCI trials. PMID:26618145

  10. Durable recovery of the macular architecture and functionality of a diagnosed age-related macular degeneration 1 year after a single intravitreal injection of dobesilate.

    PubMed

    Cuevas, P; Outeiriño, L A; Azanza, C; Giménez-Gallego, G

    2013-11-13

    Among the age-related diseases that affect vision, age-related macular degeneration is the most frequent cause of blindness in patients older than 60 years. In this communication, we report the full anatomical and functional recovery of a patient diagnosed with wet age-related macular degeneration 1 year after a single intravitreal injection of dobesilate.

  11. Durable recovery of the macular architecture and functionality of a diagnosed age-related macular degeneration 1 year after a single intravitreal injection of dobesilate

    PubMed Central

    Cuevas, P; Outeiriño, L A; Azanza, C; Giménez-Gallego, G

    2013-01-01

    Among the age-related diseases that affect vision, age-related macular degeneration is the most frequent cause of blindness in patients older than 60 years. In this communication, we report the full anatomical and functional recovery of a patient diagnosed with wet age-related macular degeneration 1 year after a single intravitreal injection of dobesilate. PMID:24225910

  12. Divergence of Age-Related Differences in Social-Communication: Improvements for Typically Developing Youth but Declines for Youth with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Wallace, Gregory L.; Dudley, Katerina; Anthony, Laura; Pugliese, Cara E.; Orionzi, Bako; Clasen, Liv; Lee, Nancy Raitano; Giedd, Jay N.; Martin, Alex; Raznahan, Armin; Kenworthy, Lauren

    2017-01-01

    Although social-communication difficulties and repetitive behaviors are hallmark features of autism spectrum disorder (ASD) and persist across the lifespan, very few studies have compared age-related differences in these behaviors between youth with ASD and same-age typically developing (TD) peers. We examined this issue using SRS-2 (Social…

  13. Critical Roles of Reactive Oxygen Species in Age-Related Impairment in Ischemia-Induced Neovascularization by Regulating Stem and Progenitor Cell Function

    PubMed Central

    Lam, Yuen Ting

    2016-01-01

    Reactive oxygen species (ROS) regulate bone marrow microenvironment for stem and progenitor cells functions including self-renewal, differentiation, and cell senescence. In response to ischemia, ROS also play a critical role in mediating the mobilization of endothelial progenitor cells (EPCs) from the bone marrow to the sites of ischemic injury, which contributes to postnatal neovascularization. Aging is an unavoidable biological deteriorative process with a progressive decline in physiological functions. It is associated with increased oxidative stress and impaired ischemia-induced neovascularization. This review discusses the roles of ROS in regulating stem and progenitor cell function, highlighting the impact of unbalanced ROS levels on EPC dysfunction and the association with age-related impairment in ischemia-induced neovascularization. Furthermore, it discusses strategies that modulate the oxidative levels of stem and progenitor cells to enhance the therapeutic potential for elderly patients with cardiovascular disease. PMID:26697140

  14. Functional brain and age-related changes associated with congruency in task switching.

    PubMed

    Eich, Teal S; Parker, David; Liu, Dan; Oh, Hwamee; Razlighi, Qolamreza; Gazes, Yunglin; Habeck, Christian; Stern, Yaakov

    2016-10-01

    Alternating between completing two simple tasks, as opposed to completing only one task, has been shown to produce costs to performance and changes to neural patterns of activity, effects which are augmented in old age. Cognitive conflict may arise from factors other than switching tasks, however. Sensorimotor congruency (whether stimulus-response mappings are the same or different for the two tasks) has been shown to behaviorally moderate switch costs in older, but not younger adults. In the current study, we used fMRI to investigate the neurobiological mechanisms of response-conflict congruency effects within a task switching paradigm in older (N=75) and younger (N=62) adults. Behaviorally, incongruency moderated age-related differences in switch costs. Neurally, switch costs were associated with greater activation in the dorsal attention network for older relative to younger adults. We also found that older adults recruited an additional set of brain areas in the ventral attention network to a greater extent than did younger adults to resolve congruency-related response-conflict. These results suggest both a network and an age-based dissociation between congruency and switch costs in task switching.

  15. 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

  16. Assessment of Age-related Changes in Cognitive Functions Using EmoCogMeter, a Novel Tablet-computer Based Approach

    PubMed Central

    Weigand, Anne; Fan, Yan; Gärtner, Matti; Feeser, Melanie; Bajbouj, Malek

    2014-01-01

    The main goal of this study was to assess the usability of a tablet-computer-based application (EmoCogMeter) in investigating the effects of age on cognitive functions across the lifespan in a sample of 378 healthy subjects (age range 18-89 years). Consistent with previous findings we found an age-related cognitive decline across a wide range of neuropsychological domains (memory, attention, executive functions), thereby proving the usability of our tablet-based application. Regardless of prior computer experience, subjects of all age groups were able to perform the tasks without instruction or feedback from an experimenter. Increased motivation and compliance proved to be beneficial for task performance, thereby potentially increasing the validity of the results. Our promising findings underline the great clinical and practical potential of a tablet-based application for detection and monitoring of cognitive dysfunction. PMID:24561917

  17. 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

  18. Age-Related Changes in Children's Executive Functions and Strategy Selection: A Study in Computational Estimation

    ERIC Educational Resources Information Center

    Lemaire, Patrick; Lecacheur, Mireille

    2011-01-01

    Third, fifth, and seventh graders selected the best strategy (rounding up or rounding down) for estimating answers to two-digit addition problems. Executive function measures were collected for each individual. Data showed that (a) children's skill at both strategy selection and execution improved with age and (b) increased efficiency in executive…

  19. Age-related changes in mitochondrial function and antioxidative enzyme activity in fischer 344 rats.

    PubMed

    Meng, Qingying; Wong, Yee Ting; Chen, Jie; Ruan, Runsheng

    2007-03-01

    We have previously reported the changes of mitochondrial function and/or antioxidative enzyme efficiency in a few organs of rats as a result of aging. However, there is a further need to reach a conclusion about their interactions in biological functions based on other evaluation tips like the usage of advanced methods and the exploring of crucial biochemical parameters. Therefore, we investigated the mitochondrial inner membrane functional integrity by the analysis of respiration control ratio and membrane potential in the liver and brain of young (8 months) and old (26 months) Fischer 344 rats. The disintegration of mitochondrial membrane integrity was determined higher in the liver of old rats than that of young rats. This was well correlated with the decrease of total superoxide dismutase (SOD), Cu/Zn-SOD, Mn-SOD and glutathione peroxidase activities in most of the organs, except for the increase of catalase activity in heart of old rats. Similarly, the protein expressions of these enzymes were down regulated in the liver and kidney of old rats. Taken together, we suggest that the mitochondrial malfunction in old rats is associated with the decrease of antioxidative enzyme efficiency. And the data are also discussed with changes in the results from inter-laboratories.

  20. Why are there different age relations in cross-sectional and longitudinal comparisons of cognitive functioning?

    PubMed Central

    Salthouse, Timothy A.

    2014-01-01

    A major challenge for researchers interested in investigating relations between aging and cognitive functioning is distinguishing influences of aging from other determinants of cognitive performance. For example, cross-sectional comparisons may be distorted because people of different ages were born and grew up in different time periods, and longitudinal comparisons may be distorted because performance on a second occasion is influenced by the experience of performing the tests on the first occasion. One way in which these different types of influences might be investigated is with research designs involving comparisons of people of different ages from the same birth cohorts who are all tested for the first time in different years. Results from several recent studies using these types of designs suggest that the age trends in some cognitive abilities more closely resemble those from cross-sectional comparisons than those from longitudinal comparisons. These findings imply that a major reason for different age trends in longitudinal and cross-sectional comparisons of cognitive functioning is that the prior experience with the tests inflates scores on the second occasion in longitudinal studies. PMID:25382943

  1. The aging of elite male athletes: age-related changes in performance and skeletal muscle structure and function

    PubMed Central

    Faulkner, John A.; Davis, Carol S.; Mendias, Christopher L.; Brooks, Susan V.

    2009-01-01

    Objective The paper addresses the degree to which the attainment of the status as an elite athlete in different sports ameliorates the known age-related losses in skeletal muscle structure and function. Design The retrospective design, based on comparisons of published data on former elite and masters athletes and data on control subjects, assessed the degree to which the attainment of ‘elite and masters athlete status’ ameliorated the known age-related changes in skeletal muscle structure and function. Setting Institutional. Participants Elite male athletes. Interventions Participation in selected individual and team sports. Main Outcome Measurements Strength, power, VO2 max and performance. Results For elite athletes in all sports, as for the general population, age-related muscle atrophy begins at about 50 years of age. Despite the loss of muscle mass, elite athletes who maintain an active life style age gracefully with few health problems. Conversely, those who lapse into inactivity regress toward general population norms for fitness, weight control, and health problems. Elite athletes in the dual and team sports have careers that rarely extend into the thirties. Conclusions Life long physical activity does not appear to have any impact on the loss in fiber number. The loss of fibers can be buffered to some degree by hypertrophy of fibers that remain. Surprisingly, the performance of elite athletes in all sports appears to be impaired before the onset of the fiber loss. Even with major losses in physical capacity and muscle mass, the performance of elite and masters athletes is remarkable. PMID:19001883

  2. Age-related changes in expression and function of Toll-like receptors in human skin.

    PubMed

    Iram, Nousheen; Mildner, Michael; Prior, Marion; Petzelbauer, Peter; Fiala, Christian; Hacker, Stefan; Schöppl, Alice; Tschachler, Erwin; Elbe-Bürger, Adelheid

    2012-11-01

    Toll-like receptors (TLRs) initiate innate immune responses and direct subsequent adaptive immunity. They play a major role in cutaneous host defense against micro-organisms and in the pathophysiology of several inflammatory skin diseases. To understand the role of TLRs in the acquisition of immunological competence, we conducted a comprehensive study to evaluate TLR expression and function in the developing human skin before and after birth and compared it with adults. We found that prenatal skin already expresses the same spectrum of TLRs as adult skin. Strikingly, many TLRs were significantly higher expressed in prenatal (TLRs 1-5) and infant and child (TLRs 1 and 3) skin than in adult skin. Surprisingly, neither dendritic cell precursors in prenatal skin nor epidermal Langerhans cells and dermal dendritic cells in adult skin expressed TLRs 3 and 6, whereas the staining pattern and intensity of both TLRs in fetal basal keratinocytes was almost comparable to those of adults. Stimulation of primary human keratinocytes from fetal, neonatal and adult donors with selected TLR agonists revealed that the synthetic TLR3 ligand poly (I:C) specifically, mimicking viral double-stranded RNA, induced a significantly enhanced secretion of CXCL8/IL8, CXCL10/IP-10 and TNFα in fetal and neonatal keratinocytes compared with adult keratinocytes. This study demonstrates quantitative age-specific modifications in TLR expression and innate skin immune reactivity in response to TLR activation. Thus, antiviral innate immunity already in prenatal skin may contribute to protect the developing human body from viral infections in utero in a scenario where the adaptive immune system is not yet fully functional.

  3. Age-related change in executive function: developmental trends and a latent variable analysis.

    PubMed

    Huizinga, Mariëtte; Dolan, Conor V; van der Molen, Maurits W

    2006-01-01

    This study examined the developmental trajectories of three frequently postulated executive function (EF) components, Working Memory, Shifting, and Inhibition of responses, and their relation to performance on standard, but complex, neuropsychological EF tasks, the Wisconsin Card Sorting Task (WCST), and the Tower of London (ToL). Participants in four age groups (7-, 11-, 15-, and 21-year olds) carried out nine basic experimental tasks (three tasks for each EF), the WCST, and the ToL. Analyses were done in two steps: (1) analyses of (co)variance to examine developmental trends in individual EF tasks while correcting for basic processing speed, (2) confirmatory factor analysis to extract latent variables from the nine basic EF tasks, and to explain variance in the performance on WCST and ToL, using these latent variables. Analyses of (co)variance revealed a continuation of EF development into adolescence. Confirmatory factor analysis yielded two common factors: Working Memory and Shifting. However, the variables assumed to tap Inhibition proved unrelated. At a latent level, again correcting for basic processing speed, the development of Shifting was seen to continue into adolescence, while Working Memory continued to develop into young-adulthood. Regression analyses revealed that Working Memory contributed most strongly to WCST performance in all age groups. These results suggest that EF component processes develop at different rates, and that it is important to recognize both the unity and diversity of EF component processes in studying the development of EF.

  4. Age-Related Decline in Brain and Hepatic Clearance of Amyloid-Beta is Rectified by the Cholinesterase Inhibitors Donepezil and Rivastigmine in Rats.

    PubMed

    Mohamed, Loqman A; Qosa, Hisham; Kaddoumi, Amal

    2015-05-20

    In Alzheimer's disease (AD), accumulation of brain amyloid-β (Aβ) depends on imbalance between production and clearance of Aβ. Several pathways for Aβ clearance have been reported including transport across the blood-brain barrier (BBB) and hepatic clearance. The incidence of AD increases with age and failure of Aβ clearance correlates with AD. The cholinesterase inhibitors (ChEIs) donepezil and rivastigmine are used to ease the symptoms of dementia associated with AD. Besides, both drugs have been reported to provide neuroprotective and disease-modifying effects. Here, we investigated the effect of ChEIs on age-related reduced Aβ clearance. Findings from in vitro and in vivo studies demonstrated donepezil and rivastigmine to enhance (125)I-Aβ40 clearance. Also, the increase in brain and hepatic clearance of (125)I-Aβ40 was more pronounced in aged compared to young rats, and was associated with significant reduction in brain Aβ endogenous levels determined by ELISA. Furthermore, the enhanced clearance was concomitant with up-regulation in the expression of Aβ major transport proteins P-glycoprotein and LRP1. Collectively, our findings that donepezil and rivastigmine enhance Aβ clearance across the BBB and liver are novel and introduce an additional mechanism by which both drugs could affect AD pathology. Thus, optimizing their clinical use could help future drug development by providing new drug targets and possible mechanisms involved in AD pathology.

  5. Expression and function of PDGF-α in columnar epithelial cells of age-related cataracts patients.

    PubMed

    Wei, J; Tang, H; Xu, Z Q; Li, B; Xie, L Q; Xu, G X

    2015-10-27

    We studied the expression and function of platelet-derived growth factor A (PDGF-α) in the lens epithelial cells of cataracts patients. Ninety age-related cataracts patients were recruited in our hospital between January 2012 and January 2014. The expression levels of platelet-derived growth factor receptor (PDGFR) in the anterior capsule of the lens at different degrees of turbidity, and PDGF-α in the aqueous humor were detected. A human lens epithelium cell line was also cultured and studied. To investigate its function, PDGF-α was used to treat a PDGFR-silenced human lens epithelium cell line to observe changes in the proliferation, transfer, and epithelial mesenchymal transition (EMT). The expression of PDGF-α and its receptor increased in patients with more serious cataracts. Lens epithelium cells stimulated by PDGF-α showed greater proliferation and migration. The degree of EMT was also upregulated in cells stimulated by PDGF-α. However, silencing the expression of PDGFR inhibited the effects. The development and severity of age-related cataracts was related to the secretion and expression of PDGF-α. This may be a new therapeutic target for cataracts treatment.

  6. Age-Related Changes in the Functional Network Underlying Specific and General Autobiographical Memory Retrieval: A Pivotal Role for the Anterior Cingulate Cortex

    PubMed Central

    Martinelli, Pénélope; Sperduti, Marco; Devauchelle, Anne-Dominique; Kalenzaga, Sandrine; Gallarda, Thierry; Lion, Stéphanie; Delhommeau, Marion; Anssens, Adèle; Amado, Isabelle; Meder, Jean François; Krebs, Marie-Odile; Oppenheim, Catherine; Piolino, Pascale

    2013-01-01

    Age-related changes in autobiographical memory (AM) recall are characterized by a decline in episodic details, while semantic aspects are spared. This deleterious effect is supposed to be mediated by an inefficient recruitment of executive processes during AM retrieval. To date, contrasting evidence has been reported on the neural underpinning of this decline, and none of the previous studies has directly compared the episodic and semantic aspects of AM in elderly. We asked 20 young and 17 older participants to recall specific and general autobiographical events (i.e., episodic and semantic AM) elicited by personalized cues while recording their brain activity by means of fMRI. At the behavioral level, we confirmed that the richness of episodic AM retrieval is specifically impoverished in aging and that this decline is related to the reduction of executive functions. At the neural level, in both age groups, we showed the recruitment of a large network during episodic AM retrieval encompassing prefrontal, cortical midline and posterior regions, and medial temporal structures, including the hippocampus. This network was very similar, but less extended, during semantic AM retrieval. Nevertheless, a greater activity was evidenced in the dorsal anterior cingulate cortex (dACC) during episodic, compared to semantic AM retrieval in young participants, and a reversed pattern in the elderly. Moreover, activity in dACC during episodic AM retrieval was correlated with inhibition and richness of memories in both groups. Our findings shed light on the direct link between episodic AM retrieval, executive control, and their decline in aging, proposing a possible neuronal signature. They also suggest that increased activity in dACC during semantic AM retrieval in the elderly could be seen as a compensatory mechanism underpinning successful AM performance observed in aging. These results are discussed in the framework of recently proposed models of neural reorganization in aging

  7. Age-Related Changes in BOLD Activation Pattern in Phonemic Fluency Paradigm: An Investigation of Activation, Functional Connectivity and Psychophysiological Interactions

    PubMed Central

    La, Christian; Garcia-Ramos, Camille; Nair, Veena A.; Meier, Timothy B.; Farrar-Edwards, Dorothy; Birn, Rasmus; Meyerand, Mary E.; Prabhakaran, Vivek

    2016-01-01

    Healthy aging is associated with decline of cognitive functions. However, even before those declines become noticeable, the neural architecture underlying those mechanisms has undergone considerable restructuring and reorganization. During performance of a cognitive task, not only have the task-relevant networks demonstrated reorganization with aging, which occurs primarily by recruitment of additional areas to preserve performance, but the task-irrelevant network of the “default-mode” network (DMN), which is normally deactivated during task performance, has also consistently shown reduction of this deactivation with aging. Here, we revisited those age-related changes in task-relevant (i.e., language system) and task-irrelevant (i.e., DMN) systems with a language production paradigm in terms of task-induced activation/deactivation, functional connectivity, and context-dependent correlations between the two systems. Our task fMRI data demonstrated a late increase in cortical recruitment in terms of extent of activation, only observable in our older healthy adult group, when compared to the younger healthy adult group, with recruitment of the contralateral hemisphere, but also other regions from the network previously underutilized. Our middle-aged individuals, when compared to the younger healthy adult group, presented lower levels of activation intensity and connectivity strength, with no recruitment of additional regions, possibly reflecting an initial, uncompensated, network decline. In contrast, the DMN presented a gradual decrease in deactivation intensity and deactivation extent (i.e., low in the middle-aged, and lower in the old) and similar gradual reduction of functional connectivity within the network, with no compensation. The patterns of age-related changes in the task-relevant system and DMN are incongruent with the previously suggested notion of anti-correlation of the two systems. The context-dependent correlation by psycho

  8. The Need for Standardized Assessment of Muscle Quality in Skeletal Muscle Function Deficit and Other Aging-Related Muscle Dysfunctions: A Symposium Report.

    PubMed

    Correa-de-Araujo, Rosaly; Harris-Love, Michael O; Miljkovic, Iva; Fragala, Maren S; Anthony, Brian W; Manini, Todd M

    2017-01-01

    A growing body of scientific literature suggests that not only changes in skeletal muscle mass, but also other factors underpinning muscle quality, play a role in the decline in skeletal muscle function and impaired mobility associated with aging. A symposium on muscle quality and the need for standardized assessment was held on April 28, 2016 at the International Conference on Frailty and Sarcopenia Research in Philadelphia, Pennsylvania. The purpose of this symposium was to provide a venue for basic science and clinical researchers and expert clinicians to discuss muscle quality in the context of skeletal muscle function deficit and other aging-related muscle dysfunctions. The present article provides an expanded introduction concerning the emerging definitions of muscle quality and a potential framework for scientific inquiry within the field. Changes in muscle tissue composition, based on excessive levels of inter- and intra-muscular adipose tissue and intramyocellular lipids, have been found to adversely impact metabolism and peak force generation. However, methods to easily and rapidly assess muscle tissue composition in multiple clinical settings and with minimal patient burden are needed. Diagnostic ultrasound and other assessment methods continue to be developed for characterizing muscle pathology, and enhanced sonography using sensors to provide user feedback and improve reliability is currently the subject of ongoing investigation and development. In addition, measures of relative muscle force such as specific force or grip strength adjusted for body size have been proposed as methods to assess changes in muscle quality. Furthermore, performance-based assessments of muscle power via timed tests of function and body size estimates, are associated with lower extremity muscle strength may be responsive to age-related changes in muscle quality. Future aims include reaching consensus on the definition and standardized assessments of muscle quality, and

  9. The Need for Standardized Assessment of Muscle Quality in Skeletal Muscle Function Deficit and Other Aging-Related Muscle Dysfunctions: A Symposium Report

    PubMed Central

    Correa-de-Araujo, Rosaly; Harris-Love, Michael O.; Miljkovic, Iva; Fragala, Maren S.; Anthony, Brian W.; Manini, Todd M.

    2017-01-01

    A growing body of scientific literature suggests that not only changes in skeletal muscle mass, but also other factors underpinning muscle quality, play a role in the decline in skeletal muscle function and impaired mobility associated with aging. A symposium on muscle quality and the need for standardized assessment was held on April 28, 2016 at the International Conference on Frailty and Sarcopenia Research in Philadelphia, Pennsylvania. The purpose of this symposium was to provide a venue for basic science and clinical researchers and expert clinicians to discuss muscle quality in the context of skeletal muscle function deficit and other aging-related muscle dysfunctions. The present article provides an expanded introduction concerning the emerging definitions of muscle quality and a potential framework for scientific inquiry within the field. Changes in muscle tissue composition, based on excessive levels of inter- and intra-muscular adipose tissue and intramyocellular lipids, have been found to adversely impact metabolism and peak force generation. However, methods to easily and rapidly assess muscle tissue composition in multiple clinical settings and with minimal patient burden are needed. Diagnostic ultrasound and other assessment methods continue to be developed for characterizing muscle pathology, and enhanced sonography using sensors to provide user feedback and improve reliability is currently the subject of ongoing investigation and development. In addition, measures of relative muscle force such as specific force or grip strength adjusted for body size have been proposed as methods to assess changes in muscle quality. Furthermore, performance-based assessments of muscle power via timed tests of function and body size estimates, are associated with lower extremity muscle strength may be responsive to age-related changes in muscle quality. Future aims include reaching consensus on the definition and standardized assessments of muscle quality, and

  10. Reduced release and binding of perforin at the immunological synapse underlies the age-related decline in natural killer cell cytotoxicity.

    PubMed

    Hazeldine, Jon; Hampson, Peter; Lord, Janet M

    2012-10-01

    Physiological aging is accompanied by a marked reduction in natural killer (NK) cell cytotoxicity (NKCC) at the single cell level, but the underlying mechanisms are unknown. To address this issue, we isolated NK cells from healthy young (≤ 35 years) and old (≤ 60 years) subjects and examined the effect of age on events fundamental to the process of NKCC. Simultaneous assessment of NKCC and NK cell-target cell conjugate formation revealed a marked age-associated decline in NK cell killing but comparable conjugate formation, indicating a post-target cell binding defect was responsible for impaired NKCC. Despite a reduction in the proportion of NK cells expressing the activatory receptor NKp46, NK cells from old donors were not hyporesponsive to stimulation, as no age-associated difference was observed in the expression of the early activation marker CD69 following target cell coculture. Furthermore, intracellular levels of the key cytotoxic effector molecules perforin and granzyme B, and the fusion of secretory lysosomes with the NK cell membrane were also similar between the two groups. However, when we examined the binding of the pore-forming protein perforin to the surface of its target cell, an event that correlated strongly with target cell lysis, we found the percentage of perforin positive target cells was lower following coculture with NK cells from old subjects. Underlying this reduction in binding was an age-associated impairment in perforin secretion, which was associated with defective polarization of lytic granules towards the immunological synapse. We propose that reduced perforin secretion underlies the reduction in NKCC that accompanies physiological aging.

  11. A phytochemical-rich diet may explain the absence of age-related decline in visual acuity of Amazonian hunter-gatherers in Ecuador.

    PubMed

    London, Douglas S; Beezhold, Bonnie

    2015-02-01

    Myopia is absent in undisturbed hunter-gatherers but ubiquitous in modern populations. The link between dietary phytochemicals and eye health is well established, although transition away from a wild diet has reduced phytochemical variety. We hypothesized that when larger quantities and greater variety of wild, seasonal phytochemicals are consumed in a food system, there will be a reduced prevalence of degenerative-based eye disease as measured by visual acuity. We compared food systems and visual acuity across isolated Amazonian Kawymeno Waorani hunter-gatherers and neighboring Kichwa subsistence agrarians, using dietary surveys, dietary pattern observation, and Snellen Illiterate E visual acuity examinations. Hunter-gatherers consumed more food species (130 vs. 63) and more wild plants (80 vs. 4) including 76 wild fruits, thereby obtaining larger variety and quantity of phytochemicals than agrarians. Visual acuity was inversely related to age only in agrarians (r = -.846, P < .001). As hypothesized, when stratified by age (<40 and ≥ 40 years), Mann-Whitney U tests revealed that hunter-gatherers maintained high visual acuity throughout life, whereas agrarian visual acuity declined (P values < .001); visual acuity of younger participants was high across the board, however, did not differ between groups (P > .05). This unusual absence of juvenile-onset vision problems may be related to local, organic, whole food diets of subsistence food systems isolated from modern food production. Our results suggest that intake of a wider variety of plant foods supplying necessary phytochemicals for eye health may help maintain visual acuity and prevent degenerative eye conditions as humans age.

  12. Functional connectivity differences in autism during face and car recognition: underconnectivity and atypical age-related changes.

    PubMed

    Lynn, Andrew C; Padmanabhan, Aarthi; Simmonds, Daniel; Foran, William; Hallquist, Michael N; Luna, Beatriz; O'Hearn, Kirsten

    2016-10-16

    Face recognition abilities improve between adolescence and adulthood over typical development (TD), but plateau in autism, leading to increasing face recognition deficits in autism later in life. Developmental differences between autism and TD may reflect changes between neural systems involved in the development of face encoding and recognition. Here, we focused on whole-brain connectivity with the fusiform face area (FFA), a well-established face-preferential brain region. Older children, adolescents, and adults with and without autism completed the Cambridge Face Memory Test, and a matched car memory test, during fMRI scanning. We then examined task-based functional connectivity between the FFA and the rest of the brain, comparing autism and TD groups during encoding and recognition of face and car stimuli. The autism group exhibited underconnectivity, relative to the TD group, between the FFA and frontal and primary visual cortices, independent of age. Underconnectivity with the medial and rostral lateral prefrontal cortex was face-specific during encoding and recognition, respectively. Conversely, underconnectivity with the L orbitofrontal cortex was evident for both face and car encoding. Atypical age-related changes in connectivity emerged between the FFA and the R temporoparietal junction, and R dorsal striatum for face stimuli only. Similar differences in age-related changes in autism emerged for FFA connectivity with the amygdala across both face and car recognition. Thus, underconnectivity and atypical development of functional connectivity may lead to a less optimal face-processing network in the context of increasing general and social cognitive deficits in autism.

  13. 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.

  14. [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.

  15. Investigation of age-related changes in brain activity during the divalent task-switching paradigm using functional MRI.

    PubMed

    Kunimi, Mitsunobu; Kiyama, Sachiko; Nakai, Toshiharu

    2016-02-01

    This study compared the brain activation of young and older subjects during the use of the task-switching paradigm (TSP) at various task speeds to examine the relationship between task load and brain activation. Specifically, it attempted to examine whether the task load-dependent BOLD response gradient is a useful tool for functional magnetic resonance imaging-based assessments of age-related changes in cognitive function. We predicted that the extent of the activation of the brain regions responsible for task-set reconfiguration and the inhibition of task switching functions induced during the performance of a TSP-based task would vary according to age. Task difficulty was controlled by altering the inter-stimulus interval. Although similar brain regions were activated in both age groups, significant differences in the extent of the activation were detected between the young and older groups. In particular, some regions were activated in the older group, but not the young group. This study indicated that TSP-based task performance-induced activation of the brain regions linked to executive function increases with age and that the degree and pattern of such activation depend on the content and difficulty of the task being performed. This indicates that the age- and task difficulty-dependent augmentation of brain activation varies between brain regions.

  16. The Use of Microperimetry to Detect Functional Progression in Non-Neovascular Age-Related Macular Degeneration: A Systematic Review.

    PubMed

    Wong, Evan N; Chew, Avenell L; Morgan, William H; Patel, Praveen J; Chen, Fred K

    2017-01-01

    We reviewed the current literature on the ability of microperimetry to detect non-neovascular age-related macular degeneration (AMD) disease progression. The index test was retinal sensitivity measurement assessed by microperimetry and comparators were other functional measures (best-corrected and low-luminance visual acuities, and fixation stability) and structural parameters [retinal thickness, choroidal thickness, and area of geographic atrophy (GA) determined by color fundus photographs, short-wave or near-infrared fundus autofluorescence]. The reference standard was area of GA. The literature search was conducted in January 2016 and included MEDLINE, EMBASE, the Cochrane Library, Biosis, Science Citation Index, ProQuest Health and Medicine, CINAHL, and Highwire Press. We included 6 studies that enrolled 41 eyes with intermediate AMD (from a single study) and 80 eyes with GA secondary to AMD. Retinal sensitivity measured by microperimetry was the only functional measure that consistently detected progression in each cohort. Insufficient reported data precluded meta-analysis. Various microperimetry parameters were used to assess cohort-level change in retinal sensitivity, but the methods of analysis have yet to mature in complexity in comparison with established glaucoma field progression analysis. Microperimetry-assessed retinal sensitivity measurement may be more sensitive in detecting progression than other functional measures in non-neovascular AMD. However, the lack of standardized testing protocol and methods of progression analysis hindered comparison. Harmonization of testing protocol and development of more robust methods of analyzing raw microperimetric data will facilitate clinical implementation of this valuable retinal assessment tool.

  17. Positive long-term effects of Pilates exercise on the aged-related decline in balance and strength in older, community-dwelling men and women.

    PubMed

    Bird, Marie-Louise; Fell, James

    2014-07-01

    This study investigated the effect of Pilates exercise on physical fall risk factors 12 months after an initial 5-week Pilates intervention. The authors hypothesized that ongoing Pilates participation would have a positive effect on physical fall risk factors in those who continued with Pilates exercise compared with those who ceased. Thirty older ambulatory adults (M = 69 years, SD = 7) participated in Pilates classes for 5 weeks with testing preintevention (Time 1 [T1]) and postintervention (Time 2 [T2]) and 12 months later (Time 3 [T3]). Balance and leg strength were compared using a 2-way analysis of variance with repeated measures. Postural sway, dynamic balance, and function improvements evident after the initial Pilates training (T1-T2) were maintained at T3 (p < .01). Significant differences existed at T3 for dynamic balance and strength between participants who continued performing Pilates (n = 14) and those who had ceased. Balance improvements after a short Pilates intervention were maintained 1 year later in all participants, with increased benefits from ongoing participation.

  18. Age-related disorders of sleep and motor control in the rat models of functionally distinct cholinergic neuropathology.

    PubMed

    Ciric, Jelena; Lazic, Katarina; Petrovic, Jelena; Kalauzi, Aleksandar; Saponjic, Jasna

    2016-03-15

    We studied the impact of aging during sleep in the rat models of Alzheimer's (AD) and Parkinson's (PD) disease cholinergic neuropathology to determine the possible different and earlier onset of age-related sleep disorder during the neurodegenerative diseases vs. healthy aging. We used the bilateral nucleus basalis (NB) and pedunculopontine tegmental nucleus (PPT) lesioned rats as the in vivo models of functionally distinct cholinergic neuropathology, and we followed the impact of aging on sleep architecture, the electroencephalographic (EEG) microstructure and motor control across sleep/wake states. Our results have shown for the first time that the earliest signs of aging during distinct cholinergic neuropathology were expressed through a different and topographically specific EEG microstructure during rapid eye movement sleep (REM). EEG delta amplitude attenuation within the sensorimotor cortex (SMCx) during REM was the earliest sign of aging in the NB lesion. EEG sigma amplitude augmentation within the motor cortex (MCx) during REM was the earliest sign of aging in the PPT lesion. In addition, aging was differently expressed through the SMCx drive alterations, but it was commonly expressed through the MCx drive alterations during all sleep/wake states. Our study provided evidence of distinct REM sleep disorders and sleep state related cortical drives as the signs of aging onset during functionally distinct cholinergic neuropathologies (NB lesion vs. PPT lesion).

  19. Age-related functional recruitment for famous name recognition: an event-related fMRI study.

    PubMed

    Nielson, Kristy A; Douville, Kelli L; Seidenberg, Michael; Woodard, John L; Miller, Sarah K; Franczak, Malgorzata; Antuono, Piero; Rao, Stephen M

    2006-10-01

    Recent neuroimaging research shows that older adults exhibit recruitment, or increased activation on various cognitive tasks. The current study evaluated whether a similar pattern also occurs in semantic memory by evaluating age-related differences during recognition of Recent (since the 1990s) and Enduring (1950s to present) famous names. Fifteen healthy older and 15 healthy younger adults performed the name recognition task with a high and comparable degree of accuracy, although older adults had slower reaction time in response to Recent famous names. Event-related functional MRI showed extensive networks of activation in the two groups including posterior cingulate, right hippocampus, temporal lobe and left prefrontal regions. The Recent condition produced more extensive activation than the Enduring condition. Older adults had more extensive and greater magnitude of activation in 15 of 20 regions, particularly for the Recent condition (15 of 15; 7 of 15 also differed for Enduring); young adults did not show greater activation magnitude in any region. There were no group differences for non-famous names, indicating that age differences are task-specific. The results support and extend the existing literature to semantic memory tasks, indicating that older adult brains use functional recruitment to support task performance, even when task performance accuracy is high.

  20. 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…

  1. Membrane lipid rafts and neurobiology: age-related changes in membrane lipids and loss of neuronal function.

    PubMed

    Egawa, Junji; Pearn, Matthew L; Lemkuil, Brian P; Patel, Piyush M; Head, Brian P

    2016-08-15

    A better understanding of the cellular physiological role that plasma membrane lipids, fatty acids and sterols play in various cellular systems may yield more insight into how cellular and whole organ function is altered during the ageing process. Membrane lipid rafts (MLRs) within the plasma membrane of most cells serve as key organizers of intracellular signalling and tethering points of cytoskeletal components. MLRs are plasmalemmal microdomains enriched in sphingolipids, cholesterol and scaffolding proteins; they serve as a platform for signal transduction, cytoskeletal organization and vesicular trafficking. Within MLRs are the scaffolding and cholesterol binding proteins named caveolin (Cav). Cavs not only organize a multitude of receptors including neurotransmitter receptors (NMDA and AMPA receptors), signalling proteins that regulate the production of cAMP (G protein-coupled receptors, adenylyl cyclases, phosphodiesterases (PDEs)), and receptor tyrosine kinases involved in growth (Trk), but also interact with components that modulate actin and tubulin cytoskeletal dynamics (e.g. RhoGTPases and actin binding proteins). MLRs are essential for the regulation of the physiology of organs such as the brain, and age-related loss of cholesterol from the plasma membrane leads to loss of MLRs, decreased presynaptic vesicle fusion, and changes in neurotransmitter release, all of which contribute to different forms of neurodegeneration. Thus, MLRs provide an active membrane domain that tethers and reorganizes the cytoskeletal machinery necessary for membrane and cellular repair, and genetic interventions that restore MLRs to normal cellular levels may be exploited as potential therapeutic means to reverse the ageing and neurodegenerative processes.

  2. Association of Serum Ferritin and Kidney Function with Age-Related Macular Degeneration in the General Population

    PubMed Central

    Oh, Il Hwan; Choi, Eun Young; Park, Joon-Sung; Lee, Chang Hwa

    2016-01-01

    Ferritin is considered to be a marker of the body’s iron stores and has a potential relationship with the systemic manifestations of inflammatory reactions. Data on the association between increased levels of serum ferritin and ocular problems are limited, particularly in relation to age-related macular degeneration (AMD). Serum ferritin levels, as a possible clinical parameter for predicting AMD, were analyzed in anthropometric, biochemical, and ophthalmologic data from a nation-wide, population-based, case-control study (KNHNES IV and V). All native Koreans aged ≥ 20 years and who had no medical illness were eligible to participate. Among them, 2.9% had AMD, and its prevalence was found to increase in the higher ferritin quintile groups (Ptrend < 0.0001). In multiple linear regression analysis, serum ferritin level was closely related to conventional risk factors for AMD. Comparison of early AMD with a control group showed that serum ferritin levels were closely associated with AMD (OR = 1.004, 95% CI = 1.002–1.006), and further adjustment for age, gender, serum iron, and kidney function did not reduce this association (OR = 1.003, 95% CI = 1.001–1.006). Furthermore, the relationship between ferritin quintile and early AMD was dose-dependent. Thus, an increased level of serum ferritin in a healthy person may be a useful indicator of neurodegenerative change in the macula. A large population-based prospective clinical study is needed to confirm these findings. PMID:27096155

  3. Visual Function and Its Relationship with Severity of Early, and Activity of Neovascular, Age-Related Macular Degeneration

    PubMed Central

    Loughman, James; Sabour-Pickett, Sarah; Nolan, John M.; Klein, Barbara; Klein, Ronald; Beatty, Stephen

    2017-01-01

    Purpose To investigate the relationship between visual function and severity of early age-related macular degeneration (AMD) and activity of neovascular (nv-) AMD. Methods The following data was collected from 66 eyes of 66 subjects with early AMD and 47 eyes of 47 subjects with active nv-AMD: corrected distance visual acuity (CDVA); contrast sensitivity (CS); glare disability (GD); and retinotopic ocular sensitivity (ROS) of the central 5° of the retina, by microperimetry. Fundus photographic grading of early AMD was performed in a masked fashion. Mean foveal thickness (MFT) was measured by spectral domain optical coherence tomography in patients with nv-AMD. Results In subjects with early AMD, there was an inverse and statistically significant relationship between measures of ROS within the central 5° of retina (including fixation) and severity of early AMD (p=0.01). In eyes with active nv-AMD, an inverse and statistically significant relationship was observed between measures of MFT and measures of ROS at the central 5° of retina (r=-0.34; p=0.02). No other measures, including CDVA, were significantly related to severity of early AMD, or to MFT in nv-AMD. Conclusion Although ROS was cross-sectionally associated with disease severity, and inversely related to MFT, an important determinant of need-to-treat in cases of nv-AMD, further research is required to determine the appropriateness of ROS for monitoring early and active neovascular forms of this disease.

  4. A prospective study of visual function and quality of life following PDT in patients with wet age related macular degeneration

    PubMed Central

    Armbrecht, A M; Aspinall, P A; Dhillon, B

    2004-01-01

    Aims: (1) A prospective study to assess visual function measures and quality of life (QoL) in patients with wet age related macular degeneration (AMD) treated with photodynamic therapy (PDT). (2) To assess if PDT prevents severe visual loss (loss of six or more lines of distance visual acuity) in the treated eye. Methods: 48 of 51 recruited patients with predominantly classic subfoveal choroidal neovascularisation (CNV) secondary AMD who were treated with PDT were followed up for 1 year. Assessment included distance and near visual acuity, contrast sensitivity, vision related quality of life and fluorescein angiography. Photodynamic therapy using Visudyne was carried out according to standard protocol. Patients were followed up every 3 months and treatment repeated if there was significant leakage from CNV. Results: At the 12 month follow up, 71% (n = 34) of the patients lost less than three lines of best corrected distance visual acuity. Although there were significant decreases in some of the QoL items tested, patients were significantly less anxious and more independent outdoors at the 12 month follow up. Conclusion: This study is in keeping with published literature with PDT preventing severe visual loss in two thirds of treated patients with predominantly classic CNV. PMID:15377549

  5. Age-Related Differences in Functional Nodes of the Brain Cortex – A High Model Order Group ICA Study

    PubMed Central

    Littow, Harri; Elseoud, Ahmed Abou; Haapea, Marianne; Isohanni, Matti; Moilanen, Irma; Mankinen, Katariina; Nikkinen, Juha; Rahko, Jukka; Rantala, Heikki; Remes, Jukka; Starck, Tuomo; Tervonen, Osmo; Veijola, Juha; Beckmann, Christian; Kiviniemi, Vesa J.

    2010-01-01

    Functional MRI measured with blood oxygen dependent (BOLD) contrast in the absence of intermittent tasks reflects spontaneous activity of so-called resting state networks (RSN) of the brain. Group level independent component analysis (ICA) of BOLD data can separate the human brain cortex into 42 independent RSNs. In this study we evaluated age-related effects from primary motor and sensory, and, higher level control RSNs. One hundred sixty-eight healthy subjects were scanned and divided into three groups: 55 adolescents (ADO, 13.2 ± 2.4 years), 59 young adults (YA, 22.2 ± 0.6 years), and 54 older adults (OA, 42.7 ± 0.5 years), all with normal IQ. High model order group probabilistic ICA components (70) were calculated and dual-regression analysis was used to compare 21 RSN's spatial differences between groups. The power spectra were derived from individual ICA mixing matrix time series of the group analyses for frequency domain analysis. We show that primary sensory and motor networks tend to alter more in younger age groups, whereas associative and higher level cognitive networks consolidate and re-arrange until older adulthood. The change has a common trend: both spatial extent and the low frequency power of the RSN's reduce with increasing age. We interpret these result as a sign of normal pruning via focusing of activity to less distributed local hubs. PMID:20953235

  6. Quantitative assessment of age-related macular degeneration using parametric modeling of the leakage transfer function: preliminary results.

    PubMed

    Eldeeb, Safaa M; Abdelmoula, Walid M; Shah, Syed M; Fahmy, Ahmed S

    2012-01-01

    Age-related macular degeneration (AMD) is a major cause of blindness and visual impairment in older adults. The wet form of the disease is characterized by abnormal blood vessels forming a choroidal neovascular membrane (CNV), that result in destruction of normal architecture of the retina. Current evaluation and follow up of wet AMD include subjective evaluation of Fluorescein Angiograms (FA) to determine the activity of the lesion and monitor the progression or regression of the disease. However, this subjective evaluation prevents accurate monitoring of the disease progression or regression in response to a pharmacologic agent. In this work, we present a method that allows objective assessment of the activity of a CNV lesion which can be statistically compared across different patient and time points. The method is based on a hypothesis that the discrepancy in the time-intensity signals among the diseased and normal retinal areas are due to an implicit transfer function whose parameters can be used to characterize the retina. The method begins with parametric modeling of the temporal variation of the lesion and background intensities. Then, the values of the model parameters are used to evaluate the change in the activity of the disease. Preliminary results on five datasets show that the calculated parameters are highly correlated with the Visual Acuity (VA) of the patients.

  7. Age-related changes in natural killer cell repertoires: impact on NK cell function and immune surveillance.

    PubMed

    Manser, Angela R; Uhrberg, Markus

    2016-04-01

    A key feature of human natural killer (NK) cells, which enables efficient recognition of infected and malignant target cells, is the expression of HLA class I-specific receptors of the KIR and NKG2 gene families. Cell-to-cell variability in receptor expression leads to the formation of complex NK cell repertoires. As outlined here, NK cells go through major changes from newborns to adults characterized by downregulation of the inhibitory NKG2A receptor and concomitant upregulation of KIR family members. This process is completed in young adults, and in the majority of individuals, KIR/NKG2A repertoires remain remarkably stable until old age. Nonetheless, age-related factors have the potential to majorly influence the complexity of NK cell repertoires: Firstly infection with HCMV is associated with major clonal expansions of terminally differentiated NKG2C- and KIR-expressing NK cells in certain individuals. Secondly, ineffective hematopoiesis can lead to immature and less diversified NK cell repertoires as observed in myelodysplastic syndrome (MDS), a malignant disease of the elderly. Thus, whereas in the majority of elderly the NK cell compartment appears to be highly stable in terms of function and phenotype, in a minority of subjects a breakdown of NK cell repertoire diversity is observed that might influence immune surveillance and healthy aging.

  8. Functional and structural brain modifications induced by oculomotor training in patients with age-related macular degeneration.

    PubMed

    Rosengarth, Katharina; Keck, Ingo; Brandl-Rühle, Sabine; Frolo, Jozef; Hufendiek, Karsten; Greenlee, Mark W; Plank, Tina

    2013-01-01

    Patients with age-related macular degeneration (AMD) are reliant on their peripheral visual field. Oculomotor training can help them to find the best area on intact peripheral retina and to efficiently stabilize eccentric fixation. In this study, nine patients with AMD were trained over a period of 6 months using oculomotor training protocols to improve fixation stability. They were followed over an additional period of 6 months, where they completed an auditory memory training as a sham training. In this cross-over design five patients started with the sham training and four with the oculomotor training. Seven healthy age-matched subjects, who did not take part in any training procedure, served as controls. During the 6 months of training the AMD subjects and the control group took part in three functional and structural magnetic resonance imaging (MRI) sessions to assess training-related changes in the brain function and structure. The sham-training phase was accompanied by two more fMRI measurements, resulting in five MRI sessions at intervals of 3 months for all participants. Despite substantial variability in the training effects, on average, AMD patients benefited from the training measurements as indexed by significant improvements in their fixation stability, visual acuity, and reading speed. The patients showed a significant positive correlation between brain activation changes and improvements in fixation stability in the visual cortex during training. These correlations were less pronounced on the long-term after training had ceased. We also found a significant increase in gray and white matter in the posterior cerebellum after training in the patient group. Our results show that functional and structural brain changes can be associated, at least on the short-term, with benefits of oculomotor and/or reading training in patients with central scotomata resulting from AMD.

  9. Functional and structural brain modifications induced by oculomotor training in patients with age-related macular degeneration

    PubMed Central

    Rosengarth, Katharina; Keck, Ingo; Brandl-Rühle, Sabine; Frolo, Jozef; Hufendiek, Karsten; Greenlee, Mark W.; Plank, Tina

    2013-01-01

    Patients with age-related macular degeneration (AMD) are reliant on their peripheral visual field. Oculomotor training can help them to find the best area on intact peripheral retina and to efficiently stabilize eccentric fixation. In this study, nine patients with AMD were trained over a period of 6 months using oculomotor training protocols to improve fixation stability. They were followed over an additional period of 6 months, where they completed an auditory memory training as a sham training. In this cross-over design five patients started with the sham training and four with the oculomotor training. Seven healthy age-matched subjects, who did not take part in any training procedure, served as controls. During the 6 months of training the AMD subjects and the control group took part in three functional and structural magnetic resonance imaging (MRI) sessions to assess training-related changes in the brain function and structure. The sham-training phase was accompanied by two more fMRI measurements, resulting in five MRI sessions at intervals of 3 months for all participants. Despite substantial variability in the training effects, on average, AMD patients benefited from the training measurements as indexed by significant improvements in their fixation stability, visual acuity, and reading speed. The patients showed a significant positive correlation between brain activation changes and improvements in fixation stability in the visual cortex during training. These correlations were less pronounced on the long-term after training had ceased. We also found a significant increase in gray and white matter in the posterior cerebellum after training in the patient group. Our results show that functional and structural brain changes can be associated, at least on the short-term, with benefits of oculomotor and/or reading training in patients with central scotomata resulting from AMD. PMID:23882237

  10. The association of geographic atrophy and decreased renal function in patients with age-related macular degeneration.

    PubMed

    Leisy, H B; Rastogi, A; Guevara, G; Ahmad, M; Smith, R T

    2017-01-01

    PurposeThe purpose of the study was to investigate the association between area and presence of geographic atrophy (GA) and renal function, as measured by glomerular filtration rate (GFR).Patients and methodsWe retrospectively identified patients aged 50-90 years who were assigned an ICD-9 diagnosis code for age-related macular generation (AMD) between January 2012 and January 2016. Patients met inclusion criteria if they had at least one macular spectral domain optical coherence tomography volume scan, one provider note, and one GFR value in the electronic medical record. Images were evaluated for the presence of GA, area of GA, drusen, and subretinal drusenoid deposits (SDD) and for subfoveal choroidal thickness (CTh) by standard criteria. Imaging findings were correlated with the most recent GFR from the patient's chart.ResultsWe identified 107 patients who met our inclusion criteria (mean age=74 years, range 50-90 years). Overall, we found a significant correlation between the presence of GA and reduced GFR (P=0.002), which was maintained even after accounting for age and other confounders. No association between GFR and GA area was found. CTh was significantly lower in patients with GA (P=0.038) and those with decreased GFR (P=0.004). Within the SDD-positive population, GA was associated with reduced GFR (P=0.007) but only trended toward significance after controlling for age.ConclusionOur study findings demonstrate an association between impaired renal function and the presence, but not area, of GA within an AMD population. These findings may shed light on common pathogenic mechanisms for these two diseases.

  11. Age-related changes in cerebellar and hypothalamic function accompany non-microglial immune gene expression, altered synapse organization, and excitatory amino acid neurotransmission deficits

    PubMed Central

    Bonasera, Stephen J.; Arikkath, Jyothi; Boska, Michael D.; Chaudoin, Tammy R.; DeKorver, Nicholas W.; Goulding, Evan H.; Hoke, Traci A.; Mojtahedzedah, Vahid; Reyelts, Crystal D.; Sajja, Balasrinivasa; Schenk, A. Katrin; Tecott, Laurence H.; Volden, Tiffany A.

    2016-01-01

    We describe age-related molecular and neuronal changes that disrupt mobility or energy balance based on brain region and genetic background. Compared to young mice, aged C57BL/6 mice exhibit marked locomotor (but not energy balance) impairments. In contrast, aged BALB mice exhibit marked energy balance (but not locomotor) impairments. Age-related changes in cerebellar or hypothalamic gene expression accompany these phenotypes. Aging evokes upregulation of immune pattern recognition receptors and cell adhesion molecules. However, these changes do not localize to microglia, the major CNS immunocyte. Consistent with a neuronal role, there is a marked age-related increase in excitatory synapses over the cerebellum and hypothalamus. Functional imaging of these regions is consistent with age-related synaptic impairments. These studies suggest that aging reactivates a developmental program employed during embryogenesis where immune molecules guide synapse formation and pruning. Renewed activity in this program may disrupt excitatory neurotransmission, causing significant behavioral deficits. PMID:27689748

  12. Central Determinants of Age-Related Declines in Motor Function (Annals of the New York Academy of Sciences. Volume 515)

    DTIC Science & Technology

    1988-01-18

    treatment - for example, with nootropics, as wa. demonstrated with piracetam and pyritinol. " " When motor tasks are performed under more strenuous...5-hydroxytryptophan, clonazepam, valproate, lisuride, piracetam Tics: clonidine, neuroleptics, tetrabenazine, clonazepam Restlessness & Akathisia...models of aging and dementia, little is known of its pharmacological actions in improving cognitive performance." Piracetam , a com- pound with a number

  13. Functional consequences of age-related morphologic changes to pyramidal neurons of the rhesus monkey prefrontal cortex.

    PubMed

    Coskren, Patrick J; Luebke, Jennifer I; Kabaso, Doron; Wearne, Susan L; Yadav, Aniruddha; Rumbell, Timothy; Hof, Patrick R; Weaver, Christina M

    2015-04-01

    Layer 3 (L3) pyramidal neurons in the lateral prefrontal cortex (LPFC) of rhesus monkeys exhibit dendritic regression, spine loss and increased action potential (AP) firing rates during normal aging. The relationship between these structural and functional alterations, if any, is unknown. To address this issue, morphological and electrophysiological properties of L3 LPFC pyramidal neurons from young and aged rhesus monkeys were characterized using in vitro whole-cell patch-clamp recordings and high-resolution digital reconstruction of neurons. Consistent with our previous studies, aged neurons exhibited significantly reduced dendritic arbor length and spine density, as well as increased input resistance and firing rates. Computational models using the digital reconstructions with Hodgkin-Huxley and AMPA channels allowed us to assess relationships between demonstrated age-related changes and to predict physiological changes that have not yet been tested empirically. For example, the models predict that in both backpropagating APs and excitatory postsynaptic currents (EPSCs), attenuation is lower in aged versus young neurons. Importantly, when identical densities of passive parameters and voltage- and calcium-gated conductances were used in young and aged model neurons, neither input resistance nor firing rates differed between the two age groups. Tuning passive parameters for each model predicted significantly higher membrane resistance (R m ) in aged versus young neurons. This R m increase alone did not account for increased firing rates in aged models, but coupling these R m values with subtle differences in morphology and membrane capacitance did. The predicted differences in passive parameters (or parameters with similar effects) are mathematically plausible, but must be tested empirically.

  14. 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

  15. Evaluating Functional Decline in Patients with Multiple Sclerosis

    ERIC Educational Resources Information Center

    Rosenblum, Sara; Weiss, Patrice L.

    2010-01-01

    Multiple Sclerosis (MS) is a disease with a wide-ranging impact on functional status. The aim of the study was to examine the added value of simultaneously evaluating fatigue, personal ADL and handwriting performance as indicators for functional decline among patients with MS. Participants were 50 outpatients with MS and 26 matched healthy…

  16. 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.

  17. 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…

  18. Targeted Vision Function Goals and Use of Vision Resources in Ophthalmology Patients with Age-Related Macular Degeneration and Comorbid Depressive Symptoms

    ERIC Educational Resources Information Center

    Casten, Robin; Rovner, Barry W.; Fontenot, Joseph L.

    2016-01-01

    Introduction: This study characterizes self-reported functional vision goals and the use of low vision resources (for example, services and devices) in ophthalmology clinic patients with age-related macular degeneration (AMD) and comorbid depressive symptoms. Methods: From July 2009 to February 2013, we assessed 188 consecutive patients (age 65+;…

  19. Decline in renal functioning is associated with longitudinal decline in global cognitive functioning, abstract reasoning and verbal memory

    PubMed Central

    Davey, Adam; Elias, Merrill F.; Robbins, Michael A.; Seliger, Stephen L.; Dore, Gregory A.

    2013-01-01

    Background Decreased estimated glomerular filtration rate (eGFR) and higher serum creatinine (sCR) levels have been associated with longitudinal decline in global mental status measures. Longitudinal data describing change in multiple domains of cognitive functioning are needed in order to determine which specific abilities are most affected in individuals with impaired renal function. Methods We conducted a 5-year longitudinal study with 590 community-living individuals (mean age 62.1 years, 60.2% female, 93.2% white, 11.4% with diabetes mellitus, mean eGFR 78.4 mL/min/1.73 m²) free from dementia, acute stroke and end-stage renal disease. To measure longitudinal change-over-time, cognitive performance measures were regressed on eGFR adjusting for baseline eGFR and cognitive performance, comorbidity and vascular risk factors. Outcome measures were scores from 17 separate tests of cognitive abilities that were used to index 5 theoretically relevant domains: verbal episodic memory, visual-spatial organization and memory, scanning and tracking, working memory and similarities (abstract reasoning). Results Declines in eGFR values were associated with cognitive declines, when adjusted for eGFR and cognitive function scores at baseline. Change in renal functioning over time was related to change observed in global cognitive ability [b = 0.21SD decline per unit ln(eGFR), 95% CI: 0.04–0.38, P = .018], verbal episodic memory [b = 0.28 SD decline per unit ln(eGFR), 95% CI: 0.02–0.54, P = 0.038] and abstract reasoning [b = 0.36 SD decline per unit ln(eGFR), 95% CI: 0.04–0.67, P = 0.025]. Decline in cognitive functioning in association with declining renal functioning was observed despite statistical adjustment for demographic variables and CVD risk factors and the exclusion of persons with dementia or a history of acute stroke. Conclusions Early detection of mild to moderate kidney disease is an important public health concern with regard to cognitive decline. PMID

  20. Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome1

    PubMed Central

    Chang, Qing; Gold, Paul E.

    2008-01-01

    Spatial working memory and the ability of a cholinesterase inhibitor to enhance memory were assessed at 4, 10, and 16 months of ages in control and Ts65Dn mice, a partial trisomy model of Down syndrome, with possibly significant relationships to Alzheimer’s Disease as well. In addition, ACh release during memory testing was measured in samples collected from the hippocampus using in vivo microdialysis at 4, 10, and 22–25 months of age. When tested on a four-arm spontaneous alternation task, the Ts65Dn mice exhibited impaired memory scores at both 4 and 10 months. At 16 months, control performance had declined toward that of the Ts65Dn mice and the difference in scores across genotypes was not significant. Physostigmine (50 μg/kg) fully reversed memory deficits in the Ts65Dn mice in the 4-month-old group but not in older mice. Ts65Dn and control mice exhibited comparable baseline levels of ACh release at all ages tested; these levels did not decline significantly across age in either genotype. ACh release increased significantly during alternation testing only in the young Ts65Dn and control mice. However, the increase in ACh release during alternation testing was significantly greater in control than Ts65Dn mice at this age. The controls exhibited a significant age-related decline in the testing-related increase in ACh release. With only a small increase during testing in young Ts65Dn mice, the age-related decline in responsiveness of ACh release to testing was not significant in these mice. Overall, these results suggest that diminished responsiveness of ACh release in the hippocampus to behavioral testing may contribute memory impairments in Ts65Dn mice. PMID:17644430

  1. Declining resilience of ecosystem functions under biodiversity loss.

    PubMed

    Oliver, Tom H; Isaac, Nick J B; August, Tom A; Woodcock, Ben A; Roy, David B; Bullock, James M

    2015-12-08

    The composition of species communities is changing rapidly through drivers such as habitat loss and climate change, with potentially serious consequences for the resilience of ecosystem functions on which humans depend. To assess such changes in resilience, we analyse trends in the frequency of species in Great Britain that provide key ecosystem functions--specifically decomposition, carbon sequestration, pollination, pest control and cultural values. For 4,424 species over four decades, there have been significant net declines among animal species that provide pollination, pest control and cultural values. Groups providing decomposition and carbon sequestration remain relatively stable, as fewer species are in decline and these are offset by large numbers of new arrivals into Great Britain. While there is general concern about degradation of a wide range of ecosystem functions, our results suggest actions should focus on particular functions for which there is evidence of substantial erosion of their resilience.

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

    ERIC Educational Resources Information Center

    Bender, Andrew R.; Raz, Naftali

    2012-01-01

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

  3. Ear length and kidney function decline after kidney donation.

    PubMed

    Katavetin, Pisut; Watanatorn, Salin; Townamchai, Natavudh; Avihingsanon, Yingyos; Praditpornsilpa, Kearkiat

    2016-11-01

    The preservation of kidney function after kidney donation depends on the kidney reserve - the potential of the remaining kidney to boost their function after loss of the other kidney. In Traditional Chinese Medicine, size and shape of the external ears are examined to evaluate the person's kidney health. We hypothesized that ear size might be a practical yet overlooked marker of kidney reserve. Fifty kidney transplantation donors were participated in this study. The length and width of both ears of all participants were measured during one of the post-donation visits. Pre-donation serum creatinine and post-donation serum creatinine as well as other relevant parameters (age, sex, weight, height, etc.) of the participants were extracted from medical records. The estimated GFR was calculated from serum creatinine, age and sex using the CKD-EPI equation. Ear length negatively associated with %GFR decline after kidney donation. For every 1 cm increase in ear length, it was associated with 5.7% less GFR decline after kidney donation (95% Confidence Interval 0.2 to 11.3, P = 0.04). Ear width, as well as age, sex, body weight, height, body mass index, and pre-donation eGFR did not significantly associate with the GFR decline. Our findings support the notion of Traditional Chinese Medicine that ear morphology may be associated with kidney health and suggest that ear length might be a useful predictor of kidney function decline after kidney donation.

  4. 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.

  5. Declining resilience of ecosystem functions under biodiversity loss

    PubMed Central

    Oliver, Tom H.; Isaac, Nick J. B.; August, Tom A.; Woodcock, Ben A.; Roy, David B.; Bullock, James M.

    2015-01-01

    The composition of species communities is changing rapidly through drivers such as habitat loss and climate change, with potentially serious consequences for the resilience of ecosystem functions on which humans depend. To assess such changes in resilience, we analyse trends in the frequency of species in Great Britain that provide key ecosystem functions—specifically decomposition, carbon sequestration, pollination, pest control and cultural values. For 4,424 species over four decades, there have been significant net declines among animal species that provide pollination, pest control and cultural values. Groups providing decomposition and carbon sequestration remain relatively stable, as fewer species are in decline and these are offset by large numbers of new arrivals into Great Britain. While there is general concern about degradation of a wide range of ecosystem functions, our results suggest actions should focus on particular functions for which there is evidence of substantial erosion of their resilience. PMID:26646209

  6. Loss and gain of Drosophila TDP-43 impair synaptic efficacy and motor control leading to age-related neurodegeneration by loss-of-function phenotypes

    PubMed Central

    Diaper, Danielle C.; Adachi, Yoshitsugu; Sutcliffe, Ben; Humphrey, Dickon M.; Elliott, Christopher J.H.; Stepto, Alan; Ludlow, Zoe N.; Vanden Broeck, Lies; Callaerts, Patrick; Dermaut, Bart; Al-Chalabi, Ammar; Shaw, Christopher E.; Robinson, Iain M.; Hirth, Frank

    2013-01-01

    Cytoplasmic accumulation and nuclear clearance of TDP-43 characterize familial and sporadic forms of amyotrophic lateral sclerosis and frontotemporal lobar degeneration, suggesting that either loss or gain of TDP-43 function, or both, cause disease formation. Here we have systematically compared loss- and gain-of-function of Drosophila TDP-43, TAR DNA Binding Protein Homolog (TBPH), in synaptic function and morphology, motor control, and age-related neuronal survival. Both loss and gain of TBPH severely affect development and result in premature lethality. TBPH dysfunction caused impaired synaptic transmission at the larval neuromuscular junction (NMJ) and in the adult. Tissue-specific knockdown together with electrophysiological recordings at the larval NMJ also revealed that alterations of TBPH function predominantly affect pre-synaptic efficacy, suggesting that impaired pre-synaptic transmission is one of the earliest events in TDP-43-related pathogenesis. Prolonged loss and gain of TBPH in adults resulted in synaptic defects and age-related, progressive degeneration of neurons involved in motor control. Toxic gain of TBPH did not downregulate or mislocalize its own expression, indicating that a dominant-negative effect leads to progressive neurodegeneration also seen with mutational inactivation of TBPH. Together these data suggest that dysfunction of Drosophila TDP-43 triggers a cascade of events leading to loss-of-function phenotypes whereby impaired synaptic transmission results in defective motor behavior and progressive deconstruction of neuronal connections, ultimately causing age-related neurodegeneration. PMID:23307927

  7. Loss and gain of Drosophila TDP-43 impair synaptic efficacy and motor control leading to age-related neurodegeneration by loss-of-function phenotypes.

    PubMed

    Diaper, Danielle C; Adachi, Yoshitsugu; Sutcliffe, Ben; Humphrey, Dickon M; Elliott, Christopher J H; Stepto, Alan; Ludlow, Zoe N; Vanden Broeck, Lies; Callaerts, Patrick; Dermaut, Bart; Al-Chalabi, Ammar; Shaw, Christopher E; Robinson, Iain M; Hirth, Frank

    2013-04-15

    Cytoplasmic accumulation and nuclear clearance of TDP-43 characterize familial and sporadic forms of amyotrophic lateral sclerosis and frontotemporal lobar degeneration, suggesting that either loss or gain of TDP-43 function, or both, cause disease formation. Here we have systematically compared loss- and gain-of-function of Drosophila TDP-43, TAR DNA Binding Protein Homolog (TBPH), in synaptic function and morphology, motor control, and age-related neuronal survival. Both loss and gain of TBPH severely affect development and result in premature lethality. TBPH dysfunction caused impaired synaptic transmission at the larval neuromuscular junction (NMJ) and in the adult. Tissue-specific knockdown together with electrophysiological recordings at the larval NMJ also revealed that alterations of TBPH function predominantly affect pre-synaptic efficacy, suggesting that impaired pre-synaptic transmission is one of the earliest events in TDP-43-related pathogenesis. Prolonged loss and gain of TBPH in adults resulted in synaptic defects and age-related, progressive degeneration of neurons involved in motor control. Toxic gain of TBPH did not downregulate or mislocalize its own expression, indicating that a dominant-negative effect leads to progressive neurodegeneration also seen with mutational inactivation of TBPH. Together these data suggest that dysfunction of Drosophila TDP-43 triggers a cascade of events leading to loss-of-function phenotypes whereby impaired synaptic transmission results in defective motor behavior and progressive deconstruction of neuronal connections, ultimately causing age-related neurodegeneration.

  8. 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.

  9. A functional variant in the CFI gene confers a high risk of age-related macular degeneration.

    PubMed

    van de Ven, Johannes P H; Nilsson, Sara C; Tan, Perciliz L; Buitendijk, Gabriëlle H S; Ristau, Tina; Mohlin, Frida C; Nabuurs, Sander B; Schoenmaker-Koller, Frederieke E; Smailhodzic, Dzenita; Campochiaro, Peter A; Zack, Donald J; Duvvari, Maheswara R; Bakker, Bjorn; Paun, Codrut C; Boon, Camiel J F; Uitterlinden, Andre G; Liakopoulos, Sandra; Klevering, B Jeroen; Fauser, Sascha; Daha, Mohamed R; Katsanis, Nicholas; Klaver, Caroline C W; Blom, Anna M; Hoyng, Carel B; den Hollander, Anneke I

    2013-07-01

    Up to half of the heritability of age-related macular degeneration (AMD) is explained by common variants. Here, we report the identification of a rare, highly penetrant missense mutation in CFI encoding a p.Gly119Arg substitution that confers high risk of AMD (P = 3.79 × 10⁻⁶; odds ratio (OR) = 22.20, 95% confidence interval (CI) = 2.98-164.49). Plasma and sera from cases carrying the p.Gly119Arg substitution mediated the degradation of C3b, both in the fluid phase and on the cell surface, to a lesser extent than those from controls. Recombinant protein studies showed that the Gly119Arg mutant protein is both expressed and secreted at lower levels than wild-type protein. Consistent with these findings, human CFI mRNA encoding Arg119 had reduced activity compared to wild-type mRNA encoding Gly119 in regulating vessel thickness and branching in the zebrafish retina. Taken together, these findings demonstrate that rare, highly penetrant mutations contribute to the genetic burden of AMD.

  10. 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.

  11. Association between a functional genetic polymorphism (rs2230199) and age-related macular degeneration risk: a meta-analysis.

    PubMed

    Zhang, M X; Zhao, X F; Ren, Y C; Geng, T T; Yang, H; Feng, T; Jin, T B; Chen, C

    2015-10-16

    The association between the rs2230199 C>G single nucleotide polymorphism (SNP) in complement component 3 and age-related macular degeneration (AMD) risk has been examined extensively but the results are not consistent among studies. The aim of this study was to perform a meta-analysis of all available studies on this SNP in relation to AMD. The comprehensive databases of PubMed, Medline, Web of Knowledge, CNKI, and Google Scholar were searched for case-control studies investigating the association between the rs2230199 polymorphism and AMD susceptibility. ORs with 95%CIs were estimated to assess the association. Sensitivity analysis, test of heterogeneity, cumulative meta-analysis, and assessment of bias were also performed. A total of 15 published studies including 5593 cases and 5181 controls were used in this meta-analysis. Overall, the rs2230299 SNP was significantly associated with the risk of AMD in the overall population under the additive model (OR = 1.571, 95%CI = 1.414-1.745, P = 0.000), dominant model (OR = 1.681, 95%CI = 1.521-1.858, P = 0.000), and allelic model (OR = 1.597, 95%CI = 1.470-1.734, P = 0.000). In the subgroup analysis by ethnicity, the same results were found in Caucasian populations, while no significant correlations were found in Asian populations for all comparison models. In conclusion, our meta-analysis provides evidence that the rs2230199 polymorphism contributes to the development of AMD. Further large-scale multicenter epidemiological studies are warranted to confirm this finding.

  12. Visual function 5 years or more after macular translocation surgery for myopic choroidal neovascularisation and age-related macular degeneration

    PubMed Central

    Takeuchi, K; Kachi, S; Iwata, E; Ishikawa, K; Terasaki, H

    2012-01-01

    Purpose To evaluate the changes in the best-corrected visual acuity (BCVA) after 1 year and after ≥5 years after macular translocation for age-related macular degeneration (AMD) or myopic choroidal neovascularisation (mCNV). Methods The medical records of 61 consecutive patients who underwent macular translocation with 360° retinotomy for AMD (35 eyes) or mCNV (26 eyes) were reviewed. Overall, 40 patients, 17 mCNV and 23 AMD, were followed for at least 5 years. BCVA and area of the Goldmann visual field (VF) measured before, 12 months after surgery, and at the final visit. Results In the 23 AMD eyes followed for ≥5 years, the mean preoperative BCVA was 1.149±0.105 logMAR units, which significantly improved to 0.69±0.06 logMAR units at 1 year (P<0.001). This BCVA was maintained at 0.633±0.083 logMAR units on their final examination. In the 17 eyes with mCNV followed for ≥5 years, the mean preoperative BCVA was 1.083±0.119 logMAR units, which was significantly improved to 0.689±0.121 logMAR units at 1 year (P=0.001). This BCVA was maintained at 0.678±0.142 logMAR units on their final examination. The area of the VF was significantly decreased at 12 months and did not change significantly thereafter. Conclusions Our results show that macular translocation surgery significantly improves the BCVA and significantly decreases the VF area of eyes with mCNV or AMD after first 1 year. The BCVA and VF area do not change significantly from the values at 1 year for at least 5 years. PMID:22173070

  13. Growth differentiation factor 6 derived from mesenchymal stem/stromal cells reduces age-related functional deterioration in multiple tissues

    PubMed Central

    Hisamatsu, Daisuke; Ohno-Oishi, Michiko; Nakamura, Shiho; Mabuchi, Yo; Naka-Kaneda, Hayato

    2016-01-01

    The senescence-associated secretory phenotype (SASP) has attracted attention as a mechanism that connects cellular senescence to tissue dysfunction, and specific SASP factors have been identified as systemic pro-aging factors. However, little is known about the age-dependent changes in the secretory properties of stem cells. Young, but not old, mesenchymal stem/stromal cells (MSCs) are a well-known source of critical regenerative factors, but the identity of these factors remains elusive. In this study, we identified growth differentiation factor 6 (Gdf6; also known as Bmp13 and CDMP-2) as a regenerative factor secreted from young MSCs. The expression of specific secretory factors, including Gdf6, was regulated by the microRNA (miRNA) miR-17, whose expression declined with age. Upregulation of Gdf6 restored the osteogenic capacity of old MSCs in vitro and exerted positive effects in vivo on aging-associated pathologies such as reduced lymphopoiesis, insufficient muscle repair, reduced numbers of neural progenitors in the brain, and chronic inflammation. Our results suggest that manipulation of miRNA could enable control of the SASP, and that regenerative factors derived from certain types of young cells could be used to treat geriatric diseases. PMID:27311402

  14. Age-related differences in function and structure of rSMG and reduced functional connectivity with DLPFC explains heightened emotional egocentricity bias in childhood

    PubMed Central

    Bernhardt, Boris C.; Singer, Tania

    2015-01-01

    Humans often judge others egocentrically, assuming that they feel or think similarly to themselves. Emotional egocentricity bias (EEB) occurs in situations when others feel differently to oneself. Using a novel paradigm, we investigated the neurocognitive mechanisms underlying the developmental capacity to overcome such EEB in children compared with adults. We showed that children display a stronger EEB than adults and that this correlates with reduced activation in right supramarginal gyrus (rSMG) as well as reduced coupling between rSMG and left dorsolateral prefrontal cortex (lDLPFC) in children compared with adults. Crucially, functional recruitment of rSMG was associated with age-related differences in cortical thickness of this region. Although in adults the mere presence of emotional conflict occurs between self and other recruited rSMG, rSMG-lDLPFC coupling was only observed when implementing empathic judgements. Finally, resting state analyses comparing connectivity patterns of rSMG with that of right temporoparietal junction suggested a unique role of rSMG for self-other distinction in the emotional domain for adults as well as for children. Thus, children’s difficulties in overcoming EEB may be due to late maturation of regions distinguishing between conflicting socio-affective information and relaying this information to regions necessary for implementing accurate judgments. PMID:24771281

  15. 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

  16. Evidence of an Age Related Threshold Effect of Polychlorinated Biphenyls (PCBs) on Neuropsychological Functioning in a Native American Population

    PubMed Central

    Haase, Richard F.; McCaffrey, Robert J.; Santiago-Rivera, Azara L.; Morse, Gayle S.; Tarbell, Alice

    2009-01-01

    Polychlorinated biphenyls (PCBs) have been suspected for some time of having adverse effects on neuropsychological functioning in humans. While there is evidence of slowing of cognitive function in children associated with exposure to PCBs, the evidence of comparable effects on adults is far less well understood. We report here on the neuropsychological evaluation of 277 Native American adults, ranging in age from 18 -79, who were exposed to PCBs by way of environmental contamination in the St. Lawrence region of upstate New York. PCB body burden was estimated by 101 PCB congeners and neuropsychological functioning was assessed by a battery of 18 tests. Spline regression models were fitted to the latent variables of memory, motor function, and higher-order executive functioning. After adjusting for age, gender, and education the analyses revealed a threshold effect of PCBs at approximately 2 ppb. An age-by-PCB interaction effect was also observed for several variables which suggests that the threshold effect was largely confined to the age range of 40-79 and was not observable in the 18-40 year old group. Implications of these results are discussed in comparison to previously published similar work with adults and in terms of its potential clinical meaningfulness. PMID:19041090

  17. Plasma Polyunsaturated Fatty Acids and the Decline of Renal Function

    PubMed Central

    Lauretani, Fulvio; Semba, Richard D.; Bandinelli, Stefania; Miller, Edgar R.; Ruggiero, Carmelinda; Cherubini, Antonio; Guralnik, Jack M.; Ferrucci, Luigi

    2009-01-01

    Background Recent studies suggest an association between polyunsaturated fatty acids (PUFAs) and the development of chronic kidney disease. The aim of this study was to examine the relationship between PUFAs and renal function in older adults. Methods We performed a cross-sectional and prospective analysis of 931 adults, ≥65 years old, enrolled in the InCHIANTI study, a population-based cohort in Tuscany, Italy. Plasma PUFAs were measured at enrollment, and creatinine clearance was estimated by the Cockcroft-Gault equation at baseline and after 3-year follow-up. Results At enrollment, participants with higher creatinine clearance had higher concentrations of HDL cholesterol, total plasma PUFAs, plasma n-3 fatty acid (FA), and plasma n-6 FA and lower triglycerides. From enrollment to the 3-year follow-up visit, creatinine clearance declined by 7.8 (12.2) mL/min (P <0.0001). Baseline total plasma PUFAs, n-3 FA, n-6 FA, and linoleic, linolenic, and arachidonic acids were strong independent predictors of less steep decline in creatinine clearance from baseline to follow-up (P <0.0001, after adjusting for baseline creatinine clearance). After adjusting for baseline creatinine, baseline total plasma PUFAs, n-3 FA, and linoleic, linolenic, and arachidonic acids were negatively associated with creatinine at 3-year follow-up. Participants with higher plasma PUFAs at enrollment had a lower risk of developing renal insufficiency, defined by a creatinine clearance <60 mL/min, during 3-year follow-up. Conclusion High PUFA concentrations, both n-3 FA and n-6 FA, may attenuate the age-associated decline in renal function among older community-dwelling women and men. PMID:18202159

  18. 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

  19. 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.

  20. Long-term administration of the mitochondria-targeted antioxidant mitoquinone mesylate fails to attenuate age-related oxidative damage or rescue the loss of muscle mass and function associated with aging of skeletal muscle

    PubMed Central

    Sakellariou, Giorgos K.; Pearson, Timothy; Lightfoot, Adam P.; Nye, Gareth A.; Wells, Nicola; Giakoumaki, Ifigeneia I.; Griffiths, Richard D.; McArdle, Anne; Jackson, Malcolm J.

    2016-01-01

    Age-related skeletal muscle dysfunction is the underlying cause of morbidity that affects up to half the population aged 80 and over. Considerable evidence indicates that oxidative damage and mitochondrial dysfunction contribute to the sarcopenic phenotype that occurs with aging. To examine this, we administered the mitochondria-targeted antioxidant mitoquinone mesylate {[10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)decyl] triphenylphosphonium; 100 μM} to wild-type C57BL/6 mice for 15 wk (from 24 to 28 mo of age) and investigated the effects on age-related loss of muscle mass and function, changes in redox homeostasis, and mitochondrial organelle integrity and function. We found that mitoquinone mesylate treatment failed to prevent age-dependent loss of skeletal muscle mass associated with myofiber atrophy or alter a variety of in situ and ex vivo muscle function analyses, including maximum isometric tetanic force, decline in force after a tetanic fatiguing protocol, and single-fiber-specific force. We also found evidence that long-term mitoquinone mesylate administration did not reduce mitochondrial reactive oxygen species or induce significant changes in muscle redox homeostasis, as assessed by changes in 4-hydroxynonenal protein adducts, protein carbonyl content, protein nitration, and DNA damage determined by the content of 8-hydroxydeoxyguanosine. Mitochondrial membrane potential, abundance, and respiration assessed in permeabilized myofibers were not significantly altered in response to mitoquinone mesylate treatment. Collectively, these findings demonstrate that long-term mitochondria-targeted mitoquinone mesylate administration failed to attenuate age-related oxidative damage in skeletal muscle of old mice or provide any protective effect in the context of muscle aging.—Sakellariou, G. K., Pearson, T., Lightfoot, A. P., Nye, G. A., Wells, N., Giakoumaki, I. I., Griffiths, R. D., McArdle, A., Jackson, M. J. Long-term administration of the

  1. Long-term administration of the mitochondria-targeted antioxidant mitoquinone mesylate fails to attenuate age-related oxidative damage or rescue the loss of muscle mass and function associated with aging of skeletal muscle.

    PubMed

    Sakellariou, Giorgos K; Pearson, Timothy; Lightfoot, Adam P; Nye, Gareth A; Wells, Nicola; Giakoumaki, Ifigeneia I; Griffiths, Richard D; McArdle, Anne; Jackson, Malcolm J

    2016-11-01

    Age-related skeletal muscle dysfunction is the underlying cause of morbidity that affects up to half the population aged 80 and over. Considerable evidence indicates that oxidative damage and mitochondrial dysfunction contribute to the sarcopenic phenotype that occurs with aging. To examine this, we administered the mitochondria-targeted antioxidant mitoquinone mesylate {[10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)decyl] triphenylphosphonium; 100 μM} to wild-type C57BL/6 mice for 15 wk (from 24 to 28 mo of age) and investigated the effects on age-related loss of muscle mass and function, changes in redox homeostasis, and mitochondrial organelle integrity and function. We found that mitoquinone mesylate treatment failed to prevent age-dependent loss of skeletal muscle mass associated with myofiber atrophy or alter a variety of in situ and ex vivo muscle function analyses, including maximum isometric tetanic force, decline in force after a tetanic fatiguing protocol, and single-fiber-specific force. We also found evidence that long-term mitoquinone mesylate administration did not reduce mitochondrial reactive oxygen species or induce significant changes in muscle redox homeostasis, as assessed by changes in 4-hydroxynonenal protein adducts, protein carbonyl content, protein nitration, and DNA damage determined by the content of 8-hydroxydeoxyguanosine. Mitochondrial membrane potential, abundance, and respiration assessed in permeabilized myofibers were not significantly altered in response to mitoquinone mesylate treatment. Collectively, these findings demonstrate that long-term mitochondria-targeted mitoquinone mesylate administration failed to attenuate age-related oxidative damage in skeletal muscle of old mice or provide any protective effect in the context of muscle aging.-Sakellariou, G. K., Pearson, T., Lightfoot, A. P., Nye, G. A., Wells, N., Giakoumaki, I. I., Griffiths, R. D., McArdle, A., Jackson, M. J. Long-term administration of the

  2. Age-Related Differences in Advantageous Decision Making Are Associated with Distinct Differences in Functional Community Structure

    PubMed Central

    Wesley, Michael J.; Porrino, Linda J.; Hayasaka, Satoru; Bechara, Antoine; Burdette, Jonathan H.; Laurienti, Paul J.

    2014-01-01

    Abstract Human decision making is dependent on not only the function of several brain regions but also their synergistic interaction. The specific function of brain areas within the ventromedial prefrontal cortex has long been studied in an effort to understand choice evaluation and decision making. These data specifically focus on whole-brain functional interconnectivity using the principles of network science. The Iowa Gambling Task (IGT) was the first neuropsychological task used to model real-life decisions in a way that factors reward, punishment, and uncertainty. Clinically, it has been used to detect decision-making impairments characteristic of patients with prefrontal cortex lesions. Here, we used performance on repeated blocks of the IGT as a behavioral measure of advantageous and disadvantageous decision making in young and mature adults. Both adult groups performed poorly by predominately making disadvantageous selections in the beginning stages of the task. In later phases of the task, young adults shifted to more advantageous selections and outperformed mature adults. Modularity analysis revealed stark underlying differences in visual, sensorimotor and medial prefrontal cortex community structure. In addition, changes in orbitofrontal cortex connectivity predicted behavioral deficits in IGT performance. Contrasts were driven by a difference in age but may also prove relevant to neuropsychiatric disorders associated with poor decision making, including the vulnerability to alcohol and/or drug addiction. PMID:24575804

  3. 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.

  4. Executive function in daily life: Age-related influences of executive processes on instrumental activities of daily living.

    PubMed

    Vaughan, Leslie; Giovanello, Kelly

    2010-06-01

    The present study of older adults used structural equation modeling (SEM) to examine the relationships between 3 executive processes underlying executive function (EF) (inhibition, task switching, updating in working memory), and 2 types of instrumental activities of daily living (IADLs) (self-report, performance based). Experimental tasks of executive attention and self-report or performance-based IADL tests were administered to create latent constructs of EF and IADLs. Confirmatory factor analysis (CFA) was used to examine the construct validity of EF and IADLs. This analysis indicated a 3-factor model of inhibition, updating, and task switching and a 2-factor model of self-report and performance-based IADLs. As predicted, when the latent variable relationships were analyzed, executive processes had a significant relationship with performance-based, but not self-report, IADLs. In addition, task switching had a strong and significant relationship with performance-based IADLs. The results of this study uniquely show a direct relationship between executive processes and performance-based IADLs, thus demonstrating the ecological utility of experimental measures of EF to predict daily function. Furthermore, these results point to areas of cognitive training that may strategically impact older adults' performance on daily life activities.

  5. Responsiveness of the National Eye Institute Visual Function Questionnaire to Progression to Advanced Age-Related Macular Degeneration, Vision Loss, and Lens Opacity

    PubMed Central

    2006-01-01

    Objective To describe the ability of the National Eye Institute Visual Function Questionnaire (NEI-VFQ) to detect meaningful change over time (responsiveness) to the primary Age-Related Eye Disease Study outcomes. Methods The 25-item NEI-VFQ plus appendix was administered at 2 visits at 1- to 4-year intervals to 4119 participants in the Age-Related Eye Disease Study. Events evaluated were progression to advanced age-related macular degeneration (AMD), visual acuity (VA) loss of at least 15 letters, and lens opacity progression. Responsiveness was measured by the t statistic, effect size (ES), responsiveness statistic, and area under the receiver operating characteristic curve. Variance components were used to estimate the contributions of events to variability of the NEI-VFQ score. Results Overall NEI-VFQ score was responsive to AMD progression (t = 14.0; P<.001; ES=0.81) and VA (t = 16.2; P<.001; ES=0.74). Mean changes ranged from 11 to 25 points for the subscales of general vision, near and distance activities, social functioning, mental health, role difficulties, dependency, and driving. The NEI-VFQ was unresponsive to lens opacity progression, although when the event occurred in the eye with the best vision at the first administration, the lens opacity ES was moderate for the color vision (ES = 0.62) and driving subscales (ES=0.66). Progression to advanced AMD and VA loss contributed significantly to the variation in the mean difference in overall VFQ score. Conclusions Changes in the NEI-VFQ overall and subscale scores of 10 points or more are associated with clinically significant changes in vision and AMD. This finding may assist the design of interventional studies of AMD and VA loss that include the NEI-VFQ as an outcome measure. PMID:16157800

  6. Aging-Related Hyperexcitability in CA3 Pyramidal Neurons Is Mediated by Enhanced A-Type K+ Channel Function and Expression

    PubMed Central

    Simkin, Dina; Hattori, Shoai; Ybarra, Natividad; Musial, Timothy F.; Buss, Eric W.; Richter, Hannah; Oh, M. Matthew

    2015-01-01

    Aging-related impairments in hippocampus-dependent cognition have been attributed to maladaptive changes in the functional properties of pyramidal neurons within the hippocampal subregions. Much evidence has come from work on CA1 pyramidal neurons, with CA3 pyramidal neurons receiving comparatively less attention despite its age-related hyperactivation being postulated to interfere with spatial processing in the hippocampal circuit. Here, we use whole-cell current-clamp to demonstrate that aged rat (29–32 months) CA3 pyramidal neurons fire significantly more action potentials (APs) during theta-burst frequency stimulation and that this is associated with faster AP repolarization (i.e., narrower AP half-widths and enlarged fast afterhyperpolarization). Using a combination of patch-clamp physiology, pharmacology, Western blot analyses, immunohistochemistry, and array tomography, we demonstrate that these faster AP kinetics are mediated by enhanced function and expression of Kv4.2/Kv4.3 A-type K+ channels, particularly within the perisomatic compartment, of CA3 pyramidal neurons. Thus, our study indicates that inhibition of these A-type K+ channels can restore the intrinsic excitability properties of aged CA3 pyramidal neurons to a young-like state. SIGNIFICANCE STATEMENT Age-related learning deficits have been attributed, in part, to altered hippocampal pyramidal neuronal function with normal aging. Much evidence has come from work on CA1 neurons, with CA3 neurons receiving comparatively less attention despite its age-related hyperactivation being postulated to interfere with spatial processing. Hence, we conducted a series of experiments to identify the cellular mechanisms that underlie the hyperexcitability reported in the CA3 region. Contrary to CA1 neurons, we demonstrate that postburst afterhyperpolarization is not altered with aging and that aged CA3 pyramidal neurons are able to fire significantly more action potentials and that this is associated with

  7. Vitamin D prevents cognitive decline and enhances hippocampal synaptic function in aging rats

    PubMed Central

    Latimer, Caitlin S.; Brewer, Lawrence D.; Searcy, James L.; Chen, Kuey-Chu; Popović, Jelena; Kraner, Susan D.; Thibault, Olivier; Blalock, Eric M.; Landfield, Philip W.; Porter, Nada M.

    2014-01-01

    Vitamin D is an important calcium-regulating hormone with diverse functions in numerous tissues, including the brain. Increasing evidence suggests that vitamin D may play a role in maintaining cognitive function and that vitamin D deficiency may accelerate age-related cognitive decline. Using aging rodents, we attempted to model the range of human serum vitamin D levels, from deficient to sufficient, to test whether vitamin D could preserve or improve cognitive function with aging. For 5–6 mo, middle-aged F344 rats were fed diets containing low, medium (typical amount), or high (100, 1,000, or 10,000 international units/kg diet, respectively) vitamin D3, and hippocampal-dependent learning and memory were then tested in the Morris water maze. Rats on high vitamin D achieved the highest blood levels (in the sufficient range) and significantly outperformed low and medium groups on maze reversal, a particularly challenging task that detects more subtle changes in memory. In addition to calcium-related processes, hippocampal gene expression microarrays identified pathways pertaining to synaptic transmission, cell communication, and G protein function as being up-regulated with high vitamin D. Basal synaptic transmission also was enhanced, corroborating observed effects on gene expression and learning and memory. Our studies demonstrate a causal relationship between vitamin D status and cognitive function, and they suggest that vitamin D-mediated changes in hippocampal gene expression may improve the likelihood of successful brain aging. PMID:25267625

  8. Age-related differences in practice-dependent resting-state functional connectivity related to motor sequence learning.

    PubMed

    Mary, Alison; Wens, Vincent; Op de Beeck, Marc; Leproult, Rachel; De Tiège, Xavier; Peigneux, Philippe

    2017-02-01

    Decreased neural plasticity is observed with healthy ageing in the primary sensorimotor (SM1) cortex thought to participate in motor learning and memory consolidation processes. In the present magnetoencephalography study, the post-training reorganization of resting-state functional connectivity (rsFC) and its relation with motor learning and early consolidation in 14 young (19-30 years) and 14 old (66-70 years) healthy participants were investigated. At the behavioral level, participants were trained on a motor sequence learning task then retested 20-30 min later for transient offline gains in performance. Using a sensorimotor seed-based approach, rsFC relying on beta band power envelope correlation was estimated immediately before and 10 min after the learning episode. Post-training changes in rsFC (from before to after learning) were correlated with motor learning performance and with the offline improvement in performance within the hour after learning. Young and old participants exhibited differential patterns of sensorimotor-related rsFC, bearing specific relationships with motor learning and consolidation. Our findings suggest that rsFC changes following learning reflect the offline processing of the new motor skill and contribute to the early memory consolidation within the hour after learning. Furthermore, differences in post-training changes in rsFC between young and old participants support the hypothesis that ageing modulates the neural circuits underlying the learning of a new motor skill and the early subsequent consolidation stages. Hum Brain Mapp 38:923-937, 2017. © 2016 Wiley Periodicals, Inc.

  9. Age-related changes in the activation of the intraparietal sulcus during nonsymbolic magnitude processing: an event-related functional magnetic resonance imaging study.

    PubMed

    Ansari, Daniel; Dhital, Bibek

    2006-11-01

    Numerical magnitude processing is an essential everyday skill. Functional brain imaging studies with human adults have repeatedly revealed that bilateral regions of the intraparietal sulcus are correlated with various numerical and mathematical skills. Surprisingly little, however, is known about the development of these brain representations. In the present study, we used functional neuroimaging to compare the neural correlates of nonsymbolic magnitude judgments between children and adults. Although behavioral performance was similar across groups, in comparison to the group of children the adult participants exhibited greater effects of numerical distance on the left intraparietal sulcus. Our findings are the first to reveal that even the most basic aspects of numerical cognition are subject to age-related changes in functional neuroanatomy. We propose that developmental impairments of number may be associated with atypical specialization of cortical regions underlying magnitude processing.

  10. Age-related variability in performance of a motor action selection task is related to differences in brain function and structure among older adults.

    PubMed

    Stewart, Jill Campbell; Tran, Xuan; Cramer, Steven C

    2014-02-01

    Task performance for behaviors that engage motor cognitive processes may be particularly sensitive to age-related changes. One well-studied model of cognitive motor function involves engagement of action selection (AS) processes. In young adults, task conditions that add AS demands result in increased preparation times and greater engagement of bilateral dorsal premotor (PMd) and parietal cortices. The current study investigated the behavioral and neural response to a change in motor cognitive demands in older adults through the addition of AS to a movement task. Sixteen older adults made a joystick movement under two conditions during functional magnetic resonance imaging. In the AS condition, participants moved right or left based on an abstract rule; in the execution only (EO) condition, participants moved in the same direction on every trial. Across participants, the AS condition, as compared to the EO condition, was associated with longer reaction time and increased activation of left inferior parietal lobule. Variability in behavioral response to the AS task between participants related to differences in brain function and structure. Overall, individuals with poorer AS task performance showed greater activation in left PMd and dorsolateral prefrontal cortex and decreased structural integrity of white matter tracts that connect sensorimotor, frontal, and parietal regions-key regions for AS task performance. Additionally, two distinct patterns of functional connectivity were found. Participants with a pattern of decreased primary motor-PMd connectivity in response to the AS condition, compared to those with a pattern of increased connectivity, were older and had poorer behavioral performance. These neural changes in response to increased motor cognitive demands may be a marker for age-related changes in the motor system and have an impact on the learning of novel, complex motor skills in older adults.

  11. An Evidence-Based Construction of the Models of Decline of Functioning. Part 1: Two Major Models of Decline of Functioning

    ERIC Educational Resources Information Center

    Okawa, Yayoi; Nakamura, Shigemi; Kudo, Minako; Ueda, Satoshi

    2009-01-01

    The purpose of this study is to confirm the working hypothesis on two major models of functioning decline and two corresponding models of rehabilitation program in an older population through detailed interviews with the persons who have functioning declines and on-the-spot observations of key activities on home visits. A total of 542…

  12. [Effect of vasoactive agents on visual functions and ocular blood flow in patients with early manifestations of age-related macular degeneration].

    PubMed

    Avetisov, S E; Kiseleva, T N; Lagutina, Iu M; Kravchuk, E A

    2007-01-01

    Forty patients aged 40 to 65 years who had non-exudative forms of age-related macular degeneration (AMD), including 20 patients with degeneration of the retinal pigment epithelium (RPE), 15 with retinal drusen, and 5 with RPE atrophy were examined. All the patients were divided into 2 groups. Group 1 comprised 20 patients receiving, in addition to conventional therapy, cavinton forte (1 tablet contains 10 mg of vinpocetine). Group 2 (control) included 20 patients receiving conventional therapy (antioxidants, peptide bioregulators, lutein-containing agents). Medical treatment was performed during 2 months. After a course of cavinton therapy, patients with AMD were observed to have better visual acuity, improved retinal function, and increased a- and b-wave amplitudes on a macular electroretinogram. There was improvement of ocular blood flow values, which is indicative of better uveal blood supply.

  13. Age-related changes in functional postsynaptic nicotinic acetylcholine receptor subunits in neurons of the laterodorsal tegmental nucleus, a nucleus important in drug addiction.

    PubMed

    Christensen, Mark H; Kohlmeier, Kristi A

    2016-03-01

    The earlier an individual initiates cigarette smoking, the higher the likelihood of development of dependency to nicotine, the addictive ingredient in cigarettes. One possible mechanism underlying this higher addiction liability is an ontogenetically differential cellular response induced by nicotine in neurons mediating the reinforcing or euphoric effects of this drug, which could arise from age-related differences in the composition of nicotinic acetylcholine receptor (nAChR) subunits. In the current study, we examined whether the subunit composition of nAChRs differed between neurons within the laterodorsal tegmentum (LDT), a nucleus importantly involved in drug addiction associated behaviours, across two periods of ontogeny in which nicotine-mediated excitatory responses were shown to depend on age. To this end, whole-cell patch-clamp recordings in mouse brain slices from identified LDT neurons, in combination with nAChR subunit-specific receptor antagonists, were conducted. Comparison of the contribution of different nAChR subunits to acetylcholine (ACh)-induced inward currents indicated that the contributions of the β2 and/or β4 and α7 nAChR subunits alter across age. Taken together, we conclude that across a limited ontogenetic period, there is plasticity in the subunit composition of nAChRs in LDT neurons. In addition, our data indicate, for the first time, functional presence of α6 nAChR subunits in LDT neurons within the age ranges studied. Changes in subunit composition of nAChRs across ontogeny could contribute to the age-related differential excitability induced by nicotine. Differences in the subunit composition of nAChRs within the LDT would be expected to contribute to ontogenetic-dependent outflow from the LDT to target regions, which include reward-related circuitry.

  14. Age-related changes in insulin sensitivity and β-cell function among European-American and African-American women.

    PubMed

    Chandler-Laney, Paula C; Phadke, Radhika P; Granger, Wesley M; Fernández, José R; Muñoz, Julian A; Man, Chiara Dalla; Cobelli, Claudio; Ovalle, Fernando; Gower, Barbara A

    2011-03-01

    Type 2 diabetes (T2D) is more prevalent among African-American (AA) than European-American (EA) women for reasons that are unknown. Ethnic differences in physiological processes related to insulin sensitivity (S(I)) and secretion, and age-related changes in these processes, may play a role. The purpose of this study was to identify ethnicity- and age-related differences in S(I) and β-cell responsivity among AA and EA females, and to determine whether these differences are independent of body composition and fat distribution. Healthy, normoglycemic females aged 7-12 years (n = 62), 18-32 years (n = 57), and 40-70 years (n = 49) were recruited for entry into this study. Following an overnight fast, S(I), intravenous glucose tolerance (Kg), acute C-peptide secretion (X0), and basal, first-phase, second-phase, and total β-cell responsivity to glucose (PhiB, Phi1, Phi2, and Phi(TOT), respectively) were measured by an intravenous glucose tolerance test. Total % body fat was assessed by dual-energy X-ray absorptiometry, and intra-abdominal adiposity (IAAT) by computed tomography. Main effects of age group and ethnicity were measured with analysis of covariance, adjusting for % fat, IAAT, and S(I) as indicated. AA had lower S(I), and higher Kg, X0, Phi1, and Phi(TOT) (P < 0.05), which remained after adjustment for % fat and IAAT. Greater X0, Phi1, and Phi(TOT) among AA were independent of S(I). Advancing age was associated with greater Phi2 among both EA and AA. To conclude, inherent ethnic differences in β-cell function exist independently of adiposity and S(I). Future research should examine whether ethnic differences in β-cell physiology contribute to disparities in T2D risk.

  15. Functional visual improvement after cataract surgery in eyes with age-related macular degeneration; Results of the Ophthalmic Surgical Outcomes Data (OSOD) Project.

    PubMed

    Stock, Michael V; Vollman, David E; Baze, Elizabeth F; Chomsky, Amy S; Daly, Mary K; Lawrence, Mary

    2015-03-03

    Purpose: To determine if cataract surgery on eyes with age-related macular degeneration (AMD) confers as much functional visual improvement as on eyes without retinal pathology. Methods: This is a retrospective analysis of 4,924 cataract surgeries from the VA Ophthalmic Surgical Outcomes Data Project. We included cases of eyes with AMD which had both preoperative and postoperative NEI-VFQ-25 questionnaires submitted and compared their outcomes to controls without retinal pathology. We excluded patients with other retinal pathologies. The analyses compared changes in visual acuity and overall functional visual improvement and its subscales. Results: Preoperative and postoperative questionnaires were submitted by 58.3% of AMD and 63.8% of controls. Analysis of overall score showed that cataract surgery on eyes with AMD led to increased visual function (13.8± 2.4 NEI-VFQ units, P<0.0001); however, increases were significantly less when compared to controls (-6.4± 2.9 NEI-VFQ units, P<0.0001). Preoperative best corrected visual acuity (preBCVA) in AMD was predictive of postoperative visual function (r=-0.38, P<0.0001). In controls, postoperative visual function was only weakly associated with preBCVA (r=-0.075, P=0.0002). AMD patients with vision of 20/40 or better had overall outcomes similar to controls (-2.2± 4.7 NEI-VFQ units, P=0.37). Conclusions: Cataract surgery on eyes with AMD offers an increase in functional visual improvement; however, the amount of benefit is associated with the eye's preBCVA. For eyes with preBCVA ≥20/40, the improvement is similar to that of patients without retinal pathology. However, if preBCVA is <20/40, the amount of improvement was shown to be significantly less and decreased with decreasing preBCVA.

  16. Exploratory Decision-Making as a Function of Lifelong Experience, Not Cognitive Decline

    PubMed Central

    2016-01-01

    Older adults perform worse than younger adults in some complex decision-making scenarios, which is commonly attributed to age-related declines in striatal and frontostriatal processing. Recently, this popular account has been challenged by work that considered how older adults’ performance may differ as a function of greater knowledge and experience, and by work showing that, in some cases, older adults outperform younger adults in complex decision-making tasks. In light of this controversy, we examined the performance of older and younger adults in an exploratory choice task that is amenable to model-based analyses and ostensibly not reliant on prior knowledge. Exploration is a critical aspect of decision-making poorly understood across the life span. Across 2 experiments, we addressed (a) how older and younger adults differ in exploratory choice and (b) to what extent observed differences reflect processing capacity declines. Model-based analyses suggested that the strategies used by the 2 groups were qualitatively different, resulting in relatively worse performance for older adults in 1 decision-making environment but equal performance in another. Little evidence was found that differences in processing capacity drove performance differences. Rather the results suggested that older adults’ performance might result from applying a strategy that may have been shaped by their wealth of real-word decision-making experience. While this strategy is likely to be effective in the real world, it is ill suited to some decision environments. These results underscore the importance of taking into account effects of experience in aging studies, even for tasks that do not obviously tap past experiences. PMID:26726916

  17. Shared and Unique Genetic and Environmental Influences on Aging-Related Changes in Multiple Cognitive Abilities

    ERIC Educational Resources Information Center

    Tucker-Drob, Elliot M.; Reynolds, Chandra A.; Finkel, Deborah; Pedersen, Nancy L.

    2014-01-01

    Aging-related declines occur in many different domains of cognitive function during middle and late adulthood. However, whether a global dimension underlies individual differences in changes in different domains of cognition and whether global genetic influences on cognitive changes exist is less clear. We addressed these issues by applying…

  18. 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.

  19. Rumen development process in goats as affected by supplemental feeding v. grazing: age-related anatomic development, functional achievement and microbial colonisation.

    PubMed

    Jiao, Jinzhen; Li, Xiaopeng; Beauchemin, Karen A; Tan, Zhiliang; Tang, Shaoxun; Zhou, Chuanshe

    2015-03-28

    The aim of the present study was to describe age-related changes in anatomic, functional and microbial variables during the rumen development process, as affected by the feeding system (supplemental feeding v. grazing), in goats. Goats were slaughtered at seven time points that were selected to reflect the non-rumination (0, 7 and 14 d), transition (28 and 42 d) and rumination (56 and 70 d) phases of rumen development. Total volatile fatty acid (TVFA) concentration (P= 0·002), liquid-associated bacterial and archaeal copy numbers (P< 0·01) were greater for supplemental feeding v. grazing, while rumen pH (P< 0·001), acetate molar proportion (P= 0·003) and solid-associated microbial copy numbers (P< 0·05) were less. Rumen papillae length (P= 0·097) and extracellular (P= 0·093) and total (P= 0·073) protease activity potentials in supplemented goats tended to be greater than those in grazing goats. Furthermore, from 0 to 70 d, irrespective of the feeding system, rumen weight, rumen wall thickness, rumen papillae length and area, TVFA concentration, xylanase, carboxymethylcellulase activity potentials, and microbial copy numbers increased (P< 0·01) with age, while the greatest amylase and protease activity potentials occurred at 28 d. Most anatomic and functional variables evolved progressively from 14 to 42 d, while microbial colonisation was fastest from birth to 28 d. These outcomes suggest that the supplemental feeding system is more effective in promoting rumen development than the grazing system; in addition, for both the feeding systems, microbial colonisation in the rumen is achieved at 1 month, functional achievement at 2 months, and anatomic development after 2 months.

  20. Flow cytometric analysis of age-related changes in intestine intraepithelial lymphocyte subsets and their functional preservation after feeding mice on spirulina.

    PubMed

    Hayashi, Osamu; Katayanagi, Yuki; Ishii, Kyoko; Kato, Toshimitsu

    2009-10-01

    We investigated age-related changes in intestinal intraepithelial lymphocyte (IEL) subsets in mice by flow cytometric analysis and their functional preservation as affected by feeding Spirulina, a cyanobacterium that is known to possess various therapeutic effects, including immune modulation activity. The number of cells possessing the leukocyte-common antigen CD45(+) cells in mice (43 weeks old) of the aged group, used as a representative marker for IELs, was significantly lower than that of adult mice (5 weeks old). Either the proportion or the number of CD45(+)CD8(+) cells of the aged mice was significantly lower than that of adult mice, corresponding to previous reports. Proportions and numbers of CD4(+)CD8(+) cells in aged mice, on the other hand, were higher than those in adult mice. Increased or decreased levels of the cell surface antigens observed in the aged mice tended to be restored in aged mice fed Spirulina (aged-SP group), which ingested a hot water extract of Spirulina (SpHW). In fact, the proportions of CD45(+)CD8(+) cells and CD45(+)TCRgammadelta(+) cells in the aged-SP group significantly increased in comparison to the control aged group, which ingested ordinary chow and water ad libitum. These results suggest that ingestion of SpHW in the aged-SP group may contribute to the functional preservation of the intestinal epithelium as a first line of mucosal barrier against infectious agents through retaining the number of certain IELs. Changes in the number of other IEL subsets and blood cells are also discussed.

  1. 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.

  2. Physical activity as intervention for age-related loss of muscle mass and function: protocol for a randomised controlled trial (the LISA study)

    PubMed Central

    Eriksen, Christian Skou; Garde, Ellen; Reislev, Nina Linde; Wimmelmann, Cathrine Lawaetz; Bieler, Theresa; Ziegler, Andreas Kraag; Gylling, Anne Theil; Dideriksen, Kasper Juel; Siebner, Hartwig Roman; Mortensen, Erik Lykke; Kjaer, Michael

    2016-01-01

    Introduction Physical and cognitive function decline with age, accelerating during the 6th decade. Loss of muscle power (force×velocity product) is a dominant physical determinant for loss of functional ability, especially if the lower extremities are affected. Muscle strength training is known to maintain or even improve muscle power as well as physical function in older adults, but the optimal type of training for beneficial long-term training effects over several years is unknown. Moreover, the impact of muscle strength training on cognitive function and brain structure remains speculative. The primary aim of this randomised controlled trial is to compare the efficacy of two different 1 year strength training regimens on immediate and long-lasting improvements in muscle power in retirement-age individuals. Secondary aims are to evaluate the effect on muscle strength, muscle mass, physical and cognitive function, mental well-being, health-related quality of life and brain morphology. Methods and analysis The study includes 450 home-dwelling men and women (62–70 years). Participants are randomly allocated to (1) 1 year of supervised, centre-based heavy resistance training, (2) home-based moderate intensity resistance training or (3) habitual physical activity (control). Changes in primary (leg extensor power) and secondary outcomes are analysed according to the intention to treat principle and per protocol at 1, 2, 4, 7 and 10 years. Ethics and dissemination The study is expected to generate new insights into training-induced promotion of functional ability and independency after retirement and will help to formulate national recommendations regarding physical activity schemes for the growing population of older individuals in western societies. Results will be published in scientific peer-reviewed journals, in PhD theses and at public meetings. The study is approved by the Regional Ethical Committee (Capital Region, Copenhagen, Denmark, number H-3

  3. COPD Patients with Exertional Desaturation Are at a Higher Risk of Rapid Decline in Lung Function

    PubMed Central

    Kim, Changhwan; Park, Yong Bum; Park, So Young; Park, Sunghoon; Kim, Cheol-Hong; Park, Sang Myeon; Lee, Myung-Goo; Hyun, In-Gyu; Jung, Ki-Suck

    2014-01-01

    Purpose A recent study demonstrated that exertional desaturation is a predictor of rapid decline in lung function in patients with chronic obstructive pulmonary disease (COPD); however, the study was limited by its method used to detect exertional desaturation. The main purpose of this study was to explore whether exertional desaturation assessed using nadir oxygen saturation (SpO2) during the 6-minute walk test (6MWT) can predict rapid lung function decline in patients with COPD. Materials and Methods A retrospective analysis was performed on 57 patients with moderate to very severe COPD who underwent the 6MWT. Exertional desaturation was defined as a nadir SpO2 of <90% during the 6MWT. Rapid decline was defined as an annual rate of decline in forced expiratory volume in 1 second (FEV1) ≥50 mL. Patients were divided into rapid decliner (n=26) and non-rapid decliner (n=31) groups. Results A statistically significant difference in exertional desaturation was observed between rapid decliners and non-rapid decliners (17 vs. 8, p=0.003). No differences were found between the groups for age, smoking status, BODE index, and FEV1. Multivariate analysis showed that exertional desaturation was a significant independent predictor of rapid decline in patients with COPD (relative risk, 6.8; 95% CI, 1.8 to 25.4; p=0.004). Conclusion This study supports that exertional desaturation is a predictor of rapid lung function decline in male patients with COPD. PMID:24719141

  4. Age-related commonalities and differences in the relationship between executive functions and intelligence: Analysis of the NAB executive functions module and WAIS-IV scores.

    PubMed

    Buczylowska, Dorota; Petermann, Franz

    2016-08-02

    Data from five subtests of the Executive Functions Module of the German Neuropsychological Assessment Battery (NAB) and all ten core subtests of the German Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) were used to examine the relationship between executive functions and intelligence in a comparison of two age groups: individuals aged 18-59 years and individuals aged 60-88 years. The NAB subtests Categories and Word Generation demonstrated a consistent correlation pattern for both age groups. However, the NAB Judgment subtest correlated more strongly with three WAIS-IV indices, the Full Scale IQ (FSIQ), and the General Ability Index (GAI) in the older adult group than in the younger group. Additionally, in the 60-88 age group, the Executive Functions Index (EFI) was more strongly correlated with the Verbal Comprehension Index (VCI) than with the Perceptual Reasoning Index (PRI). Both age groups demonstrated a strong association of the EFI with the FSIQ and the Working Memory Index (WMI). The results imply the potential diagnostic utility of the Judgment subtest and a significant relationship between executive functioning and crystallized intelligence at older ages. Furthermore, it may be concluded that there is a considerable age-independent overlap between the EFI and general intelligence, as well as between the EFI and working memory.

  5. 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 ...

  6. Age-related changes in rat myocardium involve altered capacities of glycosaminoglycans to potentiate growth factor functions and heparan sulfate-altered sulfation.

    PubMed

    Huynh, Minh Bao; Morin, Christophe; Carpentier, Gilles; Garcia-Filipe, Stephanie; Talhas-Perret, Sofia; Barbier-Chassefière, Véronique; van Kuppevelt, Toin H; Martelly, Isabelle; Albanese, Patricia; Papy-Garcia, Dulce

    2012-03-30

    Glycosaminoglycans (GAGs) are essential components of the extracellular matrix, the natural environment from which cell behavior is regulated by a number or tissue homeostasis guarantors including growth factors. Because most heparin-binding growth factor activities are regulated by GAGs, structural and functional alterations of these polysaccharides may consequently affect the integrity of tissues during critical physiological and pathological processes. Here, we investigated whether the aging process can induce changes in the myocardial GAG composition in rats and whether these changes can affect the activities of particular heparin-binding growth factors known to sustain cardiac tissue integrity. Our results showed an age-dependent increase of GAG levels in the left ventricle. Biochemical and immunohistological studies pointed out heparan sulfates (HS) as the GAG species that increased with age. ELISA-based competition assays showed altered capacities of the aged myocardial GAGs to bind FGF-1, FGF-2, and VEGF but not HB EGF. Mitogenic assays in cultured cells showed an age-dependent decrease of the elderly GAG capacities to potentiate FGF-2 whereas the potentiating effect on VEGF(165) was increased, as confirmed by augmented angiogenic cell proliferation in Matrigel plugs. Moreover, HS disaccharide analysis showed considerably altered 6-O-sulfation with modest changes in N- and 2-O-sulfations. Together, these findings suggest a physiological significance of HS structural and functional alterations during aging. This can be associated with an age-dependent decline of the extracellular matrix capacity to efficiently modulate not only the activity of resident or therapeutic growth factors but also the homing of resident or therapeutic cells.

  7. The Effect of the Human Peptide GHK on Gene Expression Relevant to Nervous System Function and Cognitive Decline.

    PubMed

    Pickart, Loren; Vasquez-Soltero, Jessica Michelle; Margolina, Anna

    2017-02-15

    Neurodegeneration, the progressive death of neurons, loss of brain function, and cognitive decline is an increasing problem for senior populations. Its causes are poorly understood and therapies are largely ineffective. Neurons, with high energy and oxygen requirements, are especially vulnerable to detrimental factors, including age-related dysregulation of biochemical pathways caused by altered expression of multiple genes. GHK (glycyl-l-histidyl-l-lysine) is a human copper-binding peptide with biological actions that appear to counter aging-associated diseases and conditions. GHK, which declines with age, has health promoting effects on many tissues such as chondrocytes, liver cells and human fibroblasts, improves wound healing and tissue regeneration (skin, hair follicles, stomach and intestinal linings, boney tissue), increases collagen, decorin, angiogenesis, and nerve outgrowth, possesses anti-oxidant, anti-inflammatory, anti-pain and anti-anxiety effects, increases cellular stemness and the secretion of trophic factors by mesenchymal stem cells. Studies using the Broad Institute Connectivity Map show that GHK peptide modulates expression of multiple genes, resetting pathological gene expression patterns back to health. GHK has been recommended as a treatment for metastatic cancer, Chronic Obstructive Lung Disease, inflammation, acute lung injury, activating stem cells, pain, and anxiety. Here, we present GHK's effects on gene expression relevant to the nervous system health and function.

  8. The Effect of the Human Peptide GHK on Gene Expression Relevant to Nervous System Function and Cognitive Decline

    PubMed Central

    Pickart, Loren; Vasquez-Soltero, Jessica Michelle; Margolina, Anna

    2017-01-01

    Neurodegeneration, the progressive death of neurons, loss of brain function, and cognitive decline is an increasing problem for senior populations. Its causes are poorly understood and therapies are largely ineffective. Neurons, with high energy and oxygen requirements, are especially vulnerable to detrimental factors, including age-related dysregulation of biochemical pathways caused by altered expression of multiple genes. GHK (glycyl-l-histidyl-l-lysine) is a human copper-binding peptide with biological actions that appear to counter aging-associated diseases and conditions. GHK, which declines with age, has health promoting effects on many tissues such as chondrocytes, liver cells and human fibroblasts, improves wound healing and tissue regeneration (skin, hair follicles, stomach and intestinal linings, boney tissue), increases collagen, decorin, angiogenesis, and nerve outgrowth, possesses anti-oxidant, anti-inflammatory, anti-pain and anti-anxiety effects, increases cellular stemness and the secretion of trophic factors by mesenchymal stem cells. Studies using the Broad Institute Connectivity Map show that GHK peptide modulates expression of multiple genes, resetting pathological gene expression patterns back to health. GHK has been recommended as a treatment for metastatic cancer, Chronic Obstructive Lung Disease, inflammation, acute lung injury, activating stem cells, pain, and anxiety. Here, we present GHK’s effects on gene expression relevant to the nervous system health and function. PMID:28212278

  9. Functional decline and survival in dependent elderly people.

    PubMed Central

    Crawford, V.; Campbell, H.; Hodkinson, E.; Stout, R. W.

    1990-01-01

    A survey of dependency levels was carried out in 1985 and 1989 in 41 residents of old peoples homes and 25 patients in geriatric continuing care wards. There was an increase in all levels of dependency for those in both types of care. In the hospital patients surveyed in 1985, mortality was greatest in the most dependent, particularly those with impaired mental function. There was a positive correlation between length of survival and mental function. The results of this study emphasise the important role of dementia in the health and survival of old people. PMID:2126156

  10. Prevention of Functional Decline by Reframing the Role of Nursing Homes?

    PubMed

    Laffon de Mazières, Clarisse; Morley, John E; Levy, Cari; Agenes, Fabien; Barbagallo, Mario; Cesari, Matteo; De Souto Barreto, Philipe; Donini, Lorenzo Maria; Fitten, Jaime; Franco, Alain; Izquierdo, Mikel; Kane, Rosalie A; Martin, Finbarr C; Onder, Graziano; Ouslander, Joseph; Pitkälä, Kaisu; Saliba, Debra; Sinclair, Alan; Manas, Leocadio Rodriguez; Vellas, Bruno; Rolland, Yves

    2017-02-01

    Institutionalization is generally a consequence of functional decline driven by physical limitations, cognitive impairments, and/or loss of social supports. At this stage, intervention to reverse functional losses is often too late. To be more effective, geriatric medicine must evolve to intervene at an earlier stage of the disability process. Could nursing homes (NHs) transform from settings in which many residents dwell to settings in which the NH residents and those living in neighboring communities benefit from staff expertise to enhance quality of life and maintain or slow functional decline? A task force of clinical researchers met in Toulouse on December 2, 2015, to address some of these challenges: how to prevent or slow functional decline and disabilities for NH residents and how NHs may promote the prevention of functional decline in community-dwelling frail elderly. The present article reports the main results of the Task Force discussions to generate a new paradigm.

  11. Network functional connectivity and whole-brain functional connectomics to investigate cognitive decline in neurodegenerative conditions.

    PubMed

    Dipasquale, O; Cercignani, Mara

    Non-invasive mapping of brain functional connectivity (FC) has played a fundamental role in neuroscience, and numerous scientists have been fascinated by its ability to reveal the brain's intricate morphology and functional properties. In recent years, two different techniques have been developed that are able to explore FC in pathophysiological conditions and to provide simple and non-invasive biomarkers for the detection of disease onset, severity and progression. These techniques are independent component analysis, which allows a network-based functional exploration of the brain, and graph theory, which provides a quantitative characterization of the whole-brain FC. In this paper we provide an overview of these two techniques and some examples of their clinical applications in the most common neurodegenerative disorders associated with cognitive decline, including mild cognitive impairment, Alzheimer's disease, Parkinson's disease, dementia with Lewy Bodies and behavioral variant frontotemporal dementia.

  12. Network functional connectivity and whole-brain functional connectomics to investigate cognitive decline in neurodegenerative conditions

    PubMed Central

    Dipasquale, Ottavia; Cercignani, Mara

    2016-01-01

    Summary Non-invasive mapping of brain functional connectivity (FC) has played a fundamental role in neuroscience, and numerous scientists have been fascinated by its ability to reveal the brain’s intricate morphology and functional properties. In recent years, two different techniques have been developed that are able to explore FC in pathophysiological conditions and to provide simple and non-invasive biomarkers for the detection of disease onset, severity and progression. These techniques are independent component analysis, which allows a network-based functional exploration of the brain, and graph theory, which provides a quantitative characterization of the whole-brain FC. In this paper we provide an overview of these two techniques and some examples of their clinical applications in the most common neurodegenerative disorders associated with cognitive decline, including mild cognitive impairment, Alzheimer’s disease, Parkinson’s disease, dementia with Lewy Bodies and behavioral variant frontotemporal dementia. PMID:28072380

  13. Handgrip strength predicts functional decline at discharge in hospitalized male elderly: a hospital cohort study.

    PubMed

    García-Peña, Carmen; García-Fabela, Luis C; Gutiérrez-Robledo, Luis M; García-González, Jose J; Arango-Lopera, Victoria E; Pérez-Zepeda, Mario U

    2013-01-01

    Functional decline after hospitalization is a common adverse outcome in elderly. An easy to use, reproducible and accurate tool to identify those at risk would aid focusing interventions in those at higher risk. Handgrip strength has been shown to predict adverse outcomes in other settings. The aim of this study was to determine if handgrip strength measured upon admission to an acute care facility would predict functional decline (either incident or worsening of preexisting) at discharge among older Mexican, stratified by gender. In addition, cutoff points as a function of specificity would be determined. A cohort study was conducted in two hospitals in Mexico City. The primary endpoint was functional decline on discharge, defined as a 30-point reduction in the Barthel Index score from that of the baseline score. Handgrip strength along with other variables was measured at initial assessment, including: instrumental activities of daily living, cognition, depressive symptoms, delirium, hospitalization length and quality of life. All analyses were stratified by gender. Logistic regression to test independent association between handgrip strength and functional decline was performed, along with estimation of handgrip strength test values (specificity, sensitivity, area under the curve, etc.). A total of 223 patients admitted to an acute care facility between 2007 and 2009 were recruited. A total of 55 patients (24.7%) had functional decline, 23.46% in male and 25.6% in women. Multivariate analysis showed that only males with low handgrip strength had an increased risk of functional decline at discharge (OR 0.88, 95% CI 0.79-0.98, p = 0.01), with a specificity of 91.3% and a cutoff point of 20.65 kg for handgrip strength. Females had not a significant association between handgrip strength and functional decline. Measurement of handgrip strength on admission to acute care facilities may identify male elderly patients at risk of having functional decline, and intervene

  14. Handgrip Strength Predicts Functional Decline at Discharge in Hospitalized Male Elderly: A Hospital Cohort Study

    PubMed Central

    García-Peña, Carmen; García-Fabela, Luis C.; Gutiérrez-Robledo, Luis M.; García-González, Jose J.; Arango-Lopera, Victoria E.; Pérez-Zepeda, Mario U.

    2013-01-01

    Functional decline after hospitalization is a common adverse outcome in elderly. An easy to use, reproducible and accurate tool to identify those at risk would aid focusing interventions in those at higher risk. Handgrip strength has been shown to predict adverse outcomes in other settings. The aim of this study was to determine if handgrip strength measured upon admission to an acute care facility would predict functional decline (either incident or worsening of preexisting) at discharge among older Mexican, stratified by gender. In addition, cutoff points as a function of specificity would be determined. A cohort study was conducted in two hospitals in Mexico City. The primary endpoint was functional decline on discharge, defined as a 30-point reduction in the Barthel Index score from that of the baseline score. Handgrip strength along with other variables was measured at initial assessment, including: instrumental activities of daily living, cognition, depressive symptoms, delirium, hospitalization length and quality of life. All analyses were stratified by gender. Logistic regression to test independent association between handgrip strength and functional decline was performed, along with estimation of handgrip strength test values (specificity, sensitivity, area under the curve, etc.). A total of 223 patients admitted to an acute care facility between 2007 and 2009 were recruited. A total of 55 patients (24.7%) had functional decline, 23.46% in male and 25.6% in women. Multivariate analysis showed that only males with low handgrip strength had an increased risk of functional decline at discharge (OR 0.88, 95% CI 0.79–0.98, p = 0.01), with a specificity of 91.3% and a cutoff point of 20.65 kg for handgrip strength. Females had not a significant association between handgrip strength and functional decline. Measurement of handgrip strength on admission to acute care facilities may identify male elderly patients at risk of having functional decline, and

  15. Subclinical Cardiac Abnormalities and Kidney Function Decline: The Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Shlipak, Michael G.; Katz, Ronit; Agarwal, Subhashish; Ix, Joachim H.; Hsu, Chi-yuan; Peralta, Carmen A.

    2012-01-01

    Summary Background and objectives Clinical heart failure (HF) is associated with CKD and faster rates of kidney function decline. Whether subclinical abnormalities of cardiac structure are associated with faster kidney function decline is not known. The association between cardiac concentricity and kidney function decline was evaluated. Design, setting, participants, & measurements This is a longitudinal study of 3866 individuals from the Multi-Ethnic Study of Atherosclerosis (2000–2007) who were free of clinical cardiovascular disease, with an estimated GFR (eGFR) ≥60 ml/min per 1.73 m2 at baseline and 5 years of follow-up. Concentricity, a measurement of abnormal cardiac size, was assessed by magnetic resonance imaging and evaluated as a continuous measurement and in quartiles. GFR was estimated by creatinine (eGFRcr) and cystatin C (eGFRcys). The association of concentricity with annual eGFR decline, incident CKD, and rapid kidney function decline (>5% per year) was investigated using linear mixed models as well as Poisson and logistic regression, respectively. Analyses adjusted for demographics, BP, diabetes, and inflammatory markers. Results Median decline was −0.8 (interquartile range, −3.1, −0.5) by eGFRcr. Compared with the lowest quartile of concentricity, persons in the highest quartile had an additional 21% (9%–32%) decline in mean eGFRcr in fully adjusted models. Concentricity was also associated with incident CKD and with rapid kidney function decline after adjustment. Conclusions Subclinical abnormalities in cardiac structure are associated with longitudinal kidney function decline independent of diabetes and hypertension. Future studies should examine mechanisms to explain these associations. PMID:22580783

  16. Factors affecting longitudinal functional decline and survival in amyotrophic lateral sclerosis patients.

    PubMed

    Watanabe, Hazuki; Atsuta, Naoki; Nakamura, Ryoichi; Hirakawa, Akihiro; Watanabe, Hirohisa; Ito, Mizuki; Senda, Jo; Katsuno, Masahisa; Izumi, Yuishin; Morita, Mitsuya; Tomiyama, Hiroyuki; Taniguchi, Akira; Aiba, Ikuko; Abe, Koji; Mizoguchi, Kouichi; Oda, Masaya; Kano, Osamu; Okamoto, Koichi; Kuwabara, Satoshi; Hasegawa, Kazuko; Imai, Takashi; Aoki, Masashi; Tsuji, Shoji; Nakano, Imaharu; Kaji, Ryuji; Sobue, Gen

    2015-06-01

    Our objective was to elucidate the clinical factors affecting functional decline and survival in Japanese amyotrophic lateral sclerosis (ALS) patients. We constructed a multicenter prospective ALS cohort that included 451 sporadic ALS patients in the analysis. We longitudinally utilized the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) as the functional scale, and determined the timing of introduction of a tracheostomy for positive-pressure ventilation and death. A joint modelling approach was employed to identify prognostic factors for functional decline and survival. Age at onset was a common prognostic factor for both functional decline and survival (p < 0.001, p < 0.001, respectively). Female gender (p = 0.019) and initial symptoms, including upper limb weakness (p = 0.010), lower limb weakness (p = 0.008) or bulbar symptoms (p = 0.005), were related to early functional decline, whereas neck weakness as an initial symptom (p = 0.018), non-use of riluzole (p = 0.030) and proximal dominant muscle weakness in the upper extremities (p = 0.01) were related to a shorter survival time. A decline in the ALSFRS-R score was correlated with a shortened survival time (p < 0.001). In conclusion, the factors affecting functional decline and survival in ALS were common in part but different to some extent. This difference has not been previously well recognized but is informative in clinical practice and for conducting trials.

  17. [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.

  18. Relationship Between Quality of Care and Functional Decline in Hospitalized Vulnerable Elders

    PubMed Central

    Arora, Vineet M.; Plein, Colleen; Chen, Stuart; Siddique, Juned; Sachs, Greg A.; Meltzer, David O.

    2009-01-01

    Background While process of care is a valuable dimension of quality, process-of-care-based quality indicators (POC-QIs) are ideally associated with meaningful patient outcomes. The relationship between POC-QIs for hospitalized older patients and functional decline, a relevant outcome for older patients, is unknown. Objective To assess the relationship between POC-QIs for hospitalized elders and functional decline Research Design Observational cohort study. Subjects Hospitalized vulnerable elder patients age 65 or older admitted to a general medicine inpatient service from 1 June 2004 to 1 June 2007. Measures POC-QIs received by hospitalized patients (measured by ACOVE QIs) and functional decline (increased Activities of Daily Living impairments post discharge). Results For 898 vulnerable elder patients, mean adherence to six universally applied quality indicators was 57.8%. After adjustment for factors likely associated with functional decline (comorbidity, vulnerability, baseline functional limitation, number of POC-QIs triggered, length of stay, code status, and interaction between frailty and QI adherence), there was no association between higher quality of care (using the composite score) and increased risk of functional decline. Patients who received a mobility plan were 1.48 (95% CI 1.07-2.05; p=0.017) times more likely to suffer functional decline after discharge. Patients who received an assessment of nutritional status had a lower odds of suffering functional decline after discharge (OR 0.37 (95% CI 0.21-0.64; p<0.001). Conclusions Hospitalized vulnerable elders who receive higher quality of care, as measured by ACOVE QIs, are not less likely to suffer decline after discharge. PMID:19597372

  19. Investigating Discontinuity of Age Relations in Cognitive Functioning, General Health Status, Activity Participation, and Life Satisfaction between Young-Old and Old-Old Age

    PubMed Central

    Ihle, Andreas; Jopp, Daniela S.; Oris, Michel; Fagot, Delphine; Kliegel, Matthias

    2016-01-01

    Health research suggests that findings on young-old adults cannot be generalized to old-old adults and thus that old-old age seems not a simple continuation of young-old age due to qualitative changes that result in a discontinuity in old age. Specifically, it would be of conceptual and methodological importance to inform research regarding estimates around which chronological age the beginning of old-old age could be placed at a population level, and whether this is universal or domain-specific. To derive such criteria, we investigated potential discontinuity of age relations between young-old and old-old age in a large population-based sample considering measures in different domains (processing speed, verbal abilities, general health status, activity participation, and life satisfaction). For processing speed, verbal abilities, general health status, and life satisfaction we observed some very small indication that there might be a discontinuity of age relations at the end of individuals’ eighties, and for activity participation already at the beginning of individuals’ eighties. In conclusion, models conceptualizing aging as a gradual development might not suffice to adequately represent the differences between the stages of young-old and old-old age due to some very small indication that there might be discontinuity in late adulthood. PMID:27827960

  20. 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.

  1. Intrinsically photosensitive retinal ganglion cell function in relation to age: A pupillometric study in humans with special reference to the age-related optic properties of the lens

    PubMed Central

    2012-01-01

    Background The activity of melanopsin containing intrinsically photosensitive ganglion retinal cells (ipRGC) can be assessed by a means of pupil responses to bright blue (appr.480 nm) light. Due to age related factors in the eye, particularly, structural changes of the lens, less light reaches retina. The aim of this study was to examine how age and in vivo measured lens transmission of blue light might affect pupil light responses, in particular, mediated by the ipRGC. Methods Consensual pupil responses were explored in 44 healthy subjects aged between 26 and 68 years. A pupil response was recorded to a continuous 20 s light stimulus of 660 nm (red) or 470 nm (blue) both at 300 cd/m2 intensity (14.9 and 14.8 log photons/cm2/s, respectively). Additional recordings were performed using four 470 nm stimulus intensities of 3, 30, 100 and 300 cd/m2. The baseline pupil size was measured in darkness and results were adjusted for the baseline pupil and gender. The main outcome parameters were maximal and sustained pupil contraction amplitudes and the postillumination response assessed as area under the curve (AUC) over two time-windows: early (0–10 s after light termination) and late (10–30 s after light termination). Lens transmission was measured with an ocular fluorometer. Results The sustained pupil contraction and the early poststimulus AUC correlated positively with age (p = 0.02, p = 0.0014, respectively) for the blue light stimulus condition only. The maximal pupil contraction amplitude did not correlate to age either for bright blue or red light stimulus conditions. Lens transmission decreased linearly with age (p < 0.0001). The pupil response was stable or increased with decreasing transmission, though only significantly for the early poststimulus AUC to 300 cd/m2 light (p = 0.02). Conclusions Age did not reduce, but rather enhance pupil responses mediated by ipRGC. The age related decrease of blue light transmission led

  2. Reduced Nrf2 expression mediates the decline in neural stem cell function during a critical middle-age period.

    PubMed

    Corenblum, Mandi J; Ray, Sneha; Remley, Quentin W; Long, Min; Harder, Bryan; Zhang, Donna D; Barnes, Carol A; Madhavan, Lalitha

    2016-08-01

    Although it is known that the regenerative function of neural stem/progenitor cells (NSPCs) declines with age, causal mechanisms underlying this phenomenon are not understood. Here, we systematically analyze subventricular zone (SVZ) NSPCs, in various groups of rats across the aging spectrum, using in vitro and in vivo histological and behavioral techniques. These studies indicate that although NSPC function continuously declines with advancing age, there is a critical time period during middle age (13-15 months) when a striking reduction in NSPC survival and regeneration (proliferation and neuronal differentiation) occurs. The studies also indicate that this specific temporal pattern of NSPC deterioration is functionally relevant at a behavioral level and correlates with the decreasing expression of the redox-sensitive transcription factor, Nrf2, in the NSPCs. When Nrf2 expression was suppressed in 'young' NSPCs, using short interfering RNAs, the survival and regeneration of the NSPCs was significantly compromised and mirrored 'old' NSPCs. Conversely, Nrf2 overexpression in 'old' NSPCs rendered them similar to 'young' NSPCs, and they showed increased survival and regeneration. Furthermore, examination of newborn Nrf2 knockout (Nrf2 -/-) mice revealed a lower number of SVZ NSPCs in these animals, when compared to wild-type controls. In addition, the proliferative and neurogenic potential of the NSPCs was also compromised in the Nrf2-/- mice. These results identify a novel regulatory role for Nrf2 in NSPC function during aging and have important implications for developing NSPC-based strategies to support healthy aging and to treat age-related neurodegenerative disorders.

  3. The Natural History of Cardiac and Pulmonary Function Decline in Patients with Duchenne Muscular Dystrophy

    PubMed Central

    Roberto, Rolando; Fritz, Anto; Hagar, Yolanda; Boice, Braden; Skalsky, Andrew; Hwang, HoSun; Beckett, Laurel; McDonald, Craig; Gupta, Munish

    2010-01-01

    Study Design Retrospective review of scoliosis progression, pulmonary and cardiac function in a series of patients with Duchenne Muscular Dystrophy (DMD). Objective To determine whether operative treatment of scoliosis decreases the rate of pulmonary function loss in patients with DMD. Summary of Background Data It is generally accepted that surgical intervention should be undertaken in DMD scoliosis once curve sizes reach 35 degrees to allow intervention before critical respiratory decline has occurred. There are conflicting reports, however, regarding the effect of scoliosis stabilization on the rate of pulmonary function decline when compared to non operative cohorts. Methods We reviewed spinal radiographs, echocardiograms, and spirometry, hospital, and operative records of all patients seen at our tertiary referral center from July 1, 1992 to June 1, 2007 Data was recorded to Microsoft Excel and analyzed with SAS and R statistical processing software. Results The percent predicted forced vital capacity (PPFVC) decreased 5% /year prior to operation. The mean PPFVC was 54% (sd=21%) prior to operation with a mean postoperative PPFVC of 43% (sd=14%). Surgical treatment was associated with a 12% decline in PPFVC independent of other treatment variables. PPFVC after operation declined at a rate of 1% per year and while this rate was lower, it was not significantly different than the rate of decline present prior to operation (p=0.18). Cardiac function as measured by left ventricular fractional shortening declined at a rate of 1%/year with most individuals exhibiting an LVFS rate of >30 prior to operation. Conclusion Operative treatment of scoliosis in DMD using the Luque Galveston method was associated with a reduction of FVC related to operation. The rate of pulmonary function decline after operation was not significantly reduced when compared to the rate of preoperative FVC decline. PMID:21289561

  4. Rate of Cognitive Decline Before and After the Onset of Functional Limitations in Older Persons

    PubMed Central

    Rajan, Kumar B.; Hebert, Liesi E.; Scherr, Paul A.; Mendes de Leon, Carlos F.; Evans, Denis A.

    2015-01-01

    Background: Loss in physical function is indicative of deterioration in physiological health that may also be associated with deterioration in neurological health. The objective of this study was to examine whether the onset of functional limitations and their severity is associated with increases in cognitive decline among older adults. Methods: The study sample consists of 3825 (65% African Americans and 53% females) participants over the age of 65 with no functional limitations. Cognitive function was assessed using a standardized global cognitive score, and functional limitations using a summary measure of 8 Rosow-Breslau and Nagi limitations (ROS-B/Nagi). Cognitive decline before and after the onset of limitations were analyzed using a linear piecewise change point model. Results: During follow-up, 2682 (70%) participants reported limitations in ROS-B/Nagi measure. The rate of cognitive decline was 0.053-units per year before any limitations, and increased to 0.069-units per year after one or more limitations in ROS-B/Nagi measure. This was about 30% (95% Confidence Interval [CI]: 18 – 42%) increase in the rate of cognitive decline comparing before and after the onset of limitations in ROS-B/Nagi measure. Also, higher number of limitations in ROS-B/Nagi measure at the time of onset was associated with faster cognitive decline. Conclusions: The rate of cognitive decline was significantly higher following functional limitations. This study suggests that self-reported measures of functional limitations may serve as an important marker of cognitive decline. PMID:25934994

  5. National Survey of Geriatricians to Define Functional Decline in Elderly People with Minor Trauma

    PubMed Central

    Abdulaziz, Kasim; Perry, Jeffrey J.; Taljaard, Monica; Émond, Marcel; Lee, Jacques S.; Wilding, Laura; Sirois, Marie-Josée; Brehaut, Jamie

    2016-01-01

    Background This study was designed to determine a clinically significant point drop in function to define functional decline and the required sensitivity for a clinical decision tool to identify elderly patients at high risk of functional decline following a minor injury. Methods After a rigorous development process, a survey questionnaire was administered to a random sample of 178 geriatricians selected from those registered in a national medical directory. The surveys were distributed using a modified Dillman technique. Results We obtained a satisfactory response rate of 70.5%. Ninety percent of the geriatricians required a sensitivity of 90% or less for a clinical decision tool to identify injured seniors at high risk of functional decline 6 months post injury. Our results indicate that 90% of the respondents considered a drop in function of at least 2 points in activities of daily living (ADL) as clinically significant when considering all 14 ADL items. Considering only the 7 basic ADL items, 90% of physicians considered a 1 point drop as clinically significant. Conclusions A tool with a sensitivity of 90% to detect patients at risk of functional decline at 6 months post minor injury would meet or exceed the sensitivity required by 90% of geriatric specialists. These findings clearly define what is a clinically significant decline following a “minor injury.” PMID:27076859

  6. Adiposity, muscle mass, and muscle strength in relation to functional decline in older persons.

    PubMed

    Schaap, Laura A; Koster, Annemarie; Visser, Marjolein

    2013-01-01

    Aging is associated with changes in body composition and muscle strength. This review aimed to determine the relation between different body composition measures and muscle strength measures and functional decline in older men and women. By use of relevant databases (PubMed, Embase, and CINAHL) and keywords in a search from 1976 to April 2012, 50 articles were reviewed that met the inclusion criteria (written in English, a prospective, longitudinal design, involving older persons aged 65 years or more, and at least one of the measures that follow: body mass index (BMI), waist circumference, waist/hip ratio, midarm circumference, fat mass, muscle fat infiltration, muscle mass, or strength as independent variables and a measure of functional decline as outcome measure). Meta-analyses were performed and revealed that BMI ≥30 and low muscle strength were associated with functional decline (pooled odds ratio (OR) = 1.60, 95% confidence interval (CI): 1.43, 1.80, for BMI ≥30 and OR = 1.86, 95% CI: 1.32, 2.64, for muscle strength). Low muscle mass was not significantly associated with functional decline (pooled OR = 1.19, 95% CI: 0.98, 1.45). Future intervention research should focus on positive changes in body composition to prevent onset or worsening of functional decline in old age.

  7. Mitochondrial ROS regulate oxidative damage and mitophagy but not age-related muscle fiber atrophy

    PubMed Central

    Sakellariou, Giorgos K.; Pearson, Timothy; Lightfoot, Adam P.; Nye, Gareth A.; Wells, Nicola; Giakoumaki, Ifigeneia I.; Vasilaki, Aphrodite; Griffiths, Richard D.; Jackson, Malcolm J.; McArdle, Anne

    2016-01-01

    Age-related loss of skeletal muscle mass and function is a major contributor to morbidity and has a profound effect on the quality of life of older people. The potential role of age-dependent mitochondrial dysfunction and cumulative oxidative stress as the underlying cause of muscle aging remains a controversial topic. Here we show that the pharmacological attenuation of age-related mitochondrial redox changes in muscle with SS31 is associated with some improvements in oxidative damage and mitophagy in muscles of old mice. However, this treatment failed to rescue the age-related muscle fiber atrophy associated with muscle atrophy and weakness. Collectively, these data imply that the muscle mitochondrial redox environment is not a key regulator of muscle fiber atrophy during sarcopenia but may play a key role in the decline of mitochondrial organelle integrity that occurs with muscle aging. PMID:27681159

  8. The emergence of the mitochondrial genome as a partial regulator of nuclear function is providing new insights into the genetic mechanisms underlying age-related complex disease.

    PubMed

    Horan, Martin P; Cooper, David N

    2014-04-01

    Mitochondrial malfunction appears to be intimately associated with age and age-related complex disorders but the precise pathological relevance of such malfunction remains unclear. Mitochondrial, and more specifically bioenergetic, malfunction is commonly encountered in cancer, degenerative disorders and aging. The identification of a mitochondrial-nuclear retrograde signaling pathway in yeast has facilitated the study of the corresponding retrograde signaling mechanisms induced in response to mitochondrial malfunction in mammals including human. Mitochondrial-nuclear crosstalk is critical for the maintenance of cellular homeostasis, and some mitochondrial DNA mutations may perturb crosstalk signaling. However, ascertaining whether mitochondrial malfunction is a cause or a consequence of disease development will be key to determining whether or not impaired crosstalk signaling is of direct pathological and hence therapeutic relevance. Here, we review what is known about the nuclear adaptive compensatory mechanisms induced in response to mitochondrial malfunction. We discuss the role of mitochondrial DNA variants in modulating the penetrance of human inherited disease caused by mutations in the nuclear genome and explore the underlying mechanisms by which they influence the retrograde response. We conclude that mitochondrial DNA variants have the potential to induce molecular signals through the mitochondrial-nuclear crosstalk mechanism, thereby promoting nuclear compensation in response to mitochondrial malfunction. The implications for the development of genetic or pharmaceutical interventions for the treatment of mitochondrial malfunction in complex disease are also explored.

  9. Lung function decline rates according to GOLD group in patients with chronic obstructive pulmonary disease

    PubMed Central

    Kim, Joohae; Yoon, Ho Il; Oh, Yeon-Mok; Lim, Seong Yong; Lee, Ji-Hyun; Kim, Tae-Hyung; Lee, Sang Yeub; Lee, Jin Hwa; Lee, Sang-Do; Lee, Chang-Hoon

    2015-01-01

    Background Since the Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups A–D were introduced, the lung function changes according to group have been evaluated rarely. Objective We investigated the rate of decline in annual lung function in patients categorized according to the 2014 GOLD guidelines. Methods Patients with COPD included in the Korean Obstructive Lung Disease (KOLD) prospective study, who underwent yearly postbronchodilator spirometry at least three times, were included. The main outcome was the annual decline in postbronchodilator forced expiratory volume in 1 second (FEV1), which was analyzed by random-slope and random-intercept mixed linear regression. Results A total 175 participants were included. No significant postbronchodilator FEV1 decline was observed between the groups (−34.4±7.9 [group A]; −26.2±9.4 [group B]; −22.7±16.0 [group C]; and −24.0±8.7 mL/year [group D]) (P=0.79). The group with less symptoms (−32.3±7.2 vs −25.0±6.5 mL/year) (P=0.44) and the low risk group (−31.0±6.1 vs −23.6±7.7 mL/year) (P=0.44) at baseline showed a more rapid decline in the postbronchodilator FEV1, but the trends were not statistically significant. However, GOLD stages classified by FEV1 were significantly related to the annual lung function decline. Conclusion There was no significant difference in lung function decline rates according to the GOLD groups. Prior classification using postbronchodilator FEV1 predicts decline in lung function better than does the new classification. PMID:26379432

  10. 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.

  11. Vitamin D deficiency is associated with functional decline and falls in frail elderly women despite supplementation.

    PubMed

    Kotlarczyk, M P; Perera, S; Ferchak, M A; Nace, D A; Resnick, N M; Greenspan, S L

    2017-04-01

    We examined the impact of daily supplementation on vitamin D deficiency, function, and falls in female long-term care residents. Initial vitamin D deficiency was associated with greater functional decline and increased fall risk despite guideline-recommended supplementation, highlighting the importance of preventing vitamin D deficiency in frail elderly.

  12. Why Adult Stem Cell Functionality Declines with Age? Studies from the Fruit Fly Drosophila Melanogaster Model Organism

    PubMed Central

    Gonen, Oren; Toledano, Hila

    2014-01-01

    Highly regenerative adult tissues are supported by rare populations of stem cells that continuously divide to self-renew and generate differentiated progeny. This process is tightly regulated by signals emanating from surrounding cells to fulfill the dynamic demands of the tissue. One of the hallmarks of aging is slow and aberrant tissue regeneration due to deteriorated function of stem and supporting cells. Several Drosophila regenerative tissues are unique in that they provide exact identification of stem and neighboring cells in whole-tissue anatomy. This allows for precise tracking of age-related changes as well as their targeted manipulation within the tissue. In this review we present the stem cell niche of Drosophila testis, ovary and intestine and describe the major changes and phenotypes that occur in the course of aging. Specifically we discuss changes in both intrinsic properties of stem cells and their microenvironment that contribute to the decline in tissue functionality. Understanding these mechanisms in adult Drosophila tissues will likely provide new paradigms in the field of aging. PMID:24955030

  13. Limited Health Literacy and Decline in Executive Function in Older Adults

    PubMed Central

    Sequeira, Shwetha S.; Eggermont, Laura H. P.; Silliman, Rebecca A.; Bickmore, Timothy W.; Henault, Lori E.; Winter, Michael R.; Nelson, Kerrie; Paasche-Orlow, Michael K.

    2013-01-01

    Limited health literacy is associated with worse executive function, but the association between limited health literacy and decline in executive function has not been established because of a lack of longitudinal studies. The authors aimed to examine this association by studying a prospective cohort in the setting of a randomized controlled trial to promote walking in older adults. Participants were community-dwelling older adults (65 years of age or older) who scored 2 or more on the Mini-Cog, without depression (score of less than 15 on the 9-item Patient Health Questionnaire), and who completed baseline and 12-month evaluations (n = 226). Health literacy was measured using the Short Test of Functional Health Literacy in Adults. Executive function measured at baseline and 12 months using the Trail Making Test (TMT), Controlled Oral Word Association Test, and Category Fluency. The associations between health literacy and 12-month decline in each test of executive function were modeled using multivariate linear regression. Health literacy was found to be limited in 37% of participants. Limited health literacy was associated with reduced performance on all 3 executive function tests. In fully adjusted models, limited health literacy was associated with greater 12-month decline in performance on the TMT than higher health literacy (p = .01). In conclusion, older adults with limited health literacy are at risk for more rapid decline in scores on the TMT, a measure of executive function. PMID:24093352

  14. 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

  15. Associations of Sugar and Artificially Sweetened Soda with Albuminuria and Kidney Function Decline in Women

    PubMed Central

    Curhan, Gary C.

    2011-01-01

    Summary Background and objectives Sugar-sweetened soda is reported to be associated with increased risk for diabetes and albuminuria, but there are currently limited data on how sugar or artificially sweetened soda may be related to kidney function decline. Design, setting, participants, & measurements This study identified 3318 women participating in the Nurses' Health Study with data on soda intake and albuminuria; of these, 3256 also had data on estimated GFR (eGFR) change between 1989 and 2000. Cumulative average beverage intake was derived from the 1984, 1986, 1990, 1994, and 1998 food frequency questionnaires. Serving categories included <1/mo (referent), 1 to 4/mo, 2 to 6/wk, 1 to 1.9/d, and ≥2/d. Microalbuminuria (MA) was considered a urinary albumin-to-creatinine ratio of 25 to 355 μg/mg. For kidney function change, the primary outcome was a ≥30% decline in eGFR over 11 years; rapid eGFR decline defined as ≥3 ml/min per 1.73 m2 per year was also examined. Results Consumption of ≥2 servings per day of artificially sweetened (diet) soda was independently associated with eGFR decline ≥30% (OR 2.02, 95% CI 1.36 to 3.01) and ≥3 ml/min per 1.73 m2 per year (OR 2.20, 95% CI 1.36 to 3.55). No increased risk for eGFR decline was observed for <2 servings per day of diet soda. No associations were noted between diet soda and MA or sugar soda and MA or eGFR decline. Conclusions Consumption of ≥2 servings per day of artificially sweetened soda is associated with a 2-fold increased odds for kidney function decline in women. PMID:20884773

  16. [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.

  17. Nutritional supplements in support of resistance exercise to counter age-related sarcopenia.

    PubMed

    Phillips, Stuart M

    2015-07-01

    Age-related sarcopenia, composed of myopenia (a decline in muscle mass) and dynapenia (a decline in muscle strength), can compromise physical function, increase risk of disability, and lower quality of life in older adults. There are no available pharmaceutical treatments for this condition, but evidence shows resistance training (RT) is a viable and relatively low-cost treatment with an exceptionally positive side effect profile. Further evidence suggests that RT-induced increases in muscle mass, strength, and function can be enhanced by certain foods, nutrients, or nutritional supplements. This brief review focuses on adjunctive nutritional strategies, which have a reasonable evidence base, to enhance RT-induced gains in outcomes relevant to sarcopenia and to reducing risk of functional declines.

  18. Age-Related Synapse Loss In Hippocampal CA3 Is Not Reversed By Caloric Restriction

    PubMed Central

    Adams, Michelle M.; Donohue, Howard S.; Linville, M. Constance; Iversen, Elizabeth A.; Newton, Isabel G.; Brunso-Bechtold, Judy K.

    2010-01-01

    Caloric restriction (CR) is a reduction of total caloric intake without a decrease in micronutrients or a disproportionate reduction of any one dietary component. While CR attenuates age-related cognitive deficits in tasks of hippocampal-dependent memory, the cellular mechanisms by which CR improves this cognitive decline are poorly understood. Previously, we have reported age-related decreases in key synaptic proteins in the CA3 region of the hippocampus that are stabilized by lifelong CR. In the present study, we examined possible age-related changes in the functional microcircuitry of the synapses in the stratum lacunosum-moleculare (SL-M) of the CA3 region of the hippocampus, and whether lifelong CR might prevent these age-related alterations. We used serial electron microscopy to reconstruct and classify SL-M synapses and their postsynaptic spines. We analyzed synapse number and size as well as spine surface area and volume in young (10 mos.) and old (29 mos) ad libitum fed rats and in old rats that were calorically restricted from 4 months of age. We limited our analysis to SL-M because previous work demonstrated age-related decreases in synaptophysin confined to this specific layer and region of the hippocampus. The results revealed an age-related decrease in macular axo-spinous synapses that was not reversed by CR that occurred in the absence of changes in the size of synapses or spines. Thus, the benefits of CR for CA3 function and synaptic plasticity may involve other biological effects including the stabilization of synaptic proteins levels in the face of age-related synapse loss. PMID:20854882

  19. Medication Use and Functional Status Decline in Older Adults: A Narrative Review

    PubMed Central

    Peron, Emily P.; Gray, Shelly L.; Hanlon, Joseph T.

    2012-01-01

    OBJECTIVE To critically review published articles that have examined the relationship between medication use and functional status decline in the elderly. METHODS The MEDLINE and EMBASE databases were searched for English-language articles published from January 1986 to December 2010. Search terms included aged, humans, drug utilization, polypharmacy, inappropriate prescribing, anticholinergics, psychotropics, antihypertensives, drug burden index, functional status, function change or decline, activities of daily living, gait, mobility limitation, and disability. A manual search of the reference lists of the identified articles and the authors’ article files, book chapters, and recent reviews was conducted to retrieve additional publications. Only articles that used rigorous observational or interventional designs were included. Cross-sectional studies and case series were excluded from this review. RESULTS Nineteenstudies met the inclusion criteria. Five studies addressed the impact of suboptimal prescribing on function, three of which found an increased risk of worse function in community-dwelling subjects receiving polypharmacy. Three of the four studies that assessed benzodiazepine use and functional status decline found a statistically significant association. One cohort study identified no relationship between antidepressant use and functional status while a randomized trial found that amitriptyline, but not desipramine or paroxetine, impaired certain measures of gait. Two studies found that increasing anticholinergic burden was associated with worse functional status. In a study of hospitalized rehabilitation patients, users of hypnotics/anxiolytics (e.g., phenobarbital, zolpidem) had lower relative Functional Independence Measure motor gains than nonusers. Use of multiple central nervous system (CNS) drugs (using different definitions) was linked to greater declines in self-reported mobility and Short Physical Performance Battery (SPPB) scores in two

  20. Risk Factors for Renal Functional Decline in Chronic Hepatitis B Patients Receiving Oral Antiviral Agents.

    PubMed

    Shin, Jung-Ho; Kwon, Hee Jin; Jang, Hye Ryoun; Lee, Jung Eun; Gwak, Geum-Youn; Huh, Wooseong; Jung, Sin-Ho; Lee, Joon Hyeok; Kim, Yoon-Goo; Kim, Dae Joong; Oh, Ha Young

    2016-01-01

    Renal functional decline that is frequently seen during chronic hepatitis B (CHB) treatment can exert adverse effects on overall prognosis. It, however, is difficult to distinguish vulnerable patients who may experience renal dysfunction because most previous CHB studies were conducted in relatively healthy individuals. In this retrospective observational study, renal functional decline in CHB patients receiving oral antiviral agents for more than 6 months was analyzed and risk factors of chronic kidney disease (CKD) progression were determined. Renal functional decline was defined when the estimated glomerular filtration rate (eGFR) decreased by more than 25% from baseline and rapid CKD progression was defined as eGFR decreased by more than 5 mL/min/1.73 m2/y among patients who experienced renal functional decline. A total of 4178 patients were followed up for a median 23 months. Antiviral agents included lamivudine (17.0%), adefovir (3.7%), entecavir (70.4%), telbivudine (0.6%), tenofovir (4.0%), or clevudine (4.3%). Renal functional decline occurred in 706 (16.9%) patients. Based on multivariate Cox regression analysis, age, hypertension, diabetes, history of liver or kidney transplantation, underlying underlying CKD, and simultaneous administration of diuretics increased the hazard ratio for renal functional decline; however, clevudine reduced risk. The eGFR significantly increased over time in patients receiving telbivudine or clevudine compared with lamivudine. Among the 3175 patients followed up for more than 1 year, 407 (12.8%) patients experienced rapid CKD progression. Patients with rapid CKD progression showed lower serum albumin, higher total bilirubin, and prolonged prothrombin time compared with patients with stable renal function, but hepatitis B envelope antigen positivity and hepatitis B virus deoxyribonucleic acid level did not differ between the control and rapid CKD progression groups. Age, diabetes, kidney transplantation, underlying CKD, and

  1. Early identification of declining balance in higher functioning older adults, an inertial sensor based method.

    PubMed

    Sheehan, K J; Greene, B R; Cunningham, C; Crosby, L; Kenny, R A

    2014-04-01

    Higher functioning older adults rarely have their balance assessed clinically and as such early decline in balance is not captured. Early identification of declining balance would facilitate earlier intervention and improved management of the ageing process. This study sought to determine if (a) a once off inertial sensor measurement and (b) changes in inertial sensor measurements one year apart can identify declining balance for higher functioning older adults. One hundred and nineteen community dwelling older adults (58 males; 72.5±5.8 years) completed a timed up and go (TUG) instrumented with inertial sensors and the Berg balance scale (BBS) at two time points, one year apart. Temporal and spatio-temporal gait parameters as well as angular velocity and turn parameters were derived from the inertial sensor data. A change in balance from baseline to follow-up was determined by sub-components of the BBS. Changes in inertial sensor parameters from baseline to follow-up demonstrated strong association with balance decline in higher functioning older adults (e.g. mean medial-lateral angular velocity odds ratio=0.2; 95% CI: 0.1-0.5). The area under the Receiver operating characteristic curve (AUC) ranged from 0.8 to 0.9, a marked improvement over change in TUG time alone (AUC 0.6-0.7). Baseline inertial sensor parameters had a similar association with declining balance as age and TUG time. For higher functioning older adults, the change in inertial sensor parameters over time may reflect declining balance. These measures may be useful clinically, to monitor the balance status of older adults and facilitate earlier identification of balance deficits.

  2. Declining ambient air pollution and lung function improvement in Austrian children

    NASA Astrophysics Data System (ADS)

    Neuberger, Manfred; Moshammer, Hanns; Kundi, Michael

    Three thousand four hundred fifty-one Austrian elementary school children were examined (between 2 and 8 times) by spirometry by standardized methods, over a 5 yr period. The districts where they lived were grouped into those where NO 2 declined during this period (by at least 30 μg/m 3 measured as half year means) and those with less or no decline in ambient NO 2. In both groups of districts, SO 2 and TSP fell by similar amounts over this period. A continuous improvement of MEF25 (maximum exspiratory flow rate at 25% vital capacity) was found in districts with declining ambient NO 2. Populations did not differ in respect of anthropometric factors, passive smoking or socioeconomic status. A birth cohort from this study population which was followed up to age 18 confirmed the improved growth of MEF25 with decline in NO 2, while the improved growth of forced vital capacity was more related to decline in SO 2. This study provides the first evidence that improvements in the outdoor air quality during the 1980s are correlated with health benefits, and suggest that adverse effects on lung function related to ambient air pollution are reversible before adulthood. Improvement of small airway functions appeared to be more dependent on reductions of NO 2 than reduction in SO 2 and TSP.

  3. Functional decline and satisfaction with nursing care among older hospitalized adults.

    PubMed

    Zisberg, Anna; Zlotnick, Cheryl; Gur-Yaish, Nurit; Admi, Hanna; Sinoff, Gary; Shadmi, Efrat

    2015-10-01

    Around hospitalization, older adults often experience functional decline which can be a reflection of their need for nursing care. Given a shortage of nurses, determining the relationship between functional change and patients' satisfaction with nursing care can help to gauge the need for care. We assessed this relationship in a mixed prospective-correlational cohort study with 393 patients, 70 years or older. The art, tangible aspects and general satisfaction with nursing care were measured through interviews conducted at discharge. Patients' functional status was assessed at admission and discharge. Decline in functioning during hospitalization was the most powerful predictor of higher satisfaction with art and tangible aspects of nursing care in multivariate regression (β = 0.17-0.19, P < 0.01). This finding suggests that patients whose functioning deteriorates during hospitalization, have a greater need for and more contact with professional nursing care, and therefore report higher satisfaction with specific aspects of nursing care.

  4. Changes in cystic fibrosis airway microbial community associated with a severe decline in lung function.

    PubMed

    Paganin, Patrizia; Fiscarelli, Ersilia Vita; Tuccio, Vanessa; Chiancianesi, Manuela; Bacci, Giovanni; Morelli, Patrizia; Dolce, Daniela; Dalmastri, Claudia; De Alessandri, Alessandra; Lucidi, Vincenzina; Taccetti, Giovanni; Mengoni, Alessio; Bevivino, Annamaria

    2015-01-01

    Cystic fibrosis (CF) is a genetic disease resulting in chronic polymicrobial infections of the airways and progressive decline in lung function. To gain insight into the underlying causes of severe lung diseases, we aimed at comparing the airway microbiota detected in sputum of CF patients with stable lung function (S) versus those with a substantial decline in lung function (SD). Microbiota composition was investigated by using culture-based and culture-independent methods, and by performing multivariate and statistical analyses. Culture-based methods identified some microbial species associated with a worse lung function, i.e. Pseudomonas aeruginosa, Rothia mucilaginosa, Streptococcus pneumoniae and Candida albicans, but only the presence of S. pneumoniae and R. mucilaginosa was found to be associated with increased severe decline in forced expiratory volume in 1 second (FEV1). Terminal-Restriction Fragment Length Polymorphism (T-RFLP) analysis revealed a higher bacterial diversity than that detected by culture-based methods. Molecular signatures with a statistically significant odds ratio for SD status were detected, and classified as Pseudomonas, Burkholderia and Shewanella, while for other Terminal Restriction Fragments (T-RFs) no species assignation was achieved. The analysis of T-RFLP data using ecological biodiversity indices showed reduced Evenness in SD patients compared to S ones, suggesting an impaired ecology of the bacterial community in SD patients. Statistically significant differences of the ecological biodiversity indices among the three sub-groups of FEV1 (normal/mild vs moderate vs severe) were also found, suggesting that the patients with moderate lung disease experienced changes in the airway assembly of taxa. Overall, changes in CF airway microbial community associated with a severe lung function decline were detected, allowing us to define some discriminatory species as well as some discriminatory T-RFs that represent good candidates for the

  5. NFE2L2 pathway polymorphisms and lung function decline in chronic obstructive pulmonary disease.

    PubMed

    Sandford, Andrew J; Malhotra, Deepti; Boezen, H Marike; Siedlinski, Mateusz; Postma, Dirkje S; Wong, Vivien; Akhabir, Loubna; He, Jian-Qing; Connett, John E; Anthonisen, Nicholas R; Paré, Peter D; Biswal, Shyam

    2012-08-01

    An oxidant-antioxidant imbalance in the lung contributes to the development of chronic obstructive pulmonary disease (COPD) that is caused by a complex interaction of genetic and environmental risk factors. Nuclear erythroid 2-related factor 2 (NFE2L2 or NRF2) is a critical molecule in the lung's defense mechanism against oxidants. We investigated whether polymorphisms in the NFE2L2 pathway affected the rate of decline of lung function in smokers from the Lung Health Study (LHS)(n = 547) and in a replication set, the Vlagtwedde-Vlaardingen cohort (n = 533). We selected polymorphisms in NFE2L2 in genes that positively or negatively regulate NFE2L2 transcriptional activity and in genes that are regulated by NFE2L2. Polymorphisms in 11 genes were significantly associated with rate of lung function decline in the LHS. One of these polymorphisms, rs11085735 in the KEAP1 gene, was previously shown to be associated with the level of lung function in the Vlagtwedde-Vlaardingen cohort but not with decline of lung function. Of the 23 associated polymorphisms in the LHS, only rs634534 in the FOSL1 gene showed a significant association in the Vlagtwedde-Vlaardingen cohort with rate of lung function decline, but the direction of the association was not consistent with that in the LHS. In summary, despite finding several nominally significant polymorphisms in the LHS, none of these associations were replicated in the Vlagtwedde-Vlaardingen cohort, indicating lack of effect of polymorphisms in the NFE2L2 pathway on the rate of decline of lung function.

  6. Monthly high dose vitamin D treatment for the prevention of functional decline: a randomized clinical trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Importance: Vitamin D deficiency has been associated with poor physical performance. Objective: To determine the effectiveness of high dose vitamin D in lowering the risk of functional decline. Design, Setting, and Participants: One-year double-blind, randomized clinical trial conducted in Zurich,...

  7. 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…

  8. 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.

  9. Age related vascular endothelial function following lifelong sedentariness: positive impact of cardiovascular conditioning without further improvement following low frequency high intensity interval training

    PubMed Central

    Grace, Fergal M.; Herbert, Peter; Ratcliffe, John W.; New, Karl J.; Baker, Julien S.; Sculthorpe, Nicholas F.

    2015-01-01

    Abstract Aging is associated with diffuse impairments in vascular endothelial function and traditional aerobic exercise is known to ameliorate these changes. High intensity interval training (HIIT) is effective at improving vascular function in aging men with existing disease, but its effectiveness remains to be demonstrated in otherwise healthy sedentary aging. However, the frequency of commonly used HIIT protocols may be poorly tolerated in older cohorts. Therefore, the present study investigated the effectiveness of lower frequency HIIT (LfHIIT) on vascular function in a cohort of lifelong sedentary (SED; n =22, age 62.7 ± 5.2 years) men compared with a positive control group of lifelong exercisers (LEX; n = 17, age 61.1 ± 5.4 years). The study consisted of three assessment phases; enrolment to the study (Phase A), following 6 weeks of conditioning exercise in SED (Phase B) and following 6 weeks of low frequency HIIT in both SED and LEX (LfHIIT; Phase C). Conditioning exercise improved FMD in SED (3.4 ± 1.5% to 4.9 ± 1.1%; P <0.01) such that the difference between groups on enrolment (3.4 ± 1.5% vs. 5.3 ± 1.4%; P <0.01) was abrogated. This was maintained but not further improved following LfHIIT in SED whilst FMD remained unaffected by LfHIIT in LEX. In conclusion, LfHIIT is effective at maintaining improvements in vascular function achieved during conditioning exercise in SED. LfHIIT is a well‐tolerated and effective exercise mode for reducing cardiovascular risk and maintaining but does not improve vascular function beyond that achieved by conditioning exercise in aging men, irrespective of fitness level. PMID:25626864

  10. Lobar microbleeds are associated with decline in executive functioning in older adults

    PubMed Central

    Meier, Irene B.; Gu, Yian; Guzman, Vanessa A.; Wiegman, Anne F.; Schupf, Nicole; Manly, Jennifer J.; Luchsinger, José A.; Viswanathan, Anand; Martinez-Ramirez, Sergi; Greenberg, Steven M.; Mayeux, Richard; Brickman, Adam M.

    2014-01-01

    Background Normal aging is associated with decline in cognitive abilities, particularly in the domains of psychomotor speed and executive functioning. However, “aging,” per se, is not a cause of cognitive decline but rather a variable that likely captures multiple accumulating biological changes over time that collectively affect mental abilities. Recent work has focused on the role of cerebrovascular disease as one of the biological changes. In the current study, we examined whether lobar microbleeds, magnetic resonance imaging (MRI) signal voids due to hemosiderin deposits secondary to cerebral amyloid angiopathy, are associated with cognitive decline in normal aging. Previous studies that reported a relationship between the presence of lobar microbleeds and decreased cognitive abilities have been primarily cross-sectional. Here, we used a retrospective longitudinal design to examine whether the presence of lobar microbleeds is associated with the rate of cognitive decline among non-demented older adults. Methods Participants came from an ongoing longitudinal community-based aging study, in which subjects are evaluated at 18-24 month intervals and received a full medical, neurological, and neuropsychological examination at each of the follow-up visits. Gradient echo MRI scans were available on 197 non-demented participants (mean age: 84.15+/-5.02 years). Microbleeds were rated visually on horizontal view and divided into subcortical (basal ganglia, cerebellum) and lobar (frontal, temporal, parietal, occipital lobe) regions, and confirmed with coronal and sagittal view to exclude artifacts. Cognition was assessed with a neuropsychological battery, providing summary scores for memory, language, executive, and visuospatial abilities calculated through exploratory and confirmatory factor analyses. Using general estimating equations (GEE), we compared cognition cross-sectionally between individuals with 2 or more (n=11) and fewer than 2 (n=186) lobar microbleeds

  11. Age-related differences in mucosal barrier function and morphology of the small intestine in low and normal birth weight piglets.

    PubMed

    Huygelen, V; De Vos, M; Willemen, S; Fransen, E; Casteleyn, C; Van Cruchten, S; Van Ginneken, C

    2014-08-01

    To test the hypothesis that the mucosal maturation of the small intestine is altered in low birth weight piglets, pairs of naturally suckled low birth weight (LBW, n = 20) and normal birth weight (NBW, n = 20) littermate piglets were selected and sampled after 0, 3, 10, and 28 d of suckling. In vivo intestinal permeability was evaluated via a lactulose-mannitol absorption test. Other indirect measurements for mucosal barrier functioning included sampling for histology and immunohistochemistry (intestinal trefoil factor [ITF]), measuring intestinal alkaline phosphatase (IAP) activity, and immunoblotting for occludin, caspase-3, and proliferating cell nuclear antigen (PCNA). The lactulose-mannitol ratio did not differ between NBW and LBW piglets, but a significant increase in this ratio was observed in 28-d-old piglets (P = 0.001). Small intestinal villus height did not differ with age (P = 0.02) or birth weight (P = 0.20). In contrast, villus width (P = 0.02) and crypt depth (P < 0.05) increased gradually with age, but no birth-weight-related differences were observed. LBW piglets had significantly (P = 0.03) more ITF immunoreactive positive cells per villus area compared to NBW piglets, whereas no age (P = 0.82) or region-related (P = 0.13) differences could be observed. The activity of IAP in the small intestine was higher in newborn piglets compared to the older piglets. No significant differences in cell proliferation in the small intestine was observed (P = 0.47) between NBW and LBW piglets; the highest proliferation was seen in piglets of 28 d of age (P = 0.01). Newborn piglets had significantly fewer apoptotic cells, whereas more apoptotic cells were seen in piglets of 10 d of age (P < 0.01). In conclusion, birth weight did not affect the parameters related to intestinal barrier function investigated in this study, suggesting that the mucosal barrier function is not altered in LBW piglets. Nevertheless, these results confirm that the mucosal barrier function

  12. How family members manage risk around functional decline: The autonomy management process in households facing dementia

    PubMed Central

    Berry, Brandon; Apesoa-Varano, Ester Carolina; Gomez, Yarin

    2015-01-01

    Most dementia research investigates the social context of declining ability through studies of decision-making around medical treatment and end-of-life care. This study seeks to fill an important gap in research about how family members manage the risks of functional decline at home. Drawing on three waves of retrospective interviewing in 2012–2014, it investigates how family members in US households manage decline in an affected individual’s natural range of daily activities over time. The findings show that early on in the study period affected individuals were perceived to have awareness of their decline and routinely drew on family members for support. Support transformed when family members detected that the individual’s deficit awareness had diminished, creating a corresponding increase in risk of self-harm around everyday activities. With a loss of confidence in the individual’s ability to regulate his or her own activities to avoid these risks, family members employed unilateral practices to manage the individual’s autonomy around his or her activity involvements. These practices typically involved various deceits and ruses to discourage elders from engaging in activities perceived as potentially dangerous. The study concludes by discussing the implications that the social context of interpretive work around awareness and risk plays an important role in how families perceive an elder’s functional ability and manage his or her activity involvements. PMID:25697634

  13. Long-Term Effects of Traffic Particles on Lung Function Decline in the Elderly

    PubMed Central

    Litonjua, Augusto A.; Coull, Brent; Koutrakis, Petros; Sparrow, David; Vokonas, Pantel S.; Schwartz, Joel

    2014-01-01

    Rationale: Few studies have been performed on air pollution effects on lung function in the elderly, a vulnerable population with low reserve capacity, and even fewer have looked at changes in the rate of lung function decline. Objectives: We evaluated the effect of long-term exposure to black carbon on levels and rates of decline in lung function in the elderly. Methods: FVC and FEV1 were measured one to six times during the period 1995–2011 in 858 men participating in the Normative Aging Study. Exposure to black carbon, a tracer of traffic emissions, was estimated by a spatiotemporal land use regression model. We investigated the effects of moving averages of black carbon of 1–5 years before the lung function measurement using linear mixed models. Measurements and Main Results: A 0.5 μg/m3 increase in long-term exposure to black carbon was associated with an additional rate of decline in FVC and FEV1 of between 0.5% and 0.9% per year, respectively, depending on the averaging time. In addition, black carbon exposure before the baseline visit was associated with lower levels of both FVC and FEV1, with effect estimates increasing up to 6–7% with a 5-year average exposure. Conclusions: Our results support adverse effects of long-term exposure to traffic particles on lung function level and rate of decline in the elderly and suggest that functionally significant differences in health and risk of disability occur below the annual Environmental Protection Agency National Air Quality Standards. PMID:25028775

  14. Age-related effect of peptide YY (PYY) on paw edema in the rat: the function of Y1 receptors on inflammatory cells.

    PubMed

    Stanojević, Stanislava; Vujić, Vesna; Kovacević-Jovanović, Vesna; Mitić, Katarina; Kosec, Dusko; Hörsten, Stephan von; Dimitrijević, Mirjana

    2006-08-01

    It is well documented that neuropeptides participate in local inflammatory reaction and modulate functions of inflammatory cells. The aim of the study was to determine a link between in vivo and in vitro effects of NPY-related peptides on inflammatory response with respect to ageing. Peptide YY (PYY) intraplantarly applied decreases concanavalin A-induced paw edema in 3 and 8 months, but not in 24 months old male rats of Albino Oxford strain. The use of NPY-related receptor-specific peptides and Y1 receptor antagonist revealed that anti-inflammatory effect of PYY is mediated via NPY Y1 receptors. PYY in vitro decreases adherence of macrophages from 8 months, but not from 3 and 24 months old rats and this effect is also mediated via NPY Y1 receptor. Additionally, PYY (10(-6)M) decreases NBT reduction in macrophages from 3 and 8 months old rats, and suppresses NO production in cells from 24 months old rats, albeit regardless of absence of in vivo effect of PYY on inflammation in aged rats. It is concluded that aged rats are less responsive to anti-inflammatory action of PYY compared to adult and young rats, and that ageing is associated with altered NPY Y1 receptor functioning.

  15. Modification by acrolein, a component of tobacco smoke and age-related oxidative stress, mediates functional impairment of human apolipoprotein E.

    PubMed

    Tamamizu-Kato, Shiori; Wong, Jason Yiu; Jairam, Vikram; Uchida, Koji; Raussens, Vincent; Kato, Hiroyuki; Ruysschaert, Jean-Marie; Narayanaswami, Vasanthy

    2007-07-17

    Oxidative damage to proteins such as apolipoprotein B-100 increases the atherogenicity of low-density lipoproteins (LDL). However, little is known about the potential oxidative damage to apolipoprotein E (apoE), an exchangeable antiatherogenic apolipoprotein. ApoE plays an integral role in lipoprotein metabolism by regulating the plasma cholesterol and triglyceride levels. Hepatic uptake of lipoproteins is facilitated by apoE's ability to bind with cell surface heparan sulfate proteoglycans and to lipoprotein receptors via basic residues in its 22 kDa N-terminal domain (NT). We investigated the effect of acrolein, an aldehydic product of endogenous lipid peroxidation and a tobacco smoke component, on the conformation and function of recombinant human apoE3-NT. Acrolein caused oxidative modification of apoE3-NT as detected by Western blot with acrolein-lysine-specific antibodies, and tertiary conformational alterations. Acrolein modification impairs the ability of apoE3-NT to interact with heparin and the LDL receptor. Furthermore, acrolein-modified apoE3-NT displayed a 5-fold decrease in its ability to interact with lipid surfaces. Our data indicate that acrolein disrupts the functional integrity of apoE3, which likely interferes with its role in regulating plasma cholesterol homeostasis. These observations have implications regarding the role of apoE in the pathogenesis of smoking- and oxidative stress-mediated cardiovascular and cerebrovascular diseases.

  16. Collateral vessel number, plaque burden, and functional decline in peripheral artery disease.

    PubMed

    McDermott, Mary M; Carr, James; Liu, Kiang; Kramer, Christopher M; Yuan, Chun; Tian, Lu; Criqui, Michael H; Guralnik, Jack M; Ferrucci, Luigi; Zhao, Lihui; Xu, Dongxiang; Kibbe, Melina; Berry, Jarett; Carroll, Timothy J

    2014-08-01

    Associations of collateral vessels and lower extremity plaque with functional decline are unknown. Among people with peripheral artery disease (PAD), we determined whether greater superficial femoral artery (SFA) plaque burden combined with fewer lower extremity collateral vessels was associated with faster functional decline, compared to less plaque and/or more numerous collateral vessels. A total of 226 participants with ankle-brachial index (ABI) <1.00 underwent magnetic resonance imaging of lower extremity collateral vessels and cross-sectional imaging of the proximal SFA. Participants were categorized as follows: Group 1 (best), maximum plaque area < median and collateral vessel number ≥6 (median); Group 2, maximum plaque area < median and collateral vessel number <6; Group 3, maximum plaque area > median and collateral vessel number ≥6; Group 4 (worst), maximum plaque area > median and collateral vessel number <6. Functional measures were performed at baseline and annually for 2 years. Analyses adjust for age, sex, race, comorbidities, and other confounders. Annual changes in usual-paced walking velocity were: Group 1, +0.01 m/s; Group 2, -0.02 m/s; Group 3, -0.01 m/s; Group 4, -0.05 m/s (p-trend=0.008). Group 4 had greater decline than Group 1 (p<0.001), Group 2 (p=0.029), and Group 3 (p=0.010). Similar trends were observed for fastest-paced 4-meter walking velocity (p-trend=0.018). Results were not substantially changed when analyses were repeated with additional adjustment for ABI. However, there were no associations of SFA plaque burden and collateral vessel number with decline in 6-minute walk. In summary, a larger SFA plaque burden combined with fewer collateral vessels is associated with a faster decline in usual and fastest-paced walking velocity in PAD.

  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. Effect of Peritoneal Dialysis Modality on the 1-Year Rate of Decline of Residual Renal Function

    PubMed Central

    Kim, Chan Ho; Oh, Hyung Jung; Lee, Mi Jung; Kwon, Young Eun; Kim, Yung Ly; Nam, Ki Heon; Park, Kyoung Sook; An, Seong Yeong; Ko, Kwang Il; Koo, Hyang Mo; Doh, Fa Mee; Han, Seung Hyeok; Yoo, Tae-Hyun; Kim, Beom Seok; Kang, Shin-Wook

    2014-01-01

    Purpose The effect of different peritoneal dialysis (PD) modalities on the decline in residual renal function (RRF) is unclear due to inconsistencies among studies. In particular, the effect of automated peritoneal dialysis (APD) modalities [continuous cyclic peritoneal dialysis (CCPD) and nightly intermittent peritoneal dialysis (NIPD)] on RRF has not been examined in a large cohort. Materials and Methods We conducted a single-center retrospective study to investigate the association between PD modalities and decline in RRF in 142 incident PD patients [34 on CCPD, 36 on NIPD, and 72 on continuous ambulatory peritoneal dialysis (CAPD)]. RRF was measured within 2 months from PD start and at 1 year after PD initiation. Results The RRF at 1 year after PD initiation was 1.98±2.20 mL/min/1.73 m2 in CCPD patients and 3.63±3.67 mL/min/1.73 m2 in NIPD patients, which were moderately lower than 4.23±3.51 mL/min/1.73 m2 in CAPD patients (p=0.064). Moreover, there was no significant difference in the 1-year rate of decline of RRF between CCPD and NIPD patients, although APD patients had a faster 1-year RRF decline rate than CAPD patients (CCPD and NIPD vs. CAPD: -45.68 and -36.69 vs. 1.17%/year, p=0.045). APD was associated with a more rapid decline in RRF in patients with end-stage renal disease undergoing PD, although multivariate analysis attenuated the significance of this finding (β=-31.50; 95% CI, -63.61 to 0.62; p=0.052). Conclusion Our results suggest that CAPD might be more helpful than APD for preserving RRF during the first year of dialysis therapy, although there was no significant difference in the 1-year rate of decline of RRF between the two APD modalities. PMID:24339299

  19. Urinary Markers of Kidney Injury and Kidney Function Decline in HIV-Infected Women

    PubMed Central

    Shlipak, Michael G.; Scherzer, Rebecca; Abraham, Alison; Tien, Phyllis C.; Grunfeld, Carl; Peralta, Carmen A.; Devarajan, Prasad; Bennett, Michael; Butch, Anthony W.; Anastos, Kathryn; Cohen, Mardge H.; Nowicki, Marek; Sharma, Anjali; Young, Mary A.; Sarnak, Mark J.; Parikh, Chirag R.

    2012-01-01

    Objective HIV-infected persons have substantially higher risk of kidney failure than persons without HIV, but serum creatinine levels are insensitive for detecting declining kidney function. We hypothesized that urine markers of kidney injury would be associated with declining kidney function among HIV-infected women. Methods In the Women's Interagency HIV Study (WIHS), we measured concentrations of albumin-to-creatinine ratio (ACR), interleukin-18 (IL-18), kidney injury marker-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) from stored urine among 908 HIV-infected and 289 uninfected participants. Primary analyses used cystatin C based estimated glomerular filtration rate (CKD-EPI eGFRcys) as the outcome, measured at baseline and two follow-up visits over eight years; secondary analyses used creatinine (CKD-EPI eGFRcr). Each urine biomarker was categorized into tertiles, and kidney decline was modeled with both continuous and dichotomized outcomes. Results Compared with the lowest tertiles, the highest tertiles of ACR (−0.15ml/min/1.73m2, p<0.0001), IL-18 (−0.09ml/min/1.73m2, p<0.0001) and KIM-1 (−0.06ml/min/1.73m2, p<0.001) were independently associated with faster eGFRcys decline after multivariate adjustment including all three biomarkers among HIV-infected women. Among these biomarkers, only IL-18 was associated with each dichotomized eGFRcys outcome: ≥3% (Relative Risk 1.40; 95%CI 1.04-1.89); ≥5% (1.88; 1.30-2.71); and ≥10% (2.16; 1.20-3.88) for the highest versus lowest tertile. In alternative models using eGFRcr, the high tertile of KIM-1 had independent associations with 5% (1.71; 1.25-2.33) and 10% (1.78; 1.07-2.96) decline, and the high IL-18 tertile with 10% decline (1.97; 1.00-3.87). Conclusions Among HIV-infected women in the WIHS cohort, novel urine markers of kidney injury detect risk for subsequent declines in kidney function. PMID:23023103

  20. [Effect of preparations melatonin and epitalon on the age-related dynamics of thyrotrophic activity of the hypophysis and thyroid gland function in different light regimes].

    PubMed

    Vinogradova, I A

    2009-01-01

    The influence of different light regimes (standard lightning--12 hours light/ 12 hours darkness; natural light regime of the North-West of Russia; constant darkness and constant lightning), melatonin and epitalon on the thyrotrophic activity of hypophysis and on the function of thyroid gland was studied. It has been found out that the maximum values of free thyroxin and triiodothyronine in blood were observed in the conditions of constant lightning and the minimal values--in the conditions of light deprivation. In the conditions of natural lightning of Karelia, with orientation on seasonal lightning, the following annual-circadian rhythms were observed: in autumn (period of short lightness duration) the level of free T3 was the lowest; in spring (period of short darkness duration) it was the highest; the inverse relationship was observed by the comparison of free T4 concentration. The lowest values of TSH were observed in old rats kept in constant light and natural light regimes. The concentration of TSH in blood was practically on the same level in the standard regime and in the regime of light deprivation. The age changes of the level of hormones appeared later in rats who received medication, in comparison with the control sets of animals. The use of melatonin and epitalon smoothened the seasonal variations of the level of thyroidal hormones in blood in the lightning conditions of Karelia.

  1. Progressive Bidirectional Age-Related Changes in Default Mode Network Effective Connectivity across Six Decades.

    PubMed

    Li, Karl; Laird, Angela R; Price, Larry R; McKay, D Reese; Blangero, John; Glahn, David C; Fox, Peter T

    2016-01-01

    The default mode network (DMN) is a set of regions that is tonically engaged during the resting state and exhibits task-related deactivation that is readily reproducible across a wide range of paradigms and modalities. The DMN has been implicated in numerous disorders of cognition and, in particular, in disorders exhibiting age-related cognitive decline. Despite these observations, investigations of the DMN in normal aging are scant. Here, we used blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) acquired during rest to investigate age-related changes in functional connectivity of the DMN in 120 healthy normal volunteers comprising six, 20-subject, decade cohorts (from 20-29 to 70-79). Structural equation modeling (SEM) was used to assess age-related changes in inter-regional connectivity within the DMN. SEM was applied both using a previously published, meta-analytically derived, node-and-edge model, and using exploratory modeling searching for connections that optimized model fit improvement. Although the two models were highly similar (only 3 of 13 paths differed), the sample demonstrated significantly better fit with the exploratory model. For this reason, the exploratory model was used to assess age-related changes across the decade cohorts. Progressive, highly significant changes in path weights were found in 8 (of 13) paths: four rising, and four falling (most changes were significant by the third or fourth decade). In all cases, rising paths and falling paths projected in pairs onto the same nodes, suggesting compensatory increases associated with age-related decreases. This study demonstrates that age-related changes in DMN physiology (inter-regional connectivity) are bidirectional, progressive, of early onset and part of normal aging.

  2. Progressive Bidirectional Age-Related Changes in Default Mode Network Effective Connectivity across Six Decades

    PubMed Central

    Li, Karl; Laird, Angela R.; Price, Larry R.; McKay, D. Reese; Blangero, John; Glahn, David C.; Fox, Peter T.

    2016-01-01

    The default mode network (DMN) is a set of regions that is tonically engaged during the resting state and exhibits task-related deactivation that is readily reproducible across a wide range of paradigms and modalities. The DMN has been implicated in numerous disorders of cognition and, in particular, in disorders exhibiting age-related cognitive decline. Despite these observations, investigations of the DMN in normal aging are scant. Here, we used blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) acquired during rest to investigate age-related changes in functional connectivity of the DMN in 120 healthy normal volunteers comprising six, 20-subject, decade cohorts (from 20–29 to 70–79). Structural equation modeling (SEM) was used to assess age-related changes in inter-regional connectivity within the DMN. SEM was applied both using a previously published, meta-analytically derived, node-and-edge model, and using exploratory modeling searching for connections that optimized model fit improvement. Although the two models were highly similar (only 3 of 13 paths differed), the sample demonstrated significantly better fit with the exploratory model. For this reason, the exploratory model was used to assess age-related changes across the decade cohorts. Progressive, highly significant changes in path weights were found in 8 (of 13) paths: four rising, and four falling (most changes were significant by the third or fourth decade). In all cases, rising paths and falling paths projected in pairs onto the same nodes, suggesting compensatory increases associated with age-related decreases. This study demonstrates that age-related changes in DMN physiology (inter-regional connectivity) are bidirectional, progressive, of early onset and part of normal aging. PMID:27378909

  3. White matter injury and microglia/macrophage polarization are strongly linked with age-related long-term deficits in neurological function after stroke.

    PubMed

    Suenaga, Jun; Hu, Xiaoming; Pu, Hongjian; Shi, Yejie; Hassan, Sulaiman Habib; Xu, Mingyue; Leak, Rehana K; Stetler, R Anne; Gao, Yanqin; Chen, Jun

    2015-10-01

    , aged mice exhibited significantly reduced M2 polarization compared to young adults. Remarkably, we discovered a strong positive correlation between favorable neurological outcomes after dMCAO and MBP levels or the number of M2 microglia/macrophages. In conclusion, our studies suggest that the distal MCAO stroke model consistently results in ischemic brain injury with long-term behavioral deficits, and is therefore suitable for the evaluation of long-term stroke outcomes. Furthermore, aged mice exhibit deterioration of functional outcomes after stroke and this deterioration is linked to white matter damage and reductions in M2 microglia/macrophage polarization.

  4. Aquaporin 5 Polymorphisms and Rate of Lung Function Decline in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Hansel, Nadia N.; Sidhaye, Venkataramana; Rafaels, Nicholas M.; Gao, Li; Gao, Peisong; Williams, Renaldo; Connett, John E.; Beaty, Terri H.; Mathias, Rasika A.; Wise, Robert A.; King, Landon S.; Barnes, Kathleen C.

    2010-01-01

    Rationale Aquaporin-5 (AQP5) can cause mucus overproduction and lower lung function. Genetic variants in the AQP5 gene might be associated with rate of lung function decline in chronic obstructive pulmonary disease (COPD). Methods Five single nucleotide polymorphisms (SNPs) in AQP5 were genotyped in 429 European American individuals with COPD randomly selected from the NHLBI Lung Health Study. Mean annual decline in FEV1 % predicted, assessed over five years, was calculated as a linear regression slope, adjusting for potential covariates and stratified by smoking status. Constructs containing the wildtype allele and risk allele of the coding SNP N228K were generated using site-directed mutagenesis, and transfected into HBE-16 (human bronchial epithelial cell line). AQP5 abundance and localization were assessed by immunoblots and confocal immunofluoresence under control, shear stress and cigarette smoke extract (CSE 10%) exposed conditions to test for differential expression or localization. Results Among continuous smokers, three of the five SNPs tested showed significant associations (0.02>P>0.004) with rate of lung function decline; no associations were observed among the group of intermittent or former smokers. Haplotype tests revealed multiple association signals (0.012>P>0.0008) consistent with the single-SNP results. In HBE16 cells, shear stress and CSE led to a decrease in AQP5 abundance in the wild-type, but not in the N228K AQP5 plasmid. Conclusions Polymorphisms in AQP5 were associated with rate of lung function decline in continuous smokers with COPD. A missense mutation modulates AQP-5 expression in response to cigarette smoke extract and shear stress. These results suggest that AQP5 may be an important candidate gene for COPD. PMID:21151978

  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. Interleukin-6 predicts short-term global functional decline in the oldest old: results from the BELFRAIL study.

    PubMed

    Adriaensen, Wim; Matheï, Catharina; Vaes, Bert; van Pottelbergh, Gijs; Wallemacq, Pierre; Degryse, Jean-Marie

    2014-01-01

    The chronic inflammatory state at old age may contribute to the pathophysiology of or reflect chronic conditions resulting in loss of physical and mental functioning. Therefore, our objective was to examine the predictive value of a large battery of serum inflammatory markers as risk indicators for global functional decline and its specific physical and mental determinants in the oldest old. Global functional decline and specific aspects of physical and mental functional decline were assessed during an average of 1.66 years (±0.21) in a sample of 303 persons aged 80 years or older of the BELFRAIL study. Serum levels of 14 inflammatory proteins, including cytokines, growth factors, and acute phase proteins, were measured at baseline. Almost 20 % of the participants had a significant global functional decline over time. Interleukin (IL)-6 serum levels were uniquely positively associated with global functional decline, even after correcting for multiple confounders (odds ratio 1.51). Odds ratios for the individual aspects (physical dependency, physical performance, cognition, and depression) of functioning were lower, and composite scores of physical or mental decline were not significant. The proportion of global functional decline exhibited a dose-response curve with increasing levels of IL-6. Thus, IL-6 is an independent risk indicator for accelerated global functional decline in the oldest old. Our results suggest that simple serum levels of IL-6 may be very useful in short-term identification or evaluation of global functional status in the oldest old.

  7. p16 loss rescues functional decline of Brca1-deficient mammary stem cells.

    PubMed

    Scott, Alexandria; Bai, Feng; Chan, Ho Lam; Liu, Shiqin; Slingerland, Joyce M; Robbins, David J; Capobianco, Anthony J; Pei, Xin-Hai

    2017-02-22

    Recent evidence indicates that the accumulation of endogenous DNA damage can induce senescence and limit the function of adult stem cells. It remains elusive whether deficiency in DNA damage repair is associated with the functional alteration of mammary stem cells. In this article, we reported that senescence was induced in mammary epithelial cells during aging along with increased expression of p16Ink4a (p16), an inhibitor of CDK4 and CKD6. Loss of p16 abrogated the age-induced senescence in mammary epithelial cells and significantly increased mammary stem cell function. We showed that loss of Brca1, a tumor suppressor that functions in DNA damage repair, in the mammary epithelium induced senescence with induction of p16 and a decline of stem cell function, which was rescued by p16 loss. These data not only answer the question as to whether deficiency in DNA damage repair is associated with the functional decline of mammary stem cells, but also identify the role of p16 in suppressing Brca1-deficient mammary stem cell function.

  8. 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.

  9. 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

  10. Decline of lymphatic vessel density and function in murine skin during aging.

    PubMed

    Karaman, Sinem; Buschle, Dorina; Luciani, Paola; Leroux, Jean-Christophe; Detmar, Michael; Proulx, Steven T

    2015-10-01

    Lymphatic vessels play important roles in the pathogenesis of many conditions that have an increased prevalence in the elderly population. However, the effects of the aging process on the lymphatic system are still relatively unknown. We have applied non-invasive imaging and whole-mount staining techniques to assess the lymphatic vessel function and morphology in three different age groups of mice: 2 months (young), 7 months (middle-aged), and 18 months (aged). We first developed and validated a new method to quantify lymphatic clearance from mouse ear skin, using a lymphatic-specific near-infrared tracer. Using this method, we found that there is a prominent decrease in lymphatic vessel function during aging since the lymphatic clearance was significantly delayed in aged mice. This loss of function correlated with a decreased lymphatic vessel density and a reduced lymphatic network complexity in the skin of aged mice as compared to younger controls. The blood vascular leakage in the skin was slightly increased in the aged mice, indicating that the decreased lymphatic function was not caused by a reduced capillary filtration in aged skin. The decreased function of lymphatic vessels with aging might have implications for the pathogenesis of a number of aging-related diseases.

  11. Predictors of Residual Renal Function Decline in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis

    PubMed Central

    Szeto, Cheuk-Chun; Kwan, Bonnie Ching-Ha; Chow, Kai-Ming; Chung, Sebastian; Yu, Vincent; Cheng, Phyllis Mei-Shan; Leung, Chi-Bon; Law, Man-Ching; Li, Philip Kam-Tao

    2015-01-01

    ♦ Background: Residual renal function (RRF) is an important prognostic indicator in continuous ambulatory peritoneal dialysis (CAPD) patients. We determined the predictors of RRF loss in a cohort of incident CAPD patients. ♦ Methods: We reviewed the record of 645 incident CAPD patients. RRF loss is represented by the slope of decline of residual glomerular filtration rate (GFR) as well as the time to anuria. ♦ Results: The average rate of residual GFR decline was -0.083 ± 0.094 mL/min/month. The rate of residual GFR decline was faster with a higher proteinuria (r = -0.506, p < 0.0001) and baseline residual GFR (r = -0.560, p < 0.0001). Multivariate analysis showed that proteinuria, baseline residual GFR, and the use of diuretics were independent predictors of residual GFR decline. Cox proportional hazard model showed that proteinuria, glucose exposure, and the number of peritonitis episodes were independent predictors of progression to anuria, while a higher baseline GFR was protective. Each 1 g/day of proteinuria is associated with a 13.2% increase in the risk of progressing to anuria, each 10 g/day higher glucose exposure is associated with a 2.5% increase in risk, while each peritonitis episode confers a 3.8% increase in risk. ♦ Conclusions: Our study shows that factors predicting the loss of residual solute clearance and urine output are different. Proteinuria, baseline residual GFR, and the use of diuretics are independently related to the rate of RRF decline in CAPD patients, while proteinuria, glucose exposure, and the number of peritonitis episodes are independent predictors for the development of anuria. The role of anti-proteinuric therapy and measures to prevent peritonitis episodes in the preservation of RRF should be tested in future studies. PMID:24497594

  12. Risk of decline in functional activities in dementia with Lewy bodies and Alzheimer disease.

    PubMed

    Gill, Dawn P; Koepsell, Thomas D; Hubbard, Rebecca A; Kukull, Walter A

    2011-01-01

    We examined the risk of 1-year decline in 4 everyday activities in patients with dementia with Lewy bodies (DLB), relative to patients with Alzheimer disease (AD). Data were from the National Alzheimer's Coordinating Center, gathered from 32 Alzheimer's Disease Centers. Participants (n=1880) were: aged 60+ years, demented with a primary clinical diagnosis of probable AD or DLB, and had a global Clinical Dementia Rating of 0.5 to 2. The activities were measured with the Functional Activities Questionnaire. In modified Poisson regression models adjusted for demographics, baseline activity, years from symptom onset, cognitive impairment, and comorbidities; DLB participants aged 67 to 81 years had 1.5 to 2 times increased risk of decline in performing basic kitchen tasks, engaging in games/hobbies, and paying attention/understanding, relative to AD participants of the same age (P<0.05). There was no significant difference between AD and DLB participants beyond this age range. For decline in ability to go shopping alone, there was also no significant difference between AD and DLB participants. In summary, the functional course of DLB, relative to AD, may depend on the age of the patient. These findings may provide anticipatory guidance to families and healthcare providers, which may be useful in the planning of care strategies.

  13. Does a physically active lifestyle attenuate decline in all cognitive functions in old age?

    PubMed

    Ballesteros, Soledad; Mayas, Julia; Reales, Jose Manuel

    2013-07-01

    In this study, the performance of a group of 20 physically active older adults was compared with that of a group of 20 sedentary healthy older adults while performing a series of cognitive tasks. These tasks were designed to assess processes that deteriorate most with age, namely executive control (assessed with the Wisconsin Card Sorting Task) and processing speed (simple and choice reaction time tasks). A repetition priming task that does not decline with age, involving attended and unattended picture outlines at encoding, was also included as a control task. The results show that a physically active lifestyle has a positive influence on executive control, processing speed, and controlled processing. As expected, a physically active lifestyle did not enhance repetition priming for attended stimuli, nor did it produce priming for unattended stimuli at encoding. Both groups exhibited robust priming for attended stimuli and no priming for unattended ones. Executive control functions are of vital importance for independent living in old age. These results have practical implications for enhancing the cognitive processes that decline most in old age. Promoting a physically active lifestyle throughout adulthood could significantly reduce the decline of effortful executive control functions in old age.

  14. NK cell activating receptor ligand expression in lymphangioleiomyomatosis is associated with lung function decline

    PubMed Central

    Osterburg, Andrew R.; Nelson, Rebecca L.; Yaniv, Benyamin Z.; Foot, Rachel; Donica, Walter R.F.; Nashu, Madison A.; Liu, Huan; Wikenheiser-Brokamp, Kathryn A.; Moss, Joel; McCormack, Francis X.; Borchers, Michael T.

    2016-01-01

    Lymphangioleiomyomatosis (LAM) is a rare lung disease of women that leads to progressive cyst formation and accelerated loss of pulmonary function. Neoplastic smooth muscle cells from an unknown source metastasize to the lung and drive destructive remodeling. Given the role of NK cells in immune surveillance, we postulated that NK cell activating receptors and their cognate ligands are involved in LAM pathogenesis. We found that ligands for the NKG2D activating receptor UL-16 binding protein 2 (ULBP2) and ULBP3 are localized in cystic LAM lesions and pulmonary nodules. We found elevated soluble serum ULBP2 (mean = 575 pg/ml ± 142) in 50 of 100 subjects and ULBP3 in 30 of 100 (mean = 8,300 pg/ml ± 1,515) subjects. LAM patients had fewer circulating NKG2D+ NK cells and decreased NKG2D surface expression. Lung function decline was associated with soluble NKG2D ligand (sNKG2DL) detection. The greatest rate of decline forced expiratory volume in 1 second (FEV1, –124 ± 30 ml/year) in the 48 months after enrollment (NHLBI LAM Registry) occurred in patients expressing both ULBP2 and ULBP3, whereas patients with undetectable sNKG2DL levels had the lowest rate of FEV1 decline (–32.7 ± 10 ml/year). These data suggest a role for NK cells, sNKG2DL, and the innate immune system in LAM pathogenesis. PMID:27734028

  15. 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

  16. Accelerated aging-related transcriptome changes in the female prefrontal cortex.

    PubMed

    Yuan, Yuan; Chen, Yi-Ping Phoebe; Boyd-Kirkup, Jerome; Khaitovich, Philipp; Somel, Mehmet

    2012-10-01

    Human female life expectancy is higher than that of males. Intriguingly, it has been reported that women display faster rates of age-related cognitive decline and a higher prevalence of Alzheimer's disease (AD). To assess the molecular bases of these contradictory trends, we analyzed differences in expression changes with age between adult males and females, in four brain regions. In the superior frontal gyrus (SFG), a part of the prefrontal cortex, we observed manifest differences between the two sexes in the timing of age-related changes, that is, sexual heterochrony. Intriguingly, age-related expression changes predominantly occurred earlier, or at a faster pace, in females compared to men. These changes included decreased energy production and neural function and up-regulation of the immune response, all major features of brain aging. Furthermore, we found that accelerated expression changes in the female SFG correlated with expression changes observed in AD, as well as stress effects in the frontal cortex. Accelerated aging-related changes in the female SFG transcriptome may provide a link between a higher stress exposure or sensitivity in women and the higher prevalence of AD.

  17. Dysregulation of the Bmi-1/p16(Ink⁴a) pathway provokes an aging-associated decline of submandibular gland function.

    PubMed

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

    2015-08-01

    Bmi-1 prevents stem cell aging, at least partly, by blocking expression of the cyclin-dependent kinase inhibitor p16(Ink4a) . Therefore, dysregulation of the Bmi-1/p16(Ink4a) pathway is considered key to the loss of tissue homeostasis and development of associated degenerative diseases during aging. However, because Bmi-1 knockout (KO) mice die within 20 weeks after birth, it is difficult to determine exactly where and when dysregulation of the Bmi-1/p16(Ink4a) pathway occurs during aging in vivo. Using real-time in vivo imaging of p16(Ink4a) expression in Bmi-1-KO mice, we uncovered a novel function of the Bmi-1/p16(Ink4a) pathway in controlling homeostasis of the submandibular glands (SMGs), which secrete saliva into the oral cavity. This pathway is dysregulated during aging in vivo, leading to induction of p16(Ink4a) expression and subsequent declined SMG function. These findings will advance our understanding of the molecular mechanisms underlying the aging-related decline of SMG function and associated salivary gland hypofunction, which is particularly problematic among the elderly.

  18. Extent of resection and postoperative functional declination of Klekamp's type A intramedullary tumors in adult patients

    PubMed Central

    Rabadán, Alejandra T.; Hernandez, Diego; Paz, Leonardo

    2016-01-01

    Background: The most commonly primary intramedullary spinal cord tumors (ISCT) in adults are the noninfiltrative lesions, corresponding to Klekamp's type A classification. There are few reports exclusively considering this type of lesions, their resectability and postoperative functional declination risk, and to our knowledge, none from Latin America. This led us to evaluate our results to provide information that might contribute to the decision making process in our region. Methods: A retrospective observational study was conducted comprising a cohort of 21 adults having primary Klekamp's type A ISCT. Diagnosis was made by magnetic resonance imaging (MRI), along with diffusion tensor/tractography in the last 7 cases. Preoperative functional status was assessed using the McCormick's modified scale (mMs), which was also used for the postoperative assessment within postoperative 90 days period. MRI was used to confirm the extent of resection. Results: Radical resection was obtained in 20/21 cases. The postoperative functional status was stable in 42.8% of the cases, and in 57.4% was even better than in the preoperative period. Temporary declination was observed in 2 cases in the early postoperative period. There were 2 cases with complications; one patient had cerebrospinal fluid fistula with meningitis, which was conservatively resolved, and another patient died from pulmonary embolism. Conclusion: Although the number of patients in this series does not allow to conclude from a statistical point of view, the outcomes showed that the modern surgery of Klekamp's type A ISCT permits a complete resection with low functional declination risk. PMID:28144469

  19. Genome-wide association study of kidney function decline in individuals of European descent

    PubMed Central

    Gorski, Mathias; Tin, Adrienne; Garnaas, Maija; McMahon, Gearoid M.; Chu, Audrey Y.; Tayo, Bamidele O.; Pattaro, Cristian; Teumer, Alexander; Chasman, Daniel I.; Chalmers, John; Hamet, Pavel; Tremblay, Johanne; Woodward, Marc; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur; Harris, Tammara B.; Launer, Lenore J.; Smith, Albert V.; Mitchell, Braxton D.; O'Connell, Jeffrey R.; Shuldiner, Alan R.; Coresh, Josef; Li, Man; Freudenberger, Paul; Hofer, Edith; Schmidt, Helena; Schmidt, Reinhold; Holliday, Elizabeth G.; Mitchell, Paul; Wang, Jie Jin; de Boer, Ian H.; Li, Guo; Siscovick, David S.; Kutalik, Zoltan; Corre, Tanguy; Vollenweider, Peter; Waeber, Gérard; Gupta, Jayanta; Kanetsky, Peter A.; Hwang, Shih-Jen; Olden, Matthias; Yang, Qiong; de Andrade, Mariza; Atkinson, Elizabeth J.; Kardia, Sharon L.R.; Turner, Stephen T.; Stafford, Jeanette M.; Ding, Jingzhong; Liu, Yongmei; Barlassina, Cristina; Cusi, Daniele; Salvi, Erika; Staessen, Jan A; Ridker, Paul M; Grallert, Harald; Meisinger, Christa; Müller-Nurasyid, Martina; Krämer, Bernhard K.; Kramer, Holly; Rosas, Sylvia E.; Nolte, Ilja M.; Penninx, Brenda W.; Snieder, Harold; Del Greco, Fabiola; Franke, Andre; Nöthlings, Ute; Lieb, Wolfgang; Bakker, Stephan J.L.; Gansevoort, Ron T.; van der Harst, Pim; Dehghan, Abbas; Franco, Oscar H.; Hofman, Albert; Rivadeneira, Fernando; Sedaghat, Sanaz; Uitterlinden, André G.; Coassin, Stefan; Haun, Margot; Kollerits, Barbara; Kronenberg, Florian; Paulweber, Bernhard; Aumann, Nicole; Endlich, Karlhans; Pietzner, Mike; Völker, Uwe; Rettig, Rainer; Chouraki, Vincent; Helmer, Catherine; Lambert, Jean-Charles; Metzger, Marie; Stengel, Benedicte; Lehtimäki, Terho; Lyytikäinen, Leo-Pekka; Raitakari, Olli; Johnson, Andrew; Parsa, Afshin; Bochud, Murielle; Heid, Iris M.; Goessling, Wolfram; Köttgen, Anna; Kao, H. Linda; Fox, Caroline S.; Böger, Carsten A.

    2014-01-01

    Genome wide association studies (GWAS) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohorts with serial kidney function measurements within the CKDGen Consortium, followed by independent replication among additional participants from 13 cohorts. In stage 1 GWAS meta-analysis, SNPs at MEOX2, GALNT11, IL1RAP, NPPA, HPCAL1 and CDH23 showed the strongest associations for at least one trait, in addition to the known UMOD locus which showed genome-wide significance with an annual change in eGFR. In stage 2 meta-analysis, the significant association at UMOD was replicated. Associations at GALNT11 with Rapid Decline (annual eGFRdecline of 3ml/min/1.73m2 or more), and CDH23 with eGFR change among those with CKD showed significant suggestive evidence of replication. Combined stage 1 and 2 meta-analyses showed significance for UMOD, GALNT11 and CDH23. Morpholino knockdowns of galnt11 and cdh23 in zebrafish embryos each had signs of severe edema 72 hours after gentamicin treatment compared to controls, but no gross morphological renal abnormalities before gentamicin administration. Thus, our results suggest a role in the deterioration of kidney function for the loci GALNT11 and CDH23, and show that the UMOD locus is significantly associated with kidney function decline. PMID:25493955

  20. Light-Intensity Activity Attenuates Functional Decline in Older Cancer Survivors

    PubMed Central

    Blair, Cindy K.; Morey, Miriam C.; Desmond, Renee A.; Cohen, Harvey Jay; Sloane, Richard; Snyder, Denise C.; Demark-Wahnefried, Wendy

    2014-01-01

    While moderate-vigorous intensity physical activities (MVPA) confer the greatest health benefits, evidence suggests that light-intensity activities are also beneficial, particularly for older adults and individuals with moderate-severe comorbidities. Purpose To examine cross-sectional and longitudinal associations between light-intensity activity and physical function in older cancer survivors at increased risk for age- and treatment-related comorbidities, including accelerated functional decline. Methods The analysis included data from 641 breast, prostate, and colorectal cancer survivors (54% female) aged 65 and older who participated in a 1-year, home-based diet and exercise intervention designed to reduce the rate of physical function decline. ANCOVA was used to compare means of physical function across levels of PA intensity (low-light (LLPA): 1.5-2.0 METs; high-light (HLPA): 2.1-2.9 METs; MVPA: ≥3.0 METs). Results In cross-sectional analyses, increasing tertiles of light-intensity activity were associated with higher scores for all 3 measures of physical function (all p-values <0.005), after adjustment for age, sex, BMI, comorbidity, symptoms, and MVPA. Associations were stronger for HLPA than for LLPA. Compared with survivors who decreased or remained stable in MVPA and HLPA at the post-intervention follow-up, those who increased in HLPA, but decreased or remained stable in MVPA, reported higher physical function scores (LSMeans (95% CI): SF-36 physical function subscale: -5.58 (-7.96, -3.20) vs. -2.54 (-5.83, 0.75), p=0.14; basic lower extremity function: -2.00 (-3.45, -0.55) vs. 0.28 (-1.72, 2.28), p=0.07; advanced lower extremity function: -2.58 (-4.00, -1.15) vs. 0.44 (-1.52, 2.40), p=0.01). Conclusion Our findings suggest that increasing light-intensity activities, especially HLPA, may be a viable approach to reducing the rate of physical function decline in individuals who are unable or reluctant to initiate or maintain adequate levels of moderate

  1. Growth Differentiation Factor 11 is a Circulating Factor that Reverses Age-Related Cardiac Hypertrophy

    PubMed Central

    Loffredo, Francesco S.; Steinhauser, Matthew L.; Jay, Steven M.; Gannon, Joseph; Pancoast, James R.; Yalamanchi, Pratyusha; Sinha, Manisha; Dall’Osso, Claudia; Khong, Danika; Shadrach, Jennifer L.; Miller, Christine M.; Singer, Britta S.; Stewart, Alex; Psychogios, Nikolaos; Gerszten, Robert E.; Hartigan, Adam J.; Kim, Mi-Jeong; Serwold, Thomas; Wagers, Amy J.; Lee, Richard T.

    2013-01-01

    Summary The most common form of heart failure occurs with normal systolic function and often involves cardiac hypertrophy in the elderly. To clarify the biological mechanisms that drive cardiac hypertrophy in aging, we tested the influence of circulating factors using heterochronic parabiosis, a surgical technique in which joining of animals of different ages leads to a shared circulation. After 4 weeks of exposure to the circulation of young mice, cardiac hypertrophy in old mice dramatically regressed, accompanied by reduced cardiomyocyte size and molecular remodeling. Reversal of age-related hypertrophy was not attributable to hemodynamic or behavioral effects of parabiosis, implicating a blood-borne factor. Using modified aptamer-based proteomics, we identified the TGFβ superfamily member GDF11 as a circulating factor in young mice that declines with age. Treatment of old mice to restore GDF11 to youthful levels recapitulated the effects of parabiosis and reversed age-related hypertrophy, revealing a new therapeutic opportunity for cardiac aging. PMID:23663781

  2. 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.

  3. CEREBRAL ATROPHY, APOLIPOPROTEIN E ε4, AND RATE OF DECLINE IN EVERYDAY FUNCTION AMONG PATIENTS WITH AMNESTIC MILD COGNITIVE IMPAIRMENT

    PubMed Central

    Okonkwo, Ozioma C.; Alosco, Michael L.; Jerskey, Beth A.; Sweet, Lawrence H.; Ott, Brian R.; Tremont, Geoffrey

    2010-01-01

    BACKGROUND Patients with amnestic mild cognitive impairment (MCI) demonstrate decline in everyday function. In this study, we investigated whether whole brain atrophy and apolipoprotein E (APOE) genotype are associated with the rate of functional decline in MCI. METHODS Participants were 164 healthy controls, 258 MCI patients, and 103 patients with mild Alzheimer’s disease (AD), enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). They underwent brain MRI scans, APOE genotyping, and completed up to 6 biannual Functional Activities Questionnaire (FAQ) assessments. Random effects regressions were used to examine trajectories of decline in FAQ across diagnostic groups, and to test the effects of ventricle-to-brain ratio (VBR) and APOE genotype on FAQ decline among MCI patients. RESULTS Rate of decline in FAQ among MCI patients was intermediate between that of controls and mild AD patients. Patients with MCI who converted to mild AD declined faster than those who remained stable. Among MCI patients, increased VBR and possession of any APOE ε4 allele were associated with faster rate of decline in FAQ. In addition, there was a significant VBR by APOE ε4 interaction such that patients who were APOE ε4 positive and had increased atrophy experienced the fastest decline in FAQ. CONCLUSIONS Functional decline occurs in MCI, particularly among patients who progress to mild AD. Brain atrophy and APOE ε4 positivity are associated with such declines, and patients who have elevated brain atrophy and are APOE ε4 positive are at greatest risk of functional degradation. These findings highlight the value of genetic and volumetric MRI information as predictors of functional decline, and thus disease progression, in MCI. PMID:20813341

  4. Functional aging in the nervous system contributes to age-dependent motor activity decline in C. elegans.

    PubMed

    Liu, Jie; Zhang, Bi; Lei, Haoyun; Feng, Zhaoyang; Liu, Jianfeng; Hsu, Ao-Lin; Xu, X Z Shawn

    2013-09-03

    Aging is characterized by a progressive decline in multiple physiological functions (i.e., functional aging). As animals age, they exhibit a gradual loss in motor activity, but the underlying mechanisms remain unclear. Here we approach this question in C. elegans by functionally characterizing its aging nervous system and muscles. We find that motor neurons exhibit a progressive functional decline, beginning in early life. Surprisingly, body-wall muscles, which were previously thought to undergo functional aging, do not manifest such a decline until mid-late life. Notably, motor neurons first develop a deficit in synaptic vesicle fusion followed by that in quantal size and vesicle docking/priming, revealing specific functional deteriorations in synaptic transmission. Pharmacological stimulation of synaptic transmission can improve motor activity in aged animals. These results uncover a critical role for the nervous system in age-dependent motor activity decline in C. elegans and provide insights into how functional aging occurs in this organism.

  5. Body mass index trajectories and functional decline in older adults: Three-City Dijon cohort study.

    PubMed

    Artaud, Fanny; Singh-Manoux, Archana; Dugravot, Aline; Tavernier, Béatrice; Tzourio, Christophe; Elbaz, Alexis

    2016-01-01

    Obesity, whose prevalence is increasing, is associated with poor functional status at older ages. However, much of this evidence is cross-sectional with little known about longitudinal associations. We examined associations of body mass index (BMI), and change in BMI, with change in objective [walking speed (WS)] and self-reported (disability) measures of motor decline. Analyses included participants (65-85 years) from the Dijon center of the Three-City study (France) with up to five WS (N = 4007) and six disability assessments (N = 4478) over 11 years. Data were analyzed using regression models for repeated measures. Mean baseline WS was 153 cm/s. Compared to normal weight persons, obese participants at baseline walked slower and reported more disability; they also experienced 45% faster WS decline (-18.63 vs. -12.85 cm/s/10 years, P = 0.002). Participants who lost or gained weight had 47% (-18.85 cm/s/10 years, P < 0.001) and 33% (-17.08 cm/s/10 years, P = 0.002) respectively greater WS decline than participants in the normal BMI change category. 24% of participants reported disability at least once during the follow-up, those who lost or gained weight had a 1.63 and 1.34 respectively higher odds of disability than participants in the normal BMI change category (P = 0.001). Associations remained after adjustment for covariates. In conclusion, obesity is associated with worse motor performances, a higher risk of disability, and faster motor decline. Our results underline the interest of repeated BMI and motor assessments to identify those at higher risk of disability.

  6. Individualized prediction of lung-function decline in chronic obstructive pulmonary disease

    PubMed Central

    Zafari, Zafar; Sin, Don D.; Postma, Dirkje S.; Löfdahl, Claes-Göran; Vonk, Judith; Bryan, Stirling; Lam, Stephen; Tammemagi, C. Martin; Khakban, Rahman; Man, S.F. Paul; Tashkin, Donald; Wise, Robert A.; Connett, John E.; McManus, Bruce; Ng, Raymond; Hollander, Zsuszanna; Sadatsafavi, Mohsen

    2016-01-01

    Background: The rate of lung-function decline in chronic obstructive pulmonary disease (COPD) varies substantially among individuals. We sought to develop and validate an individualized prediction model for forced expiratory volume at 1 second (FEV1) in current smokers with mild-to-moderate COPD. Methods: Using data from a large long-term clinical trial (the Lung Health Study), we derived mixed-effects regression models to predict future FEV1 values over 11 years according to clinical traits. We modelled heterogeneity by allowing regression coefficients to vary across individuals. Two independent cohorts with COPD were used for validating the equations. Results: We used data from 5594 patients (mean age 48.4 yr, 63% men, mean baseline FEV1 2.75 L) to create the individualized prediction equations. There was significant between-individual variability in the rate of FEV1 decline, with the interval for the annual rate of decline that contained 95% of individuals being −124 to −15 mL/yr for smokers and −83 to 15 mL/yr for sustained quitters. Clinical variables in the final model explained 88% of variation around follow-up FEV1. The C statistic for predicting severity grades was 0.90. Prediction equations performed robustly in the 2 external data sets. Interpretation: A substantial part of individual variation in FEV1 decline can be explained by easily measured clinical variables. The model developed in this work can be used for prediction of future lung health in patients with mild-to-moderate COPD. Trial registration: Lung Health Study — ClinicalTrials.gov, no. NCT00000568; Pan-Canadian Early Detection of Lung Cancer Study — ClinicalTrials.gov, no. NCT00751660 PMID:27486205

  7. Network Optimization of Functional Connectivity within Default Mode Network Regions to Detect Cognitive Decline.

    PubMed

    Chaovalitwongse, Wanpracha Art; Won, Daehan; Seref, Onur; Borghesani, Paul; Askren, Mary Katie; Willis, Sherry; Grabowski, Tom

    2017-03-07

    The rapid aging of the world's population is causing an increase in the prevalence of cognitive decline and degenerative brain disease in the elderly. Current diagnoses of amnestic and nonamnestic Mild Cognitive Impairment (MCI), which may represent early stage Alzheimer's disease or related degenerative conditions, are based on clinical grounds. The recent emergence of advanced network analyses of functional Magnetic Resonance Imaging (fMRI) data taken at cognitive rest has provided insight that declining functional connectivity of the default mode network (DMN) may be correlated with neurological disorders, and particularly prodromal Alzheimer's disease. The goal of this paper is to develop a network analysis technique using fMRI data to characterize transition stages from healthy brain aging to cognitive decline. Previous studies primarily focused on internodal connectivity of the DMN and often assume functional homogeneity within each DMN region. In this paper, we develop a technique that focuses on identifying critical intra-nodal DMN connectivity by incorporating sparsity into connectivity modeling of the k-cardinality tree (KCT) problem. Most biological networks are efficient and formed by sparse connections, and the KCT can potentially reveal sparse connectivity patterns that are biologically informative. The KCT problem is NP-hard, and existing solution approaches are mostly heuristic. Mathematical formulations of the KCT problem in the literature are not compact and do not provide good solution bounds. This paper presents new KCT formulations and a fast heuristic approach to efficiently solve the KCT models for large DMN regions. The results in this study demonstrate that traditional fMRI group analysis on DMN regions cannot detect any statistically significant connectivity differences between normal aging and cognitively impaired subjects in DMN regions, and the proposed KCT approaches are more sensitive than the state-of-the-art regional homogeneity

  8. 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

  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. Functional decline and herpes zoster in older people: an interplay of multiple factors.

    PubMed

    2015-12-01

    Herpes zoster is a frequent painful infectious disease whose incidence and severity increase with age. In older people, there is a strong bidirectional link between herpes zoster and functional decline, which refers to a decrement in ability to perform activities of daily living due to ageing and disabilities. However, the exact nature of such link remains poorly established. Based on the opinion from a multidisciplinary group of experts, we here propose a new model to account for the interplay between infection, somatic/psychiatric comorbidity, coping skills, polypharmacy, and age, which may account for the functional decline related to herpes zoster in older patients. This model integrates the risk of decompensation of underlying disease; the risk of pain becoming chronic (e.g. postherpetic neuralgia); the risk of herpes zoster non-pain complications; the detrimental impact of herpes zoster on quality of life, functioning, and mood; the therapeutic difficulties due to multimorbidity, polypharmacy, and ageing; and the role of stressful life events in the infection itself and comorbid depression. This model underlines the importance of early treatment, strengthening coping, and vaccine prevention.

  11. 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

  12. Dust exposure, respiratory symptoms, and longitudinal decline of lung function in young coal miners.

    PubMed Central

    Carta, P; Aru, G; Barbieri, M T; Avataneo, G; Casula, D

    1996-01-01

    OBJECTIVES: To study the role of dust exposure on incidence of respiratory symptoms and decline of lung function in young coal miners. METHODS: The loss of lung function (forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory flow (MEF), carbon monoxide transfer factor (TLCO)) with time and the incidence of respiratory symptoms in 909 Sardinian coal miners (followed up between 1983 and 1993 with seven separate surveys) has been compared with the past and current individual exposures to respirable mixed coal dust. Multiple linear and logistic regression models were used simultaneously controlling for age, smoking, past occupational exposures, and other relevant covariates. RESULTS: According to the relatively low dust exposures experienced during the follow up few abnormal chest x ray films were detected. In the cross sectional analysis of initial data, significant associations between individual cumulative exposure to dust, decrements in FEV1 and MEFs, and increasing prevalence of respiratory symptoms were detected after allowing for the covariates included in the model. The yearly decline of FVC, FEV1, and single breath carbon monoxide transfer factor (TLCO/VA) was still significantly related to the individual exposure to dust experienced during the follow up, even after allowing for age, smoking, initial cumulative exposure to dust, and initial level of each functional variable. In logistic models, dust exposure was a significant predictor of the onset of respiratory symptoms besides age and smoking. CONCLUSIONS: The results show that even moderate exposures to mixed coal dust, as in our study, significantly affect lung function and incidence of symptoms of underground miners. Although the frequency of chest x ray examination might be fixed at every three or four years, yearly measurements of lung function (spirometry, MEFs, and TLCO) are recommended for evaluation of the respiratory risk from the coal mine environment to

  13. Obesity-induced oxidative stress, accelerated functional decline with age and increased mortality in mice

    PubMed Central

    Zhang, Yiqiang; Fischer, Kathleen E.; Soto, Vanessa; Liu, Yuhong; Sosnowska, Danuta; Richardson, Arlan; Salmon, Adam B.

    2015-01-01

    Obesity is a serious chronic disease that increases the risk of numerous co-morbidities including metabolic syndrome, cardiovascular disease and cancer as well as increases risk of mortality leading some to suggest this represents accelerated aging. Obesity is associated with significant increases in oxidative stress in vivo and, despite the well-explored relationship between oxidative stress and aging, the role this plays in the increased mortality of obese subjects remains an unanswered question. Here, we addressed this by undertaking a comprehensive, longitudinal study of a group of high fat-fed obese mice and assessed both their changes in oxidative stress and in their performance in physiological assays known to decline with aging. In female C57BL/6J mice fed a high-fat diet starting in adulthood, mortality was significantly increased in high fat-fed mice as was oxidative damage in vivo. High fat-feeding significantly accelerated the decline in performance in several assays, including activity, gait, and rotarod. However, we also found that obesity had little effect on other markers and actually improved performance in grip strength, a marker of muscular function. Together, this first comprehensive assessment of longitudinal functional changes in high fat-fed mice suggests that obesity may induce segmental acceleration of some of the aging process. PMID:25558793

  14. Age-related gene expression changes in substantia nigra dopamine neurons of the rat.

    PubMed

    Parkinson, Gemma M; Dayas, Christopher V; Smith, Doug W

    2015-07-01

    Ageing affects most, if not all, functional systems in the body. For example, the somatic motor nervous system, responsible for initiating and regulating motor output to skeletal musculature, is vulnerable to ageing. The nigrostriatal dopamine pathway is one component of this system, with deficits in dopamine signalling contributing to major motor dysfunction, as exemplified in Parkinson's disease (PD). However, while the dopamine deficit in PD is due to degeneration of substantia nigra (SN) dopamine (DA) neurons, it is unclear whether there is sufficient loss of SN DA neurons with ageing to explain observed motor impairments. Instead, evidence suggests that age-related loss of DA neuron function may be more important than frank cell loss. To further elucidate the mechanisms of functional decline, we have investigated age-related changes in gene expression specifically in laser microdissected SN DA neurons. There were significant age-related changes in the expression of genes associated with neurotrophic factor signalling and the regulation of tyrosine hydroxylase activity. Furthermore, reduced expression of the DA neuron-associated transcription factor, Nurr1, may contribute to these changes. Together, these results suggest that altered neurotrophic signalling and tyrosine hydroxylase activity may contribute to altered DA neuron signalling and motor nervous system regulation in ageing.

  15. Age-Related Differences in Muscular Strength and Muscular Endurance among Female Masters Swimmers.

    ERIC Educational Resources Information Center

    Dummer, Gail M.; And Others

    1985-01-01

    This study investigated age-related differences in muscular strength and muscular endurance among 73 female masters swimmers aged 24 to 71 years. While an age-related decline in muscular strength was apparent, the results failed to reveal a similar trend for endurance, suggesting that swimming influences endurance more than strength among women.…

  16. 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...

  17. Occupation and three-year incidence of respiratory symptoms and lung function decline: the ARIC Study

    PubMed Central

    2012-01-01

    Background Specific occupations are associated with adverse respiratory health. Inhalation exposures encountered in these jobs may place workers at risk of new-onset respiratory disease. Methods We analyzed data from 8,967 participants from the Atherosclerosis Risk in Communities (ARIC) study, a longitudinal cohort study. Participants included in this analysis were free of chronic cough and phlegm, wheezing, asthma, chronic bronchitis, emphysema, and other chronic lung conditions at the baseline examination, when they were aged 45-64 years. Using data collected in the baseline and first follow-up examination, we evaluated associations between occupation and the three-year incidence of cough, phlegm, wheezing, and airway obstruction and changes in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) measured by spirometry. All associations were adjusted for age, cigarettes per day, race, smoking status, and study center. Results During the approximately three-year follow-up, the percentage of participants developing chronic cough was 3%; chronic phlegm, 3%; wheezing, 3%; and airway obstruction, defined as FEV1 < lower limit of normal (LLN) and FEV1/FVC < LLN, 2%. The average annual declines in FEV1 and FVC were 56 mL and 66 mL, respectively, among men and 40 mL and 52 mL, respectively, among women. Relative to a referent category of managerial and administrative support occupations, elevated risks of new-onset chronic cough and chronic phlegm were observed for mechanics and repairers (chronic cough: RR: 1.81, 95% CI: 1.02, 3.21; chronic phlegm: RR: 2.10, 95% CI: 1.23, 3.57) and cleaning and building service workers (chronic cough: RR: 1.85, 95% CI: 1.01, 3.37; chronic phlegm: RR: 2.28, 95% CI: 1.27, 4.08). Despite the elevated risk of new-onset symptoms, employment in cleaning and building services was associated with attenuated lung function decline, particularly among men, who averaged annual declines in FEV1 and FVC of 14 mL and 23 m

  18. Thoracic dust exposure is associated with lung function decline in cement production workers

    PubMed Central

    Notø, Hilde; Eduard, Wijnand; Skogstad, Marit; Fell, Anne Kristin; Thomassen, Yngvar; Skare, Øivind; Bergamaschi, Antonio; Pietroiusti, Antonio; Abderhalden, Rolf; Kongerud, Johny; Kjuus, Helge

    2016-01-01

    We hypothesised that exposure to workplace aerosols may lead to lung function impairment among cement production workers. Our study included 4966 workers in 24 cement production plants. Based on 6111 thoracic aerosol samples and information from questionnaires we estimated arithmetic mean exposure levels by plant and job type. Dynamic lung volumes were assessed by repeated spirometry testing during a mean follow-up time of 3.5 years (range 0.7–4.6 years). The outcomes considered were yearly change of dynamic lung volumes divided by the standing height squared or percentage of predicted values. Statistical modelling was performed using mixed model regression. Individual exposure was classified into quintile levels limited at 0.09, 0.89, 1.56, 2.25, 3.36, and 14.6 mg·m−3, using the lowest quintile as the reference. Employees that worked in administration were included as a second comparison group. Exposure was associated with a reduction in forced expiratory volume in 1 s (FEV1), forced expiratory volume in 6 s and forced vital capacity. For FEV1 % predicted a yearly excess decline of 0.84 percentage points was found in the highest exposure quintile compared with the lowest. Exposure at the higher levels found in this study may lead to a decline in dynamic lung volumes. Exposure reduction is therefore warranted. PMID:27103386

  19. What are the functional mechanisms underlying forest decline? A case study on a European beech (Fagus sylvatica L.) stand.

    NASA Astrophysics Data System (ADS)

    Delaporte, Alice; Bazot, Stéphane; Fresneau, Chantal; Damesin, Claire

    2013-04-01

    The ongoing climate change is altering the precipitation patterns (abundance and frequency) of most parts of the world. The consequences of these changes on forests are already visible through frequent declines. A lot of them can be linked to the occurrence of long and/or repeated drought periods. Although forest decline could severely impact the nutrient and water cycles, their underlying functional causes are not well understood. Two main hypotheses have been proposed to explain the mechanisms of decline at the tree level: • Carbon reserves deficit ("carbon starvation") • Loss of water transport ( "hydraulic failure") Although hydraulic failure has been observed in a wetland species decline (poplar), our understanding of forest decline is still lacking in many species. Our study concerns a widespread species, European beech (Fagus sylvatica L.). A severely declining mature beech plot in the Fontainebleau state forest (France) was followed. This decline can be related to repeated droughts, enhanced by unfavorable soil conditions (sandy soil with very low extractible soil water). For the first time to our knowledge, an integrative in situ functional approach coupling both hydraulic and carbon, but also nitrogen functioning was developed. More precisely, pre-dawn and midday water potentials, "native" embolism, and embolism vulnerability of branches, radial tree growth, carbon and nitrogen reserves concentrations, were measured on healthy and declining trees. Our results showed that under normal climatic conditions (summer 2012), pre-dawn and midday water potentials were the same for healthy and declining trees throughout the season. Their losses of hydraulic conductivity ("native" embolism) were not significantly different, even at the end of the summer. Moreover, the embolism vulnerability curves also showed no significant difference (50% loss of hydraulic conductivity at around - 3MPa). Concerning C and N reserves concentrations, we showed that seasonal

  20. Normal Weight with Central Obesity, Physical Activity, and Functional Decline: Data from the Osteoarthritis Initiative

    PubMed Central

    Batsis, John A.; Zbehlik, Alicia J.; Scherer, Emily A.; Barre, Laura K.; Bartels, Stephen J.

    2015-01-01

    OBJECTIVES To identify the risks of the combination of normal body mass index (BMI) and central obesity (normal weight and central obesity (NWCO)) on physical activity and function. DESIGN Longitudinal Osteoarthritis Initiative Study. SETTING Community based. PARTICIPANTS Adults aged 60 and older at risk of osteoarthritis (N= 2,210; mean age 68, range 67.1–69.0) were grouped according to BMI (normal 18.5–24.9 kg/m2, overweight 25.0–29.9 kg/m2, obese ≥30.0 kg/m2). High waist circumference (WC) was defined as greater than 88 cm for women and greater than 102 cm for men. Subjects were subcategorized according to WC (five categories). Subjects with normal BMI and a large WC were considered to have NWCO (n=280, 12.7%). MEASUREMENTS Six-year changes in the Physical Component Summary of the Medical Outcomes Study 12-item Short Form Survey (PCS), Physical Activity Scale for the Elderly (PASE), and Late-Life Function and Disability Index (LL-FDI) were examined. The association between BMI and WC over 6 years was assessed (reference normal BMI, normal WC). Stratified analyses were performed according to age (60–69; ≥70). RESULTS Physical component scores, PASE, and LL-FDI declined with time. Mean PASE scores at 6 years differed between the NWCO group and the group with normal BMI and WC (117.7 vs 141.5), but rate of change from baseline to 6 years was not significantly different (p=.35). In adjusted models, those with NWCO had greater decline in PCS over time, particularly those aged 70 and older than those with normal BMI and WC (time interaction β=–0.37, 95% confidence interval=–0.68 to –0.06). CONCLUSION NWCO in older adults at risk of osteoarthritis may be a risk factor for declining function and physical activity, particularly in those aged 70 and older, suggesting the value of targeting those with NWCO who would otherwise be labeled as low risk. PMID:26173812

  1. Brain function decline in healthy retired athletes who sustained their last sports concussion in early adulthood.

    PubMed

    De Beaumont, Louis; Théoret, Hugo; Mongeon, David; Messier, Julie; Leclerc, Suzanne; Tremblay, Sébastien; Ellemberg, Dave; Lassonde, Maryse

    2009-03-01

    Recent studies have shown that the detrimental effects of sports concussions on cognitive and motor function may persist up to a few years post-injury. The present study sought to investigate the effects of having sustained a sports concussion more than 30 years prior to testing on cognitive and motor functions. Nineteen healthy former athletes, in late adulthood (mean age = 60.79; SD = 5.16), who sustained their last sport-related concussion in early adulthood (mean age = 26.05; SD = 9.21) were compared with 21 healthy former athletes with no history of concussion (mean age = 58.89; SD = 9.07). Neuropsychological tests sensitive to age-related changes in cognition were administered. An auditory oddball paradigm was used to evoke P3a and P3b brain responses. Four TMS paradigms were employed to assess motor cortex excitability: (i) resting motor threshold; (ii) paired-pulse intracortical inhibition and intracortical facilitation; (iii) input/output curve and (iv) cortical silent period (CSP). A rapid alternating movement task was also used to characterize motor system dysfunctions. Relative to controls, former athletes with a history of concussion had: (i) lower performance on neuropsychological tests of episodic memory and response inhibition; (ii) significantly delayed and attenuated P3a/P3b components; (iii) significantly prolonged CSP and (iv) significantly reduced movement velocity (bradykinesia). The finding that the P3, the CSP as well as neuropsychological and motor indices were altered more than three decades post-concussion provides evidence for the chronicity of cognitive and motor system changes consecutive to sports concussion.

  2. Prolongevity hormone FGF21 protects against immune senescence by delaying age-related thymic involution

    PubMed Central

    Youm, Yun-Hee; Horvath, Tamas L.; Mangelsdorf, David J.; Kliewer, Steven A.; Dixit, Vishwa Deep

    2016-01-01

    Age-related thymic degeneration is associated with loss of naïve T cells, restriction of peripheral T-cell diversity, and reduced healthspan due to lower immune competence. The mechanistic basis of age-related thymic demise is unclear, but prior evidence suggests that caloric restriction (CR) can slow thymic aging by maintaining thymic epithelial cell integrity and reducing the generation of intrathymic lipid. Here we show that the prolongevity ketogenic hormone fibroblast growth factor 21 (FGF21), a member of the endocrine FGF subfamily, is expressed in thymic stromal cells along with FGF receptors and its obligate coreceptor, βKlotho. We found that FGF21 expression in thymus declines with age and is induced by CR. Genetic gain of FGF21 function in mice protects against age-related thymic involution with an increase in earliest thymocyte progenitors and cortical thymic epithelial cells. Importantly, FGF21 overexpression reduced intrathymic lipid, increased perithymic brown adipose tissue, and elevated thymic T-cell export and naïve T-cell frequencies in old mice. Conversely, loss of FGF21 function in middle-aged mice accelerated thymic aging, increased lethality, and delayed T-cell reconstitution postirradiation and hematopoietic stem cell transplantation (HSCT). Collectively, FGF21 integrates metabolic and immune systems to prevent thymic injury and may aid in the reestablishment of a diverse T-cell repertoire in cancer patients following HSCT. PMID:26755598

  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. Impact of age-related neuroglial cell responses on hippocampal deterioration

    PubMed Central

    Ojo, Joseph O.; Rezaie, Payam; Gabbott, Paul L.; Stewart, Michael G.

    2015-01-01

    Aging is one of the greatest risk factors for the development of sporadic age-related neurodegenerative diseases and neuroinflammation is a common feature of this disease phenotype. In the immunoprivileged brain, neuroglial cells, which mediate neuroinflammatory responses, are influenced by the physiological factors in the microenvironment of the central nervous system (CNS). These physiological factors include but are not limited to cell-to-cell communication involving cell adhesion molecules, neuronal electrical activity and neurotransmitter and neuromodulator action. However, despite this dynamic control of neuroglial activity, in the healthy aged brain there is an alteration in the underlying neuroinflammatory response notably seen in the hippocampus, typified by astrocyte/microglia activation and increased pro-inflammatory cytokine production and signaling. These changes may occur without any overt concurrent pathology, however, they typically correlate with deteriorations in hippocamapal or cognitive function. In this review we examine two important phenomenons, firstly the relationship between age-related brain deterioration (focusing on hippocampal function) and underlying neuroglial response(s), and secondly how the latter affects molecular and cellular processes within the hippocampus that makes it vulnerable to age-related cognitive decline. PMID:25972808

  5. Molecular Mechanism for Age-Related Memory Loss: The Histone-Binding Protein RbAp48

    PubMed Central

    Pavlopoulos, Elias; Jones, Sidonie; Kosmidis, Stylianos; Close, Maggie; Kim, Carla; Kovalerchik, Olga; Small, Scott A.; Kandel, Eric R.

    2016-01-01

    To distinguish age-related memory loss more explicitly from Alzheimer’s disease (AD), we have explored its molecular underpinning in the dentate gyrus (DG), a subregion of the hippocampal formation thought to be targeted by aging. We carried out a gene expression study in human postmortem tissue harvested from both DG and entorhinal cortex (EC), a neighboring subregion unaffected by aging and known to be the site of onset of AD. Using expression in the EC for normalization, we identified 17 genes that manifested reliable age-related changes in the DG. The most significant change was an age-related decline in RbAp48, a histone-binding protein that modifies histone acetylation. To test whether the RbAp48 decline could be responsible for age-related memory loss, we turned to mice and found that, consistent with humans, RbAp48 was less abundant in the DG of old than in young mice. We next generated a transgenic mouse that expressed a dominant-negative inhibitor of RbAp48 in the adult forebrain. Inhibition of RbAp48 in young mice caused hippocampus-dependent memory deficits similar to those associated with aging, as measured by novel object recognition and Morris water maze tests. Functional magnetic resonance imaging studies showed that within the hippocampal formation, dysfunction was selectively observed in the DG, and this corresponded to a regionally selective decrease in histone acetylation. Up-regulation of RbAp48 in the DG of aged wild-type mice ameliorated age-related hippocampus-based memory loss and age-related abnormalities in histone acetylation. Together, these findings show that the DG is a hippocampal subregion targeted by aging, and identify molecular mechanisms of cognitive aging that could serve as valid targets for therapeutic intervention. PMID:23986399

  6. Distinct aspects of frontal lobe structure mediate age-related differences in fluid intelligence and multitasking

    PubMed Central

    Kievit, Rogier A.; Davis, Simon W.; Mitchell, Daniel J.; Taylor, Jason R.; Duncan, John; Tyler, Lorraine K.; Brayne, Carol; Bullmore, Ed; Calder, Andrew; Cusack, Rhodri; Dalgleish, Tim; Matthews, Fiona; Marslen-Wilson, William; Rowe, James; Shafto, Meredith; Campbell, Karen; Cheung, Teresa; Geerligs, Linda; McCarrey, Anna; Tsvetanov, Kamen; Williams, Nitin; Bates, Lauren; Emery, Tina; Erzinçlioglu, Sharon; Gadie, Andrew; Gerbase, Sofia; Georgieva, Stanimira; Hanley, Claire; Parkin, Beth; Troy, David; Allen, Jodie; Amery, Gillian; Amunts, Liana; Barcroft, Anne; Castle, Amanda; Dias, Cheryl; Dowrick, Jonathan; Fair, Melissa; Fisher, Hayley; Goulding, Anna; Grewal, Adarsh; Hale, Geoff; Hilton, Andrew; Johnson, Frances; Johnston, Patricia; Kavanagh-Williamson, Thea; Kwasniewska, Magdalena; McMinn, Alison; Norman, Kim; Penrose, Jessica; Roby, Fiona; Rowland, Diane; Sargeant, John; Squire, Maggie; Stevens, Beth; Stoddart, Aldabra; Stone, Cheryl; Thompson, Tracy; Yazlik, Ozlem; Barnes, Dan; Dixon, Marie; Hillman, Jaya; Mitchell, Joanne; Villis, Laura; Henson, Richard N.A.

    2014-01-01

    Ageing is characterized by declines on a variety of cognitive measures. These declines are often attributed to a general, unitary underlying cause, such as a reduction in executive function owing to atrophy of the prefrontal cortex. However, age-related changes are likely multifactorial, and the relationship between neural changes and cognitive measures is not well-understood. Here we address this in a large (N=567), population-based sample drawn from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) data. We relate fluid intelligence and multitasking to multiple brain measures, including grey matter in various prefrontal regions and white matter integrity connecting those regions. We show that multitasking and fluid intelligence are separable cognitive abilities, with differential sensitivities to age, which are mediated by distinct neural subsystems that show different prediction in older versus younger individuals. These results suggest that prefrontal ageing is a manifold process demanding multifaceted models of neurocognitive ageing. PMID:25519467

  7. Distinct aspects of frontal lobe structure mediate age-related differences in fluid intelligence and multitasking.

    PubMed

    Kievit, Rogier A; Davis, Simon W; Mitchell, Daniel J; Taylor, Jason R; Duncan, John; Henson, Richard N A

    2014-12-18

    Ageing is characterized by declines on a variety of cognitive measures. These declines are often attributed to a general, unitary underlying cause, such as a reduction in executive function owing to atrophy of the prefrontal cortex. However, age-related changes are likely multifactorial, and the relationship between neural changes and cognitive measures is not well-understood. Here we address this in a large (N=567), population-based sample drawn from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) data. We relate fluid intelligence and multitasking to multiple brain measures, including grey matter in various prefrontal regions and white matter integrity connecting those regions. We show that multitasking and fluid intelligence are separable cognitive abilities, with differential sensitivities to age, which are mediated by distinct neural subsystems that show different prediction in older versus younger individuals. These results suggest that prefrontal ageing is a manifold process demanding multifaceted models of neurocognitive ageing.

  8. 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.

  9. Time of Decline in Sexual Function After External Beam Radiotherapy for Prostate Cancer

    SciTech Connect

    Siglin, Joshua; Kubicek, Gregory J.; Leiby, Benjamin; Valicenti, Richard K.

    2010-01-15

    Purpose: Erectile dysfunction is one of the most concerning toxicities for patients in the treatment of prostate cancer. The inconsistent evaluation of sexual function (SF) and limited follow-up data have necessitated additional study to clarify the rate and timing of erectile dysfunction after external beam radiotherapy (EBRT) for prostate cancer. Methods and Materials: A total of 143 men completed baseline data on SF before treatment and at the subsequent follow-up visits. A total of 1187 validated SF inventories were analyzed from the study participants. Multiple domains of SF (sex drive, erectile function, ejaculatory function, and overall satisfaction) were analyzed for <=8 years of follow-up. Results: The median follow-up was 4.03 years. The strongest predictor of SF after EBRT was SF before treatment. For all domains of SF, the only statistically significant decrease in function occurred in the first 24 months after EBRT. SF stabilized 2 years after treatment completion, with no statistically significant change in any area of SF >2 years after the end of EBRT. Conclusion: These data suggest that SF does not have a continuous decline after EBRT. Instead, SF decreases maximally within the first 24 months after EBRT, with no significant changes thereafter.

  10. Obesity and diabetes as accelerators of functional decline: can lifestyle interventions maintain functional status in high risk older adults?

    PubMed

    Anton, Stephen D; Karabetian, Christy; Naugle, Kelly; Buford, Thomas W

    2013-09-01

    Obesity and diabetes are known risk factors for the development of physical disability among older adults. With the number of seniors with these conditions rising worldwide, the prevention and treatment of physical disability in these persons have become a major public health challenge. Sarcopenia, the progressive loss of muscle mass and strength, has been identified as a common pathway associated with the initial onset and progression of physical disability among older adults. A growing body of evidence suggests that metabolic dysregulation associated with obesity and diabetes accelerates the progression of sarcopenia, and subsequently functional decline in older adults. The focus of this brief review is on the contributions of obesity and diabetes in accelerating sarcopenia and functional decline among older adults. We also briefly discuss the underexplored interaction between obesity and diabetes that may further accelerate sarcopenia and place obese older adults with diabetes at particularly high risk of disability. Finally, we review findings from studies that have specifically tested the efficacy of lifestyle-based interventions in maintaining the functional status of older persons with obesity and/or diabetes.

  11. Age-related effects on perceptual and semantic encoding in memory.

    PubMed

    Kuo, M C C; Liu, K P Y; Ting, K H; Chan, C C H

    2014-03-07

    This study examined the age-related subsequent memory effect (SME) in perceptual and semantic encoding using event-related potentials (ERPs). Seventeen younger adults and 17 older adults studied a series of Chinese characters either perceptually (by inspecting orthographic components) or semantically (by determining whether the depicted object makes sounds). The two tasks had similar levels of difficulty. The participants made studied or unstudied judgments during the recognition phase. Younger adults performed better in both conditions, with significant SMEs detected in the time windows of P2, N3, P550, and late positive component (LPC). In the older group, SMEs were observed in the P2 and N3 latencies in both conditions but were only detected in the P550 in the semantic condition. Between-group analyses showed larger frontal and central SMEs in the younger sample in the LPC latency regardless of encoding type. Aging effect appears to be stronger on influencing perceptual than semantic encoding processes. The effects seem to be associated with a decline in updating and maintaining representations during perceptual encoding. The age-related decline in the encoding function may be due in part to changes in frontal lobe function.

  12. Functional single nucleotide polymorphism in IL-17A 3' untranslated region is targeted by miR-4480 in vitro and may be associated with age-related macular degeneration.

    PubMed

    Popp, Nicholas A; Yu, Dianke; Green, Bridgett; Chew, Emily Y; Ning, Baitang; Chan, Chi-Chao; Tuo, Jingsheng

    2016-01-01

    Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in the elderly. Genetic factors contributing to AMD include single nucleotide polymorphisms (SNPs) in immune-related genes including CFH, C2, CFI, C9, and C3, thus implicating these pathways in AMD pathogenesis. MicroRNAs (miRNAs) are powerful regulators of gene expression and execute this function by binding to the 3' untranslated region (3'UTR) of target mRNAs, leading to mRNA degradation. In this study, we searched for the possible association of SNPs in the 3'UTR region of IL-17A, a gene implicated in AMD pathogenesis without any previous SNP association with AMD. Using two independent sample cohorts of Caucasian subjects, six SNPs in the IL-17A 3'-UTR were selected for genotyping based on bioinformatic predictions of the SNP effect on microRNA binding. The SNP rs7747909 was found to be associated with AMD (P < 0.05) in the NEI cohort, using a dominant model logistic regression. Luciferase reporter gene assays and RNA electrophoretic mobility shift assays were performed using ARPE-19 cells to confirm the preferential binding of microRNAs to the major allele of the SNP. Our findings support the hypothesis that microRNA-mediated gene dysregulation may play a role in the pathogenesis of AMD.

  13. Exposures and cross-shift lung function declines in wildland firefighters.

    PubMed

    Gaughan, Denise M; Piacitelli, Chris A; Chen, Bean T; Law, Brandon F; Virji, M Abbas; Edwards, Nicole T; Enright, Paul L; Schwegler-Berry, Diane E; Leonard, Stephen S; Wagner, Gregory R; Kobzik, Lester; Kales, Stefanos N; Hughes, Michael D; Christiani, David C; Siegel, Paul D; Cox-Ganser, Jean M; Hoover, Mark D

    2014-01-01

    Respiratory problems are common among wildland firefighters. However, there are few studies directly linking occupational exposures to respiratory effects in this population. Our objective was to characterize wildland fire fighting occupational exposures and assess their associations with cross-shift changes in lung function. We studied 17 members of the Alpine Interagency Hotshot Crew with environmental sampling and pulmonary function testing during a large wildfire. We characterized particles by examining size distribution and mass concentration, and conducting elemental and morphological analyses. We examined associations between cross-shift lung function change and various analytes, including levoglucosan, an indicator of wood smoke from burning biomass. The levoglucosan component of the wildfire aerosol showed a predominantly bimodal size distribution: a coarse particle mode with a mass median aerodynamic diameter about 12 μm and a fine particle mode with a mass median aerodynamic diameter < 0.5 μm. Levoglucosan was found mainly in the respirable fraction and its concentration was higher for fire line construction operations than for mop-up operations. Larger cross-shift declines in forced expiratory volume in one second were associated with exposure to higher concentrations of respirable levoglucosan (p < 0.05). Paired analyses of real-time personal air sampling measurements indicated that higher carbon monoxide (CO) concentrations were correlated with higher particulate concentrations when examined by mean values, but not by individual data points. However, low CO concentrations did not provide reliable assurance of concomitantly low particulate concentrations. We conclude that inhalation of fine smoke particles is associated with acute lung function decline in some wildland firefighters. Based on short-term findings, it appears important to address possible long-term respiratory health issues for wildland firefighters. [Supplementary materials are

  14. 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 ...

  15. 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 ...

  16. 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

  17. 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

  18. 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.

  19. 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

  20. Association of Serum Erythropoietin with Cardiovascular Events, Kidney Function Decline and Mortality: The Health ABC Study

    PubMed Central

    Garimella, Pranav S.; Katz, Ronit; Patel, Kushang V.; Kritchevsky, Stephen B.; Parikh, Chirag R.; Ix, Joachim H.; Fried, Linda F.; Newman, Anne B.; Shlipak, Michael G.; Harris, Tamara B.; Sarnak, Mark J.

    2015-01-01

    Background Studies suggest that in patients with heart failure (HF), high serum erythropoietin is associated with risk of recurrent HF and mortality. Trials of erythropoietin stimulating agents in persons with kidney disease have also suggested an increased incidence of adverse clinical events. No studies have evaluated the association of endogenous erythropoietin levels with clinical outcomes in the community living older adults. Methods and Results Erythropoietin concentration was measured in 2,488 participants aged 70–79 years in the Health, Aging and Body Composition Study. Associations of erythropoietin with incident HF, coronary heart disease (CHD), stroke, mortality, and ≥30% decline in estimated glomerular filtration rate (eGFR) were examined using Cox proportional hazards and logistic regression over 10.7 years of follow up. Mean (SD) age was 75 (3) years and median (quartile 1, quartile 3) erythropoietin was 12.3 (9.0, 17.2) mIU/mL. There were 503 incident HF events and each doubling of serum erythropoietin was associated with a 25% increased risk of incident HF 1.25 (95% CI 1.13, 1.48) after adjusting for demographics, prevalent cardiovascular disease (CVD), CVD risk factors, kidney function and serum hemoglobin. There was no interaction of serum erythropoietin with chronic kidney disease or anemia (p>0.50). There were 330 incident CHD events, 161 strokes, 1,112 deaths and 698 outcomes of ≥ 30% decline in eGFR. Serum erythropoietin was not significantly associated with these outcomes. Conclusions Higher levels of endogenous erythropoietin are associated with incident HF in older adults. Studies need to elucidate the mechanisms through which endogenous erythropoietin levels associate with specific outcomes. PMID:26721912

  1. 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

  2. Calcium dysregulation and neuroinflammation: Discrete and integrated mechanisms for age-related synaptic dysfunction

    PubMed Central

    Sama, Diana M.; Norris, Christopher M.

    2013-01-01

    Some of the best biomarkers of age-related cognitive decline are closely linked to synaptic function and plasticity. This review highlights several age-related synaptic alterations as they relate to Ca2+ dyshomeostasis, through elevation of intracellular Ca2+, and neuroinflammation, through production of pro-inflammatory cytokines including interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α). Though distinct in many ways, Ca2+ and neuroinflammatory signaling mechanisms exhibit extensive cross-talk and bidirectional interactions. For instance, cytokine production in glial cells is strongly dependent on the Ca2+ dependent protein phosphatase calcineurin, which shows elevated activity in animal models of aging and disease. In turn, pro-inflammatory cytokines, such as TNF, can augment the expression/activity of L-type voltage sensitive Ca2+ channels in neurons, leading to Ca2+ dysregulation, hyperactive calcineurin activity, and synaptic depression. Thus, in addition to discussing unique contributions of Ca2+ dyshomeostasis and neuroinflammation, this review emphasizes how these processes interact to hasten age-related synaptic changes. PMID:23751484

  3. Age-related changes in gene expression in tissues of the sea urchin Strongylocentrotus purpuratus.

    PubMed

    Loram, Jeannette; Bodnar, Andrea

    2012-05-01

    The life history of sea urchins is fundamentally different from that of traditional models of aging and therefore they provide the opportunity to gain new insight into this complex process. Sea urchins grow indeterminately, reproduce throughout their life span and some species exhibit negligible senescence. Using a microarray and qRT-PCR, age-related changes in gene expression were examined in three tissues (muscle, esophagus and nerve) of the sea urchin species Strongylocentrotus purpuratus. The results indicate age-related changes in gene expression involving many key cellular functions such as the ubiquitin-proteasome pathway, DNA metabolism, signaling pathways and apoptosis. Although there are tissue-specific differences in the gene expression profiles, there are some characteristics that are shared between tissues providing insight into potential mechanisms that promote lack of senescence in these animals. As an example, there is an increase in expression of genes encoding components of the Notch signaling pathway with age in all three tissues and a decrease in expression of the Wnt1 gene in both muscle and nerve. The interplay between the Notch and Wnt pathways may be one mechanism that ensures continued regeneration of tissues with advancing age contributing to the general lack of age-related decline in these animals.

  4. Cumulative exposure to dust causes accelerated decline in lung function in tunnel workers

    PubMed Central

    Ulvestad, B; Bakke, B; Eduard, W; Kongerud, J; Lund, M

    2001-01-01

    OBJECTIVES—To examine whether underground construction workers exposed to tunnelling pollutants over a follow up period of 8 years have an increased risk of decline in lung function and respiratory symptoms compared with reference subjects working outside the tunnel atmosphere, and relate the findings to job groups and cumulative exposure to dust and gases.
METHODS—96 Tunnel workers and a reference group of 249 other heavy construction workers were examined in 1991 and re-examined in 1999. Exposure measurements were carried out to estimate personal cumulative exposure to total dust, respirable dust, α-quartz, oil mist, and nitrogen dioxide. The subjects answered a questionnaire on respiratory symptoms and smoking habits, performed spirometry, and had chest radiographs taken. Radiological signs of silicosis were evaluated (International Labour Organisation (ILO) classification). Atopy was determined by a multiple radioallergosorbent test (RAST).
RESULTS—The mean exposure to respirable dust and α-quartz in tunnel workers varied from 1.2-3.6 mg/m3 (respirable dust) and 0.019-0.044 mg/m3 (α-quartz) depending on job task performed. Decrease in forced expiratory volume in 1 second (FEV1) was associated with cumulative exposure to respirable dust (p<0.001) and α-quartz (p=0.02). The multiple regression model predicted that in a worker 40 years of age, the annual decrease in FEV1 would be 25 ml in a non-exposed non-smoker, 35 ml in a non-exposed smoker, and 50-63 ml in a non-smoking tunnel worker (depending on job). Compared with the reference group the odds ratio for the occurrence of new respiratory symptoms during the follow up period was increased in the tunnel workers and associated with cumulative exposure to respirable dust.
CONCLUSIONS—Cumulative exposures to respirable dust and α-quartz are the most important risk factors for airflow limitation in underground heavy construction workers, and cumulative exposure to respirable dust is the

  5. Respiratory function decline and DNA mutation in mitochondria, oxidative stress and altered gene expression during aging.

    PubMed

    Wei, Yau-Huei; Wu, Shi-Bei; Ma, Yi-Shing; Lee, Hsin-Chen

    2009-01-01

    Aging is a biological process that is characterized by the gradual loss of physiological function and increases in the susceptibility to disease of an individual. During the aging process, a wide spectrum of alterations in mitochondria and mitochondrial DNA (mtDNA) has been observed in somatic tissues of humans and animals. This is associated with the decline in mitochondrial respiratory function; excess production of the reactive oxygen species (ROS); increase in the oxidative damage to mtDNA, lipids and proteins in mitochondria; accumulation of point mutations and large-scale deletions of mtDNA; and altered expression of genes involved in intermediary metabolism. It has been demonstrated that the ROS may cause oxidative damage and mutations of mtDNA and alterations of the expression of several clusters of genes in aging tissues and senescent cells. We found that intracellular levels of hydrogen peroxide (H2O2) and oxidative damage to DNA in the tissue cells and skin fibroblasts of old donors were higher than those of young donors. In H2O2-induced senescent skin fibroblasts, we observed an increase in the protein expression and activity levels of manganese-dependent superoxide dismutase and a concurrent decrease in the activity of cytochrome c oxidase and the rate of oxygen consumption. Moreover, the mRNA and protein expression levels of pyruvate dehydrogenase (PDH) were decreased but those of PDH kinase and lactate dehydrogenase were increased in senescent skin fibroblasts. The changes in the expression of these enzymes suggest a metabolic shift from mitochondrial respiration to glycolysis as a major supply of ATP in aging human cells. On the other hand, recent studies on mitochondrial mutant mice, which carry a proofreading deficient subunit of DNA polymerase gamma, revealed that mtDNA mutations accumulated in somatic tissues in the mice that displayed prominent features of aging. Taken together, we suggest that the respiratory function decline and increase in

  6. Accelerated telomere erosion is associated with a declining immune function of caregivers of Alzheimer's disease patients.

    PubMed

    Damjanovic, Amanda K; Yang, Yinhua; Glaser, Ronald; Kiecolt-Glaser, Janice K; Nguyen, Huy; Laskowski, Bryon; Zou, Yixiao; Beversdorf, David Q; Weng, Nan-ping

    2007-09-15

    Caregivers of Alzheimer's disease patients endure chronic stress associated with a decline of immune function. To assess the psychological and immunological changes of caregivers, we compared depressive symptoms, PBMC composition, in vitro activation-induced proliferation and cytokine production, and telomere length and telomerase activity of 82 individuals (41 caregivers and 41 age- and gender-matched controls). We found depressive symptoms were significantly higher in caregivers than in controls (p < 0.001). Correspondingly, caregivers had significantly lower T cell proliferation but higher production of immune-regulatory cytokines (TNF-alpha and IL-10) than controls in response to stimulation in vitro. We examined the impact of these changes on cellular replicative lifespan and found that caregivers had significantly shorter telomere lengths in PBMC than controls (6.2 and 6.4 kb, respectively, p < 0.05) with similar shortening in isolated T cells and monocytes and that this telomere attrition in caregivers was not due to an increase of shorter telomere possessing T cell subsets in PBMC. Finally, we showed that basal telomerase activity in PBMC and T cells was significantly higher in caregivers than in controls (p < 0.0001), pointing to an unsuccessful attempt of cells to compensate the excessive loss of telomeres in caregivers. These findings demonstrate that chronic stress is associated with altered T cell function and accelerated immune cell aging as suggested by excessive telomere loss.

  7. Higher tenofovir exposure is associated with longitudinal declines in kidney function in women living with HIV

    PubMed Central

    Baxi, Sanjiv M.; Scherzer, Rebecca; Greenblatt, Ruth M.; Minkoff, Howard; Sharma, Anjali; Cohen, Mardge; Young, Mary A.; Abraham, Alison G.; Shlipak, Michael G.

    2016-01-01

    Objective Tenofovir disoproxil fumarate is a commonly used antiretroviral drug, but risk factors for tenofovir (TFV)-associated kidney disease are not fully understood. We used intensive pharmacokinetic studies in a cohort of HIV-infected women on TFV-based therapy to study the relationship between TFV exposure and subsequent kidney function. Design This is a nested study within the Women's Interagency HIV Study, a multicenter, prospective cohort of HIV-infected women. Participants on TFV-based therapy underwent 24-h intensive pharmacokinetic sampling after witnessed dose. Kidney function was measured over the succeeding 7 years by serum creatinine [estimated glomerular filtration rate calculated by serum creatinine (eGFRcr)]. Methods Multivariable linear mixed models evaluated the relationship of baseline TFV area under the-time concentration curves (AUCs) with subsequent changes in kidney function. Covariates included age, diabetes, hypertension, race, BMI, ritonavir use, duration of TFV exposure, current CD4+ cell count, and HIV viral load. Results Of the 105 participants, persons within the highest baseline TFV AUC tertile had significantly lower eGFRcr compared with those in the lowest tertile (mean±stan-standard error: 80±4.3 vs. 104±2.5 ml/min per 1.73 m2, P<0.0001). By year 7, this difference widened (72±4.9 vs. 105±2.9, P<0.0001). After multivariable adjustment, TFV AUC in the highest tertile remained associated with lower eGFRcr relative to values in the lowest tertile at both baseline (−15 ml/min per 1.73 m2, P=0.0047) and year 7 (−23 ml/min per 1.73 m2, P=0.0002). Conclusion Through intensive TFV pharmacokinetic sampling, we found a strong association between greater TFV exposure and subsequent decline in kidney function. Variations in TFV drug exposure may partially account for subsequent nephrotoxicity in persons infected with HIV. PMID:26558723

  8. CDH13 gene-by-PM10 interaction effect on lung function decline in Korean men.

    PubMed

    Kim, Hyun-Jin; Min, Jin-Young; Min, Kyoung-Bok; Seo, Yong-Seok; Sung, Joohon; Yun, Jae Moon; Kwon, Hyuktae; Cho, Belong; Park, Jin-Ho; Kim, Jong-Il

    2017-02-01

    Lung function can be influenced by genetic factors, which may explain individual differences in susceptibility to the effects of air pollution. This study investigated whether the effect of particulate matter with an aerodynamic diameter ≤10 μm (PM10) on lung function is modified by Cadherin 13 (CDH13) genetic variants in Korean men. This study included a total of 1827 men who were recruited from two health check-up centers, and the annual average PM10 concentrations were used. A total of 200 single-nucleotide polymorphisms (SNPs) of the CDH13 gene were selected for this study. We found that a SNP in CHD13 intron, rs1862830, had the strongest associations with both forced expiratory volume in 1 s (FEV1) (pint = 1.90 × 10(-4)) and forced vital capacity (FVC) (pint = 1.88 × 10(-3)) by interacting with PM10 in a recessive model. A stratified association analysis according to this SNP showed that PM10 in the AG or GG genotype group was not significantly associated with either FEV1 or FVC, whereas in homozygous risk-allele carriers (AA), FEV1 and FVC decreased significantly (by 3.8% and 3.1%, respectively) per 10 μg/m(3) of increase in PM10 concentration. This pattern was also reproducible in the independent subgroups that were classified according to recruitment site. The present study replicated the CDH13 gene-by-PM10 interaction effect on lung function at the gene level, revealing that a genetic variant of CDH13 modified the relationship between PM10 and lung function decline in Korean men.

  9. Post-mortem brain pathology is related to declining respiratory function in community-dwelling older adults

    PubMed Central

    Buchman, Aron S.; Yu, Lei; Wilson, Robert S.; Dawe, Robert J.; VanderHorst, Veronique; Schneider, Julie A.; Bennett, David A.

    2015-01-01

    Damage to brain structures which constitute the distributed neural network that integrates respiratory muscle and pulmonary functions, can impair adequate ventilation and its volitional control. We tested the hypothesis that the level of brain pathology in older adults is associated with declining respiratory function measured during life. 1,409 older adults had annual testing with spirometry (SPI) and respiratory muscle strength (RMS) based on maximal inspiratory and maximal expiratory pressures (MEPs). Those who died underwent structured brain autopsy. On average, during 5 years of follow-up, SPI and RMS showed progressive decline which was moderately correlated (ρ = 0.57, p < 0.001). Among decedents (N = 447), indices of brain neuropathologies showed differential associations with declining SPI and RMS. Nigral neuronal loss was associated with the person-specific decline in SPI (Estimate, −0.016 unit/year, S.E. 0.006, p = 0.009) and reduction of the slope variance was equal to 4%. By contrast, Alzheimer’s disease (AD) pathology (Estimate, −0.030 unit/year, S.E. 0.009, p < 0.001) and macroscopic infarcts (−0.033 unit/year, S.E., 0.011, p = 0.003) were associated with the person-specific decline in RMS and reduction of the slope variance was equal to 7%. These results suggest that brain pathology is associated with the rate of declining respiratory function in older adults. PMID:26539108

  10. Effectiveness of light paths coupled with personal emergency response systems in preventing functional decline among the elderly

    PubMed Central

    Lachal, Florent; Tchalla, Achille Edem; Cardinaud, Noëlle; Saulnier, Isabelle; Nessighaoui, Hichem; Laubarie-Mouret, Cécile; Dantoine, Thierry

    2016-01-01

    Introduction: The elderly population is at high risk of functional decline, which will induce significant costs due to long-term care. Dependency could be delayed by preventing one of its major determinants: falls. Light paths coupled with personal emergency response systems could prevent the functional decline through fall prevention. Methods: This study aimed to evaluate the effectiveness of light paths coupled with personal emergency response systems on the functional decline in an elderly population living at home. It is a secondary analysis on data from a previous cohort. In all, 190 older adults (aged 65 years or more) living at home participated. Participants in the exposed group were equipped with home-based technologies: light paths coupled with personal emergency response systems. The participants’ functional status was assessed using the Functional Autonomy Measurement System scale at baseline (T0) and at the end of the study (T12-month). Baseline characteristics were evaluated by a comprehensive geriatric assessment. Results: After 1 year, 43% of the unexposed group had functional decline versus 16% of the exposed group. Light paths coupled with personal emergency response systems were significantly associated with a decrease in the functional declineFunctional Autonomy Measurement System ⩾ 5) at home (odds ratio = 0.24, 95% confidence interval (0.11–0.54), p = 0.002). Discussion: This study suggests that light paths coupled with personal emergency response systems prevent the functional decline over 12 months. This result may encourage the prescription and use of home-based technologies to postpone dependency and institutionalization, but they need a larger cost-effectiveness study to demonstrate the efficiency of these technologies. PMID:27635246

  11. [The relevance of a decline in renal function for risk of renal failure, cardiovascular events and all-cause mortality].

    PubMed

    Bots, Michiel L; Blankestijn, Peter J

    2015-01-01

    It is well established that the presence of impaired renal function is associated with an increased risk of end-stage renal disease, cardiovascular events and all-cause mortality. Irrespective of the starting level of renal function, a decline in renal function over two years is a relevant and strong risk factor for end-stage renal disease, cardiovascular death and all-cause mortality. Even a decline of 20 to 30 per cent is associated with to a considerable increased risk and requires further attention.

  12. 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.

  13. Physical Function Decline and the Risk of Elder Self-neglect in a Community-Dwelling Population

    PubMed Central

    Dong, XinQi; Simon, Melissa; Fulmer, Terry; Mendes de Leon, Carlos F.; Rajan, Bharat; Evans, Denis A.

    2010-01-01

    Purpose: This longitudinal study examines the association between physical function decline and the risk of elder self-neglect in a community-dwelling population. Design and Methods: Of the 5,570 participants in the Chicago Health Aging Project, 1,068 were reported to social services agency for suspected elder self-neglect from 1993 to 2005. The primary predictor was objectively assessed physical function using decline in physical performance testing. Secondary predictors were assessed using the decline in self-reported Katz, Nagi, and Rosow–Breslau scales. Outcome of interest was elder self-neglect. Logistic and linear regression models were used to assess these associations. Results: After adjusting for confounding factors, every 1-point decline in physical performance testing was associated with increased risk of reported elder self-neglect (odds ratio [OR], 1.05, confidence interval [CI], 1.03–1.07, p < .001). Decline in Katz (OR, 1.05, CI, 1.00–1.10, p < .05) and decline in Rosow–Breslau (OR, 1.19, CI, 1.11–1.27, p < .001) were associated with increased risk of reported elder self-neglect. Decline in physical performance testing (standardized parameter estimate [PE]: 0.19, SE: 0.06, p = .002), Katz (PE: 0.65, SE: 0.14, p < .001), Nagi (PE: 0.48, SE: 0.14, p < .001), and Rosow–Breslau (PE: 0.57, SE: 0.21, p = .006) scales were associated with increased risk of greater self-neglect severity. Implications: Decline in physical function was associated with increased risk of reported elder self-neglect and greater self-neglect severity in this community-dwelling population. PMID:20019180

  14. Needs in Nursing Homes and Their Relation with Cognitive and Functional Decline, Behavioral and Psychological Symptoms

    PubMed Central

    Ferreira, Ana Rita; Dias, Cláudia Camila; Fernandes, Lia

    2016-01-01

    Unmet needs are becoming acknowledged as better predictors of the worst prognostic outcomes than common measures of functional or cognitive decline. Their accurate assessment is a pivotal component of effective care delivery, particularly in institutionalized care where little is known about the needs of its residents, many of whom suffer from dementia and show complex needs. The aims of this study were to describe the needs of an institutionalized sample and to analyze its relationship with demographic and clinical characteristics. A cross-sectional study was conducted with a sample from three nursing homes. All residents were assessed with a comprehensive protocol that included Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS-15), Neuropsychiatric Inventory (NPI) and Adults and Older Adults Functional Inventory (IAFAI). To identify needs, the Camberwell Assessment of Need for the Elderly (CANE) was used. The final sample included 175 residents with a mean age of 81 standard deviation (SD = 10) years. From these, 58.7% presented cognitive deficit (MMSE) and 45.2% depressive symptoms (GDS). Statistically significant negative correlations were found between MMSE score and met (rs = −0.425), unmet (rs = −0.369) and global needs (rs = −0.565). Data also showed significant correlations between depressive symptoms and unmet (rs = 0.683) and global needs (rs = 0.407), and between behavioral and psychological symptoms (BPSD) and unmet (rs = 0.181) and global needs (rs = 0.254). Finally, significant correlations between functional impairment and met (rs = 0.642), unmet (rs = 0.505) and global needs (rs = 0.796) were also found. These results suggest that in this sample, more unmet needs are associated with the worst outcomes measured. This is consistent with previous findings and seems to demonstrate that the needs of those institutionalized elderly remain under-diagnosed and untreated. PMID:27148044

  15. 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

  16. [The effect of aging on the peripheral functions in farmers and chain saw operators. Part 2. Age-related changes in skin temperature and hyperemia time after pressing the nail (author's transl)].

    PubMed

    Kasamatsu, T; Miyashita, K; Shiomi, S; Iwata, H

    1981-05-01

    Vibration hazards which arise after exposure to mechanical vibration comprise various types of disorders, the most common of which are peripheral circulatory disturbances. It is now well recognized that aging effects all organ systems of the human body. The present study was therefore performed to assess the effects of aging on finger skin temperature and on hyperemia time after pressing the nail, both of which reflect peripheral circulatory functions. The subjects were 88 farmers and 86 chain saw operators ranging in age from 30 to 69 years, and 27 healthy persons aged 21 to 37 years as controls. Data were evaluated before and after cold water immersion tests in which the hand was immersed in 10 degrees C water for 10 minutes. The results obtained were as follows: 1) Before the test, skin temperature was negatively correlated with age, and hyperemia time was positively correlated with age in both farmers and chain saw operators but not in the case of the control subjects. 2)The skin temperature became lower, and hyperemia time grew longer with advancing age in both farmers and chain saw operators before and after the immersion tests. In comparison of the average skin temperature and hyperemia time between farmers and chain saw operators classified by age, the average skin temperature in chain saw operators was significantly lower than that in farmers, and the average hyperemia time in chain saw operators was significantly longer than that in farmers of every age group after the immersion test. The results suggest that we should take age-related changes into consideration to some degree when we evaluate the finger skin temperature and hyperemia time in diagnosing peripheral circulatory disturbances.

  17. 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.

  18. 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.

  19. Joint dysfunction and functional decline in middle age myostatin null mice.

    PubMed

    Guo, Wen; Miller, Andrew D; Pencina, Karol; Wong, Siu; Lee, Amanda; Yee, Michael; Toraldo, Gianluca; Jasuja, Ravi; Bhasin, Shalender

    2016-02-01

    Since its discovery as a potent inhibitor for muscle development, myostatin has been actively pursued as a drug target for age- and disease-related muscle loss. However, potential adverse effects of long-term myostatin deficiency have not been thoroughly investigated. We report herein that male myostatin null mice (mstn(-/-)), in spite of their greater muscle mass compared to wild-type (wt) mice, displayed more significant functional decline from young (3-6months) to middle age (12-15months) than age-matched wt mice, measured as gripping strength and treadmill endurance. Mstn(-/-) mice displayed markedly restricted ankle mobility and degenerative changes of the ankle joints, including disorganization of bone, tendon and peri-articular connective tissue, as well as synovial thickening with inflammatory cell infiltration. Messenger RNA expression of several pro-osteogenic genes was higher in the Achilles tendon-bone insertion in mstn(-/-) mice than wt mice, even at the neonatal age. At middle age, higher plasma concentrations of growth factors characteristic of excessive bone remodeling were found in mstn(-/-) mice than wt controls. These data collectively indicate that myostatin may play an important role in maintaining ankle and wrist joint health, possibly through negative regulation of the pro-osteogenic WNT/BMP pathway.

  20. Age-Related Changes of Adaptive and Neuropsychological Features in Persons with Down Syndrome

    PubMed Central

    Ghezzo, Alessandro; Salvioli, Stefano; Solimando, Maria Caterina; Palmieri, Alice; Chiostergi, Chiara; Scurti, Maria; Lomartire, Laura; Bedetti, Federica; Cocchi, Guido; Follo, Daniela; Pipitone, Emanuela; Rovatti, Paolo; Zamberletti, Jessica; Gomiero, Tiziano; Castellani, Gastone; Franceschi, Claudio

    2014-01-01

    Down Syndrome (DS) is characterised by premature aging and an accelerated decline of cognitive functions in the vast majority of cases. As the life expectancy of DS persons is rapidly increasing, this decline is becoming a dramatic health problem. The aim of this study was to thoroughly evaluate a group of 67 non-demented persons with DS of different ages (11 to 66 years), from a neuropsychological, neuropsychiatric and psychomotor point of view in order to evaluate in a cross-sectional study the age-related adaptive and neuropsychological features, and to possibly identify early signs predictive of cognitive decline. The main finding of this study is that both neuropsychological functions and adaptive skills are lower in adult DS persons over 40 years old, compared to younger ones. In particular, language and short memory skills, frontal lobe functions, visuo-spatial abilities and adaptive behaviour appear to be the more affected domains. A growing deficit in verbal comprehension, along with social isolation, loss of interest and greater fatigue in daily tasks, are the main features found in older, non demented DS persons evaluated in our study. It is proposed that these signs can be alarm bells for incipient dementia, and that neuro-cognitive rehabilitation and psycho-pharmacological interventions must start as soon as the fourth decade (or even earlier) in DS persons, i.e. at an age where interventions can have the greatest efficacy. PMID:25419980

  1. Age-related changes of adaptive and neuropsychological features in persons with Down Syndrome.

    PubMed

    Ghezzo, Alessandro; Salvioli, Stefano; Solimando, Maria Caterina; Palmieri, Alice; Chiostergi, Chiara; Scurti, Maria; Lomartire, Laura; Bedetti, Federica; Cocchi, Guido; Follo, Daniela; Pipitone, Emanuela; Rovatti, Paolo; Zamberletti, Jessica; Gomiero, Tiziano; Castellani, Gastone; Franceschi, Claudio

    2014-01-01

    Down Syndrome (DS) is characterised by premature aging and an accelerated decline of cognitive functions in the vast majority of cases. As the life expectancy of DS persons is rapidly increasing, this decline is becoming a dramatic health problem. The aim of this study was to thoroughly evaluate a group of 67 non-demented persons with DS of different ages (11 to 66 years), from a neuropsychological, neuropsychiatric and psychomotor point of view in order to evaluate in a cross-sectional study the age-related adaptive and neuropsychological features, and to possibly identify early signs predictive of cognitive decline. The main finding of this study is that both neuropsychological functions and adaptive skills are lower in adult DS persons over 40 years old, compared to younger ones. In particular, language and short memory skills, frontal lobe functions, visuo-spatial abilities and adaptive behaviour appear to be the more affected domains. A growing deficit in verbal comprehension, along with social isolation, loss of interest and greater fatigue in daily tasks, are the main features found in older, non demented DS persons evaluated in our study. It is proposed that these signs can be alarm bells for incipient dementia, and that neuro-cognitive rehabilitation and psycho-pharmacological interventions must start as soon as the fourth decade (or even earlier) in DS persons, i.e. at an age where interventions can have the greatest efficacy.

  2. In the Laboratory and during Free-Flight: Old Honey Bees Reveal Learning and Extinction Deficits that Mirror Mammalian Functional Decline

    PubMed Central

    Münch, Daniel; Baker, Nicholas; Kreibich, Claus D.; Bråten, Anders T.; Amdam, Gro V.

    2010-01-01

    Loss of brain function is one of the most negative and feared aspects of aging. Studies of invertebrates have taught us much about the physiology of aging and how this progression may be slowed. Yet, how aging affects complex brain functions, e.g., the ability to acquire new memory when previous experience is no longer valid, is an almost exclusive question of studies in humans and mammalian models. In these systems, age related cognitive disorders are assessed through composite paradigms that test different performance tasks in the same individual. Such studies could demonstrate that afflicted individuals show the loss of several and often-diverse memory faculties, and that performance usually varies more between aged individuals, as compared to conspecifics from younger groups. No comparable composite surveying approaches are established yet for invertebrate models in aging research. Here we test whether an insect can share patterns of decline similar to those that are commonly observed during mammalian brain aging. Using honey bees, we combine restrained learning with free-flight assays. We demonstrate that reduced olfactory learning performance correlates with a reduced ability to extinguish the spatial memory of an abandoned nest location (spatial memory extinction). Adding to this, we show that learning performance is more variable in old honey bees. Taken together, our findings point to generic features of brain aging and provide the prerequisites to model individual aspects of learning dysfunction with insect models. PMID:20976061

  3. Visit-to-visit variability of blood pressure and renal function decline in patients with diabetic chronic kidney disease.

    PubMed

    Yokota, Kei; Fukuda, Masamichi; Matsui, Yoshio; Kario, Kazuomi; Kimura, Kenjiro

    2014-05-01

    The authors previously reported that the visit-to-visit variability of blood pressure is correlated with renal function decline in nondiabetic chronic kidney disease. Little is known about the association between visit-to-visit variability and renal function decline in patients with diabetic chronic kidney disease. The authors retrospectively studied 69 patients with diabetic chronic kidney disease stage 3a, 3b, or 4. The standard deviation and coefficient of variation of blood pressure in 12 consecutive visits were defined as visit-to-visit variability of blood pressure. The median observation period was 32 months. In univariate correlation, the standard deviation and coefficient of variation of blood pressure were not significantly associated with the slope of estimated glomerular filtration rate. There was no significant association between the visit-to-visit variability of blood pressure and renal function decline in patients with diabetic chronic kidney disease, in contrast with our previous study of nondiabetic patients with chronic kidney disease.

  4. Does Sensory Function Decline Independently or Concomitantly with Age? Data from the Baltimore Longitudinal Study of Aging

    PubMed Central

    Gadkaree, Shekhar K.; Sun, Daniel Q.; Li, Carol; Lin, Frank R.; Ferrucci, Luigi; Simonsick, Eleanor M.

    2016-01-01

    Objectives. To investigate whether sensory function declines independently or in parallel with age within a single individual. Methods. Cross-sectional analysis of Baltimore Longitudinal Study of Aging (BLSA) participants who underwent vision (visual acuity threshold), proprioception (ankle joint proprioceptive threshold), vestibular function (cervical vestibular-evoked myogenic potential), hearing (pure-tone average audiometric threshold), and Health ABC physical performance battery testing. Results. A total of 276 participants (mean age 70 years, range 26–93) underwent all four sensory tests. The function of all four systems declined with age. After age adjustment, there were no significant associations between sensory systems. Among 70–79-year-olds, dual or triple sensory impairment was associated with poorer physical performance. Discussion. Our findings suggest that beyond the common mechanism of aging, other distinct (nonshared) etiologic mechanisms may contribute to decline in each sensory system. Multiple sensory impairments influence physical performance among individuals in middle old-age (age 70–79). PMID:27774319

  5. Stability and decline in gross motor function among children and youth with cerebral palsy aged 2 to 21 years.

    PubMed

    Hanna, Steven E; Rosenbaum, Peter L; Bartlett, Doreen J; Palisano, Robert J; Walter, Stephen D; Avery, Lisa; Russell, Dianne J

    2009-04-01

    This paper reports the construction of gross motor development curves for children and youth with cerebral palsy (CP) in order to assess whether function is lost during adolescence. We followed children previously enrolled in a prospective longitudinal cohort study for an additional 4 years, as they entered adolescence and young adulthood. The resulting longitudinal dataset comprised 3455 observations of 657 children with CP (369 males, 288 females), assessed up to 10 times, at ages ranging from 16 months to 21 years. Motor function was assessed using the 66-item Gross Motor Function Measure (GMFM-66). Participants were classified using the Gross Motor Function Classification System (GMFCS). We assessed the loss of function in adolescence by contrasting a model of function that assumes no loss with a model that allows for a peak and subsequent decline. We found no evidence of functional decline, on average, for children in GMFCS Levels I and II. However, in Levels III, IV, and V, average GMFM-66 was estimated to peak at ages 7 years 11 months, 6 years 11 months, and 6 years 11 months respectively, before declining by 4.7, 7.8, and 6.4 GMFM-66 points, in Levels III, IV, and V respectively, as these adolescents became young adults. We show that these declines are clinically significant.

  6. The endoplasmic reticulum stress response in aging and age-related diseases

    PubMed Central

    Brown, Marishka K.; Naidoo, Nirinjini

    2012-01-01

    The endoplasmic reticulum(ER) is a multifunctional organelle within which protein folding, lipid biosynthesis, and calcium storage occurs. Perturbations such as energy or nutrient depletion, disturbances in calcium or redox status that disrupt ER homeostasis lead to the misfolding of proteins, ER stress and up-regulation of several signaling pathways coordinately called the unfolded protein response (UPR). The UPR is characterized by the induction of chaperones, degradation of misfolded proteins and attenuation of protein translation. The UPR plays a fundamental role in the maintenance of cellular homeostasis and thus is central to normal physiology. However, sustained unresolved ER stress leads to apoptosis. Aging linked declines in expression and activity of key ER molecular chaperones and folding enzymes compromise proper protein folding and the adaptive response of the UPR. One mechanism to explain age associated declines in cellular functions and age-related diseases is a progressive failure of chaperoning systems. In many of these diseases, proteins or fragments of proteins convert from their normally soluble forms to insoluble fibrils or plaques that accumulate in a variety of organs including the liver, brain or spleen. This group of diseases, which typically occur late in life includes Alzheimer's, Parkinson's, type II diabetes and a host of less well known but often equally serious conditions such as fatal familial insomnia. The UPR is implicated in many of these neurodegenerative and familial protein folding diseases as well as several cancers and a host of inflammatory diseases including diabetes, atherosclerosis, inflammatory bowel disease and arthritis. This review will discuss age-related changes in the ER stress response and the role of the UPR in age-related diseases. PMID:22934019

  7. Canagliflozin Slows Progression of Renal Function Decline Independently of Glycemic Effects.

    PubMed

    Heerspink, Hiddo J L; Desai, Mehul; Jardine, Meg; Balis, Dainius; Meininger, Gary; Perkovic, Vlado

    2017-01-01

    Sodium-glucose cotransporter 2 inhibition with canagliflozin decreases HbA1c, body weight, BP, and albuminuria, implying that canagliflozin confers renoprotection. We determined whether canagliflozin decreases albuminuria and reduces renal function decline independently of its glycemic effects in a secondary analysis of a clinical trial in 1450 patients with type 2 diabetes receiving metformin and randomly assigned to either once-daily canagliflozin 100 mg, canagliflozin 300 mg, or glimepiride uptitrated to 6-8 mg. End points were annual change in eGFR and albuminuria over 2 years of follow-up. Glimepiride, canagliflozin 100 mg, and canagliflozin 300 mg groups had eGFR declines of 3.3 ml/min per 1.73 m(2) per year (95% confidence interval [95% CI], 2.8 to 3.8), 0.5 ml/min per 1.73 m(2) per year (95% CI, 0.0 to 1.0), and 0.9 ml/min per 1.73 m(2) per year (95% CI, 0.4 to 1.4), respectively (P<0.01 for each canagliflozin group versus glimepiride). In the subgroup of patients with baseline urinary albumin-to-creatinine ratio ≥30 mg/g, urinary albumin-to-creatinine ratio decreased more with canagliflozin 100 mg (31.7%; 95% CI, 8.6% to 48.9%; P=0.01) or canagliflozin 300 mg (49.3%; 95% CI, 31.9% to 62.2%; P<0.001) than with glimepiride. Patients receiving glimepiride, canagliflozin 100 mg, or canagliflozin 300 mg had reductions in HbA1c of 0.81%, 0.82%, and 0.93%, respectively, at 1 year and 0.55%, 0.65%, and 0.74%, respectively, at 2 years. In conclusion, canagliflozin 100 or 300 mg/d, compared with glimepiride, slowed the progression of renal disease over 2 years in patients with type 2 diabetes, and canagliflozin may confer renoprotective effects independently of its glycemic effects.

  8. Pneumocystis colonization, airway inflammation, and pulmonary function decline in acquired immunodeficiency syndrome.

    PubMed

    Norris, Karen A; Morris, Alison; Patil, Sangita; Fernandes, Eustace

    2006-01-01

    As a result of improved diagnosis, treatment, and supportive care for HIV-infected patients, AIDS in developed countries has now become a chronic infection with prolonged survival time, but longterm complications are increasing contributors to morbidity and mortality. HIV-infected patients are at increased risk for the development of pulmonary complications, including chronic obstructive pulmonary disease (COPD); however, the mechanisms associated with this increased susceptibility have not been defined. Infectious agents may contribute to the development of COPD by upregulating inflammatory mediators in the lung that act in concert with cigarette smoke to promote lung pathology. Studies in human subjects and non-human primate models of AIDS suggest that the inflammatory response to asymptomatic carriage or colonization by the opportunistic pathogen, Pneumocystis sp. (Pc), is similar to that of COPD, which is characterized by influx of CD8+ T cells, neutrophils, and macrophages into the lungs. We have shown a high frequency of Pc colonization among asymptomatic HIV-infected subjects and in non-HIV infected subjects with COPD. To investigate the role of Pc in the progression of obstructive lung disease in HIV infections, we developed a non-human primate model of Pc colonizatoin and infection in simian immunodeficiency virus (SIV)-infected macaques. These animals develop a prolonged colonization state characterized by a persistent influx of CD8+ T cells and neutrophils, and local increases in IL-8, IFN-gamma, and TNF-alpha. SIV-infected Pc-colonized monkeys show progressive decline in pulmonary function compared to SIV-infected monkeys. We hypothesize that in the context of AIDS-immune dysfunction, Pc colonization induces inflammatory responses leading to changes in pulmonary function and architecture similar to that seen in emphysema. Information gained from these studies will lead to the development of interventions to prevent lung injury associated with Pc

  9. Longitudinal lung function decline and wood dust exposure in the furniture industry.

    PubMed

    Jacobsen, G; Schlünssen, V; Schaumburg, I; Taudorf, E; Sigsgaard, T

    2008-02-01

    The aim of the present study was to investigate the relationship between change in lung function and cumulative exposure to wood dust. In total, 1,112 woodworkers (927 males, 185 females) and 235 reference workers (104 males, 185 females) participated in a 6-yr longitudinal study. Forced expiratory volume in one second (FEV(1)), forced vital capacity (FVC), height and weight were measured, and questionnaire data on respiratory symptoms, wood dust exposure and smoking habits were collected. Cumulative inhalable wood dust exposure was assessed using a study-specific job exposure matrix and exposure time. The median (range) for cumulative wood dust exposure was 3.75 (0-7.55) mg x year x m(-3). A dose-response relationship between cumulative wood dust exposure and percent annual decrease in FEV(1) was suggested for female workers. This was confirmed in a linear regression model adjusted for confounders, including smoking, height and age. An additional difference of -14.50 mL x yr(-1) and -27.97 mL x yr(-1) was revealed for females exposed to 3.75-4.71 mg x yr x m(-3) or to >4.71 mg x yr x m(-3), respectively, compared with non-/low-exposed females. For females, a positive trend between wood dust exposure and the cumulative incidence proportion of FEV(1)/FVC <70% was suggested. In conclusion, in the present low-exposed cohort, female woodworkers had an accelerated decline in lung function, which may be clinically relevant.

  10. Age-Related Deterioration of Perineuronal Nets in the Primary Auditory Cortex of Mice

    PubMed Central

    Brewton, Dustin H.; Kokash, Jamiela; Jimenez, Oliva; Pena, Eloy R.; Razak, Khaleel A.

    2016-01-01

    Age-related changes in inhibitory neurotransmission in sensory cortex may underlie deficits in sensory function. Perineuronal nets (PNNs) are extracellular matrix components that ensheath some inhibitory neurons, particularly parvalbumin positive (PV+) interneurons. PNNs may protect PV+ cells from oxidative stress and help establish their rapid spiking properties. Although PNN expression has been well characterized during development, possible changes in aging sensory cortex have not been investigated. Here we tested the hypothesis that PNN+, PV+ and PV/PNN co-localized cell densities decline with age in the primary auditory cortex (A1). This hypothesis was tested using immunohistochemistry in two strains of mice (C57BL/6 and CBA/CaJ) with different susceptibility to age-related hearing loss and at three different age ranges (1–3, 6–8 and 14–24 months old). We report that PNN+ and PV/PNN co-localized cell densities decline significantly with age in A1 in both mouse strains. In the PNN+ cells that remain in the old group, the intensity of PNN staining is reduced in the C57 strain, but not the CBA strain. PV+ cell density also declines only in the C57, but not the CBA, mouse suggesting a potential exacerbation of age-effects by hearing loss in the PV/PNN system. Taken together, these data suggest that PNN deterioration may be a key component of altered inhibition in the aging sensory cortex, that may lead to altered synaptic function, susceptibility to oxidative stress and processing deficits. PMID:27877127

  11. The impact of sleep on age-related sarcopenia: Possible connections and clinical implications.

    PubMed

    Piovezan, Ronaldo D; Abucham, Julio; Dos Santos, Ronaldo Vagner Thomatieli; Mello, Marco Tulio; Tufik, Sergio; Poyares, Dalva

    2015-09-01

    Sarcopenia is a geriatric condition that comprises declined skeletal muscle mass, strength and function, leading to the risk of multiple adverse outcomes, including death. Its pathophysiology involves neuroendocrine and inflammatory factors, unfavorable nutritional habits and low physical activity. Sleep may play a role in muscle protein metabolism, although this hypothesis has not been studied extensively. Reductions in duration and quality of sleep and increases in prevalence of circadian rhythm and sleep disorders with age favor proteolysis, modify body composition and increase the risk of insulin resistance, all of which have been associated with sarcopenia. Data on the effects of age-related slow-wave sleep decline, circadian rhythm disruptions and obstructive sleep apnea (OSA) on hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary-gonadal (HPG), somatotropic axes, and glucose metabolism indicate that sleep disorder interventions may affect muscle loss. Recent research associating OSA with the risk of conditions closely related to the sarcopenia process, such as frailty and sleep quality impairment, indirectly suggest that sleep can influence skeletal muscle decline in the elderly. Several protein synthesis and degradation pathways are mediated by growth hormone (GH), insulin-like growth factor-1 (IGF-1), testosterone, cortisol and insulin, which act on the cellular and molecular levels to increase or reestablish muscle fiber, strength and function. Age-related sleep problems potentially interfere intracellularly by inhibiting anabolic hormone cascades and enhancing catabolic pathways in the skeletal muscle. Specific physical exercises combined or not with nutritional recommendations are the current treatment options for sarcopenia. Clinical studies testing exogenous administration of anabolic hormones have not yielded adequate safety profiles. Therapeutic approaches targeting sleep disturbances to normalize circadian rhythms and sleep homeostasis may

  12. [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.

  13. [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.

  14. Rate of change in kidney function and the risk of death: the case for incorporating the rate of kidney function decline into the CKD staging system.

    PubMed

    Al-Aly, Ziyad; Cepeda, Oscar

    2011-01-01

    Chronic kidney disease (CKD) is associated with increased risk of death. A wave of recent studies used longitudinal data to examine the effect of the rate of decline of kidney function on the risk of death. The results from these studies show that there is an independent and graded association between the rate of kidney function decline and the risk of death. There is a need to incorporate the rate of decline in the definition of CKD. This redefinition of CKD will transform a static definition into a dynamic one that more accurately describes the disease state in an individual patient.

  15. Interventions to delay functional decline in people with dementia: a systematic review of systematic reviews

    PubMed Central

    Laver, Kate; Dyer, Suzanne; Whitehead, Craig; Clemson, Lindy; Crotty, Maria

    2016-01-01

    Objective To summarise existing systematic reviews that assess the effects of non-pharmacological, pharmacological and alternative therapies on activities of daily living (ADL) function in people with dementia. Design Overview of systematic reviews. Methods A systematic search in the Cochrane Database of Systematic Reviews, DARE, Medline, EMBASE and PsycInfo in April 2015. Systematic reviews of randomised controlled trials conducted in people with Alzheimer's disease or dementia measuring the impact on ADL function were included. Methodological quality of the systematic reviews was independently assessed by two authors using the AMSTAR tool. The quality of evidence of the primary studies for each intervention was assessed using GRADE. Results A total of 23 systematic reviews were included in the overview. The quality of the reviews varied; however most (65%) scored 8/11 or more on the AMSTAR tool, indicating high quality. Interventions that were reported to be effective in minimising decline in ADL function were: exercise (6 studies, 289 participants, standardised mean difference (SMD) 0.68, 95% CI 0.08 to 1.27; GRADE: low), dyadic interventions (8 studies, 988 participants, SMD 0.37, 95% CI 0.05 to 0.69; GRADE: low) acetylcholinesterase inhibitors and memantine (12 studies, 4661 participants, donepezil 10 mg SMD 0.18, 95% CI 0.03 to 0.32; GRADE: moderate), selegiline (7 studies, 810 participants, SMD 0.27, 95% CI 0.13 to 0.41; GRADE: low), huperzine A (2 studies, 70 participants, SMD 1.48, 95% CI 0.95 to 2.02; GRADE: very low) and Ginkgo biloba (7 studies, 2530 participants, SMD 0.36, 95% CI 0.28 to 0.44; GRADE: very low). Conclusions Healthcare professionals should ensure that people with dementia are encouraged to exercise and that primary carers are trained and supported to provide safe and effective care for the person with dementia. Acetylcholinesterase inhibitors or memantine should be trialled unless contraindicated. Trial registration number CRD

  16. 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,…

  17. 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…

  18. 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…

  19. Retinoid X receptor activation reverses age-related deficiencies in myelin debris phagocytosis and remyelination

    PubMed Central

    Natrajan, Muktha S.; de la Fuente, Alerie G.; Crawford, Abbe H.; Linehan, Eimear; Nuñez, Vanessa; Johnson, Kory R.; Wu, Tianxia; Fitzgerald, Denise C.; Ricote, Mercedes; Bielekova, Bibiana

    2015-01-01

    The efficiency of central nervous system remyelination declines with age. This is in part due to an age-associated decline in the phagocytic removal of myelin debris, which contains inhibitors of oligodendrocyte progenitor cell differentiation. In this study, we show that expression of genes involved in the retinoid X receptor pathway are decreased with ageing in both myelin-phagocytosing human monocytes and mouse macrophages using a combination of in vivo and in vitro approaches. Disruption of retinoid X receptor function in young macrophages, using the antagonist HX531, mimics ageing by reducing myelin debris uptake. Macrophage-specific RXRα (Rxra) knockout mice revealed that loss of function in young mice caused delayed myelin debris uptake and slowed remyelination after experimentally-induced demyelination. Alternatively, retinoid X receptor agonists partially restored myelin debris phagocytosis in aged macrophages. The agonist bexarotene, when used in concentrations achievable in human subjects, caused a reversion of the gene expression profile in multiple sclerosis patient monocytes to a more youthful profile and enhanced myelin debris phagocytosis by patient cells. These results reveal the retinoid X receptor pathway as a positive regulator of myelin debris clearance and a key player in the age-related decline in remyelination that may be targeted by available or newly-developed therapeutics. PMID:26463675

  20. IgA-mesangial nephropathy (Berger's disease) with rapid decline in renal function.

    PubMed

    D'Amico, G; Ferrario, F; Colasanti, G; Ragni, A; Bestetti Bosisio, M

    1981-11-01

    End-stage renal failure requiring dialysis treatment developed within 5 years in 11 patients with IgA mesangial glomerulonephritis (out of 94 affected by this nephropathy) whose serum creatinine levels were less than 2 mg/100 ml at the time of biopsy. We compared these patients (Group 1) with 10 patients (Group 2) whose serum creatinine was comparable at the time of biopsy (1.2 +/- 0.3 vs 1.4 +/- 0.3 mg/100 ml) but remained unchanged (1.1 +/- 0.4 mg/100 ml) at the end of a minimum post-biopsy follow-up of 5 years. The analysis of clinical findings, at the time of biopsy, showed that the mean duration of disease, from apparent onset, was shorter in Group 1. Recurrent macroscopic hematuria, never reported in this group, was present in 40% of patients of Group 2, whereas minimal urinary abnormalities, discovered by chance, were the only findings in 73% of patients of Group 1 and in 30% of Group 2. No difference was present between the patients in the two groups in the amount of proteinuria and in the incidence of high IgA serum levels, whereas hypertension was more frequent (45% vs 20%) in Group 1. The analysis of histological lesions demonstrated that in Group 1 there was a greater incidence of diffuse mesangial proliferation (82% vs 30%), of extensive glomerular obsolescence (64% vs 0) and of severe interstitial fibrosis (54% vs 0). Immunofluorescence findings were similar in the two groups. Although no single clinical or morphological parameter was characteristic of the patients with subsequent rapid decline of renal function, some features were more commonly observed, or more severe, in these patients, and therefore should be considered reliable predictors of an unfavourable outcome.

  1. Blood cadmium levels are associated with a decline in lung function in males

    SciTech Connect

    Oh, Chang-Mo; Oh, In-Hwan; Lee, Jong-Keun; Park, Yoon Hyung; Choe, Bong-Keun; Yoon, Tai-Young; Choi, Joong-Myung

    2014-07-15

    Background: Cadmium exposure was found to cause a decline in lung function among the general population, but these findings were limited to smokers and gender differences were not explored. Objectives: To examine the relationship between cadmium and chronic obstructive pulmonary disease (COPD) according to gender and smoking status in Korea. Methods: Cross-sectional data from the Korean National Health and Nutrition Examination Survey from 2008 to 2011 were analyzed. COPD was defined by a pre-bronchodilator forced expiratory volume in 1 s divided by forced vital capacity of <0.70. A logistic regression model was used to elucidate the association between blood cadmium levels and COPD according to gender and smoking status. Results: Among 3861 eligible participants, 3622 were included in the analysis. The prevalence of COPD demonstrated an increasing trend in males (P for trend<0.001), but not in females (P for trend=0.67). After adjusting for covariates, a higher blood cadmium level, but within the normal range, was associated with COPD in males, including those who had never-smoked (P for trend <0.001 and P for trend=0.008). However, a higher blood cadmium level was not significantly associated with COPD in females, including those who had never smoked (P for trend=0.39 and P for trend=0.43). Conclusions: A higher blood cadmium level, within the normal range, was associated with COPD in males, including those who had never smoked. However, there was no significant association between blood cadmium levels and COPD in females. - Highlights: • Elevated blood cadmium level is associated with chronic obstructive pulmonary disease in male. • This association can be seen even in never smoked male. • However, this association is present only in male, but not in female.

  2. Executive Function [Capacity for Behavioral Self-regulation]and Decline Predicted Mortality in a Longitudinal Study in Southern Colorado

    PubMed Central

    Amirian, E.; Baxter, Judith; Grigsby, Jim; Curran-Everett, Douglas; Hokanson, John E; Bryant, Lucinda L

    2009-01-01

    Objective To assess the relationship between mortality and impairment and decline in a specific executive cognitive function, the capacity for behavioral self-regulation. Study Design & Setting This study examined the association between mortality and baseline and 22-month decline in the capacity for behavioral self-regulation, as measured by the Behavioral Dyscontrol Scale, among 1,293 participants of the San Luis Valley Health and Aging Study (SLVHAS), a population-based longitudinal study. The Behavioral Dyscontrol Scale and a measure of overall mental status, the Mini-Mental State Examination, were administered at baseline and follow-up interviews. Cox regression was used to examine baseline and decline in capacity for behavioral self-regulation as possible predictors of morality. Results Baseline Behavioral Dyscontrol Scale score was predictive of mortality, independent of demographics and comorbidity count (HR=1.07; 95% CI:1.04–1.09). It remained a significant predictor with further adjustment for Mini-Mental State Examination score. Decline in this specific executive cognitive function was associated with mortality after adjustment for covariates and baseline cognitive scores (HR=1.09; 95% CI:1.04–1.13). Conclusion Thus, both baseline capacity for behavioral self-regulation and its decline over time predicted mortality in the SLVHAS cohort. These associations may partly be due to maintaining the ability for self-care. Understanding how specific forms of impairment contribute to mortality may help identify patients who could benefit from early intervention. PMID:19716261

  3. Physical Function Decline and the Risk of Elder Self-Neglect in a Community-Dwelling Population

    ERIC Educational Resources Information Center

    Dong, XinQi; Simon, Melissa; Fulmer, Terry; de Leon, Carlos F. Mendes; Rajan, Bharat; Evans, Denis A.

    2010-01-01

    Purpose: This longitudinal study examines the association between physical function decline and the risk of elder self-neglect in a community-dwelling population. Design and Methods: Of the 5,570 participants in the Chicago Health Aging Project, 1,068 were reported to social services agency for suspected elder self-neglect from 1993 to 2005. The…

  4. Slow Gait Speed and Rapid Renal Function Decline Are Risk Factors for Postoperative Delirium after Urological Surgery

    PubMed Central

    Sato, Tendo; Okamoto, Teppei; Yamamoto, Hayato; Hosogoe, Shogo; Tobisawa, Yuki; Yoneyama, Tohru; Hashiba, Eiji; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Koie, Takuya; Hirota, Kazuyoshi; Ohyama, Chikara

    2016-01-01

    Objectives The aim of this study was to identify risk factors associated with postoperative delirium in patients undergoing urological surgery. Methods We prospectively evaluated pre- and postoperative risk factors for postoperative delirium in consecutive 215 patients who received urological surgery between August 2013 and November 2014. Preoperative factors included patient demographics, comorbidities, and frailty assessment. Frailty was measured by handgrip strength, fatigue scale of depression, fall risk assessment, and gait speed (the timed Get-up and Go test). Postoperative factors included types of anesthesia, surgical procedure, renal function and serum albumin decline, blood loss, surgery time, highest body temperature, and complications. Uni- and multivariate logistic regression analyses were performed to assess pre- and postoperative predictors for the development of postoperative delirium. Results Median age of this cohort was 67 years. Ten patients (4.7%) experienced postoperative delirium. These patients were significantly older, had weak handgrip strength, a higher fall risk assessment score, slow gait speed, and greater renal function decline compared with patients without delirium. Multivariate analysis revealed slow gait speed (>13.0 s) and rapid renal function decline (>30%) were independent risk factors for postoperative delirium. Conclusions Slow gait speed and rapid renal function decline after urological surgery are significant factors for postoperative delirium. These data will be helpful for perioperative patient management. This study was registered as a clinical trial: UMIN: R000018809. PMID:27145178

  5. Age-related changes in dentate gyrus cell numbers, neurogenesis, and associations with cognitive impairments in the rhesus monkey

    PubMed Central

    Ngwenya, Laura B.; Heyworth, Nadine C.; Shwe, Yamin; Moore, Tara L.; Rosene, Douglas L.

    2015-01-01

    The generation of new neurons in the adult mammalian brain is well-established for the hippocampal dentate gyrus (DG). However, the role of neurogenesis in hippocampal function and cognition, how it changes in aging, and the mechanisms underlying this are yet to be elucidated in the monkey brain. To address this, we investigated adult neurogenesis in the DG of 42 rhesus monkeys (39 cognitively tested) ranging in age from young adult to the elderly. We report here that there is an age-related decline in proliferation and a delayed development of adult neuronal phenotype. Additionally, we show that many of the new neurons survive throughout the lifetime of the animal and may contribute to a modest increase in total neuron number in the granule cell layer of the DG over the adult life span. Lastly, we find that measures of decreased adult neurogenesis are only modestly predictive of age-related cognitive impairment. PMID:26236203

  6. Age-related differences in effective connectivity of brain regions involved in Japanese kanji processing with homophone judgment task.

    PubMed

    Wu, Chiao-Yi; Koh, Jia Ying Serene; Ho, Moon-Ho Ringo; Miyakoshi, Makoto; Nakai, Toshiharu; Chen, Shen-Hsing Annabel

    2014-08-01

    Reading is a complex process involving neural networks in which connections may be influenced by task demands and other factors. We employed functional magnetic resonance imaging and dynamic causal modeling to examine age-related influences on left-hemispheric kanji reading networks. During a homophone judgment task, activation in the middle frontal gyrus, and dorsal and ventral inferior frontal gyri were identified, representing areas involved in orthographic, phonological, and semantic processing, respectively. The young adults showed a preference for a semantically-mediated pathway from orthographic inputs to the retrieval of phonological representations, whereas the elderly preferred a direct connection from orthographic inputs to phonological lexicons prior to the activation of semantic representations. These sequential pathways are in line with the lexical semantic and non-semantic routes in the dual-route cascaded model. The shift in reading pathways accompanied by slowed reaction time for the elderly might suggest age-related declines in the efficiency of network connectivity.

  7. Clinical Characteristics and Outcomes of Hospitalized Older Patients with Distinct Risk Profiles for Functional Decline: A Prospective Cohort Study

    PubMed Central

    Buurman, Bianca M.; Hoogerduijn, Jita G.; van Gemert, Elisabeth A.; de Haan, Rob J.; Schuurmans, Marieke J.; de Rooij, Sophia E.

    2012-01-01

    Background The aim of this research was to study the clinical characteristics and mortality and disability outcomes of patients who present distinct risk profiles for functional decline at admission. Methods Multicenter, prospective cohort study conducted between 2006 and 2009 in three hospitals in the Netherlands in consecutive patients of ≥65 years, acutely admitted and hospitalized for at least 48 hours. Nineteen geriatric conditions were assessed at hospital admission, and mortality and functional decline were assessed until twelve months after admission. Patients were divided into risk categories for functional decline (low, intermediate or high risk) according to the Identification of Seniors at Risk-Hospitalized Patients. Results A total of 639 patients were included, with a mean age of 78 years. Overall, 27%, 33% and 40% of the patients were at low, intermediate or high risk, respectively, for functional decline. Low-risk patients had fewer geriatric conditions (mean 2.2 [standard deviation [SD] 1.3]) compared with those at intermediate (mean 3.8 [SD 2.1]) or high risk (mean 5.1 [SD 1.8]) (p<0.001). Twelve months after admission, 39% of the low-risk group had an adverse outcome, compared with 50% in the intermediate risk group and 69% in the high risk group (p<0.001). Conclusion By using a simple risk assessment instrument at hospital admission, patients at low, intermediate or high risk for functional decline could be identified, with distinct clinical characteristics and outcomes. This approach should be tested in clinical practice and research and might help appropriately tailor patient care. PMID:22238628

  8. 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...

  9. The Effects of Aerobic Exercise on Cognitive and Neural Decline in Aging and Cardiovascular Disease

    PubMed Central

    Alosco, Michael L.; Forman, Daniel E.

    2015-01-01

    Aging is characterized by a decline in cognitive functions, particularly in the domains of executive function, processing speed and episodic memory. These age-related declines are exacerbated by cardiovascular disease (CVD) and cardiovascular risk factors (hypertension, diabetes, obesity, elevated total cholesterol). Structural and functional alterations in brain regions, including the fronto-parietal and medial temporal lobes, have been linked to age- and CVD-related cognitive decline. Multiple recent studies indicate that aerobic exercise programs may slow the progression of age-related neural changes and reduce the risk for mild cognitive impairment as well as dementia. We review age- and CVD-related decline in cognition and the underlying changes in brain morphology and function, and then clarify the impact of aerobic exercise on moderating these patterns. PMID:25750853

  10. The Effects of Aerobic Exercise on Cognitive and Neural Decline in Aging and Cardiovascular Disease.

    PubMed

    Hayes, Scott M; Alosco, Michael L; Forman, Daniel E

    2014-12-01

    Aging is characterized by a decline in cognitive functions, particularly in the domains of executive function, processing speed and episodic memory. These age-related declines are exacerbated by cardiovascular disease (CVD) and cardiovascular risk factors (hypertension, diabetes, obesity, elevated total cholesterol). Structural and functional alterations in brain regions, including the fronto-parietal and medial temporal lobes, have been linked to age- and CVD-related cognitive decline. Multiple recent studies indicate that aerobic exercise programs may slow the progression of age-related neural changes and reduce the risk for mild cognitive impairment as well as dementia. We review age- and CVD-related decline in cognition and the underlying changes in brain morphology and function, and then clarify the impact of aerobic exercise on moderating these patterns.

  11. Impact of Long-Term Tiotropium Bromide Therapy on Annual Lung Function Decline in Adult Patients with Cystic Fibrosis

    PubMed Central

    Brandt, Claudia; Thronicke, Anja; Roehmel, Jobst F.; Krannich, Alexander; Staab, Doris; Schwarz, Carsten

    2016-01-01

    Background Chronic lung disease is the leading cause of death in patients with Cystic Fibrosis (CF) and is often treated with bronchodilators. It is not known whether long-term tiotropium bromide treatment may have a positive impact on lung function. Methods This retrospective cohort study estimated annual lung function decline utilizing longitudinal data for forced expiratory volume in 1 s (FEV1). Results A total of 160 adult patients with CF were analyzed. The subjects treated for 24 months with tiotropium bromide had a significantly slower decline of mean annual change of FEV1 (treated: -0.3±4.0%; control: -2.3±5.0%; p = 0.0130). In patients with FEV1 ≥70% predicted, long-term tiotropium bromide treatment was associated with greater improvements in annual lung function decline (FEV1 ≥70% predicted: treated: +0.5±4.7%; control: -4.0±6.3%; p = 0.0132; FEV1 50–69% predicted: treated: -0.5±4.4%; control: -0.8±3.8%; p = 0.7142; FEV1 ≤49% predicted: treated: -0.6±3.4%; control: -2.4±4.8%; p = 0.0898). Conclusion This study suggests that long-term tiotropium bromide treatment may be associated with reduced annual decline of FEV1 in patients with CF, particularly in adults with a mild degree of severity. PMID:27351829

  12. 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

  13. Age-Related Changes in Processing Speed: Unique Contributions of Cerebellar and Prefrontal Cortex

    PubMed Central

    Eckert, Mark A.; Keren, Noam I.; Roberts, Donna R.; Calhoun, Vince D.; Harris, Kelly C.

    2010-01-01

    Age-related declines in processing speed are hypothesized to underlie the widespread changes in cognition experienced by older adults. We used a structural covariance approach to identify putative neural networks that underlie age-related structural changes associated with processing speed for 42 adults ranging in age from 19 to 79 years. To characterize a potential mechanism by which age-related gray matter changes lead to slower processing speed, we examined the extent to which cerebral small vessel disease influenced the association between age-related gray matter changes and processing speed. A frontal pattern of gray matter and white matter variation that was related to cerebral small vessel disease, as well as a cerebellar pattern of gray matter and white matter variation were uniquely related to age-related declines in processing speed. These results demonstrate that at least two distinct factors affect age-related changes in processing speed, which might be slowed by mitigating cerebral small vessel disease and factors affecting declines in cerebellar morphology. PMID:20300463

  14. Ageing-related stereotypes in memory: When the beliefs come true.

    PubMed

    Bouazzaoui, Badiâa; Follenfant, Alice; Ric, François; Fay, Séverine; Croizet, Jean-Claude; Atzeni, Thierry; Taconnat, Laurence

    2016-01-01

    Age-related stereotype concerns culturally shared beliefs about the inevitable decline of memory with age. In this study, stereotype priming and stereotype threat manipulations were used to explore the impact of age-related stereotype on metamemory beliefs and episodic memory performance. Ninety-two older participants who reported the same perceived memory functioning were divided into two groups: a threatened group and a non-threatened group (control). First, the threatened group was primed with an ageing stereotype questionnaire. Then, both groups were administered memory complaints and memory self-efficacy questionnaires to measure metamemory beliefs. Finally, both groups were administered the Logical Memory task to measure episodic memory, for the threatened group the instructions were manipulated to enhance the stereotype threat. Results indicated that the threatened individuals reported more memory complaints and less memory efficacy, and had lower scores than the control group on the logical memory task. A multiple mediation analysis revealed that the stereotype threat effect on the episodic memory performance was mediated by both memory complaints and memory self-efficacy. This study revealed that stereotype threat impacts belief in one's own memory functioning, which in turn impairs episodic memory performance.

  15. Establishing a Functional Link Between African Dust and Region-wide Coral Reef Decline

    NASA Astrophysics Data System (ADS)

    Hayes, M. L.; Barber, R. T.

    2003-12-01

    For nearly thirty years, coral reefs in the Western Atlantic and Caribbean basin have experienced historically unprecedented declines. Algal blooms, mass coral bleaching, disease outbreaks and shifts in the dominance of benthic coral-competitors were first documented in the 1970s and have increased in frequency, intensity, variety and range over the past two decades. Recent studies of decreasing coral cover document regional losses averaging nearly 80% over this period. Here, we provide experimental evidence that increased supplies of iron-rich eolian dust from Africa to typically iron-poor marine environments throughout the region could have played a key role in these profound changes. Atmospheric inputs of "new" micronutrients, especially iron, have the potential to overcome limitations to the growth of opportunistic coral-competitors and the virulence of coral pathogens. Microcosm and mesocosm experiments with a putative bacterial pathogen of stony corals, Aurantimonas coralicida, and a temperate stony coral, Oculina arbuscula, provide a means to test the functional relationship between iron availability, microbial growth and coral health. Iron limitation of A. coralicida growth rates is readily induced by the addition of synthetic chelators such as 2,2' Dipyridyl to bacterial cultures at relatively low concentrations (e.g. 10 μ M). This growth limitation is reversed by 100 nM over-enrichments of pure reagent-grade iron as well as iron-rich "synthetic dust" derived from African lake-bed sediments. The Chrome-azurol S assay demonstrates that A. coralicida also synthesizes high-affinity iron-capture mechanisms (i.e. siderophores) that may serve as critical determinants of virulence. Finally, our experimental mesocosms are based on oligotrophic Mediterranean seawater and permit controlled experimentation under relatively low iron ( ˜5 nM) conditions. Using this system, denaturing gradient gel electrophoresis (DGGE) analysis of PCR-amplified ribosomal DNA

  16. Exotic plant traits lead to functional diversity decline in novel ecosystems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Exotic species have become common and even dominant in some grasslands forming novel ecosystems because the species in them have no common evolutionary history. Recent work on these novel ecosystems suggest that exotic species contribute to diversity declines. In order to identify the plant traits...

  17. Apathy and cognitive and functional decline in community-dwelling older adults: Results from the Baltimore ECA longitudinal study

    PubMed Central

    Clarke, Diana E.; Ko, Jean Y.; Lyketsos, Constantine; Rebok, George W.; Eaton, William W.

    2010-01-01

    Background Apathy, a complex neuropsychiatric syndrome, commonly affects patients with Alzheimer’s disease. Prevalence estimates for apathy range widely and are based on cross-sectional data and / or clinic samples. This study examines the relationships between apathy and cognitive and functional declines in non-depressed community-based older adults. Methods Data on 1,136 community-dwelling adults age 50 and older from the Baltimore Epidemiologic Catchment Area (ECA) study, with 1 and 13 years of follow-up, were used. Apathy was assessed with a subscale of items from the General Health Questionnaire. Chi-square, t-tests, logistic regression, and Generalized Estimating Equations were used to accomplish the study’s objectives. Results The prevalence of apathy at Wave 1 was 23.7%. Compared to those without, individuals with apathy were on average older, more likely to be female, and have lower MMSE scores and impairments in basic and instrumental functioning at baseline. Apathy was significantly associated with cognitive decline (OR = 1.65, 95% CI = 1.06, 2.60) and declines in instrumental (OR = 4.42; 95% CI = 2.65, 7.38) and basic (OR=2.74; 95%CI= 1.35, 5.57) function at 1 year follow-up, even after adjustment for baseline age, level of education, race, and depression at follow-up. At 13 years of follow-up, apathetic individuals were not at greater risk for cognitive decline but were 2-fold more likely to have functional decline. Incidence of apathy at 1- year follow up and 13- year follow-up was respectively, 22.6% and 29.4%. Conclusions These results underline the public health importance of apathy and the need for further population-based studies in this area. PMID:20478091

  18. Total Cerebral Small Vessel Disease MRI Score Is Associated with Cognitive Decline in Executive Function in Patients with Hypertension

    PubMed Central

    Uiterwijk, Renske; van Oostenbrugge, Robert J.; Huijts, Marjolein; De Leeuw, Peter W.; Kroon, Abraham A.; Staals, Julie

    2016-01-01

    Objectives: Hypertension is a major risk factor for white matter hyperintensities (WMH), lacunes, cerebral microbleeds, and perivascular spaces, which are MRI markers of cerebral small vessel disease (SVD). Studies have shown associations between these individual MRI markers and cognitive functioning and decline. Recently, a “total SVD score” was proposed in which the different MRI markers were combined into one measure of SVD, to capture total SVD-related brain damage. We investigated if this SVD score was associated with cognitive decline over 4 years in patients with hypertension. Methods: In this longitudinal cohort study, 130 hypertensive patients (91 patients with uncomplicated hypertension and 39 hypertensive patients with a lacunar stroke) were included. They underwent a neuropsychological assessment at baseline and after 4 years. The presence of WMH, lacunes, cerebral microbleeds, and perivascular spaces were rated on baseline MRI. Presence of each individual marker was added to calculate the total SVD score (range 0–4) in each patient. Results: Uncorrected linear regression analyses showed associations between SVD score and decline in overall cognition (p = 0.017), executive functioning (p < 0.001) and information processing speed (p = 0.037), but not with memory (p = 0.911). The association between SVD score and decline in overall cognition and executive function remained significant after adjustment for age, sex, education, anxiety and depression score, potential vascular risk factors, patient group, and baseline cognitive performance. Conclusion: Our study shows that a total SVD score can predict cognitive decline, specifically in executive function, over 4 years in hypertensive patients. This emphasizes the importance of considering total brain damage due to SVD. PMID:28018214

  19. Total Cerebral Small Vessel Disease MRI Score Is Associated with Cognitive Decline in Executive Function in Patients with Hypertension.

    PubMed

    Uiterwijk, Renske; van Oostenbrugge, Robert J; Huijts, Marjolein; De Leeuw, Peter W; Kroon, Abraham A; Staals, Julie

    2016-01-01

    Objectives: Hypertension is a major risk factor for white matter hyperintensities (WMH), lacunes, cerebral microbleeds, and perivascular spaces, which are MRI markers of cerebral small vessel disease (SVD). Studies have shown associations between these individual MRI markers and cognitive functioning and decline. Recently, a "total SVD score" was proposed in which the different MRI markers were combined into one measure of SVD, to capture total SVD-related brain damage. We investigated if this SVD score was associated with cognitive decline over 4 years in patients with hypertension. Methods: In this longitudinal cohort study, 130 hypertensive patients (91 patients with uncomplicated hypertension and 39 hypertensive patients with a lacunar stroke) were included. They underwent a neuropsychological assessment at baseline and after 4 years. The presence of WMH, lacunes, cerebral microbleeds, and perivascular spaces were rated on baseline MRI. Presence of each individual marker was added to calculate the total SVD score (range 0-4) in each patient. Results: Uncorrected linear regression analyses showed associations between SVD score and decline in overall cognition (p = 0.017), executive functioning (p < 0.001) and information processing speed (p = 0.037), but not with memory (p = 0.911). The association between SVD score and decline in overall cognition and executive function