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Sample records for age related decline

  1. Consequences of Age-Related Cognitive Declines

    PubMed Central

    Salthouse, Timothy

    2013-01-01

    Adult age differences in a variety of cognitive abilities are well documented, and many of those abilities have been found to be related to success in the workplace and in everyday life. However, increased age is seldom associated with lower levels of real-world functioning, and the reasons for this lab-life discrepancy are not well understood. This article briefly reviews research concerned with relations of age to cognition, relations of cognition to successful functioning outside the laboratory, and relations of age to measures of work performance and achievement. The final section discusses several possible explanations for why there are often little or no consequences of age-related cognitive declines in everyday functioning. PMID:21740223

  2. 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…

  3. The suprachiasmatic nucleus: age-related decline in biological rhythms.

    PubMed

    Nakamura, Takahiro J; Takasu, Nana N; Nakamura, Wataru

    2016-09-01

    Aging is associated with changes in sleep duration and quality, as well as increased rates of pathologic/disordered sleep. While several factors contribute to these changes, emerging research suggests that age-related changes in the mammalian central circadian clock within the suprachiasmatic nucleus (SCN) may be a key factor. Prior work from our group suggests that circadian output from the SCN declines because of aging. Furthermore, we have previously observed age-related infertility in female mice, caused by a mismatch between environmental light-dark cycles and the intrinsic, internal biological clocks. In this review, we address regulatory mechanisms underlying circadian rhythms in mammals and summarize recent literature describing the effects of aging on the circadian system.

  4. Veterans have less age-related cognitive decline.

    PubMed

    McLay, R N; Lyketsos, C G

    2000-08-01

    Military service involves exposure to a number of stresses, both psychological and physical. On the other hand, military personnel generally maintain excellent fitness, and veterans have increased access to education and health care. The overall effect on age-related cognitive decline, whether for good or ill, of having served in the armed forces has not been investigated previously. In this study, we examined a diverse population of 208 veterans and 1,216 civilians followed as part of the Epidemiologic Catchment Area Study in 1981, 1982, and 1993 to 1996. We examined change in Mini-Mental State Examination (MMSE) score after a median of 11.5 years. Veterans were found to have significantly less decrease in MMSE scores at follow-up even after sex, race, and education were taken into account. These results suggest an overall positive effect of military service on the rate of age-related cognitive decline. PMID:10957857

  5. Aging-related episodic memory decline: are emotions the key?

    PubMed

    Kinugawa, Kiyoka; Schumm, Sophie; Pollina, Monica; Depre, Marion; Jungbluth, Carolin; Doulazmi, Mohamed; Sebban, Claude; Zlomuzica, Armin; Pietrowsky, Reinhard; Pause, Bettina; Mariani, Jean; Dere, Ekrem

    2013-01-01

    Episodic memory refers to the recollection of personal experiences that contain information on what has happened and also where and when these events took place. Episodic memory function is extremely sensitive to cerebral aging and neurodegerative diseases. We examined episodic memory performance with a novel test in young (N = 17, age: 21-45), middle-aged (N = 16, age: 48-62) and aged but otherwise healthy participants (N = 8, age: 71-83) along with measurements of trait and state anxiety. As expected we found significantly impaired episodic memory performance in the aged group as compared to the young group. The aged group also showed impaired working memory performance as well as significantly decreased levels of trait anxiety. No significant correlation between the total episodic memory and trait or state anxiety scores was found. The present results show an age-dependent episodic memory decline along with lower trait anxiety in the aged group. Yet, it still remains to be determined whether this difference in anxiety is related to the impaired episodic memory performance in the aged group.

  6. Aging-related episodic memory decline: are emotions the key?

    PubMed Central

    Kinugawa, Kiyoka; Schumm, Sophie; Pollina, Monica; Depre, Marion; Jungbluth, Carolin; Doulazmi, Mohamed; Sebban, Claude; Zlomuzica, Armin; Pietrowsky, Reinhard; Pause, Bettina; Mariani, Jean; Dere, Ekrem

    2013-01-01

    Episodic memory refers to the recollection of personal experiences that contain information on what has happened and also where and when these events took place. Episodic memory function is extremely sensitive to cerebral aging and neurodegerative diseases. We examined episodic memory performance with a novel test in young (N = 17, age: 21–45), middle-aged (N = 16, age: 48–62) and aged but otherwise healthy participants (N = 8, age: 71–83) along with measurements of trait and state anxiety. As expected we found significantly impaired episodic memory performance in the aged group as compared to the young group. The aged group also showed impaired working memory performance as well as significantly decreased levels of trait anxiety. No significant correlation between the total episodic memory and trait or state anxiety scores was found. The present results show an age-dependent episodic memory decline along with lower trait anxiety in the aged group. Yet, it still remains to be determined whether this difference in anxiety is related to the impaired episodic memory performance in the aged group. PMID:23378831

  7. 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. PMID:26498865

  8. Neuroanatomical Substrates of Age-Related Cognitive Decline

    ERIC Educational Resources Information Center

    Salthouse, Timothy A.

    2011-01-01

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

  9. 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.

  10. 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. PMID:14590204

  11. 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).…

  12. 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.

  13. 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.

  14. 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

  15. Age-related hearing decline in individuals with and without occupational noise exposure.

    PubMed

    Hederstierna, Christina; Rosenhall, Ulf

    2016-01-01

    This study was conducted to compare the pattern of age-related hearing decline in individuals with and without self-reported previous occupational noise exposure. This was a prospective, population-based, longitudinal study of individuals aged 70-75 years, from an epidemiological investigation, comprising three age cohorts. In total there were 1013 subjects (432 men and 581 women). Participants were tested with pure tone audiometry, and they answered a questionnaire to provide information regarding number of years of occupational noise exposure. There were no significant differences in hearing decline, at any frequency, for those aged 70-75 years between the noise-exposed (N= 62 men, 22 women) and the nonexposed groups (N = 96 men, 158 women). This study supports the additive model of noise-induced hearing loss (NIHL) and age-related hearing loss (ARHL). The concept of different patterns of hearing decline between persons exposed and not exposed to noise could not be verified.

  16. 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. PMID:26867182

  17. 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.

  18. 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. PMID:23978008

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

    PubMed Central

    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. PMID:24653697

  20. Age-related differences in associative memory: the role of sensory decline.

    PubMed

    Naveh-Benjamin, Moshe; Kilb, Angela

    2014-09-01

    Numerous studies show age-related decline in episodic memory. One of the explanations for this decline points to older adults' deficit in associative memory, reflecting the difficulties they have in binding features of episodes into cohesive entities and retrieving these bindings. Here, we evaluate the degree to which this deficit may be mediated by sensory loss associated with increased age. In 2 experiments, young adults studied word pairs that were degraded at encoding either visually (Experiment 1) or auditorily (Experiment 2). We then tested their memory for both the component words and the associations with recognition tests. For both experiments, young adults under nondegraded conditions showed an advantage in associative over item memory, relative to a group of older adults. In contrast, under perceptually degraded conditions younger adults performed similarly to the older adults who were tested under nondegraded conditions. More specifically, under perceptual degradation, young adults' associative memory declined and their component memory improved somewhat, resulting in an associative deficit, similar to that shown by older adults. This evidence is consistent with a sensory acuity decline in old age being one mediator in the associative deficit of older adults. These results broaden our understanding of age-related memory changes and how sensory and cognitive processes interact to shape these changes. The theoretical implications of these results are discussed with respect to mechanisms underlying age-related changes in episodic memory and resource tradeoffs in the encoding of component and associative memory.

  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. Grip strength is potentially an early indicator of age-related decline in mice

    PubMed Central

    Ge, Xuan; Cho, Anthony; Ciol, Marcia A.; Pettan-Brewer, Christina; Snyder, Jessica; Rabinovitch, Peter; Ladiges, Warren

    2016-01-01

    The hand grip test has been correlated with mobility and physical performance in older people and has been shown to be a long-term predictor of mortality. Implementation of new strategies for enhancing healthy aging and maintaining independent living are dependent on predictable preclinical studies. The mouse is used extensively as a model in these types of studies, and the paw grip strength test is similar to the hand grip test for people in that it assesses the ability to grip a device with the paw, is non-invasive and easy to perform, and provides reproducible information. However, little has been reported on how grip strength declines with increasing age in mice. This report shows that grip strength was decreased in C57BL/6 (B6) NIA and C57BL/6×BALB/c F1 (CB6F1) NIA male mice at 12 months of age compared to 8-month-old mice, and continued a robust decline to 20 months and then 28 months of age, when the study was terminated. The decline was not related to lean muscle mass, but extensive age-related carpal and digital exostosis could help explain the decreased grip strength times with increasing age. In conclusion, the grip strength test could be useful in mouse preclinical studies to help make translational predictions on treatment strategies to enhance healthy aging. PMID:27613499

  3. Grip strength is potentially an early indicator of age-related decline in mice.

    PubMed

    Ge, Xuan; Cho, Anthony; Ciol, Marcia A; Pettan-Brewer, Christina; Snyder, Jessica; Rabinovitch, Peter; Ladiges, Warren

    2016-01-01

    The hand grip test has been correlated with mobility and physical performance in older people and has been shown to be a long-term predictor of mortality. Implementation of new strategies for enhancing healthy aging and maintaining independent living are dependent on predictable preclinical studies. The mouse is used extensively as a model in these types of studies, and the paw grip strength test is similar to the hand grip test for people in that it assesses the ability to grip a device with the paw, is non-invasive and easy to perform, and provides reproducible information. However, little has been reported on how grip strength declines with increasing age in mice. This report shows that grip strength was decreased in C57BL/6 (B6) NIA and C57BL/6×BALB/c F1 (CB6F1) NIA male mice at 12 months of age compared to 8-month-old mice, and continued a robust decline to 20 months and then 28 months of age, when the study was terminated. The decline was not related to lean muscle mass, but extensive age-related carpal and digital exostosis could help explain the decreased grip strength times with increasing age. In conclusion, the grip strength test could be useful in mouse preclinical studies to help make translational predictions on treatment strategies to enhance healthy aging. PMID:27613499

  4. Axonal transport declines with age in two distinct phases separated by a period of relative stability☆

    PubMed Central

    Milde, Stefan; Adalbert, Robert; Elaman, M. Handan; Coleman, Michael P.

    2015-01-01

    Axonal transport is critical for supplying newly synthesized proteins, organelles, mRNAs, and other cargoes from neuronal cell bodies into axons. Its impairment in many neurodegenerative conditions appears likely to contribute to pathogenesis. Axonal transport also declines during normal aging, but little is known about the timing of these changes, or about the effect of aging on specific cargoes in individual axons. This is important for understanding mechanisms of age-related axon loss and age-related axonal disorders. Here we use fluorescence live imaging of peripheral nerve and central nervous system tissue explants to investigate vesicular and mitochondrial axonal transport. Interestingly, we identify 2 distinct periods of change, 1 period during young adulthood and the other in old age, separated by a relatively stable plateau during most of adult life. We also find that after tibial nerve regeneration, even in old animals, neurons are able to support higher transport rates of each cargo for a prolonged period. Thus, the age-related decline in axonal transport is not an inevitable consequence of either aging neurons or an aging systemic milieu. PMID:25443288

  5. 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

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

    PubMed

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

    2015-09-15

    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

  7. 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

  8. Mechanisms of age-related decline in memory search across the adult life span.

    PubMed

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

    2013-12-01

    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.

  9. 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.

  10. Association Between Age-Related Decline of Kidney Function and Plasma Malondialdehyde

    PubMed Central

    Chen, Yaqin; Hu, Hui; Liu, Li; Hu, Xiaofei; Wang, Jun; Shi, Wang; Yin, Dazhong

    2012-01-01

    Abstract Oxidative stress is a key factor linked renal function decline with age. However, there is still no large cohort study exploring the potential role of oxidative stress in mild insufficiency of kidney function (MIKF) and chronic kidney disease (CKD) after adjusting for confounding factors. This study tested the hypothesis that oxidative stress, indicated by plasma malondialdehyde (MDA), is associated with the prevalence of MIKF and CKD after controlling the effects of confounding factors. Plasma levels of MDA and serum levels of fasting glucose, cholesterol, triglycerides, creatinine, alanine aminotransferase, and aspartate aminotransferase were analyzed from 2,169 Chinese Han adults. A questionnaire and physical examination were performed to identify and suspect risk factors of renal function decline with age. Kidney function, as indicated by estimated glomerular filtration rate, showed a significant decline with age in both male and female. Although the association between age and plasma MDA levels was nonlinear, MDA was negatively related to kidney function. The multivariate-adjusted odds ratios showed that plasma MDA had a significantly graded relation to the prevalence of MIKF and CKD with or without adjustment for covariates. By comparison with the lowest quartile, individuals with the highest quartile of MDA level had a 99% and 223% increased risk of developing MIKF and CKD, respectively. Further results from multiinteraction analysis demonstrated that plasma MDA may be the mediator linking different covariates with renal function decline. The most striking finding of this study was that oxidative stress, as indicated by plasma MDA levels, is associated with the prevalence of MIKF and/or CKD. Although imposing an increasing burden on the kidney and/or promoting a cyclical process of oxidative stress in the body, high levels of MDA in plasma may link the decline of kidney function with age. PMID:22530729

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

    PubMed

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

    2013-01-01

    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.

  12. 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

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

    PubMed

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

    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

  14. 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

  15. 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

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

    PubMed

    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.

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

    PubMed

    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

  18. Declining expression of a single epithelial cell-autonomous gene accelerates age-related thymic involution

    PubMed Central

    Sun, Liguang; Guo, Jianfei; Brown, Robert; Amagai, Takashi; Zhao, Yong; Su, Dong-Ming

    2010-01-01

    SUMMARY Age-related thymic involution may be triggered by gene expression changes in lymphohematopoietic and/or non-hematopoietic thymic epithelial cells (TECs). The role of epithelial cell-autonomous gene FoxN1 may be involved in the process, but it is still a puzzle due to shortage of evidence from gradual loss-of-function and exogenous gain-of-function studies. Using our recently generated loxP-floxed-FoxN1(fx) mouse carrying the ubiquitous CreERT (uCreERT) transgene with a low dose of spontaneous activation, which causes gradual FoxN1 deletion with age, we found that the uCreERT-fx/fx mice showed an accelerated age-related thymic involution due to progressive loss of FoxN1+ TECs. The thymic aging phenotypes were clearly observable as early as at 3–6 months of age, resembling the naturally aged (18–22-month-old) murine thymus. By intrathymically supplying aged wild-type mice with exogenous FoxN1-cDNA, thymic involution and defective peripheral CD4+ T-cell function could be partially rescued. The results support the notion that decline of a single epithelial cell-autonomous gene FoxN1 levels with age causes primary deterioration in TECs followed by impairment of the total postnatal thymic microenvironment, and potentially triggers age-related thymic involution in mice. PMID:20156205

  19. A novel radial water tread maze tracks age-related cognitive decline in mice

    PubMed Central

    Pettan-Brewer, Christina; Touch, Dylan V.; Wiley, Jesse C.; Hopkins, Heather C.; Rabinovitch, Peter S.; Ladiges, Warren C.

    2013-01-01

    There is currently no treatment and cure for age-related dementia and cognitive impairment in humans. Mice suffer from age-related cognitive decline just as people do, but assessment is challenging because of cumbersome and at times stressful performance tasks. We developed a novel radial water tread (RWT) maze and tested male C57BL/6 (B6) and C57BL/6 x Balb/c F1 (CB6F1) mice at ages 4, 12, 20, and 28 months. B6 mice showed a consistent learning experience and memory retention that gradually decreased with age. CB6F1 mice showed a moderate learning experience in the 4 and 12 month groups, which was not evident in the 20 and 28 month groups. In conclusion, CB6F1 mice showed more severe age-related cognitive impairment compared to B6 mice and might be a suitable model for intervention studies. In addition, the RWT maze has a number of operational advantages compared to currently accepted tasks and can be used to assess age-related cognition impairment in B6 and CB6F1 mice as early as 12 months of age. PMID:24106580

  20. Superficial white matter as a novel substrate of age-related cognitive decline.

    PubMed

    Nazeri, Arash; Chakravarty, M Mallar; Rajji, Tarek K; Felsky, Daniel; Rotenberg, David J; Mason, Mikko; Xu, Li N; Lobaugh, Nancy J; Mulsant, Benoit H; Voineskos, Aristotle N

    2015-06-01

    Studies of diffusion tensor imaging have focused mainly on the role of deep white matter tract microstructural abnormalities associated with aging and age-related cognitive decline. However, the potential role of superficial white matter (SWM) in aging and, by extension, cognitive-aging, is less clear. Healthy individuals (n = 141; F/M: 66/75 years) across the adult lifespan (18-86 years) underwent diffusion tensor imaging and a battery of cognitive testing. SWM was assessed via a combination of probabilistic tractography and tract-based spatial statistics (TBSS). A widespread inverse relationship of fractional anisotropy (FA) values in SWM with age was observed. SWM-FA adjacent to the precentral gyri was associated with fine-motor-speed, whereas performance in visuomotor-attention/processing speed correlated with SWM-FA in all 4 lobes of the left-hemisphere and in right parieto-occipital SWM-FA (family-wise error corrected p < 0.05). Independent of deep white matter-FA, right frontal and right occipital SWM-FA-mediated age effects on motor-speed and visuomotor-attention/processing speed, respectively. Altogether, our results indicate that SWM-FA contributes uniquely to age-related cognitive performance, and should be considered as a novel biomarker of cognitive-aging. PMID:25834938

  1. 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.

  2. Age-related declines in the fidelity of newly acquired category representations.

    PubMed

    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 impaired in older adults. Consistent with this prediction, we find that older adults are impaired relative to younger adults at learning nuanced category structures that contain exceptions to the rule. Model-based analysis reveals that this deficit arises from older adults' failure to engage clustering mechanisms to separate exception and rule-following items in memory. PMID:22815536

  3. Can psychosocial work conditions protect against age-related cognitive decline? Results from a systematic review.

    PubMed

    Nexø, Mette Andersen; Meng, Annette; Borg, Vilhelm

    2016-07-01

    According to the use it or lose it hypothesis, intellectually stimulating activities postpone age-related cognitive decline. A previous systematic review concluded that a high level of mental work demands and job control protected against cognitive decline. However, it did not distinguish between outcomes that were measured as cognitive function at one point in time or as cognitive decline. Our study aimed to systematically review which psychosocial working conditions were prospectively associated with high levels of cognitive function and/or changes in cognitive function over time. Articles were identified by a systematic literature search (MEDLINE, Web of Science (WOS), PsycNET, Occupational Safety and Health (OSH)). We included only studies with longitudinal designs examining the impact of psychosocial work conditions on outcomes defined as cognitive function or changes in cognitive function. Two independent reviewers compared title-abstract screenings, full-text screenings and quality assessment ratings. Eleven studies were included in the final synthesis and showed that high levels of mental work demands, occupational complexity or job control at one point in time were prospectively associated with higher levels of cognitive function in midlife or late life. However, the evidence to clarify whether these psychosocial factors also affected cognitive decline was insufficient, conflicting or weak. It remains speculative whether job control, job demands or occupational complexity can protect against cognitive decline. Future studies using methodological advancements can reveal whether workers gain more cognitive reserve in midlife and late life than the available evidence currently suggests. The public health implications of a previous review should thereby be redefined accordingly. PMID:27178844

  4. Can psychosocial work conditions protect against age-related cognitive decline? Results from a systematic review

    PubMed Central

    Nexø, Mette Andersen; Meng, Annette; Borg, Vilhelm

    2016-01-01

    According to the use it or lose it hypothesis, intellectually stimulating activities postpone age-related cognitive decline. A previous systematic review concluded that a high level of mental work demands and job control protected against cognitive decline. However, it did not distinguish between outcomes that were measured as cognitive function at one point in time or as cognitive decline. Our study aimed to systematically review which psychosocial working conditions were prospectively associated with high levels of cognitive function and/or changes in cognitive function over time. Articles were identified by a systematic literature search (MEDLINE, Web of Science (WOS), PsycNET, Occupational Safety and Health (OSH)). We included only studies with longitudinal designs examining the impact of psychosocial work conditions on outcomes defined as cognitive function or changes in cognitive function. Two independent reviewers compared title-abstract screenings, full-text screenings and quality assessment ratings. Eleven studies were included in the final synthesis and showed that high levels of mental work demands, occupational complexity or job control at one point in time were prospectively associated with higher levels of cognitive function in midlife or late life. However, the evidence to clarify whether these psychosocial factors also affected cognitive decline was insufficient, conflicting or weak. It remains speculative whether job control, job demands or occupational complexity can protect against cognitive decline. Future studies using methodological advancements can reveal whether workers gain more cognitive reserve in midlife and late life than the available evidence currently suggests. The public health implications of a previous review should thereby be redefined accordingly. PMID:27178844

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

    PubMed

    Iwasaki, Shinichi; Yamasoba, Tatsuya

    2015-02-01

    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

  6. 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

  7. Neural correlates of age-related decline and compensation in visual attention capacity.

    PubMed

    Wiegand, Iris; Töllner, Thomas; Dyrholm, Mads; Müller, Hermann J; Bundesen, Claus; Finke, Kathrin

    2014-09-01

    We identified neural correlates of declined and preserved basic visual attention functions in aging individuals based on Bundesen "Theory of Visual Attention". In an interindividual difference approach, we contrasted electrophysiology of higher- and lower-performing younger and older participants. In both age groups, the same distinct components indexed performance levels of parameters visual processing speed C and visual short-term memory storage capacity K. The posterior N1 marked interindividual differences in C and the contralateral delay activity marked interindividual differences in K. Moreover, both parameters were selectively related to 2 further event-related potential waves in older age. The anterior N1 was reduced for older participants with lower processing speed, indicating that age-related loss of attentional resources slows encoding. An enhanced right-central positivity was found only for older participants with high storage capacity, suggesting compensatory recruitment for retaining visual short-term memory performance. Together, our results demonstrate that attentional capacity in older age depends on both preservation and successful reorganization of the underlying brain circuits.

  8. 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. PMID:26888036

  9. 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

  10. Connecting Age-Related Biological Decline to Frailty and Late-Life Vulnerability.

    PubMed

    Walston, Jeremy D

    2015-01-01

    Frailty is an important construct in aging which allows for the identification of the most vulnerable subset of older adults. At least two conceptual models of frailty have been developed that have in turn facilitated the development of multiple frailty screening tools. This has enabled the study of populations of frail and nonfrail older adults, and facilitated the risk assessment for adverse health outcomes. In addition, using the syndromic approach to frailty, numerous biological hypotheses have been tested, which have identified chronic inflammatory pathway activation, hypothalamic-pituitary-adrenal axis activation, and sympathetic nervous system activity as important in the development of frailty. In addition, age-related molecular changes related to autophagy, mitochondrial decline, apoptosis, senescent cell development, and necroptosis likely contribute to the heterogeneous phenotype of frailty. The recent development of a frail mouse model with chronic inflammatory pathway activation has helped to facilitate further whole organism biological discoveries. The following article attempts to create an understanding of the connections between these age-related biological changes and frailty. PMID:26485518

  11. Age-related decline of perforin expression in human cytotoxic T lymphocytes and natural killer cells.

    PubMed

    Rukavina, D; Laskarin, G; Rubesa, G; Strbo, N; Bedenicki, I; Manestar, D; Glavas, M; Christmas, S E; Podack, E R

    1998-10-01

    In this study a flow cytometric technique for detecting cytoplasmic perforin (P) has been used to quantify age-related changes in perforin expression in human peripheral blood lymphocytes (PBL). Proportions of P+ lymphocytes increased after birth, but declined rapidly after the age of 70 years. This was true for both T cells and CD16(+) and CD56(+) natural killer (NK) cells. Children showed in addition to high levels of perforin positive CD8(+) cells a much higher proportion of CD4(+)P+ cells than the other age groups. In elderly individuals there was also a highly significant reduction in mean levels of perforin per cell as compared with all other groups (P < .05 to .001). Adult women had consistently higher mean levels of perforin per cell than adult men for all P+ cell phenotypes. Functional tests clearly showed the deficiency in early spontaneous cytotoxic potential of PBL from elderly persons due to relative P deficiency, which can be corrected by stimulation of cytolytic cells with target cells and interleukin-2 (IL-2). The deficiency in cytolytic activity on the contact with target cells may have implications for antiviral and antitumor immunity in elderly persons.

  12. Age-related decline in bottom-up processing and selective attention in the very old.

    PubMed

    Zhuravleva, Tatyana Y; Alperin, Brittany R; Haring, Anna E; Rentz, Dorene M; Holcomb, Philip J; Daffner, Kirk R

    2014-06-01

    Previous research demonstrating age-related deficits in selective attention have not included old-old adults, an increasingly important group to study. The current investigation compared event-related potentials in 15 young-old (65-79 years old) and 23 old-old (80-99 years old) subjects during a color-selective attention task. Subjects responded to target letters in a specified color (Attend) while ignoring letters in a different color (Ignore) under both low and high loads. There were no group differences in visual acuity, accuracy, reaction time, or latency of early event-related potential components. The old-old group showed a disruption in bottom-up processing, indexed by a substantially diminished posterior N1 (smaller amplitude). They also demonstrated markedly decreased modulation of bottom-up processing based on selected visual features, indexed by the posterior selection negativity (SN), with similar attenuation under both loads. In contrast, there were no group differences in frontally mediated attentional selection, measured by the anterior selection positivity (SP). There was a robust inverse relationship between the size of the SN and SP (the smaller the SN, the larger the SP), which may represent an anteriorly supported compensatory mechanism. In the absence of a decline in top-down modulation indexed by the SP, the diminished SN may reflect age-related degradation of early bottom-up visual processing in old-old adults.

  13. Age-related decline in metabolic competence of small and medium-sized synaptic mitochondria

    NASA Astrophysics Data System (ADS)

    Bertoni-Freddari, Carlo; Fattoretti, Patrizia; Giorgetti, Belinda; Spazzafumo, Liana; Solazzi, Moreno; Balietti, Marta

    2005-02-01

    A computer-assisted morphometric investigation of cytochrome oxidase (COX) activity, selectively evidenced by preferential diaminobenzidine cytochemistry, has been carried out on synaptic mitochondria in the cerebellar cortex of adult and old rats. The ratio (R) of the area of the cytochemical precipitate (CPA) to the overall area of each mitochondrion (MA) was calculated. R refers to the fraction of the inner mitochondrial membrane actively involved in cellular respiration, thus its quantitative estimation constitutes a reliable index of the mitochondrial metabolic competence (MMC). In adult rats a significant negative correlation between MA and R values was found, while in old animals there was just a positive trend. Paired-quartile comparisons of R values showed a significant age-related decrease in small and medium-sized mitochondria, whereas the lowest and not significant age-related reduction was found in oversized organelles. A paired decrease in number and increase in size is reported to be a general trend for mitochondria during aging, but oversized organelles, according to their low R value, constitute a scanty, though functional, compensating reaction. Thus, the present findings support the argument that the currently reported age-related cellular metabolic decay appears to rely both on the decline in MMC of the small and medium-sized mitochondria, and on their specific reduction in number. This novel result is of biological relevance since it is largely the small and medium-sized mitochondria that are required for the provision of adequate amounts of ATP for actual cellular performance, while the significantly enlarged organelles are thought to represent an intermediate ultrastructural feature in mitochondrial genesis and/or remodelling.

  14. 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

  15. Age-related decline in ovarian follicle stocks differ between chimpanzees (Pan troglodytes) and humans.

    PubMed

    Cloutier, Christina T; Coxworth, James E; Hawkes, Kristen

    2015-02-01

    Similarity in oldest parturitions in humans and great apes suggests that we maintain ancestral rates of ovarian aging. Consistent with that hypothesis, previous counts of primordial follicles in postmortem ovarian sections from chimpanzees (Pan troglodytes) showed follicle stock decline at the same rate that human stocks decline across the same ages. Here, we correct that finding with a chimpanzee sample more than three times larger than the previous one, which also allows comparison into older ages. Analyses show depletion rates similar until about age 35, but after 35, the human counts continue to fall with age, while the change is much less steep in chimpanzees. This difference implicates likely effects on ovarian dynamics from other physiological systems that are senescing at different rates, and, potentially, different perimenopausal experience for chimpanzees and humans.

  16. 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…

  17. 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

  18. 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…

  19. Endothelin-1 vasoconstriction and the age-related decline in endothelium-dependent vasodilatation in men.

    PubMed

    Westby, Christian M; Weil, Brian R; Greiner, Jared J; Stauffer, Brian L; DeSouza, Christopher A

    2011-06-01

    ET (endothelin)-1, a potent vasoconstrictor peptide released by the endothelium, plays an important role in vasomotor regulation and has been linked to diminished endothelial vasodilator capacity in several pathologies associated with human aging, including hypertension, Type 2 diabetes and coronary artery disease. However, it is currently unknown whether the decline in endothelial vasodilatation with advancing age is due to elevated ET-1 vasoconstrictor activity. Accordingly, we tested the hypothesis that the age-related impairment in ACh (acetylcholine)-mediated endothelium-dependent vasodilatation is due, at least in part, to increased ET-1-mediated vasoconstrictor tone. FBF (forearm blood flow) responses to ACh, SNP (sodium nitroprusside) and BQ-123 (ET(A) receptor blocker) were determined in 14 young (age, 25 ± 1 years) and 14 older (age, 61 ± 2 years) healthy non-obese men. Additionally, FBF responses to ACh were determined in the presence of ETA blockade. Vasodilatation to ACh was lower (approx. 25%; P<0.05) in the older men (from 4.9 ± 0.2 to 13.9 ± 0.9 ml·100 ml(-1) of tissue·min(-1)) compared with the young men (4.6 ± 0.3 to 17.2 ± 1.0 ml·100 ml(-1) of tissue·min(-1)). There were no differences in FBF responses to SNP between the young (4.8 ± 0.3 to 18.5 ± 0.3 ml·100 ml(-1) of tissue·min(-1)) and older (5.1 ± 0.3 to 17.3 ± 0.8 ml·100 ml(-1) of tissue·min(-1)) men. In the young men, resting FBF was not significantly altered by BQ-123, whereas, in the older men, FBF increased approx. 25% in response to BQ-123 infusion (P<0.05). Co-infusion of ACh with BQ-123 resulted in an approx. 20% increase in the ACh-induced vasodilatation in older men compared with saline. In contrast, FBF responses to ACh were not significantly altered by ET(A) blockade in the young men. In conclusion, these results demonstrate that ET-1 vasoconstrictor activity contributes, at least in part, to diminished endothelium-dependent vasodilatation in older men.

  20. Age-Related Declines and Disease-Associated Variation in Immune Cell Telomere Length in a Wild Mammal

    PubMed Central

    Beirne, Christopher; Delahay, Richard; Hares, Michelle; Young, Andrew

    2014-01-01

    Immunosenescence, the deterioration of immune system capability with age, may play a key role in mediating age-related declines in whole-organism performance, but the mechanisms that underpin immunosenescence are poorly understood. Biomedical research on humans and laboratory models has documented age and disease related declines in the telomere lengths of leukocytes (‘immune cells’), stimulating interest their having a potentially general role in the emergence of immunosenescent phenotypes. However, it is unknown whether such observations generalise to the immune cell populations of wild vertebrates living under ecologically realistic conditions. Here we examine longitudinal changes in the mean telomere lengths of immune cells in wild European badgers (Meles meles). Our findings provide the first evidence of within-individual age-related declines in immune cell telomere lengths in a wild vertebrate. That the rate of age-related decline in telomere length appears to be steeper within individuals than at the overall population level raises the possibility that individuals with short immune cell telomeres and/or higher rates of immune cell telomere attrition may be selectively lost from this population. We also report evidence suggestive of associations between immune cell telomere length and bovine tuberculosis infection status, with individuals detected at the most advanced stage of infection tending to have shorter immune cell telomeres than disease positive individuals. While male European badgers are larger and show higher rates of annual mortality than females, we found no evidence of a sex difference in either mean telomere length or the average rate of within-individual telomere attrition with age. Our findings lend support to the view that age-related declines in the telomere lengths of immune cells may provide one potentially general mechanism underpinning age-related declines in immunocompetence in natural populations. PMID:25268841

  1. Age-related declines and disease-associated variation in immune cell telomere length in a wild mammal.

    PubMed

    Beirne, Christopher; Delahay, Richard; Hares, Michelle; Young, Andrew

    2014-01-01

    Immunosenescence, the deterioration of immune system capability with age, may play a key role in mediating age-related declines in whole-organism performance, but the mechanisms that underpin immunosenescence are poorly understood. Biomedical research on humans and laboratory models has documented age and disease related declines in the telomere lengths of leukocytes ('immune cells'), stimulating interest their having a potentially general role in the emergence of immunosenescent phenotypes. However, it is unknown whether such observations generalise to the immune cell populations of wild vertebrates living under ecologically realistic conditions. Here we examine longitudinal changes in the mean telomere lengths of immune cells in wild European badgers (Meles meles). Our findings provide the first evidence of within-individual age-related declines in immune cell telomere lengths in a wild vertebrate. That the rate of age-related decline in telomere length appears to be steeper within individuals than at the overall population level raises the possibility that individuals with short immune cell telomeres and/or higher rates of immune cell telomere attrition may be selectively lost from this population. We also report evidence suggestive of associations between immune cell telomere length and bovine tuberculosis infection status, with individuals detected at the most advanced stage of infection tending to have shorter immune cell telomeres than disease positive individuals. While male European badgers are larger and show higher rates of annual mortality than females, we found no evidence of a sex difference in either mean telomere length or the average rate of within-individual telomere attrition with age. Our findings lend support to the view that age-related declines in the telomere lengths of immune cells may provide one potentially general mechanism underpinning age-related declines in immunocompetence in natural populations. PMID:25268841

  2. Age-related decline of presumptive inhibitory synapses in the sensorimotor cortex as revealed by the physical disector.

    PubMed

    Poe, B H; Linville, C; Brunso-Bechtold, J

    2001-10-01

    The synapse, as the site of functional neural interaction, has been suggested as a possible substrate for age-related impairment of cognitive ability. Using the physical disector probe with tissue prepared for ultrastructural analysis, we find an age-related decline in the numerical density of presumptive inhibitory synapses in layer 2 of the sensorimotor cortex of the Brown Norway x Fisher 344 rat. This age-related decline in presumptive inhibitory synapses is maintained when the density of synapses is combined with the numerical density of neurons quantified from the same anatomical space to arrive at a ratio of synapses per neuron. The numerical density of these synapses declines between middle-aged (18 months) and old (29 months) animals by 36% whereas numerical density of neurons does not change between these ages, resulting in a decline in the ratio of presumptive inhibitory synapses per neuron in this cortical area. This study demonstrates a deficit in the intrinsic inhibitory circuitry of the aging neocortex, which suggests an anatomical substrate for age-related cognitive impairment.

  3. ESTROGENS AND AGE-RELATED MEMORY DECLINE IN RODENTS: WHAT HAVE WE LEARNED AND WHERE DO WE GO FROM HERE?

    PubMed Central

    Frick, Karyn M.

    2009-01-01

    The question of whether ovarian hormone therapy can prevent or reduce age-related memory decline in menopausal women has been the subject of much recent debate. Although numerous studies have demonstrated a beneficial effect of estrogen and/or progestin therapy for certain types of memory in menopausal women, recent clinical trials suggest that such therapy actually increases the risk of cognitive decline and dementia. Because rodent models have been frequently used to examine the effects of age and/or ovarian hormone deficiency on mnemonic function, rodent models of age-related hormone and memory decline may be useful in helping to resolve this issue. This review will focus on evidence suggesting that estradiol modulates memory, particularly hippocampal-dependent memory, in young and aging female rats and mice. Various factors affecting the mnemonic response to estradiol in aging females will be highlighted to illustrate the complications inherent to studies of estrogen therapy in aging females. Avenues for future development of estradiol-based therapies will also be discussed, and it is argued that an approach to drug development based on identifying the molecular mechanisms underlying estrogenic modulation of memory may lead to promising future treatments for reducing age-related mnemonic decline. PMID:18835561

  4. Age-Related Decline in Cognitive Pain Modulation Induced by Distraction: Evidence From Event-Related Potentials.

    PubMed

    Zhou, Shu; Després, Olivier; Pebayle, Thierry; Dufour, André

    2015-09-01

    Distraction is known to reduce perceived pain but not always efficiently. Overlapping cognitive resources play a role in both pain processing and executive functions. We hypothesized that with aging, the analgesic effects of cognitive modulation induced by distraction would be reduced as a result of functional decline of frontal networks. Twenty-eight elderly and 28 young participants performed a tonic heat pain test with and without distraction (P + D vs P condition), and 2 executive tasks involving the frontal network (1-back [working memory] and go/no-go [response inhibition]), during which event-related potentials were recorded. A significant age-related difference in modulatory effect was observed during the pain-distraction test, with the older group reporting higher pain perception than the younger group during the P + D than during the P condition. Greater brain activity of early processes (P2 component) in both go/no-go and 1-back tasks correlated with less perceived pain during distraction in younger participants. For later processes, more cognitive control and attentional resources (increased N2 and P3 amplitude) needed for working memory processes were associated with greater pain perception in the older group. Inhibition processes were related to conscious distraction estimation in both groups. These findings indicate that cognitive processes subtended by resources in the frontal network, particularly working memory processes, are elicited more in elderly than in younger individuals for pain tolerance when an irrelevant task is performed simultaneously. Perspective: This study suggests that age-related declines in pain modulation are caused by functional degeneration of frontal cerebral networks, which may contribute to a higher prevalence of chronic pain. Analyzing the impact of frontal network function on pain modulation may assist in the development of more effective targeted treatment plans. PMID:26080043

  5. 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.

  6. 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

  7. A mutation in APP protects against Alzheimer's disease and age-related cognitive decline.

    PubMed

    Jonsson, Thorlakur; Atwal, Jasvinder K; Steinberg, Stacy; Snaedal, Jon; Jonsson, Palmi V; Bjornsson, Sigurbjorn; Stefansson, Hreinn; Sulem, Patrick; Gudbjartsson, Daniel; Maloney, Janice; Hoyte, Kwame; Gustafson, Amy; Liu, Yichin; Lu, Yanmei; Bhangale, Tushar; Graham, Robert R; Huttenlocher, Johanna; Bjornsdottir, Gyda; Andreassen, Ole A; Jönsson, Erik G; Palotie, Aarno; Behrens, Timothy W; Magnusson, Olafur T; Kong, Augustine; Thorsteinsdottir, Unnur; Watts, Ryan J; Stefansson, Kari

    2012-08-01

    The prevalence of dementia in the Western world in people over the age of 60 has been estimated to be greater than 5%, about two-thirds of which are due to Alzheimer's disease. The age-specific prevalence of Alzheimer's disease nearly doubles every 5 years after age 65, leading to a prevalence of greater than 25% in those over the age of 90 (ref. 3). Here, to search for low-frequency variants in the amyloid-β precursor protein (APP) gene with a significant effect on the risk of Alzheimer's disease, we studied coding variants in APP in a set of whole-genome sequence data from 1,795 Icelanders. We found a coding mutation (A673T) in the APP gene that protects against Alzheimer's disease and cognitive decline in the elderly without Alzheimer's disease. This substitution is adjacent to the aspartyl protease β-site in APP, and results in an approximately 40% reduction in the formation of amyloidogenic peptides in vitro. The strong protective effect of the A673T substitution against Alzheimer's disease provides proof of principle for the hypothesis that reducing the β-cleavage of APP may protect against the disease. Furthermore, as the A673T allele also protects against cognitive decline in the elderly without Alzheimer's disease, the two may be mediated through the same or similar mechanisms.

  8. 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. PMID:24051310

  9. 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…

  10. 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

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

    PubMed

    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.

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

    PubMed

    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

  13. Impact of the hypothalamic-pituitary-adrenal/gonadal axes on trajectory of age-related cognitive decline.

    PubMed

    Conrad, Cheryl D; Bimonte-Nelson, Heather A

    2010-01-01

    Life expectancies have increased substantially in the last century, dramatically amplifying the proportion of individuals who will reach old age. As individuals age, cognitive ability declines, although the rate of decline differs amongst the forms of memory domains and for different individuals. Memory domains especially impacted by aging are declarative and spatial memories. The hippocampus facilitates the formation of declarative and spatial memories. Notably, the hippocampus is particularly vulnerable to aging. Genetic predisposition and lifetime experiences and exposures contribute to the aging process, brain changes and subsequent cognitive outcomes. In this review, two factors to which an individual is exposed, the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-gonadal (HPG) axis, will be considered regarding the impact of age on hippocampal-dependent function. Spatial memory can be affected by cumulative exposure to chronic stress via glucocorticoids, released from the HPA axis, and from gonadal steroids (estrogens, progesterone and androgens) and gonadotrophins, released from the HPG axis. Additionally, this review will discuss how these hormones impact age-related hippocampal function. We hypothesize that lifetime experiences and exposure to these hormones contribute to the cognitive makeup of the aged individual, and contribute to the heterogeneous aged population that includes individuals with cognitive abilities as astute as their younger counterparts, as well as individuals with severe cognitive decline or neurodegenerative disease.

  14. Complement C3-Deficient Mice Fail to Display Age-Related Hippocampal Decline.

    PubMed

    Shi, Qiaoqiao; Colodner, Kenneth J; Matousek, Sarah B; Merry, Katherine; Hong, Soyon; Kenison, Jessica E; Frost, Jeffrey L; Le, Kevin X; Li, Shaomin; Dodart, Jean-Cosme; Caldarone, Barbara J; Stevens, Beth; Lemere, Cynthia A

    2015-09-23

    The complement system is part of the innate immune response responsible for removing pathogens and cellular debris, in addition to helping to refine CNS neuronal connections via microglia-mediated pruning of inappropriate synapses during brain development. However, less is known about the role of complement during normal aging. Here, we studied the role of the central complement component, C3, in synaptic health and aging. We examined behavior as well as electrophysiological, synaptic, and neuronal changes in the brains of C3-deficient male mice (C3 KO) compared with age-, strain-, and gender-matched C57BL/6J (wild-type, WT) control mice at postnatal day 30, 4 months, and 16 months of age. We found the following: (1) region-specific and age-dependent synapse loss in aged WT mice that was not observed in C3 KO mice; (2) age-dependent neuron loss in hippocampal CA3 (but not in CA1) that followed synapse loss in aged WT mice, neither of which were observed in aged C3 KO mice; and (3) significantly enhanced LTP and cognition and less anxiety in aged C3 KO mice compared with aged WT mice. Importantly, CA3 synaptic puncta were similar between WT and C3 KO mice at P30. Together, our results suggest a novel and prominent role for complement protein C3 in mediating aged-related and region-specific changes in synaptic function and plasticity in the aging brain. Significance statement: The complement cascade, part of the innate immune response to remove pathogens, also plays a role in synaptic refinement during brain development by the removal of weak synapses. We investigated whether complement C3, a central component, affects synapse loss during aging. Wild-type (WT) and C3 knock-out (C3 KO) mice were examined at different ages. The mice were similar at 1 month of age. However, with aging, WT mice lost synapses in specific brain regions, especially in hippocampus, an area important for memory, whereas C3 KO mice were protected. Aged C3 KO mice also performed better on

  15. Age-related reduction in microcolumnar structure in area 46 of the rhesus monkey correlates with behavioral decline

    PubMed Central

    Cruz, Luis; Roe, Daniel L.; Urbanc, Brigita; Cabral, Howard; Stanley, H. E.; Rosene, Douglas L.

    2004-01-01

    Many age-related declines in cognitive function are attributed to the prefrontal cortex, area 46 being especially critical. Yet in normal aging, studies indicate that neurons are not lost in area 46, suggesting that impairments result from more subtle processes. One cortical feature that is functionally important, but that has not been examined in normal aging because of a lack of efficient quantitative methods, is the vertical arrangement of neurons into microcolumns, a fundamental computational unit of the cortex. By using a density-map method derived from condensed-matter physics, we quantified microcolumns in area 46 of seven young and seven aged rhesus monkeys that had been cognitively tested. This analysis demonstrated that there is no age-related reduction in total neuronal density or in microcolumn width, length, or periodicity. There was, however, a statistically significant decrease in the strength of microcolumns, indicating microcolumnar disorganization. This reduction in strength was significantly correlated with age-related cognitive decline on tests of spatial working memory and recognition memory independent of the effect of age. Modeling demonstrated that random neuron displacements of ≈30% of a neuronal diameter (<3 μm) produced the observed reduction in strength. Hence, it is possible that, with changes in dendrites and myelinated axons, subtle displacements of neurons occur that alter microcolumnar structure and correlate with age-induced dysfunction. Therefore, quantitative measurement of microcolumnar structure may provide a sensitive morphological method to assay microcolumnar function in aging and other conditions. PMID:15520373

  16. Protective effect of myostatin gene deletion on aging-related muscle metabolic decline.

    PubMed

    Chabi, B; Pauly, M; Carillon, J; Carnac, G; Favier, F B; Fouret, G; Bonafos, B; Vanterpool, F; Vernus, B; Coudray, C; Feillet-Coudray, C; Bonnieu, A; Lacan, D; Koechlin-Ramonatxo, C

    2016-06-01

    While myostatin gene deletion is a promising therapy to fight muscle loss during aging, this approach induces also skeletal muscle metabolic changes such as mitochondrial deficits, redox alteration and increased fatigability. In the present study, we evaluated the effects of aging on these features in aged wild-type (WT) and mstn knockout (KO) mice. Moreover, to determine whether an enriched-antioxidant diet may be useful to prevent age-related disorders, we orally administered to the two genotypes a melon concentrate rich in superoxide dismutase for 12 weeks. We reported that mitochondrial functional abnormalities persisted (decreased state 3 and 4 of respiration; p<0.05) in skeletal muscle from aged KO mice; however, differences with WT mice were attenuated at old age in line with reduced difference on running endurance between the two genotypes. Interestingly, we showed an increase in glutathione levels, associated with lower lipid peroxidation levels in KO muscle. Enriched antioxidant diet reduced the aging-related negative effects on maximal aerobic velocity and running limit time (p<0.05) in both groups, with systemic adaptations on body weight. The redox status and the hypertrophic phenotype appeared to be beneficial to KO mice, mitigating the effect of aging on the skeletal muscle metabolic remodeling.

  17. 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

  18. 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. PMID:23378841

  19. 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.

  20. Video Games as a Means to Reduce Age-Related Cognitive Decline: Attitudes, Compliance, and Effectiveness

    PubMed Central

    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. PMID:23378841

  1. 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

  2. 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. PMID:26845022

  3. Age-Related Decline in Brain Resources Modulates Genetic Effects on Cognitive Functioning

    PubMed Central

    Lindenberger, Ulman; Nagel, Irene E.; Chicherio, Christian; Li, Shu-Chen; Heekeren, Hauke R.; Bäckman, Lars

    2008-01-01

    Individual differences in cognitive performance increase from early to late adulthood, likely reflecting influences of a multitude of factors. We hypothesize that losses in neurochemical and anatomical brain resources in normal aging modulate the effects of common genetic variations on cognitive functioning. Our hypothesis is based on the assumption that the function relating brain resources to cognition is nonlinear, so that genetic differences exert increasingly large effects on cognition as resources recede from high to medium levels in the course of aging. Direct empirical support for this hypothesis comes from a study by Nagel et al. (2008), who reported that the effects of the Catechol-O-Methyltransferase (COMT) gene on cognitive performance are magnified in old age and interacted with the Brain-Derived Neurotrophic Factor (BDNF) gene. We conclude that common genetic polymorphisms contribute to the increasing heterogeneity of cognitive functioning in old age. Extensions of the hypothesis to other polymorphisms are discussed. (150 of 150 words) PMID:19225597

  4. Age-related cognitive decline and electroencephalogram slowing in Down's syndrome as a model of Alzheimer's disease.

    PubMed

    Soininen, H; Partanen, J; Jousmäki, V; Helkala, E L; Vanhanen, M; Majuri, S; Kaski, M; Hartikainen, P; Riekkinen, P

    1993-03-01

    We studied quantitative electroencephalogram and neuropsychological performance in an aging series of 31 patients with Down's syndrome and compared the findings with those of 36 patients with probable Alzheimer's disease and age-matched controls. We found an age-related decline of cortical functions and slowing of the electroencephalogram in Down's syndrome patients aged from 20 to 60 years. Slowing of the electroencephalogram, i.e. the decrease of the peak frequency, was significantly related to Mini-Mental status scores, and visual, praxic and speech functions, as well as memory in the Down patients, similar to the Alzheimer patients. Similar correlations were not demonstrated for young or elderly controls. This study provides neuropsychological and electrophysiological data to suggest that studying Down's syndrome patients of different ages can serve as a model for progression of Alzheimer's disease. PMID:8469312

  5. 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

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

    PubMed

    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

  7. Religiosity is negatively associated with later-life intelligence, but not with age-related cognitive decline.

    PubMed

    Ritchie, Stuart J; Gow, Alan J; Deary, Ian J

    2014-09-01

    A well-replicated finding in the psychological literature is the negative correlation between religiosity and intelligence. However, several studies also conclude that one form of religiosity, church attendance, is protective against later-life cognitive decline. No effects of religious belief per se on cognitive decline have been found, potentially due to the restricted measures of belief used in previous studies. Here, we examined the associations between religiosity, intelligence, and cognitive change in a cohort of individuals (initial n = 550) with high-quality measures of religious belief taken at age 83 and multiple cognitive measures taken in childhood and at four waves between age 79 and 90. We found that religious belief, but not attendance, was negatively related to intelligence. The effect size was smaller than in previous studies of younger participants. Longitudinal analyses showed no effect of either religious belief or attendance on cognitive change either from childhood to old age, or across the ninth decade of life. We discuss differences between our cohort and those in previous studies - including in age and location - that may have led to our non-replication of the association between religious attendance and cognitive decline.

  8. Age-related differences in memory-encoding fMRI responses after accounting for decline in vascular reactivity.

    PubMed

    Liu, Peiying; Hebrank, Andrew C; Rodrigue, Karen M; Kennedy, Kristen M; Section, Jarren; Park, Denise C; Lu, Hanzhang

    2013-09-01

    BOLD fMRI has provided a wealth of information about the aging brain. A common finding is that posterior regions of the brain manifest an age-related decrease in activation while the anterior regions show an age-related increase. Several neurocognitive models have been proposed to interpret these findings. However, one issue that has not been sufficiently considered to date is that the BOLD signal is based on vascular responses secondary to neural activity. Thus the above findings could be in part due to a vascular change, especially in view of the expected decline of vascular health with age. In the present study, we aim to examine age-related differences in memory-encoding fMRI response in the context of vascular aging. One hundred and thirty healthy subjects ranging from 20 to 89 years old underwent a scene-viewing fMRI task and, in the same session, cerebrovascular reactivity (CVR) was measured in each subject using a CO2-inhalation task. Without accounting for the influence of vascular changes, the task-activated fMRI signal showed the typical age-related decrease in visual cortex and medial temporal lobe (MTL), but manifested an increase in the right inferior frontal gyrus (IFG). In the same individuals, an age-related CVR reduction was observed in all of these regions. We then used a previously proposed normalization approach to calculate a CVR-corrected fMRI signal, which was defined as the uncorrected signal divided by CVR. Based on the CVR-corrected fMRI signal, an age-related increase is now seen in both the left and right sides of IFG; and no brain regions showed a signal decrease with age. We additionally used a model-based approach to examine the fMRI data in the context of CVR, which again suggested an age-related change in the two frontal regions, but not in the visual and MTL regions.

  9. ROLE OF SOLUBLE EPOXIDE HYDROLASE IN AGE-RELATED VASCULAR COGNITIVE DECLINE

    PubMed Central

    Nelson, Jonathan W.; Young, Jennifer M.; Borkar, Rohan; Woltjer, Randy L.; Quinn, Joseph F.; Silbert, Lisa C.; Grafe, Marjorie R.; Alkayed, Nabil J.

    2014-01-01

    P450 eicosanoids are important regulators of the cerebral microcirculation, but their role in cerebral small vessel disease is unclear. We tested the hypothesis that vascular cognitive impairment (VCI) is linked to reduced cerebral microvascular eicosanoid signaling. We analyzed human brain tissue from individuals formerly enrolled in the Oregon Brain Aging Study, who had a history of cognitive impairment histopathological evidence of microvascular disease. VCI subjects had significantly higher lesion burden both on premortem MRI and postmortem histopathology compared to age- and sex-matched controls. Mass spectrometry-based eicosanoid analysis revealed that 14,15-dihydroxyeicosatrienoic acid (DHET) was elevated in cortical brain tissue from VCI subjects. Immunoreactivity of soluble epoxide hydrolase (sEH), the enzyme responsible for 14,15-DHET formation, was localized to cerebral microvascular endothelium, and was enhanced in microvessels of affected tissue. Finally, we evaluated the genotype frequency of two functional single nucleotide polymorphisms of sEH gene EPHX2 in VCI and control groups. Our findings support a role for sEH and a potential benefit from sEH inhibitors in age-related VCI. PMID:25277097

  10. Ginseng berry extract supplementation improves age-related decline of insulin signaling in mice.

    PubMed

    Seo, Eunhui; Kim, Sunmi; Lee, Sang Jun; Oh, Byung-Chul; Jun, Hee-Sook

    2015-04-01

    The aim of this study was to evaluate the effects of ginseng berry extract on insulin sensitivity and associated molecular mechanisms in aged mice. C57BL/6 mice (15 months old) were maintained on a regular diet (CON) or a regular diet supplemented with 0.05% ginseng berry extract (GBD) for 24 or 32 weeks. GBD-fed mice showed significantly lower serum insulin levels (p = 0.016) and insulin resistance scores (HOMA-IR) (p = 0.012), suggesting that GBD improved insulin sensitivity. Pancreatic islet hypertrophy was also ameliorated in GBD-fed mice (p = 0.007). Protein levels of tyrosine phosphorylated insulin receptor substrate (IRS)-1 (p = 0.047), and protein kinase B (AKT) (p = 0.037), were up-regulated in the muscle of insulin-injected GBD-fed mice compared with CON-fed mice. The expressions of forkhead box protein O1 (FOXO1) (p = 0.036) and peroxisome proliferator-activated receptor gamma (PPARγ) (p = 0.032), which are known as aging- and insulin resistance-related genes, were also increased in the muscle of GBD-fed mice. We conclude that ginseng berry extract consumption might increase activation of IRS-1 and AKT, contributing to the improvement of insulin sensitivity in aged mice. PMID:25912041

  11. Ginseng Berry Extract Supplementation Improves Age-Related Decline of Insulin Signaling in Mice

    PubMed Central

    Seo, Eunhui; Kim, Sunmi; Lee, Sang Jun; Oh, Byung-Chul; Jun, Hee-Sook

    2015-01-01

    The aim of this study was to evaluate the effects of ginseng berry extract on insulin sensitivity and associated molecular mechanisms in aged mice. C57BL/6 mice (15 months old) were maintained on a regular diet (CON) or a regular diet supplemented with 0.05% ginseng berry extract (GBD) for 24 or 32 weeks. GBD-fed mice showed significantly lower serum insulin levels (p = 0.016) and insulin resistance scores (HOMA-IR) (p = 0.012), suggesting that GBD improved insulin sensitivity. Pancreatic islet hypertrophy was also ameliorated in GBD-fed mice (p = 0.007). Protein levels of tyrosine phosphorylated insulin receptor substrate (IRS)-1 (p = 0.047), and protein kinase B (AKT) (p = 0.037), were up-regulated in the muscle of insulin-injected GBD-fed mice compared with CON-fed mice. The expressions of forkhead box protein O1 (FOXO1) (p = 0.036) and peroxisome proliferator-activated receptor gamma (PPARγ) (p = 0.032), which are known as aging- and insulin resistance-related genes, were also increased in the muscle of GBD-fed mice. We conclude that ginseng berry extract consumption might increase activation of IRS-1 and AKT, contributing to the improvement of insulin sensitivity in aged mice. PMID:25912041

  12. Viewing forests from below: fine root mass declines relative to leaf area in aging lodgepole pine stands.

    PubMed

    Schoonmaker, A S; Lieffers, V J; Landhäusser, S M

    2016-07-01

    In the continued quest to explain the decline in productivity and vigor with aging forest stands, the most poorly studied area relates to root system change in time. This paper measures the wood production, root and leaf area (and mass) in a chronosequence of fire-origin lodgepole pine (Pinus contorta Loudon) stands consisting of four age classes (12, 21, 53, and ≥100 years), each replicated ~ five times. Wood productivity was greatest in the 53-year-old stands and then declined in the ≥100-year-old stands. Growth efficiency, the quantity of wood produced per unit leaf mass, steadily declined with age. Leaf mass and fine root mass plateaued between the 53- and ≥100-year-old stands, but leaf area index actually increased in the older stands. An increase in the leaf area index:fine root area ratio supports the idea that older stand are potentially limited by soil resources. Other factors contributing to slower growth in older stands might be lower soil temperatures and increased self-shading due to the clumped nature of crowns. Collectively, the proportionally greater reduction in fine roots in older stands might be the variable that predisposes these forests to be at a potentially greater risk of stress-induced mortality. PMID:27041684

  13. Effect of IP3R3 and NPY on age-related declines in olfactory stem cell proliferation.

    PubMed

    Jia, Cuihong; Hegg, Colleen C

    2015-02-01

    Losing the sense of smell because of aging compromises health and quality of life. In the mouse olfactory epithelium, aging reduces the capacity for tissue homeostasis and regeneration. The microvillous cell subtype that expresses both inositol trisphosphate receptor type 3 (IP3R3) and the neuroproliferative factor neuropeptide Y (NPY) is critical for regulation of homeostasis, yet its role in aging is undefined. We hypothesized that an age-related decline in IP3R3 expression and NPY signaling underlie age-related homeostatic changes and olfactory dysfunction. We found a decrease in IP3R3(+) and NPY(+) microvillous cell numbers and NPY protein and a reduced sensitivity to NPY-mediated proliferation over 24 months. However, in IP3R3-deficient mice, there was no further age-related reduction in cell numbers, proliferation, or olfactory function compared with wild type. The proliferative response was impaired in aged IP3R3-deficient mice when injury was caused by satratoxin G, which induces IP3R3-mediated NPY release, but not by bulbectomy, which does not evoke NPY release. These data identify IP3R3 and NPY signaling as targets for improving recovery following olfactotoxicant exposure.

  14. Aging- and task-related resilience decline is linked to food responsiveness in highly social honey bees.

    PubMed

    Speth, Martin T; Kreibich, Claus D; Amdam, Gro V; Münch, Daniel

    2015-05-01

    Conventional invertebrate models of aging have provided striking examples for the influence of food- and nutrient-sensing on lifespan and stress resilience. On the other hand, studies in highly social insects, such as honey bees, have revealed how social context can shape very plastic life-history traits, for example flexible aging dynamics in the helper caste (workers). It is, however, not understood how food perception and stress resilience are connected in honey bee workers with different social task behaviors and aging dynamics. To explore this linkage, we tested if starvation resilience, which normally declines with age, depends on food responsiveness in honey bees. We studied two typically non-senesced groups of worker bees with different social task behaviors: mature nurses (caregivers) and mature foragers (food collectors). In addition, we included a group of old foragers for which functional senescence is well-established. Bees were individually scored for their food perception by measuring the gustatory response to different sucrose concentrations. Subsequently, individuals were tested for survival under starvation stress. We found that starvation stress resilience, but not gustatory responsiveness differed between workers with different social task behaviors (mature nurses vs. mature foragers). In addition starvation stress resilience differed between foragers with different aging progressions (mature foragers vs. old foragers). Control experiments confirmed that differences in starvation resilience between mature nurses and mature foragers were robust against changing experimental conditions, such as water provision and activity. For all worker groups we established that individuals with low gustatory responsiveness were more resilient to starvation stress. Finally, for the group of rapidly aging foragers we found that low food responsiveness was linked to a delayed age-related decline in starvation resilience. Our study highlights associations between

  15. Age-related declines in distortion product otoacoustic emissions utilizing pure tone contralateral stimulation in CBA/CaJ mice.

    PubMed

    Varghese, George I; Zhu, Xiaoxia; Frisina, Robert D

    2005-11-01

    One role of the medial olivocochlear (MOC) auditory efferent system is to suppress cochlear outer hair cell (OHC) responses when presented with a contralateral sound. Using distortion product otoacoustic emissions (DPOAEs), the effects of active changes in OHC responses due to the MOC as a function of age can be observed when contralateral stimulation with a pure tone is applied. Previous studies have shown that there are age-related declines of the MOC when broad band noise is presented to the contralateral ear. In this study, we measured age-related changes in CBA/CaJ mice by comparing DPOAE generation with and without a contralateral pure tone at three different frequencies (12, 22, and 37 kHz). Young (n = 16), middle (n = 10) and old-aged (n = 10) CBA mice were tested. DPOAE-grams were obtained using L1 = 65 and L2 = 50 dB SPL, F1/F2 = 1.25, using eight points per octave covering a frequency range from 5.6-44.8 kHz. The pure tone was presented contralaterally at 55 dB SPL. DPOAE-grams and ABR levels indicated age-related hearing loss in the old mice. In addition, there was an overall change in DPOAEs in the middle-aged and old groups relative to the young. Pure tone stimulation was not as effective as a suppressor compared to broadband noise. An increase in pure tone frequency from 12 to 22 kHz induced greater suppression of DPOAEs, but the 37 kHz was least effective. These results indicate that as the mouse ages, there are significant changes in the efficiency of the suppression mechanism as elicited by contralateral narrowband stimuli. These findings reinforce the idea that age-related changes in the MOC or the operating points of OHCs play a role in the progression of presbycusis - age-related hearing loss in mammals.

  16. 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.

  17. 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

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

    PubMed

    Pokkunuri, Indira; Ali, Quaisar; Asghar, Mohammad

    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 gp (91phox) -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

  19. Caloric restriction promotes genomic stability by induction of base excision repair and reversal of its age-related decline.

    PubMed

    Cabelof, Diane C; Yanamadala, Sunitha; Raffoul, Julian J; Guo, ZhongMao; Soofi, Abdulsalam; Heydari, Ahmad R

    2003-03-01

    Caloric restriction is a potent experimental manipulation that extends mean and maximum life span and delays the onset and progression of tumors in laboratory rodents. While caloric restriction (CR) clearly protects the genome from deleterious damage, the mechanism by which genomic stability is achieved remains unclear. We provide evidence that CR promotes genomic stability by increasing DNA repair capacity, specifically base excision repair (BER). CR completely reverses the age-related decline in BER capacity (P<0.01) in all tissues tested (brain, liver, spleen and testes) providing aged, CR animals with the BER phenotype of young, ad libitum-fed animals. This CR-induced reversal of the aged BER phenotype is accompanied by a reversal in the age-related decline in DNA polymerase beta (beta-pol), a rate-limiting enzyme in the BER pathway. CR significantly reversed the age-related loss of beta-pol protein levels (P<0.01), mRNA levels (P<0.01) and enzyme activity (P<0.01) in all tissues tested. Additionally, in young (4-6-month-old) CR animals a significant up-regulation in BER capacity, beta-pol protein and beta-pol mRNA is observed (P<0.01), demonstrating an early effect of CR that may provide insight in distinguishing the anti-tumor from the anti-aging effects of CR. This up-regulation in BER by caloric restriction in young animals corresponds to increased protection from carcinogen exposure, as mutation frequency is significantly reduced in CR animals exposed to either DMS or 2-nitropropane (2-NP) (P<0.01). Overall the data suggest an important biological consequence of moderate BER up-regulation and provides support for the hormesis theory of caloric restriction.

  20. 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

  1. AGE-RELATED DECLINES IN THE DETECTION OF PASSIVE WRIST MOVEMENT

    PubMed Central

    Wright, Melissa L.; Adamo, Diane E.; Brown, Susan H.

    2011-01-01

    Age-related changes in proprioceptive ability and their contributions to postural instability have been well documented. In contrast, and despite the known importance of proprioceptive feedback in the control of coordinated arm and hand movement, studies focusing on upper limb proprioception in older populations are few and equivocal in their findings. This study focused on kinesthetic awareness about the wrist joint in healthy young and older adults. Passive movement detection thresholds (PMDT) were twice as high in older compared to young participants. In contrast to previous findings demonstrating asymmetries in static position sense, PMDT did not differ between the dominant and non-dominant wrist joints nor did direction of joint displacement affect PMDT as has been reported for the lower limb. Preliminary analysis indicated that PMDT was significantly higher in older adults categorized as sedentary while active older adults were able to detect passive movement as well as young adults. These findings demonstrate that upper limb kinesthesia is impaired in older adults although the degree of impairment may be influenced by one’s level of physical activity. PMID:21704124

  2. Cardiopulmonary Function and Age-Related Decline Across the Breast Cancer Survivorship Continuum

    PubMed Central

    Jones, Lee W.; Courneya, Kerry S.; Mackey, John R.; Muss, Hyman B.; Pituskin, Edith N.; Scott, Jessica M.; Hornsby, Whitney E.; Coan, April D.; Herndon, James E.; Douglas, Pamela S.; Haykowsky, Mark

    2012-01-01

    Purpose To evaluate cardiopulmonary function (as measured by peak oxygen consumption [VO2peak]) across the breast cancer continuum and its prognostic significance in women with metastatic disease. Patients and Methods Patients with breast cancer representing four cross-sectional cohorts—that is, (1) before, (2) during, and (3) after adjuvant therapy for nonmetastatic disease, and (4) during therapy in metastatic disease—were studied. A cardiopulmonary exercise test (CPET) with expired gas analysis was used to assess VO2peak. A Cox proportional hazards model was used to estimate the risk of death according to VO2peak category (< 15.4 v ≥ 15.4 mL · kg−1 · min−1) with adjustment for clinical factors. Results A total of 248 women (age, 55 ± 8 years) completed a CPET. Mean VO2peak was 17.8 ± a standard deviation of 4.3 mL · kg−1 · min−1, the equivalent of 27% ± 17% below age-matched healthy sedentary women. For the entire cohort, 32% had a VO2peak less than 15.4 mL · kg−1 · min−1—the VO2peak required for functional independence. VO2peak was significantly different across breast cancer cohorts for relative (mL · kg−1 · min−1) and absolute (L · min−1) VO2peak (P = .017 and P < .001, respectively); VO2peak was lowest in women with metastatic disease. In patients with metastatic disease (n = 52), compared with patients achieving a VO2peak ≤ 1.09 L · min−1, the adjusted hazard ratio for death was 0.32 (95% CI, 0.16 to 0.67, P = .002) for a VO2peak more than 1.09 L · min−1. Conclusion Patients with breast cancer have marked impairment in VO2peak across the entire survivorship continuum. VO2peak may be an independent predictor of survival in metastatic disease. PMID:22614980

  3. A neuropsychological instrument measuring age-related cerebral decline in older drivers: development, reliability, and validity of MedDrive

    PubMed Central

    Vaucher, Paul; Cardoso, Isabel; Veldstra, Janet L.; Herzig, Daniela; Herzog, Michael; Mangin, Patrice; Favrat, Bernard

    2014-01-01

    When facing age-related cerebral decline, older adults are unequally affected by cognitive impairment without us knowing why. To explore underlying mechanisms and find possible solutions to maintain life-space mobility, there is a need for a standardized behavioral test that relates to behaviors in natural environments. The aim of the project described in this paper was therefore to provide a free, reliable, transparent, computer-based instrument capable of detecting age-related changes on visual processing and cortical functions for the purposes of research into human behavior in computational transportation science. After obtaining content validity, exploring psychometric properties of the developed tasks, we derived (Study 1) the scoring method for measuring cerebral decline on 106 older drivers aged ≥70 years attending a driving refresher course organized by the Swiss Automobile Association to test the instrument's validity against on-road driving performance (106 older drivers). We then validated the derived method on a new sample of 182 drivers (Study 2). We then measured the instrument's reliability having 17 healthy, young volunteers repeat all tests included in the instrument five times (Study 3) and explored the instrument's psychophysical underlying functions on 47 older drivers (Study 4). Finally, we tested the instrument's responsiveness to alcohol and effects on performance on a driving simulator in a randomized, double-blinded, placebo, crossover, dose-response, validation trial including 20 healthy, young volunteers (Study 5). The developed instrument revealed good psychometric properties related to processing speed. It was reliable (ICC = 0.853) and showed reasonable association to driving performance (R2 = 0.053), and responded to blood alcohol concentrations of 0.5 g/L (p = 0.008). Our results suggest that MedDrive is capable of detecting age-related changes that affect processing speed. These changes nevertheless do not necessarily affect

  4. Longitudinal Attentional Engagement Rescues Mice from Age-Related Cognitive Declines and Cognitive Inflexibility

    ERIC Educational Resources Information Center

    Matzel, Louis D.; Light, Kenneth R.; Wass, Christopher; Colas-Zelin, Danielle; Denman-Brice, Alexander; Waddel, Adam C.; Kolata, Stefan

    2011-01-01

    Learning, attentional, and perseverative deficits are characteristic of cognitive aging. In this study, genetically diverse CD-1 mice underwent longitudinal training in a task asserted to tax working memory capacity and its dependence on selective attention. Beginning at 3 mo of age, animals were trained for 12 d to perform in a dual radial-arm…

  5. Age-Related Decline and Diagnostic Performance of More and Less Prevalent Clinical Cases

    ERIC Educational Resources Information Center

    St-Onge, Christina; Landry, Marjolaine; Xhignesse, Marianne; Voyer, Gilles; Tremblay-Lavoie, Stéphanie; Mamede, Sílvia; Schmidt, Henk; Rikers, Remy

    2016-01-01

    Since cognitive abilities have been shown to decrease with age, it is expected that older physicians would not perform as well as their younger counterparts on clinical cases unless their expertise can counteract the cognitive effects of aging. However, studies on the topic have shown contradictory results. This study aimed to further investigate…

  6. 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.

  7. Age-related decline of myelin proteins is highly correlated with activation of astrocytes and microglia in the rat CNS.

    PubMed

    Xie, Fang; Zhang, Jiu-Cong; Fu, Han; Chen, Jun

    2013-11-01

    It has been shown that aging can greatly influence the integrity and ultrastructure of white matter and the myelin sheath; however, studies regarding the effects of aging on the expression of myelin proteins are still limited. In the present study, immunohistochemical mapping was used to investigate the overall expression of myelin basic protein (Mbp) and myelin oligodendrocyte glycoprotein (Mog) in the central nervous system (CNS) of rats in postnatal months 2, 5, 18 and 26. Astrocyte and microglia activation was also detected by glial fibrillary acidic protein (GFAP) or ionized calcium-binding adaptor molecule 1 (Iba1) staining and western blotting. A significant decline of Mbp and Mog was identified as a universal alteration in the CNS of aged rats. Aging also induced significant astrocyte and microglial activation. Correlation analysis indicated a negative correlation between the reduction of age‑related myelin proteins and glial activation in aging. This correlation of myelin breakdown and glial activation in aging may reveal new evidence in connecting the inflammation and myelin breakdown mechanism of age‑related neurodegenerative diseases.

  8. 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. PMID:27125385

  9. Age-related decline in the matrix contents and functional properties of human periodontal ligament stem cell sheets.

    PubMed

    Wu, Rui-Xin; Bi, Chun-Sheng; Yu, Yang; Zhang, Lin-Lin; Chen, Fa-Ming

    2015-08-01

    In this study, periodontal ligament (PDL) stem cells (PDLSCs) derived from different-aged donors were used to evaluate the effect of aging on cell sheet formation. The activity of PDLSCs was first determined based on their colony-forming ability, surface markers, proliferative/differentiative potentials, senescence-associated β-galactosidase (SA-βG) staining, and expression of pluripotency-associated transcription factors. The ability of these cells to form sheets, based on their extracellular matrix (ECM) contents and their functional properties necessary for osteogenic differentiation, was evaluated to predict the age-related changes in the regenerative capacity of the cell sheets in their further application. It was found that human PDLSCs could be isolated from the PDL tissue of different-aged subjects. However, the ability of the PDLSCs to proliferate and to undergo osteogenic differentiation and their expression of pluripotency-associated transcription factors displayed age-related decreases. In addition, these cells exhibited an age-related increase in SA-βG expression. Aged cells showed an impaired ability to form functional cell sheets, as determined by morphological observations and Ki-67 immunohistochemistry staining. Based on the production of ECM proteins, such as fibronectin, integrin β1, and collagen type I; alkaline phosphatase (ALP) activity; and the expression of osteogenic genes, such as ALP, Runt-related transcription factor 2, and osteocalcin, cell sheets formed by PDLSCs derived from older donors demonstrated a less potent osteogenic capacity compared to those formed by PDLSCs from younger donors. Our data suggest that the age-associated decline in the matrix contents and osteogenic properties of PDLSC sheets should be taken into account in cell sheet engineering research and clinical periodontal regenerative therapy.

  10. 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

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

    PubMed

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

    2016-01-01

    Aging-related bradykinesia affects ∼ 15% of those reaching age 65 and 50% of those reaching their 80s. Given this high risk and lack of pharmacologic therapeutics, noninvasive 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 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 that 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 dopamine neurotransmission may be one component of preserving locomotor capabilities during aging.

  12. Quantitative SPET 99Tcm-DMSA uptake by the kidneys: age-related decline in healthy males.

    PubMed

    Groshar, D; Gorenberg, M; Osamah, H

    1998-09-01

    To evaluate if 99Tcm-dimercaptosuccinic acid (99Tcm-DMSA) uptake by the kidneys is related to age and creatinine clearance in males with normal renal function, quantitative single photon emission tomography (SPET) of DMSA uptake by the kidneys was performed in 18 volunteers aged 20-79 years. The quantitative uptake of DMSA in the right kidney was 13.9 +/- 2.9% and in the left kidney 14.2 +/- 3.0%. There was no statistically significant difference between left and right kidney uptake (t = 1.2, N.S.). Global kidney uptake (right + left) was 28.1 +/- 5.9%. There was a statistically significant age-related decline in global DMSA uptake. The estimated DMSA uptake (%) was given by -0.27 x age + 42 (r = -0.87, P < 0.001). A good correlation was found between creatinine clearance and global DMSA uptake (r = 0.87, y = 2.8x + 28.3, P < 0.001). The results suggest that normal values of DMSA uptake by the kidneys are age-dependent.

  13. Why NAD(+) Declines during Aging: It's Destroyed.

    PubMed

    Schultz, Michael B; Sinclair, David A

    2016-06-14

    NAD(+) is required not only for life but for a long life. In this issue, Camacho-Pereira et al. (2016) implicate CD38 in the decline of NAD(+) during aging, with implications for combating age-related diseases. PMID:27304496

  14. Computer Simulations of Loss of Organization of Neurons as a Model for Age-related Cognitive Decline

    NASA Astrophysics Data System (ADS)

    Cruz, Luis; Fengometidis, Elene; Jones, Frank; Jampani, Srinivas

    2011-03-01

    In normal aging, brains suffer from progressive cognitive decline not linked with loss of neurons common in neurodegenerative disorders such as Alzheimer's disease. However, in some brain areas neurons have lost positional organization specifically within microcolumns: arrays of interconnected neurons which may constitute fundamental computational units in the brain. This age-related loss of organization, likely a result of micron-sized random displacements in neuronal positions, is hypothesized to be a by-product of the loss of support from the surrounding medium, including dendrites. Using a dynamical model applied to virtual 3D representation of neuronal arrangements, that previously showed loss of organization in brains of cognitively tested rhesus monkeys, the relationship between these displacements and changes to the surrounding dendrite network are presented. The consequences of these displacements on the structure of the dendritic network, with possible disruptions in signal synchrony important to cognitive function, are discussed. NIH R01AG021133.

  15. Women's intentions to use fertility preservation to prevent age-related fertility decline.

    PubMed

    Ter Keurst, Anne; Boivin, Jacky; Gameiro, Sofia

    2016-01-01

    The optimal age to cryopreserve oocytes for later use is before 36 years. Current users are on average 38 years old. In this cross-sectional study an online survey was constructed about the factors associated with the intentions of childless women aged 28-35 years to use fertility preservation (FP). Questions were derived from the Theory of Planned Behaviour (attitudes and subjective norms regarding FP and perceived behaviour control to do FP) and the Health Belief Model (perceived susceptibility of infertility, perceived severity of childlessness, barriers and benefits of FP and cue to use FP). Also addressed were parenthood goals, fertility knowledge and intentions to use FP within 2 years. The data were analysed using structural equation modelling. The Health Belief Model showed a good fit to the data (χ(2) [14, n = 257] = 13.63, P = 0.477; CFI = 1.000: RMSEA = 00, 90% CI [0.00-0.06]). Higher intentions to use FP were associated with feeling susceptible to infertility, considering FP useful to achieve parenthood, perceiving the implications of infertility as severe, expecting to have children at a later age and having fewer ethical concerns. This suggests an increase of fertility awareness is necessary for the optimal use of FP. PMID:26611498

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

    PubMed

    Michel, Jean-Pierre

    2016-09-01

    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.

  17. 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

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

    PubMed

    Michel, Jean-Pierre

    2016-09-01

    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

  19. 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.

  20. Accelerated age-related olfactory decline among type 1 Usher patients

    PubMed Central

    Ribeiro, João Carlos; Oliveiros, Bárbara; Pereira, Paulo; António, Natália; Hummel, Thomas; Paiva, António; Silva, Eduardo D.

    2016-01-01

    Usher Syndrome (USH) is a rare disease with hearing loss, retinitis pigmentosa and, sometimes, vestibular dysfunction. A phenotype heterogeneity is reported. Recent evidence indicates that USH is likely to belong to an emerging class of sensory ciliopathies. Olfaction has recently been implicated in ciliopathies, but the scarce literature about olfaction in USH show conflicting results. We aim to evaluate olfactory impairment as a possible clinical manifestation of USH. Prospective clinical study that included 65 patients with USH and 65 normal age-gender-smoking-habits pair matched subjects. A cross culturally validated version of the Sniffin’ Sticks olfaction test was used. Young patients with USH have significantly better olfactory scores than healthy controls. We observe that USH type 1 have a faster ageing olfactory decrease than what happens in healthy subjects, leading to significantly lower olfactory scores in older USH1 patients. Moreover, USH type 1 patients showed significantly higher olfactory scores than USH type 2, what can help distinguishing them. Olfaction represents an attractive tool for USH type classification and pre diagnostic screening due to the low cost and non-invasive nature of the testing. Olfactory dysfunction should be considered among the spectrum of clinical manifestations of Usher syndrome. PMID:27329700

  1. 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

  2. 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. PMID:27516713

  3. 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.

  4. A critical review of Vitamin C for the prevention of age-related cognitive decline and Alzheimer’s disease

    PubMed Central

    Harrison, Fiona E

    2013-01-01

    Antioxidants in the diet have long been thought to confer some level of protection against the oxidative damage that is involved in the pathology of Alzheimer’s disease as well as general cognitive decline in normal aging. Nevertheless, support for this hypothesis in the literature is equivocal. In the case of vitamin C (ascorbic acid) in particular, lack of consideration of some of the specific features of vitamin C metabolism has led to studies in which classification of participants according to vitamin C status is inaccurate, and the absence of critical information precludes the drawing of appropriate conclusions. Vitamin C levels in plasma are not always reported, and estimated daily intake from food diaries may not be accurate or reflect actual plasma values. The ability to transport ingested vitamin C from the intestines into blood is limited by the saturable sodium-dependent vitamin C transporter (SVCT1) and thus very high intakes, and the use of supplements are often erroneously considered to be of greater benefit that they really are. The current review documents differences among the studies in terms of vitamin C status of participants. Overall, there is a large body of evidence that maintaining healthy vitamin C levels can have a protective function against age-related cognitive decline and Alzheimer’s disease, but avoiding vitamin C deficiency is likely to be more beneficial than taking supplements on top of a normal, healthy diet. PMID:22366772

  5. Time-restricted feeding attenuates age-related cardiac decline in Drosophila.

    PubMed

    Gill, Shubhroz; Le, Hiep D; Melkani, Girish C; Panda, Satchidananda

    2015-03-13

    Circadian clocks orchestrate periods of rest or activity and feeding or fasting over the course of a 24-hour day and maintain homeostasis. To assess whether a consolidated 24-hour cycle of feeding and fasting can sustain health, we explored the effect of time-restricted feeding (TRF; food access limited to daytime 12 hours every day) on neural, peripheral, and cardiovascular physiology in Drosophila melanogaster. We detected improved sleep, prevention of body weight gain, and deceleration of cardiac aging under TRF, even when caloric intake and activity were unchanged. We used temporal gene expression profiling and validation through classical genetics to identify the TCP-1 ring complex (TRiC) chaperonin, the mitochondrial electron transport chain complexes, and the circadian clock as pathways mediating the benefits of TRF.

  6. 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.

  7. 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

  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

    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. 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

  10. High prevalence rate of pituitary incidentaloma: is it associated with the age-related decline of the sex hormones levels?

    PubMed

    Kastelan, Darko; Korsic, Mirko

    2007-01-01

    Incidental pituitary adenoma is the common finding during brain imaging. According to multistep model of pituitary tumourigenesis genetic alterations provide the initiating event that transforms cells while hormones play a role in promoting cell proliferation. Development of pituitary adenoma in a case of excessive hypophysiotrophic hormones production or reduced feedback suppression by target gland hormones emphasizes the importance of hormonal stimulation in pituitary tumourigenesis. Pituitary hyperplasia has been reported in pregnancy, hypothyroidism and conditions such as CRH or GHRH hypersecretion. Moreover, recent study reported one case of gonadotroph macroadenoma and two cases of gonadotroph cells hyperplasia in patients with Klinefelter syndrome probably due to protracted stimulation of gonadotroph cells because of lack of androgen feedback. Significant changes of the hypothalamic-pituitary-gonadal axis occurred with aging. In females, after menopause, estradiol level decreases by 35-fold and estrone level by 20-fold that results in increased gonadotropins levels. Similarly, FSH, but not LH, level is increased with advancing age in men, too, although the age-related difference in the level is less in comparison with women. Regarding these data, we hypothesised that high prevalence rate of pituitary incidentaloma in the elderly is associated with age-related decline in sex hormones levels and subsequent lack of feedback suppression leading to permanent gonadotrophs stimulation which is the crucial step in the pituitary tumour development. According to previously mentioned multistep model of pituitary tumourigenesis, incidentaloma will develop only in persons with already present intrinsic pituitary cell defects. However, further studies have to answer the questions of whether the incidence of pituitary tumours is more frequent in elderly, whether women with late onset menopause or those taking long-term hormone replacement therapy have lower rate of

  11. Auditory Brainstem Gap Responses Start to Decline in Middle Age Mice: A Novel Physiological Biomarker for Age-Related Hearing Loss

    PubMed Central

    Williamson, Tanika T.; Zhu, Xiaoxia; Walton, Joseph P.; Frisina, Robert D.

    2014-01-01

    The CBA/CaJ mouse strain's auditory function is normal during the early phases of life and gradually declines over its lifespan, much like human age-related hearing loss (ARHL), but on a mouse life cycle “time frame”. This pattern of ARHL is relatively similar to that of most humans: difficult to clinically diagnose at its onset, and currently not treatable medically. To address the challenge of early diagnosis, CBA mice were used for the present study to analyze the beginning stages and functional onset biomarkers of ARHL. The results from Auditory Brainstem Response (ABR) audiogram and Gap-in-noise (GIN) ABR tests were compared for two groups of mice of different ages, young adult and middle age. ABR peak components from the middle age group displayed minor changes in audibility, but had a significantly higher prolonged peak latency and decreased peak amplitude in response to temporal gaps in comparison to the young adult group. The results for the younger subjects revealed gap thresholds and recovery rates that were comparable to previous studies of auditory neural gap coding. Our findings suggest that age-linked degeneration of the peripheral and brainstem auditory system is already beginning in middle age, allowing for the possibility of preventative biomedical or hearing protection measures to be implemented as a possibility for attenuating further damage to the auditory system due to ARHL. PMID:25307161

  12. 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.

  13. 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…

  14. Auditory brainstem gap responses start to decline in mice in middle age: a novel physiological biomarker for age-related hearing loss.

    PubMed

    Williamson, Tanika T; Zhu, Xiaoxia; Walton, Joseph P; Frisina, Robert D

    2015-07-01

    The auditory function of the CBA/CaJ mouse strain is normal during the early phases of life and gradually declines over its lifespan, much like human age-related hearing loss (ARHL) but within the "time frame" of a mouse life cycle. This pattern of ARHL is similar to that of most humans: difficult to diagnose clinically at its onset and currently not treatable medically. To address the challenge of early diagnosis, we use CBA mice to analyze the initial stages and functional onset biomarkers of ARHL. The results from Auditory Brainstem Response (ABR) audiogram and Gap-in-noise (GIN) ABR tests were compared for two groups of mice of different ages, namely young adult and middle age. ABR peak components from the middle age group displayed minor changes in audibility but had a significantly higher prolonged peak latency and decreased peak amplitude in response to temporal gaps in comparison with the young adult group. The results for the younger subjects revealed gap thresholds and recovery rates that were comparable with previous studies of auditory neural gap coding. Our findings suggest that age-linked degeneration of the peripheral and brainstem auditory system begins in middle age, allowing for the possibility of preventative biomedical or hearing protection measures to be implemented in order to attenuate further damage to the auditory system attributable to ARHL.

  15. 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.

  16. Age-related changes in synaptic markers and monocyte subsets link the cognitive decline of APPSwe/PS1 mice

    PubMed Central

    Naert, Gaëlle; Rivest, Serge

    2012-01-01

    Alzheimer's disease (AD) is characterized by a progressive memory decline and numerous pathological abnormalities, including amyloid β (Aβ) accumulation in the brain and synaptic dysfunction. Here we wanted to study whether these brain changes were associated with alteration in the population of monocyte subsets since accumulating evidence supports the concept that the innate immune system plays a role in the etiology of this disease. We then determined the immune profile together with expression of genes encoding synaptic proteins and neurotrophins in APPSwe/PS1 mice and their age-matched wild-type (WT) littermates. We found that the progressive cognitive decline and the dramatic decrease in the expression of numerous synaptic markers and neurotrophins correlated with a major defect in the subset of circulating inflammatory monocytes. Indeed the number of CX3CR1lowLy6-ChighCCR2+Gr1+ monocytes remained essentially similar between 5 weeks and 6 months of age in APPSwe/PS1 mice, while these cells significantly increased in 6-month-old WT littermates. Of great interest is that the onset of cognitive decline was closely associated with the accumulation of soluble Aβ, disruption of synaptic activity, alteration in the BDNF system, and a defective production in the subset of CX3CR1lowLy6-ChighCCR2+Gr1+ monocytes. However, these memory impairments can be prevented or restored by boosting the monocytic production, using a short treatment of macrophage colony-stimulating factor (M-CSF). In conclusion, low CCR2+ monocyte production by the hematopoietic system may be a direct biomarker of the cognitive decline in a context of AD. PMID:23125823

  17. 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.

  18. 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. PMID:24442595

  19. Age-related decline in multiple unit action potentials of CA3 region of rat hippocampus: correlation with lipid peroxidation and lipofuscin concentration and the effect of centrophenoxine.

    PubMed

    Sharma, D; Maurya, A K; Singh, R

    1993-01-01

    Changes in lipid peroxidation, lipofuscin concentration, and multiple unit activity (MUA recorded in conscious animals) in the CA3 region were studied in the hippocampus of male Wistar rats aged 4, 8, 16, and 24 months. The lipid peroxidation and lipofuscin concentration were increased with age. The MUA, however, declined with age. Correlational analyses were performed for the four age groups to determine the relationship between the age-associated decline in MUA with the age-related alterations in lipid peroxidation and lipofuscin concentrations. The age-related increase in lipid peroxidation correlated positively with the age-associated increase in lipofuscin concentration. The age-related increases in lipid peroxidation and lipofuscin concentration correlated negatively with the changes in MUA. Since lipid peroxidation may affect neuronal electrophysiology, our data suggested that age-related increase in lipid peroxidation may contribute to an age-associated decline in neuronal electrical activity. Centrophenoxine effects were studied on the three above-mentioned age-associated changes in the hippocampus. The drug had no effect on all three parameters in 4- and 8-month-old rats. In 16- and 24-month-old rats, however, the drug significantly increased the MUA but concomitantly decreased lipofuscin concentration and lipid peroxidation. Correlational analyses of the data on MUA, lipid peroxidation and lipofuscin concentration from the centrophenoxine-treated animals showed that the drug-induced diminution in both lipofuscin and lipid peroxidation was significantly correlated with the drug-induced increase in MUA. The differential effect of the drug in younger (4-8 months) and older (16-24 months) animals indicated that the stimulation of MUA was clearly associated with concomitant decrease in lipid peroxidation and lipofuscin concentration.

  20. Perioperative Cognitive Decline in the Aging Population

    PubMed Central

    Terrando, Niccolò; Brzezinski, Marek; Degos, Vincent; Eriksson, Lars I.; Kramer, Joel H.; Leung, Jacqueline M.; Miller, Bruce L.; Seeley, William W.; Vacas, Susana; Weiner, Michael W.; Yaffe, Kristine; Young, William L.; Xie, Zhongcong; Maze, Mervyn

    2011-01-01

    Elderly patients who have an acute illness or who undergo surgery often experience cognitive decline. The pathophysiologic mechanisms that cause neurodegeneration resulting in cognitive decline, including protein deposition and neuroinflammation, also play a role in animal models of surgery-induced cognitive decline. With the aging of the population, surgical candidates of advanced age with underlying neurodegeneration are encountered more often, raising concerns that, in patients with this combination, cognitive function will precipitously decline postoperatively. This special article is based on a symposium that the University of California, San Francisco, convened to explore the contributions of surgery and anesthesia to the development of cognitive decline in the aged patient. A road map to further elucidate the mechanisms, diagnosis, risk factors, mitigation, and treatment of postoperative cognitive decline in the elderly is provided. PMID:21878601

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

    PubMed Central

    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.

    2016-01-01

    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. PMID:26997106

  2. Differential age-related decline in conflict-driven task-set shielding from emotional versus non-emotional distracters

    PubMed Central

    Monti, Jim M.; Weintraub, Sandra; Egner, Tobias

    2010-01-01

    While normal aging is associated with a marked decline in cognitive abilities, such as memory and executive functions, recent evidence suggests that control processes involved in regulating responses to emotional stimuli may remain well-preserved in the elderly. However, neither the precise nature of these preserved control processes, nor their domain-specificity with respect to comparable non-emotional control processes, are currently well-established. Here, we tested the hypothesis of domain-specific preservation of emotional control in the elderly by employing two closely matched behavioral tasks that assessed the ability to shield the processing of task-relevant stimulus information from competition by task-irrelevant distracter stimuli that could be either non-emotional or emotional in nature. The efficacy of non-emotional versus emotional task-set shielding, gauged via the ‘conflict adaptation effect’, was compared between cohorts of healthy young adults, healthy elderly adults, and individuals diagnosed with probable Alzheimer’s disease (PRAD), age-matched to the elderly subjects. It was found that, compared to the young adult cohort, the healthy elderly displayed deficits in task-set shielding in the non-emotional but not in the emotional task, whereas PRAD subjects displayed impaired performance in both tasks. These results provide new evidence that healthy aging is associated with a domain-specific preservation of emotional control functions, specifically, the shielding of a current task-set from interference by emotional distracter stimuli. This selective preservation of function supports the notion of partly dissociable affective control mechanisms, and may either reflect different time-courses of degeneration in the neuroanatomical circuits mediating task-set maintenance in the face of non-emotional versus emotional distracters, or a motivational shift towards affective processing in the elderly. PMID:20176042

  3. 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

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

    PubMed

    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 the

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

    PubMed

    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 the

  6. 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

  7. Neural mechanisms of ageing and cognitive decline

    PubMed Central

    Bishop, Nicholas A.; Lu, Tao; Yankner, Bruce A.

    2010-01-01

    During the past century, treatments for the diseases of youth and middle age have helped raise life expectancy significantly. However, cognitive decline has emerged as one of the greatest health threats of old age, with nearly 50% of adults over the age of 85 afflicted with Alzheimer’s disease. Developing therapeutic interventions for such conditions demands a greater understanding of the processes underlying normal and pathological brain ageing. Recent advances in the biology of ageing in model organisms, together with molecular and systems-level studies of the brain, are beginning to shed light on these mechanisms and their potential roles in cognitive decline. PMID:20336135

  8. Age-related testosterone decline is due to waning of both testicular and hypothalamic-pituitary function.

    PubMed

    Golan, Ron; Scovell, Jason M; Ramasamy, Ranjith

    2015-01-01

    Hypogonadism is a condition in which the endogenous secretion of testosterone is either insufficient or inadequate to maintain serum testosterone levels within normal range, and may manifest as a variety of signs and symptoms. Age-related hypogonadism is due to a combination of primary hypogonadism (testicular failure) and secondary hypogonadism (hypothalamic-pituitary axis failure). This review provides insight into the mechanisms resulting in the multifactorial nature of acquired androgen-deficiency, and outlines the current controversy regarding testosterone-replacement therapy in aging males.

  9. Egg freezing for age-related fertility decline: preventive medicine or a further medicalization of reproduction? Analyzing the new Israeli policy.

    PubMed

    Shkedi-Rafid, Shiri; Hashiloni-Dolev, Yael

    2011-08-01

    In December 2009, the Israel National Bioethics Council (INBC) issued recommendations permitting egg freezing to prevent both disease- and age-related fertility decline. The INBC report forms the basis of Israel's new policy regarding egg freezing. This article analyzes the medical section of the INBC's recommendations, comparing it with guidelines formulated by medical regulatory bodies in Europe and the United States. Our findings suggest that the INBC's recommendations consider age-related fertility decline to be a medical problem, and hence treat the new technology favorably, as preventive medicine, which we perceive as another instance of medicalization. The technology's risks are downplayed by the INBC, unlike the positions of medical organizations in both Europe and the United States, which consider the new technology experimental. This may culminate in raising false hopes about women's possible late genetic motherhood leading to involuntary future childlessness.

  10. 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

  11. 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.

  12. Depressive Mood and Testosterone Related to Declarative Verbal Memory Decline in Middle-Aged Caregivers of Children with Eating Disorders.

    PubMed

    Romero-Martínez, Ángel; Ruiz-Robledillo, Nicolás; Moya-Albiol, Luis

    2016-03-04

    Caring for children diagnosed with a chronic psychological disorder such as an eating disorder (ED) can be used as a model of chronic stress. This kind of stress has been reported to have deleterious effects on caregivers' cognition, particularly in verbal declarative memory of women caregivers. Moreover, high depressive mood and variations in testosterone (T) levels moderate this cognitive decline. The purpose of this study was to characterize whether caregivers of individuals with EDs (n = 27) show declarative memory impairments compared to non-caregivers caregivers (n = 27), using for this purpose a standardized memory test (Rey's Auditory Verbal Learning Test). Its purpose was also to examine the role of depressive mood and T in memory decline. Results showed that ED caregivers presented high depressive mood, which was associated to worse verbal memory performance, especially in the case of women. In addition, all caregivers showed high T levels. Nonetheless, only in the case of women caregivers did T show a curvilinear relationship with verbal memory performance, meaning that the increases of T were associated to the improvement in verbal memory performance, but only up to a certain point, as after such point T continued to increase and memory performance decreased. Thus, chronic stress due to caregiving was associated to disturbances in mood and T levels, which in turn was associated to verbal memory decline. These findings should be taken into account in the implementation of intervention programs for helping ED caregivers cope with caregiving situations and to prevent the risk of a pronounced verbal memory decline.

  13. Protein kinase Mζ-dependent maintenance of GluA2 at the synapse: a possible target for preventing or treating age-related memory decline?

    PubMed

    Aicardi, Giorgio

    2013-08-01

    Age-related functional alterations in the perforant path projection from the entorhinal cortex to the dentate gyrus (DG) of the hippocampus play a major role in age-related memory impairments, but little is known about the molecular mechanisms responsible for these changes. In a recent interesting study, Hara and colleagues (J Neurosci 2012;32:7336-7344) tested young and aged monkeys on the visual recognition memory test "delayed nonmatching-to-sample" (DNMS). Then they performed electron microscopy immunocytochemistry in the hippocampal DG to determine the subcellular localization of the GluA2 subunit of the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) and protein kinase Mζ (PKMζ), which promotes memory storage by regulating GluA2-containing AMPAR trafficking. The results obtained suggest that age-related deficits in visual recognition memory are coupled with impairment in PKMζ-dependent maintenance of GluA2 at the synapse. Together with previous evidence of the critical role of PKMζ in memory consolidation, these data render this enzyme an attractive potential therapeutic target for preventing or treating age-related memory decline, and support the view that the pharmacological manipulation of AMPAR trafficking in the synapses may provide new insights in the search of memory enhancers for aged individuals, including those affected by Alzheimer disease.

  14. Depressive Mood and Testosterone Related to Declarative Verbal Memory Decline in Middle-Aged Caregivers of Children with Eating Disorders

    PubMed Central

    Romero-Martínez, Ángel; Ruiz-Robledillo, Nicolás; Moya-Albiol, Luis

    2016-01-01

    Caring for children diagnosed with a chronic psychological disorder such as an eating disorder (ED) can be used as a model of chronic stress. This kind of stress has been reported to have deleterious effects on caregivers’ cognition, particularly in verbal declarative memory of women caregivers. Moreover, high depressive mood and variations in testosterone (T) levels moderate this cognitive decline. The purpose of this study was to characterize whether caregivers of individuals with EDs (n = 27) show declarative memory impairments compared to non-caregivers caregivers (n = 27), using for this purpose a standardized memory test (Rey’s Auditory Verbal Learning Test). Its purpose was also to examine the role of depressive mood and T in memory decline. Results showed that ED caregivers presented high depressive mood, which was associated to worse verbal memory performance, especially in the case of women. In addition, all caregivers showed high T levels. Nonetheless, only in the case of women caregivers did T show a curvilinear relationship with verbal memory performance, meaning that the increases of T were associated to the improvement in verbal memory performance, but only up to a certain point, as after such point T continued to increase and memory performance decreased. Thus, chronic stress due to caregiving was associated to disturbances in mood and T levels, which in turn was associated to verbal memory decline. These findings should be taken into account in the implementation of intervention programs for helping ED caregivers cope with caregiving situations and to prevent the risk of a pronounced verbal memory decline. PMID:27072418

  15. Depressive Mood and Testosterone Related to Declarative Verbal Memory Decline in Middle-Aged Caregivers of Children with Eating Disorders.

    PubMed

    Romero-Martínez, Ángel; Ruiz-Robledillo, Nicolás; Moya-Albiol, Luis

    2016-03-01

    Caring for children diagnosed with a chronic psychological disorder such as an eating disorder (ED) can be used as a model of chronic stress. This kind of stress has been reported to have deleterious effects on caregivers' cognition, particularly in verbal declarative memory of women caregivers. Moreover, high depressive mood and variations in testosterone (T) levels moderate this cognitive decline. The purpose of this study was to characterize whether caregivers of individuals with EDs (n = 27) show declarative memory impairments compared to non-caregivers caregivers (n = 27), using for this purpose a standardized memory test (Rey's Auditory Verbal Learning Test). Its purpose was also to examine the role of depressive mood and T in memory decline. Results showed that ED caregivers presented high depressive mood, which was associated to worse verbal memory performance, especially in the case of women. In addition, all caregivers showed high T levels. Nonetheless, only in the case of women caregivers did T show a curvilinear relationship with verbal memory performance, meaning that the increases of T were associated to the improvement in verbal memory performance, but only up to a certain point, as after such point T continued to increase and memory performance decreased. Thus, chronic stress due to caregiving was associated to disturbances in mood and T levels, which in turn was associated to verbal memory decline. These findings should be taken into account in the implementation of intervention programs for helping ED caregivers cope with caregiving situations and to prevent the risk of a pronounced verbal memory decline. PMID:27072418

  16. Aerobic exercise prevents age-dependent cognitive decline and reduces anxiety-related behaviors in middle-aged and old rats.

    PubMed

    Pietrelli, A; Lopez-Costa, J; Goñi, R; Brusco, A; Basso, N

    2012-01-27

    Recent research involving human and animals has shown that aerobic exercise of moderate intensity produces the greatest benefit on brain health and behavior. In this study we investigated the effects on cognitive function and anxiety-related behavior in rats at different ages of aerobic exercise, performed regularly throughout life. We designed an aerobic training program with the treadmill running following the basic principles of human training, and assuming that rats have the same physiological adaptations. The intensity was gradually adjusted to the fitness level and age, and maintained at 60-70% of maximum oxygen consumption (max.VO(2)). In middle age (8 months) and old age (18 months), we studied the cognitive response with the radial maze (RM), and anxiety-related behaviors with the open field (OF) and the elevated plus maze (EPM). Aerobically trained (AT) rats had a higher cognitive performance measured in the RM, showing that exercise had a cumulative and amplifier effect on memory and learning. The analysis of age and exercise revealed that the effects of aerobic exercise were modulated by age. Middle-aged AT rats were the most successful animals; however, the old AT rats met the criteria more often than the middle-aged sedentary controls (SC), indicating that exercise could reverse the negative effects of sedentary life, partially restore the cognitive function, and protect against the deleterious effects of aging. The results in the OF and EPM showed a significant decrease in key indicators of anxiety, revealing that age affected most of the analyzed variables, and that exercise had a prominent anxiolytic effect, particularly strong in old age. In conclusion, our results indicated that regular and chronic aerobic exercise has time and dose-dependent, neuroprotective and restorative effects on physiological brain aging, and reduces anxiety-related behaviors.

  17. Age-related decline in mitochondrial bioenergetics: Does supercomplex destabilization determine lower oxidative capacity and higher superoxide production?

    PubMed Central

    Gόmez, Luis A.; Hagen, Tory M.

    2014-01-01

    Mitochondrial decay plays a central role in the aging process. Although certainly multifactorial in nature, defective operation of the electron transport chain (ETC) constitutes a key mechanism involved in the age-associated loss of mitochondrial energy metabolism. Primarily, mitochondrial dysfunction affects the aging animal by limiting bioenergetic reserve capacity and/or increasing oxidative stress via enhanced electron leakage from the ETC. Even though the important aging characteristics of mitochondrial decay are known, the molecular events underlying inefficient electron flux that ultimately leads to higher superoxide appearance and impaired respiration are not completely understood. This review focuses on the potential role(s) that age-associated destabilization of the macromolecular organization of the ETC (i.e. supercomplexes) may be important for development of the mitochondrial aging phenotype, particularly in post-mitotic tissues. PMID:22521482

  18. A Validated Age-Related Normative Model for Male Total Testosterone Shows Increasing Variance but No Decline after Age 40 Years

    PubMed Central

    Kelsey, Thomas W.; Li, Lucy Q.; Mitchell, Rod T.; Whelan, Ashley; Anderson, Richard A.; Wallace, W. Hamish B.

    2014-01-01

    The diagnosis of hypogonadism in human males includes identification of low serum testosterone levels, and hence there is an underlying assumption that normal ranges of testosterone for the healthy population are known for all ages. However, to our knowledge, no such reference model exists in the literature, and hence the availability of an applicable biochemical reference range would be helpful for the clinical assessment of hypogonadal men. In this study, using model selection and validation analysis of data identified and extracted from thirteen studies, we derive and validate a normative model of total testosterone across the lifespan in healthy men. We show that total testosterone peaks [mean (2.5–97.5 percentile)] at 15.4 (7.2–31.1) nmol/L at an average age of 19 years, and falls in the average case [mean (2.5–97.5 percentile)] to 13.0 (6.6–25.3) nmol/L by age 40 years, but we find no evidence for a further fall in mean total testosterone with increasing age through to old age. However we do show that there is an increased variation in total testosterone levels with advancing age after age 40 years. This model provides the age related reference ranges needed to support research and clinical decision making in males who have symptoms that may be due to hypogonadism. PMID:25295520

  19. C57BL/6 life span study: age-related declines in muscle power production and contractile velocity.

    PubMed

    Graber, Ted G; Kim, Jong-Hee; Grange, Robert W; McLoon, Linda K; Thompson, LaDora V

    2015-06-01

    Quantification of key outcome measures in animal models of aging is an important step preceding intervention testing. One such measurement, skeletal muscle power generation (force * velocity), is critical for dynamic movement. Prior research focused on maximum power (P max), which occurs around 30-40 % of maximum load. However, movement occurs over the entire load range. Thus, the primary purpose of this study was to determine the effect of age on power generation during concentric contractions in the extensor digitorum longus (EDL) and soleus muscles over the load range from 10 to 90 % of peak isometric tetanic force (P 0). Adult, old, and elderly male C57BL/6 mice were examined for contractile function (6-7 months old, 100 % survival; ~24 months, 75 %; and ~28 months, <50 %, respectively). Mice at other ages (5-32 months) were also tested for regression modeling. We hypothesized and found that power decreased with age not only at P max but also over the load range. Importantly, we found greater age-associated deficits in both power and velocity when the muscles were contracting concentrically against heavy loads (>50 % P 0). The shape of the force-velocity curve also changed with age (a/P 0 increased). In addition, there were prolonged contraction times to maximum force and shifts in the distribution of the myosin light and heavy chain isoforms in the EDL. The results demonstrate that age-associated difficulty in movement during challenging tasks is likely due, in addition to overall reduced force output, to an accelerated deterioration of power production and contractile velocity under heavily loaded conditions.

  20. Decreased PM10 Exposure Attenuates Age-Related Lung Function Decline: Genetic Variants in p53, p21, and CCND1 Modify This Effect

    PubMed Central

    Imboden, Medea; Schwartz, Joel; Schindler, Christian; Curjuric, Ivan; Berger, Wolfgang; Liu, Sally L.J.; Russi, Erich W.; Ackermann-Liebrich, Ursula; Rochat, Thierry; Probst-Hensch, Nicole M.

    2009-01-01

    Background Decreasing exposure to airborne particulates was previously associated with reduced age-related decline in lung function. However, whether the benefit from improved air quality depends on genetic background is not known. Recent evidence points to the involvement of the genes p53 and p21 and of the cell cycle control gene cyclin D1 (CCND1) in the response of bronchial cells to air pollution. Objective We determined in 4,326 participants of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) whether four single-nucleotide polymorphisms in three genes [CCND1 (rs9344 [P242P], rs667515), p53 (rs1042522 [R72P]), and p21 (rs1801270 [S31R])] modified the previously observed attenuation of the decline in the forced expiratory flow between 25% and 75% of the forced vital capacity (FEF25–75) associated with improved air quality. Methods Subjects of the prospective population-based SAPALDIA cohort were assessed in 1991 and 2002 by spirometry, questionnaires, and biological sample collection for genotyping. We assigned spatially resolved concentrations of particulate matter with aerodynamic diameter ≤ 10 μm (PM10) to each participant’s residential history 12 months before the baseline and follow-up assessments. Results The effect of diminishing PM10 exposure on FEF25–75 decline appeared to be modified by p53 R72P, CCND1 P242P, and CCND1 rs667515. For example, a 10-μg/m3 decline in aver-age PM10 exposure over an 11-year period attenuated the average annual decline in FEF25–75 by 21.33 mL/year (95% confidence interval, 10.57–32.08) among participants homozygous for the CCND1 (P242P) GG genotype, by 13.72 mL/year (5.38–22.06) among GA genotypes, and by 6.00 mL/year (−4.54 to 16.54) among AA genotypes. Conclusions Our results suggest that cell cycle control genes may modify the degree to which improved air quality may benefit respiratory function in adults. PMID:19750108

  1. Beneficial effects of multisensory and cognitive stimulation on age-related cognitive decline in long-term-care institutions

    PubMed Central

    De Oliveira, Thaís Cristina Galdino; Soares, Fernanda Cabral; De Macedo, Liliane Dias E Dias; Diniz, Domingos Luiz Wanderley Picanço; Bento-Torres, Natáli Valim Oliver; Picanço-Diniz, Cristovam Wanderley

    2014-01-01

    The aim of the present report was to evaluate the effectiveness and impact of multisensory and cognitive stimulation on improving cognition in elderly persons living in long-term-care institutions (institutionalized [I]) or in communities with their families (noninstitutionalized [NI]). We compared neuropsychological performance using language and Mini-Mental State Examination (MMSE) test scores before and after 24 and 48 stimulation sessions. The two groups were matched by age and years of schooling. Small groups of ten or fewer volunteers underwent the stimulation program, twice a week, over 6 months (48 sessions in total). Sessions were based on language and memory exercises, as well as visual, olfactory, auditory, and ludic stimulation, including music, singing, and dance. Both groups were assessed at the beginning (before stimulation), in the middle (after 24 sessions), and at the end (after 48 sessions) of the stimulation program. Although the NI group showed higher performance in all tasks in all time windows compared with I subjects, both groups improved their performance after stimulation. In addition, the improvement was significantly higher in the I group than the NI group. Language tests seem to be more efficient than the MMSE to detect early changes in cognitive status. The results suggest the impoverished environment of long-term-care institutions may contribute to lower cognitive scores before stimulation and the higher improvement rate of this group after stimulation. In conclusion, language tests should be routinely adopted in the neuropsychological assessment of elderly subjects, and long-term-care institutions need to include regular sensorimotor, social, and cognitive stimulation as a public health policy for elderly persons. PMID:24600211

  2. Beneficial effects of multisensory and cognitive stimulation on age-related cognitive decline in long-term-care institutions.

    PubMed

    De Oliveira, Thaís Cristina Galdino; Soares, Fernanda Cabral; De Macedo, Liliane Dias E Dias; Diniz, Domingos Luiz Wanderley Picanço; Bento-Torres, Natáli Valim Oliver; Picanço-Diniz, Cristovam Wanderley

    2014-01-01

    The aim of the present report was to evaluate the effectiveness and impact of multisensory and cognitive stimulation on improving cognition in elderly persons living in long-term-care institutions (institutionalized [I]) or in communities with their families (noninstitutionalized [NI]). We compared neuropsychological performance using language and Mini-Mental State Examination (MMSE) test scores before and after 24 and 48 stimulation sessions. The two groups were matched by age and years of schooling. Small groups of ten or fewer volunteers underwent the stimulation program, twice a week, over 6 months (48 sessions in total). Sessions were based on language and memory exercises, as well as visual, olfactory, auditory, and ludic stimulation, including music, singing, and dance. Both groups were assessed at the beginning (before stimulation), in the middle (after 24 sessions), and at the end (after 48 sessions) of the stimulation program. Although the NI group showed higher performance in all tasks in all time windows compared with I subjects, both groups improved their performance after stimulation. In addition, the improvement was significantly higher in the I group than the NI group. Language tests seem to be more efficient than the MMSE to detect early changes in cognitive status. The results suggest the impoverished environment of long-term-care institutions may contribute to lower cognitive scores before stimulation and the higher improvement rate of this group after stimulation. In conclusion, language tests should be routinely adopted in the neuropsychological assessment of elderly subjects, and long-term-care institutions need to include regular sensorimotor, social, and cognitive stimulation as a public health policy for elderly persons. PMID:24600211

  3. Recent Declines in Induction of Labor by Gestational Age

    MedlinePlus

    ... rates at 38 weeks of gestation declined for all maternal age groups under 40. Trends in induction ... 38 weeks declined in nearly three-quarters of all states. The largest declines in labor induction for ...

  4. Cognitive control adjustments in healthy older and younger adults: Conflict adaptation, the error-related negativity (ERN), and evidence of generalized decline with age.

    PubMed

    Larson, Michael J; Clayson, Peter E; Keith, Cierra M; Hunt, Isaac J; Hedges, Dawson W; Nielsen, Brent L; Call, Vaughn R A

    2016-03-01

    Older adults display alterations in neural reflections of conflict-related processing. We examined response times (RTs), error rates, and event-related potential (ERP; N2 and P3 components) indices of conflict adaptation (i.e., congruency sequence effects) a cognitive control process wherein previous-trial congruency influences current-trial performance, along with post-error slowing, correct-related negativity (CRN), error-related negativity (ERN) and error positivity (Pe) amplitudes in 65 healthy older adults and 94 healthy younger adults. Older adults showed generalized slowing, had decreased post-error slowing, and committed more errors than younger adults. Both older and younger adults showed conflict adaptation effects; magnitude of conflict adaptation did not differ by age. N2 amplitudes were similar between groups; younger, but not older, adults showed conflict adaptation effects for P3 component amplitudes. CRN and Pe, but not ERN, amplitudes differed between groups. Data support generalized declines in cognitive control processes in older adults without specific deficits in conflict adaptation.

  5. Genes Related to Fatty Acid β-Oxidation Play a Role in the Functional Decline of the Drosophila Brain with Age

    PubMed Central

    Laranjeira, António; Schulz, Joachim; Dotti, Carlos G.

    2016-01-01

    In living organisms, ageing is widely considered to be the result of a multifaceted process consisting of the progressive accumulation of damage over time, having implications both in terms of function and survival. The study of ageing presents several challenges, from the different mechanisms implicated to the great diversity of systems affected over time. In the current study, we set out to identify genes involved in the functional decline of the brain with age and study its relevance in a tissue dependent manner using Drosophila melanogaster as a model system. Here we report the age-dependent upregulation of genes involved in the metabolic process of fatty acid β-oxidation in the nervous tissue of female wild-type flies. Downregulation of CG10814, dHNF4 and lipid mobilizing genes bmm and dAkh rescues the functional decline of the brain with age, both at the cellular and behaviour level, while over-expression worsens performance. Our data proposes the occurrence of a metabolic alteration in the fly brain with age, whereby the process of β-oxidation of fatty acids experiences a genetic gain-of-function. This event proved to be one of the main causes contributing to the functional decline of the brain with age. PMID:27518101

  6. Genes Related to Fatty Acid β-Oxidation Play a Role in the Functional Decline of the Drosophila Brain with Age.

    PubMed

    Laranjeira, António; Schulz, Joachim; Dotti, Carlos G

    2016-01-01

    In living organisms, ageing is widely considered to be the result of a multifaceted process consisting of the progressive accumulation of damage over time, having implications both in terms of function and survival. The study of ageing presents several challenges, from the different mechanisms implicated to the great diversity of systems affected over time. In the current study, we set out to identify genes involved in the functional decline of the brain with age and study its relevance in a tissue dependent manner using Drosophila melanogaster as a model system. Here we report the age-dependent upregulation of genes involved in the metabolic process of fatty acid β-oxidation in the nervous tissue of female wild-type flies. Downregulation of CG10814, dHNF4 and lipid mobilizing genes bmm and dAkh rescues the functional decline of the brain with age, both at the cellular and behaviour level, while over-expression worsens performance. Our data proposes the occurrence of a metabolic alteration in the fly brain with age, whereby the process of β-oxidation of fatty acids experiences a genetic gain-of-function. This event proved to be one of the main causes contributing to the functional decline of the brain with age. PMID:27518101

  7. 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. PMID:25636674

  8. Do plasma melatonin concentrations decline with age?

    NASA Technical Reports Server (NTRS)

    Zeitzer, J. M.; Daniels, J. E.; Duffy, J. F.; Klerman, E. B.; Shanahan, T. L.; Dijk, D. J.; Czeisler, C. A.

    1999-01-01

    PURPOSE: Numerous reports that secretion of the putative sleep-promoting hormone melatonin declines with age have led to suggestions that melatonin replacement therapy be used to treat sleep problems in older patients. We sought to reassess whether the endogenous circadian rhythm of plasma melatonin concentration changes with age in healthy drug-free adults. METHODS: We analyzed the amplitude of plasma melatonin profiles during a constant routine in 34 healthy drug-free older subjects (20 women and 14 men, aged 65 to 81 years) and compared them with 98 healthy drug-free young men (aged 18 to 30 years). RESULTS: We could detect no significant difference between a healthy and drug-free group of older men and women as compared to one of young men in the endogenous circadian amplitude of the plasma melatonin rhythm, as described by mean 24-hour average melatonin concentration (70 pmol/liter vs 73 pmol/liter, P = 0.97), or the duration (9.3 hours vs 9.1 hours, P = 0.43), mean (162 pmol/liter vs 161 pmol/liter, P = 0.63), or integrated area (85,800 pmol x min/liter vs 86,700 pmol x min/liter, P = 0.66) of the nocturnal peak of plasma melatonin. CONCLUSION: These results do not support the hypothesis that reduction of plasma melatonin concentration is a general characteristic of healthy aging. Should melatonin replacement therapy or melatonin supplementation prove to be clinically useful, we recommend that an assessment of endogenous melatonin be carried out before such treatment is used in older patients.

  9. Feather corticosterone levels are related to age and future body condition, but not to subsequent fitness, in a declining migratory songbird

    PubMed Central

    Boves, Than J.; Fairhurst, Graham D.; Rushing, Clark S.; Buehler, David A.

    2016-01-01

    In migratory species, breeding and non-breeding locations are geographically separate, yet the effects of conditions from one stage may carry over to affect a subsequent stage. Ideally, to understand the mechanisms and implications of ‘carry-over effects’, one would need to follow individuals throughout the year, quantify potential environmental causal factors and physiological mediators during multiple life-history stages, and measure downstream fitness. Owing to current limitations of tracking technology, this is impossible for small, long-distance migrants, so indirect methods to characterize carry-over effects are required. Corticosterone (CORT) is a suspected physiological mediator of carry-over effects, but when collected from blood it provides only a physiological snapshot at that point in time. When extracted from feathers, however, feather corticosterone (CORTf) provides a measure of responses to stressors from previous, and longer, time periods. We collected feathers grown during two life-history stages (post-breeding and subsequent wintering) from individuals of two age classes of a rapidly declining migratory songbird, the cerulean warbler (Setophaga cerulea), on their breeding grounds and quantified CORTf concentrations. We then monitored reproduction and survival of individuals and analysed relationships among CORTf and age, body condition and future fitness. Compared with older males, second-year males had higher CORTf concentrations during both stages. When controlling for age and year, body condition at capture was positively related to CORTf concentrations from winter (especially for older birds). However, we found no relationships between CORTf and fitness (as defined by reproduction and survival). Thus, elevated CORT may represent a beneficial physiological response (e.g. hyperphagia prior to migration), particularly for certain life-history stages, and may mediate the condition in which individuals transition between stages. But for those

  10. Current evidence for the clinical use of long-chain polyunsaturated n-3 fatty acids to prevent age-related cognitive decline and Alzheimer's disease.

    PubMed

    Dacks, P A; Shineman, D W; Fillit, H M

    2013-03-01

    An NIH State of the Science Conference panel concluded in 2010 that insufficient evidence is available to recommend the use of any primary prevention therapy for Alzheimer's disease or cognitive decline with age. Despite the insufficient evidence, candidate therapies with varying levels of evidence for safety and efficacy are taken by the public and discussed in the media. One example is the long-chain n-3 (omega-3) polyunsaturated fatty acids (n-3 LC-PUFA), DHA and EPA, found in some fish and dietary supplements. With this report, we seek to provide a practical overview and rating of the level and type of available evidence that n-3 LC-PUFA supplements are safe and protective against cognitive aging and Alzheimer's disease, with additional discussion of the evidence for effects on quality of life, vascular aging, and the rate of aging. We discuss available sources, dose, bioavailability, and variables that may impact the response to n-3 LC-PUFA treatment such as baseline n-3 LC-PUFA status, APOE ε4 genotype, depression, and background diet. Lastly, we list ongoing clinical trials and propose next research steps to validate these fatty acids for primary prevention of cognitive aging and dementia. Of particular relevance, epidemiology indicates a higher risk of cognitive decline in people in the lower quartile of n-3 LC-PUFA intake or blood levels but these populations have not been specifically targeted by RCTs. PMID:23459977

  11. Current evidence for the clinical use of long-chain polyunsaturated n-3 fatty acids to prevent age-related cognitive decline and Alzheimer's disease.

    PubMed

    Dacks, P A; Shineman, D W; Fillit, H M

    2013-03-01

    An NIH State of the Science Conference panel concluded in 2010 that insufficient evidence is available to recommend the use of any primary prevention therapy for Alzheimer's disease or cognitive decline with age. Despite the insufficient evidence, candidate therapies with varying levels of evidence for safety and efficacy are taken by the public and discussed in the media. One example is the long-chain n-3 (omega-3) polyunsaturated fatty acids (n-3 LC-PUFA), DHA and EPA, found in some fish and dietary supplements. With this report, we seek to provide a practical overview and rating of the level and type of available evidence that n-3 LC-PUFA supplements are safe and protective against cognitive aging and Alzheimer's disease, with additional discussion of the evidence for effects on quality of life, vascular aging, and the rate of aging. We discuss available sources, dose, bioavailability, and variables that may impact the response to n-3 LC-PUFA treatment such as baseline n-3 LC-PUFA status, APOE ε4 genotype, depression, and background diet. Lastly, we list ongoing clinical trials and propose next research steps to validate these fatty acids for primary prevention of cognitive aging and dementia. Of particular relevance, epidemiology indicates a higher risk of cognitive decline in people in the lower quartile of n-3 LC-PUFA intake or blood levels but these populations have not been specifically targeted by RCTs.

  12. TDP-43 Pathology, Cognitive Decline, and Dementia in Old Age

    PubMed Central

    Wilson, Robert S.; Yu, Lei; Trojanowski, John Q.; Chen, Er-Yun; Boyle, Patricia A.; Bennett, David A.; Schneider, Julie A.

    2013-01-01

    Importance Cognitive decline is a leading cause of disability and death in old age but its neurobiological bases are not well understood. Objective To test the hypothesis that transactive response DNA-binding protein 43 (TDP-43) is related to late life cognitive decline. Design Longitudinal clinical-pathologic cohort study. Setting More than 40 Catholic groups across the United States. Participants A total of 130 older Catholic nuns, priests, and monks underwent annual clinical evaluations, including detailed cognitive testing, for a mean of 10.1 years prior to death. On neuropathologic examination, we collected semiquantitative measures of TDP-43 pathology, density of neuronal neurofibrillary tangles, area occupied by amyloid-beta plaques, and the presence of alpha-synuclein Lewy bodies from multiple brain regions. Gross and microscopic cerebral infarcts and hippocampal sclerosis were also identified. Main Outcome Measure Annual rate of change in a previously established composite measure of global cognition during a mean of 10.1 years of annual observation before death. Results TDP-43 pathology ranging from sparse to severe was identified in 46% of participants and was associated with amyloid plaques, tangles, and hippocampal sclerosis but not neocortical Lewy bodies or cerebral infarcts. After controlling for amyloid plaques, tangles, and hippocampal sclerosis, TDP-43 pathology was associated with more rapid cognitive decline and accounted for nearly as much of the variability in rates of global cognitive decline as did tangles. TDP-43 pathology had a distinct cognitive profile that differed from other neuropathologic processes (related to decline in episodic and working memory but not in other cognitive domains), and it was elevated in those who developed dementia but not in those with mild cognitive impairment. Conclusion The results suggest that TDP-43 is an important brain pathology underlying cognitive decline and dementia in old age. PMID:24080705

  13. Does Vocabulary Decline Qualitatively in Old Age?

    ERIC Educational Resources Information Center

    O'Dowd, Sarah C.

    1984-01-01

    Tested both superior and average-ability subjects (N=112) from contrasting educational settings to examine the apparent decline in vocabulary skills of older adults. Results showed older adults performed better than the young, judged by either standard or qualitative criteria. (BH)

  14. Retinoid hyposignaling contributes to aging-related decline in hippocampal function in short-term/working memory organization and long-term declarative memory encoding in mice.

    PubMed

    Mingaud, Frédérique; Mormede, Cécile; Etchamendy, Nicole; Mons, Nicole; Niedergang, Betty; Wietrzych, Marta; Pallet, Véronique; Jaffard, Robert; Krezel, Wojciech; Higueret, Paul; Marighetto, Aline

    2008-01-01

    An increasing body of evidence indicates that the vitamin A metabolite retinoic acid (RA) plays a role in adult brain plasticity by activating gene transcription through nuclear receptors. Our previous studies in mice have shown that a moderate downregulation of retinoid-mediated transcription contributed to aging-related deficits in hippocampal long-term potentiation and long-term declarative memory (LTDM). Here, knock-out, pharmacological, and nutritional approaches were used in a series of radial-arm maze experiments with mice to further assess the hypothesis that retinoid-mediated nuclear events are causally involved in preferential degradation of hippocampal function in aging. Molecular and behavioral findings confirmed our hypothesis. First, a lifelong vitamin A supplementation, like short-term RA administration, was shown to counteract the aging-related hippocampal (but not striatal) hypoexpression of a plasticity-related retinoid target-gene, GAP43 (reverse transcription-PCR analyses, experiment 1), as well as short-term/working memory (STWM) deterioration seen particularly in organization demanding trials (STWM task, experiment 2). Second, using a two-stage paradigm of LTDM, we demonstrated that the vitamin A supplementation normalized memory encoding-induced recruitment of (hippocampo-prefrontal) declarative memory circuits, without affecting (striatal) procedural memory system activity in aged mice (Fos neuroimaging, experiment 3A) and alleviated their LTDM impairment (experiment 3B). Finally, we showed that (knock-out, experiment 4) RA receptor beta and retinoid X receptor gamma, known to be involved in STWM (Wietrzych et al., 2005), are also required for LTDM. Hence, aging-related retinoid signaling hypoexpression disrupts hippocampal cellular properties critically required for STWM organization and LTDM formation, and nutritional vitamin A supplementation represents a preventive strategy. These findings are discussed within current neurobiological

  15. Ginkgo biloba extract EGb 761® in the context of current developments in the diagnosis and treatment of age-related cognitive decline and Alzheimer's disease: a research perspective.

    PubMed

    Lautenschlager, Nicola T; Ihl, Ralf; Müller, Walter E

    2012-08-01

    In June 2011 a two-day expert meeting "The Ageing Brain" took place in Amsterdam, The Netherlands. The main aim was to discuss the available preclinical and clinical data on Ginkgo biloba special extract EGb 761® in the context of current developments in the diagnosis and treatment of age-related cognitive decline and Alzheimer's disease. 19 dementia experts covering the disciplines bio- and neurochemistry, gerontology, neurology, pharmacology, and psychiatry from Australia, Asia, Europe and North America reviewed available preclinical and clinical data for EGb 761® and identified core topics for future research. Based on a wide range of preclinical effects demonstrated for Ginkgo biloba, EGb 761® can be conceptualized as a multi-target compound with activity on distinct pathophysiological pathways in Alzheimer's disease (AD) and age-related cognitive decline. While symptomatic efficacy in dementia and mild cognitive impairment (MCI) has been demonstrated, interpretation of data from dementia prevention trials is complicated by important methodological issues. Bridging pre-clinical research and clinical research as well as deciding on suitable study designs for future trials with EGb 761® remain important questions. The participants of the "Ageing Brain" meeting on Ginkgo biloba special extract EGb 761® concluded that there is plenty of promising data, both pre-clinical and clinical, to consider future research with the compound targeting cognitive impairment in old age as a worthwhile activity.

  16. Phagocytic ability declines with age in adult Drosophila hemocytes

    PubMed Central

    Horn, Lucas; Leips, Jeff; Starz-Gaiano, Michelle

    2014-01-01

    Most multicellular organisms show a physiological decline in immune function with age. However, little is known about the mechanisms underlying these changes. We examined Drosophila melanogaster, an important model for identifying genes affecting innate immunity and senescence, to explore the role of phagocytosis in age-related immune dysfunction. We characterized the localized response of immune cells at the dorsal vessel to bacterial infection in 1-week- and 5-week-old flies. We developed a quantitative phagocytosis assay for adult Drosophila and utilized this to characterize the effect of age on phagocytosis in transgenic and natural variant lines. We showed that genes necessary for bacterial engulfment in other contexts are also required in adult flies. We found that blood cells from young and old flies initially engulf bacteria equally well, while cells from older flies accumulate phagocytic vesicles and thus are less capable of destroying pathogens. Our results have broad implications for understanding how the breakdown in cellular processes influences immune function with age. PMID:24828474

  17. 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.

  18. 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.

  19. 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 Central

    Frick, Karyn M.

    2012-01-01

    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. PMID:22289043

  20. Environmental enrichment attenuates the age-related decline in the mRNA expression of steroidogenic enzymes and reduces the methylation state of the steroid 5α-reductase type 1 gene in the rat hippocampus.

    PubMed

    Rossetti, María F; Varayoud, Jorgelina; Moreno-Piovano, Guillermo S; Luque, Enrique H; Ramos, Jorge G

    2015-09-01

    We analyzed the effects of aging and environmental enrichment on the mRNA expression and DNA methylation state of steroidogenic enzymes in the hippocampus. The effects of aging were evaluated by comparing young adult (90-day-old) and middle-aged (450-day-old) female Wistar rats. To elucidate the effects of environmental enrichment, a subgroup of middle-aged rats exposed to sensory and social stimulation for 105 days was compared to rats housed under standard laboratory conditions. Aging decreased the transcription of neurosteroidogenic-related genes and increased the promoter methylation state of cytochrome P450 side chain cleavage, 3α-hydroxysteroid dehydrogenase (3α-HSD) and 5α-reductase-1. Exposure of middle-aged rats to environmental enrichment increased mRNA levels of 5α-reductase-1, 3α-HSD and cytochrome P450 17α-hydroxylase/c17,20-lyase and decreased the methylation state of the 5α-reductase-1 gene. Thus, sensory and social stimulation attenuate the age-related decline in the mRNA expression of hippocampal steroidogenic enzymes. Epigenetic mechanisms associated with differential promoter methylation could be involved.

  1. Environmental enrichment attenuates the age-related decline in the mRNA expression of steroidogenic enzymes and reduces the methylation state of the steroid 5α-reductase type 1 gene in the rat hippocampus.

    PubMed

    Rossetti, María F; Varayoud, Jorgelina; Moreno-Piovano, Guillermo S; Luque, Enrique H; Ramos, Jorge G

    2015-09-01

    We analyzed the effects of aging and environmental enrichment on the mRNA expression and DNA methylation state of steroidogenic enzymes in the hippocampus. The effects of aging were evaluated by comparing young adult (90-day-old) and middle-aged (450-day-old) female Wistar rats. To elucidate the effects of environmental enrichment, a subgroup of middle-aged rats exposed to sensory and social stimulation for 105 days was compared to rats housed under standard laboratory conditions. Aging decreased the transcription of neurosteroidogenic-related genes and increased the promoter methylation state of cytochrome P450 side chain cleavage, 3α-hydroxysteroid dehydrogenase (3α-HSD) and 5α-reductase-1. Exposure of middle-aged rats to environmental enrichment increased mRNA levels of 5α-reductase-1, 3α-HSD and cytochrome P450 17α-hydroxylase/c17,20-lyase and decreased the methylation state of the 5α-reductase-1 gene. Thus, sensory and social stimulation attenuate the age-related decline in the mRNA expression of hippocampal steroidogenic enzymes. Epigenetic mechanisms associated with differential promoter methylation could be involved. PMID:26021641

  2. Disentangling the effects of age and APOE on neuropathology and late life cognitive decline.

    PubMed

    Yu, Lei; Boyle, Patricia A; Leurgans, Sue; Schneider, Julie A; Bennett, David A

    2014-04-01

    Age and APOE are the most robust risk factors for dementia and cognitive decline, but the underlying neurobiology remains unclear. We examined the extent to which the hallmark pathologies of Alzheimer's disease, Lewy body disease, and cerebrovascular diseases account for the association of age and APOE with decline in episodic memory versus nonepisodic cognitive abilities. Up to 20 waves of longitudinal cognitive data were collected from 858 autopsied participants in 2 ongoing clinical-pathologic cohort studies of aging. Neuropathologic examinations quantified measures of beta amyloid (Aβ) plaque, mesial temporal and neocortical neurofibrillary tangles, macro- and microinfarcts, and neocortical Lewy bodies. Random coefficient models estimated person-specific slopes of decline in episodic memory and nonepisodic cognition. Path analysis examined the relation of age, APOE, and the 6 pathologic indices to the slopes of cognitive decline. The effect of age on decline in episodic memory was mediated by Aβ, mesial temporal and neocortical tau tangles, and macroscopic infarcts; age on decline in nonepisodic cognition was mediated by Aβ, neocortical tangles, and macroscopic infarcts. The effect of APOE on decline in episodic memory was mediated by Aβ, mesial temporal and neocortical tangles, and neocortical Lewy bodies; APOE on nonepisodic cognition was mediated by Aβ, neocortical tangles, and neocortical Lewy bodies. There were no direct effects of age and APOE on decline after accounting for these pathologic pathways.

  3. Age-related decline in melatonin and its MT1 receptor are associated with decreased sensitivity to melatonin and enhanced mammary tumor growth.

    PubMed

    Hill, Steven M; Cheng, Chi; Yuan, Lin; Mao, Lulu; Jockers, Rolf; Dauchy, Bob; Blask, David E

    2013-02-01

    induced by N-nitroso-n-methyl-urea (NMU) showed a significant increase in the senescent rats, but not in the young or adult rats Additionally, diminished response to the inhibitory action on tumor growth of exogenous MLT was noted in senescent rats such that tumor growth was suppressed by only 33% compared to 48% and 66% in adult and young rats, respectively. The diminution of the response of tumors to exogenous MLT was found to correlate with reduced MT1 receptor expression in senescent compared to young and adult rats. These data suggest that the observed age-associated enhanced growth of tumors is related to the much reduced levels of MLT and its receptor in aged animals which reduce the sensitivity of tumors to inhibition by exogenous MLT. PMID:23895529

  4. Declines in physiological functional capacity with age: a longitudinal study in peak swimming performance

    PubMed Central

    DONATO, ANTHONY J.; TENCH, KATHLEEN; GLUECK, DEBORAH H.; SEALS, DOUGLAS R.; ESKURZA, IRATXE; TANAKA, HIROFUMI

    2016-01-01

    We followed up swimming performance times of 321 women and 319 men who participated in the US Masters Swimming Championships over a 12-yr period. All swimmers placed in the top 10 in their age group over 3 yr (mean = 5 yr). A random coefficients model for repeated measures was used to derive a line of best fit from a group of regression lines for each subject. Both 50- and 1,500-m swimming performance declined modestly until ~70 yr of age, where a more rapid decline was observed in both men and women. Compared with 1,500-m swimming, the 50-m freestyle declined more modestly and slowly with age. The rate and magnitude of declines in swimming performance with age were greater in women than in men in 50-m freestyle; such sex-related differences were not observed in 1,500-m freestyle. Overall, the variability along a population regression line increased markedly with advancing age. The present longitudinal findings indicate that 1) swimming performance declines progressively until age 70, where the decrease becomes quadratic; 2) the rates of the decline in swimming performance with age are greater in a long-duration than in a short-duration event, suggesting a relatively smaller loss of anaerobic muscular power with age compared with cardiovascular endurance; 3) the age-related rates of decline are greater in women than in men only in a short-duration event; and 4) the variability of the age-related decline in performance increases markedly with advancing age. PMID:12391125

  5. Dissecting the age-related decline on spatial learning and memory tasks in rodent models: N-methyl-D-aspartate receptors and voltage-dependent Ca2+ channels in senescent synaptic plasticity

    PubMed Central

    Foster, Thomas C.

    2012-01-01

    In humans, heterogeneity in the decline of hippocampal-dependent episodic memory is observed during aging. Rodents have been employed as models of age-related cognitive decline and the spatial water maze has been used to show variability in the emergence and extent of impaired hippocampal-dependent memory. Impairment in the consolidation of intermediate-term memory for rapidly acquired and flexible spatial information emerges early, in middle-age. As aging proceeds, deficits may broaden to include impaired incremental learning of a spatial reference memory. The extent and time course of impairment has been be linked to senescence of calcium (Ca2+) regulation and Ca2+-dependent synaptic plasticity mechanisms in region CA1. Specifically, aging is associated with altered function of N-methyl-D-aspartate receptors (NMDARs), voltage-dependent Ca2+ channels (VDCCs), and ryanodine receptors (RyRs) linked to intracellular Ca2+ stores (ICS). In young animals, NMDAR activation induces long-term potentiation of synaptic transmission (NMDAR-LTP), which is thought to mediate the rapid consolidation of intermediate-term memory. Oxidative stress, starting in middle-age, reduces NMDAR function. In addition, VDCCs and ICS can actively inhibit NMDAR-dependent LTP and oxidative stress enhances the role of VDCC and RyR-ICS in regulating synaptic plasticity. Blockade of L-type VDCCs promotes NMDAR-LTP and memory in older animals. Interestingly, pharmacological or genetic manipulations to reduce hippocampal NMDAR function readily impair memory consolidation or rapid learning, generally leaving incremental learning intact. Finally, evidence is mounting to indicate a role for VDCC-dependent synaptic plasticity in associative learning and the consolidation of remote memories. Thus, VDCC-dependent synaptic plasticity and extrahippocampal systems may contribute to incremental learning deficits observed with advanced aging. PMID:22307057

  6. Self-Reported Body Fat Change in HIV-Infected Men Is a Marker of Decline in Physical Health-Related Quality of Life with Aging, Independent of Co-Morbidity

    PubMed Central

    Erlandson, Kristine M.; Reynolds, Sandra M.; Cox, Christopher; Palella, Frank J.; Witt, Mallory D.; Kingsley, Lawrence A.; Brown, Todd T.; Plankey, Michael

    2014-01-01

    Objective Self-perception of changes in body fat among HIV+ persons is associated with decreased health related quality of life in cross-sectional studies. The longitudinal impact of body fat changes on health related quality of life, while accounting for comorbidity and anatomic location or severity of body fat changes, is unknown. Design This was a longitudinal analysis of HIV+ and HIV- Multicenter AIDS Cohort Study (MACS) participants who completed questionnaires assessing self-perceived body fat changes (baseline visit) and a health related quality of life (Short Form-36) at baseline and then ≥5 years later. Methods Relationships between body fat changes and change in Short Form-36 Physical and Mental Component Summary scores were investigated using mixed-model regression. Results We studied 270 HIV+ and 247 HIV- men. At baseline, ≥50% of HIV+ men reported body fat changes; physical component but not mental component summary scores were lower among HIV+ men who reported moderate/severe leg or abdominal fat changes (p<0.05). At follow-up, physical component summary scores were significantly lower among men with face, leg, or abdominal fat changes compared to men without perceived fat changes (p<0.05). No significant changes were seen in mental component scores by fat change location or severity. In the final model, body fat changes at any site or severity were significant predictors of a decline in physical component summary score (p<0.05), independent of demographics or comorbidities. Mental component summary score was not associated with body fat changes, but higher mental component summary score was associated with increasing age and time. Conclusions Negative self-perceived body fat changes were associated with decline in physical health related quality of life, independent of comorbidities, and may be a marker of an increased risk for physical function decline with aging. PMID:25436612

  7. Age-Dependent Terminal Declines in Reproductive Output in a Wild Bird

    PubMed Central

    Hammers, Martijn; Richardson, David S.; Burke, Terry; Komdeur, Jan

    2012-01-01

    In many iteroparous species individual fitness components, such as reproductive output, first increase with age and then decline during late-life. However, individuals differ greatly in reproductive lifespan, but reproductive declines may only occur in the period just before their death as a result of an age-independent decline in physiological condition. To fully understand reproductive senescence it is important to investigate to what extent declines in late-life reproduction can be explained by age, time until death, or both. However, the study of late-life fitness performance in natural populations is challenging as the exact birth and death dates of individuals are often not known, and most individuals succumb to extrinsic mortality before reaching old age. Here, we used an exceptional long-term longitudinal dataset of individuals from a natural, closed, and predator-free population of the Seychelles warbler (Acrocephalus sechellensis) to investigate reproductive output, both in relation to age and to the time until the death of an individual (reverse-age approach). We observed an initial age-dependent increase in reproductive output that was followed by a decline in old age. However, we found no significant decline in reproductive output in the years directly preceding death. Although post-peak reproductive output declined with age, this pattern differed between terminal and non-terminal reproductive attempts, and the age-dependence of the terminal breeding attempt explained much of the variation in age-specific reproductive output. In fact, terminal declines in reproductive output were steeper in very old individuals. These results indicate that not only age-dependent, but also age-independent factors, such as physiological condition, need to be considered to understand reproductive senescence in wild-living animals. PMID:22792307

  8. Muscle weakness during aging: a deficiency state involving declining angiogenesis.

    PubMed

    Ambrose, Charles

    2015-09-01

    This essay begins by proposing that muscle weakness of old age from sarcopenia is due in large part to reduced capillary density in the muscles, as documented in 9 reports of aged persons and animals. Capillary density (CD) is determined by local levels of various angiogenic factors, which also decline in muscles with aging, as reported in 7 studies of old persons and animals. There are also numerous reports of reduced CD in the aged brain and other studies showing reduced CD in the kidney and heart of aged animals. Thus a waning angiogenesis throughout the body may be a natural occurrence in later years and may account significantly for the lesser ailments (physical and cognitive) of elderly people. Old age is regarded here as a deficiency state which may be corrected by therapeutic angiogenesis, much as a hormonal deficiency can be relieved by the appropriate hormone therapy. Such therapy could employ recombinant angiogenic factors which are now commercially available. PMID:26093038

  9. Aging in male primates: reproductive decline, effects of calorie restriction and future research potential.

    PubMed

    Sitzmann, Brandon D; Urbanski, Henryk F; Ottinger, Mary Ann

    2008-09-01

    Although less dramatic than in females, male mammals experience decreasing reproductive function during aging. In primates, multiple facets of the hypothalamic-pituitary-gonadal axis show evidence of gradual age-related decline, including behavioral, neuroendocrine and endocrine alterations such as decreased testosterone levels, reduced circulating dehydroepiandrosterone sulfate (DHEAS) levels, increased numbers of sperm abnormalities, and a general decline in physiological responses. In this review we consider a range of age-related changes in males. These measures, including more subtle aging characteristics, are interesting additional indices for detecting the timing of age-related changes in behavioral, neuroendocrine, and endocrine responses. Evidence of potential effects of calorie restriction as an intervention in reproductive aging is also discussed. A discernable decline occurs in both metabolic and reproductive endocrine processes during male aging. This cascade of events includes neuroendocrine and behavioral changes; biomarkers such as circulating DHEAS also show clear age-related decline. The varied changes that occur during male aging are considered in the context of primate aging in general.

  10. Cognitive Declines Precede and Predict Functional Declines in Aging and Alzheimer’s Disease

    PubMed Central

    Zahodne, Laura B.; Manly, Jennifer J.; MacKay-Brandt, Anna; Stern, Yaakov

    2013-01-01

    Objective To investigate the temporal ordering of cognitive and functional declines separately in older adults with or without Alzheimer’s disease (AD). Design and Setting A community-based longitudinal study of aging and dementia in Northern Manhattan (Washington Heights/Hamilton Heights Inwood Columbia Aging Project) and a multicenter, clinic-based longitudinal study of prevalent AD at Columbia University Medical Center, Johns Hopkins School of Medicine, Massachusetts General Hospital, and the Hôpital de la Salpêtrière in Paris, France (the Predictors Study). Participants 3,443 initially non-demented older adults (612 with eventual incident dementia) and 517 patients with AD. Main Outcome Measures Cognitive measures included the modified Mini-Mental State Exam and composite scores of memory and language derived from a standardized neuropsychological battery. Function was measured with the Blessed Dementia Rating Scale, completed by the participant (in the sample of non-demented older adults) or an informant (in the sample of prevalent AD patients). Data were analyzed with autoregressive cross-lagged panel analysis. Results Cognitive scores more consistently predicted subsequent functional abilities than vice versa in non-demented older adults, participants with eventual incident dementia, and patients with prevalent AD. Conclusions Cognitive declines appear to precede and cause functional declines prior to and following dementia diagnosis. Standardized neuropsychological tests are valid predictors of later functional changes in both non-demented and demented older adults. PMID:24023894

  11. The Hippocampal Neuroproteome with Aging and Cognitive Decline: Past Progress and Future Directions

    PubMed Central

    VanGuilder, Heather D.; Freeman, Willard M.

    2011-01-01

    Although steady progress on understanding brain aging has been made over recent decades through standard anatomical, immunohistochemical, and biochemical techniques, the biological basis of non-neurodegenerative cognitive decline with aging remains to be determined. This is due in part to technical limitations of traditional approaches, in which only a small fraction of neurobiologically relevant proteins, mRNAs or metabolites can be assessed at a time. With the development and refinement of proteomic technologies that enable simultaneous quantitative assessment of hundreds to thousands of proteins, neuroproteomic studies of brain aging and cognitive decline are becoming more widespread. This review focuses on the contributions of neuroproteomic investigations to advances in our understanding of age-related deficits of hippocampus-dependent spatial learning and memory. Accumulating neuroproteomic data demonstrate that hippocampal aging involves common themes of dysregulated metabolism, increased oxidative stress, altered protein processing, and decreased synaptic function. Additionally, growing evidence suggests that cognitive decline does not represent a “more aged” phenotype, but rather is associated with specific neuroproteomic changes that occur in addition to age-related alterations. Understanding if and how age-related changes in the hippocampal neuroproteome contribute to cognitive decline and elucidating the pathways and processes that lead to cognitive decline are critical objectives that remain to be achieved. Progress in the field and challenges that remain to be addressed with regard to animal models, behavioral testing, and proteomic reporting are also discussed. PMID:21647399

  12. Parental support during young adulthood: Why does assistance decline with age?

    PubMed Central

    Hartnett, Caroline Sten; Furstenberg, Frank; Birditt, Kira; Fingerman, Karen

    2013-01-01

    Previous research has found that financial transfers from parents to young adult children decline as children age and that age is one of the strongest predictors of support. Using data collected from young adults (ages 18 to 34) and their parents (ages 40 to 60; N=536 parent-child dyads), we explore the possibility that the relationship between age and financial support is mediated by offspring needs, acquisition of adult roles, or geographical and emotional closeness. We find that age-related declines in offspring’s needs help to explain why financial support falls with age. However, offspring age remains a robust predictor of financial support after controlling for a wide range of factors, suggesting that age norms condition support from parents to offspring. PMID:23976811

  13. The senescence-accelerated prone mouse (SAMP8): a model of age-related cognitive decline with relevance to alterations of the gene expression and protein abnormalities in Alzheimer's disease.

    PubMed

    Butterfield, D Allan; Poon, H Fai

    2005-10-01

    The senescence-accelerated mouse (SAM) is an accelerated aging model that was established through phenotypic selection from a common genetic pool of AKR/J strain of mice. The SAM model was established in 1981, including nine major senescence-accelerated mouse prone (SAMP) substrains and three major senescence-accelerated mouse resistant (SAMR) substrains, each of which exhibits characteristic disorders. Recently, SAMP8 have drawn attention in gerontological research due to its characteristic learning and memory deficits at old age. Many recent reports provide insight into mechanisms of the cognitive impairment and pathological changes in SAMP8. Therefore, this mini review examines the recent findings of SAMP8 mice abnormalities at the gene and protein levels. The genes and proteins described in this review are functionally categorized into neuroprotection, signal transduction, protein folding/degradation, cytoskeleton/transport, immune response and reactive oxygen species (ROS) production. All of these processes are involved in learning and memory. Although these studies provide insight into the mechanisms that contribute to the learning and memory decline in aged SAMP8 mice, higher throughput techniques of proteomics and genomics are necessary to study the alterations of gene expression and protein abnormalities in SAMP8 mice brain in order to more completely understand the central nervous system dysfunction in this mouse model. The SAMP8 is a good animal model to investigate the fundamental mechanisms of age-related learning and memory deficits at the gene and protein levels. PMID:16026957

  14. Age-Related Declines Evident Before 60

    MedlinePlus

    ... and independent later in life, according to the study researchers. "The good news is, with proper attention and effort, the ability to function independently can often be preserved with regular exercise," said lead author Katherine Hall, an assistant professor of medicine. "Our research reinforces ...

  15. Age-associated Cognitive Decline: Insights into Molecular Switches and Recovery Avenues

    PubMed Central

    Konar, Arpita; Singh, Padmanabh; Thakur, Mahendra K.

    2016-01-01

    Age-associated cognitive decline is an inevitable phenomenon that predisposes individuals for neurological and psychiatric disorders eventually affecting the quality of life. Scientists have endeavored to identify the key molecular switches that drive cognitive decline with advancing age. These newly identified molecules are then targeted as recovery of cognitive aging and related disorders. Cognitive decline during aging is multi-factorial and amongst several factors influencing this trajectory, gene expression changes are pivotal. Identifying these genes would elucidate the neurobiological underpinnings as well as offer clues that make certain individuals resilient to withstand the inevitable age-related deteriorations. Our laboratory has focused on this aspect and investigated a wide spectrum of genes involved in crucial brain functions that attribute to senescence induced cognitive deficits. We have recently identified master switches in the epigenome regulating gene expression alteration during brain aging. Interestingly, these factors when manipulated by chemical or genetic strategies successfully reverse the age-related cognitive impairments. In the present article, we review findings from our laboratory and others combined with supporting literary evidences on molecular switches of brain aging and their potential as recovery targets. PMID:27114845

  16. Oxidative stress in the etiology of age-associated decline in glucose metabolism.

    PubMed

    Salmon, Adam B

    2012-01-01

    One of the most common pathologies in aging humans is the development of glucose metabolism dysfunction. The high incidence of metabolic dysfunction, in particular type 2 diabetes mellitus, is a significant health and economic burden on the aging population. However, the mechanisms that regulate this age-related physiological decline, and thus potential preventative treatments, remain elusive. Even after accounting for age-related changes in adiposity, lean mass, blood lipids, etc., aging is an independent factor for reduced glucose tolerance and increased insulin resistance. Oxidative stress has been shown to have significant detrimental impacts on the regulation of glucose homeostasis in vitro and in vivo. Furthermore, oxidative stress has been shown to be modulated by age and diet in several model systems. This review provides an overview of these data and addresses whether increases in oxidative stress with aging may be a primary determinant of age-related metabolic dysfunction.

  17. Consumption of alcoholic beverages and cognitive decline at middle age: the Doetinchem Cohort Study.

    PubMed

    Nooyens, Astrid C J; Bueno-de-Mesquita, H Bas; van Gelder, Boukje M; van Boxtel, Martin P J; Verschuren, W M Monique

    2014-02-01

    Accelerated cognitive decline increases the risk of dementia. Slowing down the rate of cognitive decline leads to the preservation of cognitive functioning in the elderly, who can live independently for a longer time. Alcohol consumption may influence the rate of cognitive decline. The aim of the present study was to evaluate the associations between the total consumption of alcoholic beverages and different types of alcoholic beverages and cognitive decline at middle age. In 2613 men and women of the Doetinchem Cohort Study, aged 43-70 years at baseline (1995-2002), cognitive function (global cognitive function and the domains memory, speed and flexibility) was assessed twice, with a 5-year time interval. In linear regression analyses, the consumption of different types of alcoholic beverages was analysed in relation to cognitive decline, adjusting for confounders. We observed that, in women, the total consumption of alcoholic beverages was inversely associated with the decline in global cognitive function over a 5-year period (P for trend = 0·02), while no association was observed in men. Regarding the consumption of different types of alcoholic beverages in men and women together, red wine consumption was inversely associated with the decline in global cognitive function (P for trend < 0·01) as well as memory (P for trend < 0·01) and flexibility (P for trend = 0·03). Smallest declines were observed at a consumption of about 1·5 glasses of red wine per d. No other types of alcoholic beverages were associated with cognitive decline. In conclusion, only (moderate) red wine consumption was consistently associated with less strong cognitive decline. Therefore, it is most likely that non-alcoholic substances in red wine are responsible for any cognition-preserving effects.

  18. Greater cognitive decline with aging among elders with high serum concentrations of organochlorine pesticides.

    PubMed

    Kim, Se-A; Lee, Yu-Mi; Lee, Ho-Won; Jacobs, David R; Lee, Duk-Hee

    2015-01-01

    Although cognitive decline is very common in elders, age-related cognitive decline substantially differs among elders and the determinants of the differences in age-related cognitive decline are unclear. We investigated our hypothesis that the association between age and cognition was stronger in those with higher serum concentrations of organochlorine (OC) pesticides, common persistent and strongly lipophilic neurotoxic chemicals. Participants were 644 elders aged 60-85, participating in the National Health and Nutrition Examination Survey 1999-2002. Six OC pesticides (p,p'-dichlorodiphenyltrichloroethane (DDT), p,p'-dichlorodipenyldichloroethylene (DDE), β-hexachlorocyclohexane, trans-nonachlor, oxychlordane, and heptachlor epoxide) were evaluated. "Lower cognitive function" was defined as having a low Digit-Symbol Substitution Test (DSST) score (<25th percentile of DSST score, cutpoint 28 symbols substituted). Higher levels of β-hexachlorocyclohexane, trans-nonachlor, oxychlordane, and heptachlor epoxide modified the associations between age and lower cognitive function (Pinteraction<0.01, 0.03, <0.01, and 0.02, respectively). Elders in the 3rd tertile of these chemicals demonstrated a greater risk of lower cognitive function with aging, compared to those in the combined 1st and 2nd tertiles. Among those with highest OC pesticides (3rd tertile), the odds ratio for the risk of lower cognitive function was about 6 to 11 for the highest quintile of age (80-85 years) vs. the first quintile of age (60-63 years), while the association between age and lower cognitive function became flatter in those with lower OC pesticides (combined 1st and 2nd tertiles). Both DDT and DDE showed no interaction, with lower DSST scores for higher age irrespective of serum concentrations of DDT or DDE. Even though DSST score measures only one aspect of cognition, several OC pesticides modified aging-related prevalence of low cognitive score, a finding which should be evaluated in

  19. Iron accumulation with age, oxidative stress and functional decline.

    PubMed

    Xu, Jinze; Knutson, Mitchell D; Carter, Christy S; Leeuwenburgh, Christiaan

    2008-01-01

    Identification of biological mediators in sarcopenia is pertinent to the development of targeted interventions to alleviate this condition. Iron is recognized as a potent pro-oxidant and a catalyst for the formation of reactive oxygen species in biological systems. It is well accepted that iron accumulates with senescence in several organs, but little is known about iron accumulation in muscle and how it may affect muscle function. In addition, it is unclear if interventions which reduced age-related loss of muscle quality, such as calorie restriction, impact iron accumulation. We investigated non-heme iron concentration, oxidative stress to nucleic acids in gastrocnemius muscle and key indices of sarcopenia (muscle mass and grip strength) in male Fischer 344 X Brown Norway rats fed ad libitum (AL) or a calorie restricted diet (60% of ad libitum food intake starting at 4 months of age) at 8, 18, 29 and 37 months of age. Total non-heme iron levels in the gastrocnemius muscle of AL rats increased progressively with age. Between 29 and 37 months of age, the non-heme iron concentration increased by approximately 200% in AL-fed rats. Most importantly, the levels of oxidized RNA in gastrocnemius muscle of AL rats were significantly increased as well. The striking age-associated increase in non-heme iron and oxidized RNA levels and decrease in sarcopenia indices were all attenuated in the calorie restriction (CR) rats. These findings strongly suggest that the age-related iron accumulation in muscle contributes to increased oxidative damage and sarcopenia, and that CR effectively attenuates these negative effects.

  20. Iron Accumulation with Age, Oxidative Stress and Functional Decline

    PubMed Central

    Xu, Jinze; Knutson, Mitchell D.; Carter, Christy S.; Leeuwenburgh, Christiaan

    2008-01-01

    Identification of biological mediators in sarcopenia is pertinent to the development of targeted interventions to alleviate this condition. Iron is recognized as a potent pro-oxidant and a catalyst for the formation of reactive oxygen species in biological systems. It is well accepted that iron accumulates with senescence in several organs, but little is known about iron accumulation in muscle and how it may affect muscle function. In addition, it is unclear if interventions which reduced age-related loss of muscle quality, such as calorie restriction, impact iron accumulation. We investigated non-heme iron concentration, oxidative stress to nucleic acids in gastrocnemius muscle and key indices of sarcopenia (muscle mass and grip strength) in male Fischer 344 X Brown Norway rats fed ad libitum (AL) or a calorie restricted diet (60% of ad libitum food intake starting at 4 months of age) at 8, 18, 29 and 37 months of age. Total non-heme iron levels in the gastrocnemius muscle of AL rats increased progressively with age. Between 29 and 37 months of age, the non-heme iron concentration increased by approximately 200% in AL-fed rats. Most importantly, the levels of oxidized RNA in gastrocnemius muscle of AL rats were significantly increased as well. The striking age-associated increase in non-heme iron and oxidized RNA levels and decrease in sarcopenia indices were all attenuated in the calorie restriction (CR) rats. These findings strongly suggest that the age-related iron accumulation in muscle contributes to increased oxidative damage and sarcopenia, and that CR effectively attenuates these negative effects. PMID:18682742

  1. Age-dependent decline in dental pulp regeneration after pulpectomy in dogs.

    PubMed

    Iohara, Koichiro; Murakami, Masashi; Nakata, Kazuhiko; Nakashima, Misako

    2014-04-01

    The age-associated decline in the regenerative abilities of mesenchymal stem cells (MSCs) may be due to age-related changes in reduction in number, intrinsic properties of MSCs and extrinsic factors of the extracellular environment (the stem cell niche). The effect of age on the efficacy of MSC transplantation on regeneration, however, has not been clearly demonstrated due to variable methods of isolation of MSCs and variations in stem cell populations. In this study, dental pulp stem cell (DPSC) subsets were isolated from young and aged dog teeth based on their migratory response to granulocyte-colony stimulating factor (G-CSF) (MDPSCs). In order to study the age-associated changes, their biological properties and stability were compared and the regenerative potential was examined in a pulpectomized tooth model in aged dogs. MDPSCs from aged dogs were efficiently enriched in stem cells, expressing trophic factors with high proliferation, migration and anti-apoptotic effects as in MDPSCs from young dogs. However, pulp regeneration was retarded 120 days after autologous transplantation of aged MDPSCs. We further demonstrated that isolated periodontal ligament stem cells (PDLSCs) from aged dogs, representative of migrating stem cells from outside of the tooth compartment to regenerate pulp tissue, had lower proliferation, migration and anti-apoptotic abilities. These results therefore provide a better understanding of the mechanisms involved in the age-dependent decline in pulp regeneration, which are attributed to a decrease in the regenerative potential of resident stem cells.

  2. Impaired Sleep Predicts Cognitive Decline in Old People: Findings from the Prospective KORA Age Study

    PubMed Central

    Johar, Hamimatunnisa; Kawan, Rasmila; Emeny, Rebecca Thwing; Ladwig, Karl-Heinz

    2016-01-01

    Study Objectives: To investigate the association between sleep-related characteristics and cognitive change over 3 years of follow up in an aged population. Methods: Sleep characteristics and covariates were assessed at baseline in a standardized interview and clinical examination of the population-based KORA Age Study (n = 740, mean age = 75 years). Cognitive score (determined by telephone interview for cognitive status, TICS-m) was recorded at baseline and 3 years later. Results: At baseline, 82.83% (n = 613) of participants had normal cognitive status, 13.51% (n = 100) were classified with mild cognitive impairment (MCI), and 3.64% (n = 27) with probable dementia. The effect of three distinct patterns of poor sleep (difficulties initiating [DIS] or maintaining sleep [DMS], daytime sleepiness [DS] or sleep duration) were considered on a change in cognitive score with adjustments for potential confounders in generalized linear regression models. Cognitive decline was more pronounced in individuals with DMS compared to those with no DMS (β = 1.33, 95% CI = 0.41–2.24, P < 0.001). However, the predictive power of DMS was only significant in individuals with normal cognition and not impaired subjects at baseline. Prolonged sleep duration increased the risk for cognitive decline in cognitively impaired elderly (β = 1.86, 95% CI = 0.15–3.57, P = 0.03). Other sleep characteristics (DIS and DS) were not significantly associated with cognitive decline. Conclusions: DMS and long sleep duration were associated with cognitive decline in normal and cognitively impaired elderly, respectively. The identification of impaired sleep quality may offer intervention strategies to deter cognitive decline in the elderly with normal cognitive function. Citation: Johar H, Kawan R, Emeny RT, Ladwig KH. Impaired sleep predicts cognitive decline in old people: findings from the prospective KORA age study. SLEEP 2016;39(1):217–226. PMID:26414903

  3. Aging, frailty and age-related diseases.

    PubMed

    Fulop, T; Larbi, A; Witkowski, J M; McElhaney, J; Loeb, M; Mitnitski, A; Pawelec, G

    2010-10-01

    The concept of frailty as a medically distinct syndrome has evolved based on the clinical experience of geriatricians and is clinically well recognizable. Frailty is a nonspecific state of vulnerability, which reflects multisystem physiological change. These changes underlying frailty do not always achieve disease status, so some people, usually very elderly, are frail without a specific life threatening illness. Current thinking is that not only physical but also psychological, cognitive and social factors contribute to this syndrome and need to be taken into account in its definition and treatment. Together, these signs and symptoms seem to reflect a reduced functional reserve and consequent decrease in adaptation (resilience) to any sort of stressor and perhaps even in the absence of extrinsic stressors. The overall consequence is that frail elderly are at higher risk for accelerated physical and cognitive decline, disability and death. All these characteristics associated with frailty can easily be applied to the definition and characterization of the aging process per se and there is little consensus in the literature concerning the physiological/biological pathways associated with or determining frailty. It is probably true to say that a consensus view would implicate heightened chronic systemic inflammation as a major contributor to frailty. This review will focus on the relationship between aging, frailty and age-related diseases, and will highlight possible interventions to reduce the occurrence and effects of frailty in elderly people. PMID:20559726

  4. Intellectual Decline.

    ERIC Educational Resources Information Center

    Guilford, J.P.

    In investigations of decline of intellectual status with age, cross-sectional and longitudinal studies give divergent results--the former show almost universal declines in test performances among older groups while the latter often show gains. Although few structure-of-intellect (SI) factors have been explored in relation to adult ages, two kinds…

  5. [Presbycusis - Age Related Hearing Loss].

    PubMed

    Fischer, N; Weber, B; Riechelmann, H

    2016-07-01

    Presbycusis or age related hearing loss can be defined as a progressive, bilateral and symmetrical sensorineural hearing loss due to age related degeneration of inner ear structures. It can be considered a multifactorial complex disorder with environmental and genetic factors. The molecular, electrophysiological and histological damage at different levels of the inner ear cause a progressive hearing loss, which usually affects the high frequencies of hearing. The resulting poor speech recognition has a negative impact on cognitive, emotional and social function in older adults. Recent investigations revealed an association between hearing impairment and social isolation, anxiety, depression and cognitive decline in elderly. These findings emphasize the importance of diagnosis and treating hearing loss in the elderly population. Hearing aids are the most commonly used devices for treating presbycusis. The technical progress of implantable hearing devices allows an effective hearing rehabilitation even in elderly with severe hearing loss. However, most people with hearing impairments are not treated adequately. PMID:27392191

  6. Functional MRI evidence for the decline of word retrieval and generation during normal aging.

    PubMed

    Baciu, M; Boudiaf, N; Cousin, E; Perrone-Bertolotti, M; Pichat, C; Fournet, N; Chainay, H; Lamalle, L; Krainik, A

    2016-02-01

    This fMRI study aimed to explore the effect of normal aging on word retrieval and generation. The question addressed is whether lexical production decline is determined by a direct mechanism, which concerns the language operations or is rather indirectly induced by a decline of executive functions. Indeed, the main hypothesis was that normal aging does not induce loss of lexical knowledge, but there is only a general slowdown in retrieval mechanisms involved in lexical processing, due to possible decline of the executive functions. We used three tasks (verbal fluency, object naming, and semantic categorization). Two groups of participants were tested (Young, Y and Aged, A), without cognitive and psychiatric impairment and showing similar levels of vocabulary. Neuropsychological testing revealed that older participants had lower executive function scores, longer processing speeds, and tended to have lower verbal fluency scores. Additionally, older participants showed higher scores for verbal automatisms and overlearned information. In terms of behavioral data, older participants performed as accurate as younger adults, but they were significantly slower for the semantic categorization and were less fluent for verbal fluency task. Functional MRI analyses suggested that older adults did not simply activate fewer brain regions involved in word production, but they actually showed an atypical pattern of activation. Significant correlations between the BOLD (Blood Oxygen Level Dependent) signal of aging-related (A > Y) regions and cognitive scores suggested that this atypical pattern of the activation may reveal several compensatory mechanisms (a) to overcome the slowdown in retrieval, due to the decline of executive functions and processing speed and (b) to inhibit verbal automatic processes. The BOLD signal measured in some other aging-dependent regions did not correlate with the behavioral and neuropsychological scores, and the overactivation of these uncorrelated

  7. Functional MRI evidence for the decline of word retrieval and generation during normal aging.

    PubMed

    Baciu, M; Boudiaf, N; Cousin, E; Perrone-Bertolotti, M; Pichat, C; Fournet, N; Chainay, H; Lamalle, L; Krainik, A

    2016-02-01

    This fMRI study aimed to explore the effect of normal aging on word retrieval and generation. The question addressed is whether lexical production decline is determined by a direct mechanism, which concerns the language operations or is rather indirectly induced by a decline of executive functions. Indeed, the main hypothesis was that normal aging does not induce loss of lexical knowledge, but there is only a general slowdown in retrieval mechanisms involved in lexical processing, due to possible decline of the executive functions. We used three tasks (verbal fluency, object naming, and semantic categorization). Two groups of participants were tested (Young, Y and Aged, A), without cognitive and psychiatric impairment and showing similar levels of vocabulary. Neuropsychological testing revealed that older participants had lower executive function scores, longer processing speeds, and tended to have lower verbal fluency scores. Additionally, older participants showed higher scores for verbal automatisms and overlearned information. In terms of behavioral data, older participants performed as accurate as younger adults, but they were significantly slower for the semantic categorization and were less fluent for verbal fluency task. Functional MRI analyses suggested that older adults did not simply activate fewer brain regions involved in word production, but they actually showed an atypical pattern of activation. Significant correlations between the BOLD (Blood Oxygen Level Dependent) signal of aging-related (A > Y) regions and cognitive scores suggested that this atypical pattern of the activation may reveal several compensatory mechanisms (a) to overcome the slowdown in retrieval, due to the decline of executive functions and processing speed and (b) to inhibit verbal automatic processes. The BOLD signal measured in some other aging-dependent regions did not correlate with the behavioral and neuropsychological scores, and the overactivation of these uncorrelated

  8. Parenchyma cell respiration and survival in secondary xylem: does metabolic activity decline with cell age?

    PubMed

    Spicer, R; Holbrook, N M

    2007-08-01

    Sapwood respiration often declines towards the sapwood/heartwood boundary, but it is not known if parenchyma metabolic activity declines with cell age. We measured sapwood respiration in five temperate species (sapwood age range of 5-64 years) and expressed respiration on a live cell basis by quantifying living parenchyma. We found no effect of parenchyma age on respiration in two conifers (Pinus strobus, Tsuga canadensis), both of which had significant amounts of dead parenchyma in the sapwood. In angiosperms (Acer rubrum, Fraxinus americana, Quercus rubra), both bulk tissue and live cell respiration were reduced by about one-half in the oldest relative to the youngest sapwood, and all sapwood parenchyma remained alive. Conifers and angiosperms had similar bulk tissue respiration despite a smaller proportion of parenchyma in conifers (5% versus 15-25% in angiosperms), such that conifer parenchyma respired at rates about three times those of angiosperms. The fact that 5-year-old parenchyma cells respired at the same rate as 25-year-old cells in conifers suggests that there is no inherent or intrinsic decline in respiration as a result of cellular ageing. In contrast, it is not known whether differences observed in cellular respiration rates of angiosperms are a function of age per se, or whether active regulation of metabolic rate or positional effects (e.g. proximity to resources and/or hormones) could be the cause of reduced respiration in older sapwood.

  9. The Association of Age With Rate of Cognitive Decline in Elderly Individuals Residing in Supporting Care Facilities

    PubMed Central

    Ravona-Springer, Ramit; Luo, Xiaodong; Schmeidler, James; Wysocki, Michael; Lesser, Gerson T.; Rapp, Michael A.; Dahlman, Karen; Grossman, Hillel T.; Haroutunian, Vahram; Beeri, Michal Schnaider

    2012-01-01

    Objectives This study examines the effect of age on rate of cognitive decline in different stages of dementia, of nursing home and assisted-living residents. Methods In this longitudinal study, the Mini Mental State Examination (MMSE) was used to measure rate of cognitive decline in subjects who were nondemented [Clinical Dementia Rating (CDR)=0; n=353], questionably demented (CDR=0.5; n=121), or frankly demented (CDR≥1; n=213) at baseline. Results A generalized estimating equation was used to model the MMSE scores over time (mean follow-up 2.9±2.0 y). The generalized estimating equation model had the MMSE scores at successive follow-up time points as dependent variables and had linear and quadratic age, follow-up time from baseline, CDR at baseline, and all the interactions among them as independent variables, controlling for MMSE at baseline, sex, race, and education. The mean age of the entire sample was 85.2±7.4 years at baseline. There were no significant interactions of linear age effects with rate of cognitive decline. The analysis of interaction of quadratic age with rate of cognitive decline showed complex relationships: in the nondemented group, there was no substantial quadratic association of age with the rate of cognitive decline (P=0.13); in the questionable demented group, the oldest subjects declined relatively faster (P=0.02); and in the demented group, the youngest and oldest subjects tended to decline relatively less than subjects in the intermediate ages (P=0.07). Conclusions This study adds an additional aspect to the complexity of the association between age and rate of cognitive decline, showing that the direction and amplitude of this effect differs according to the stage along the course of cognitive decline. PMID:21572311

  10. Cognitive aging: a common decline of episodic recollection and spatial memory in rats.

    PubMed

    Robitsek, R Jonathan; Fortin, Norbert J; Koh, Ming Teng; Gallagher, Michela; Eichenbaum, Howard

    2008-09-01

    In humans, recognition memory declines with aging, and this impairment is characterized by a selective loss in recollection of previously studied items contrasted with relative sparing of familiarity for items in the study list. Rodent models of cognitive aging have focused on water maze learning and have demonstrated an age-associated loss in spatial, but not cued memory. The current study examined odor recognition memory in young and aged rats and compared performance in recognition with that in water maze learning. In the recognition task, young rats used both recollection and familiarity. In contrast, the aged rats showed a selective loss of recollection and relative sparing of familiarity, similar to the effects of hippocampal damage. Furthermore, performance on the recall component, but not the familiarity component, of recognition was correlated with spatial memory and recollection was poorer in aged rats that were also impaired in spatial memory. These results extend the pattern of impairment in recollection and relative sparing of familiarity observed in human cognitive aging to rats, and suggest a common age-related impairment in both spatial learning and the recollective component of nonspatial recognition memory.

  11. Multiple stressor effects in relation to declining amphibian populations

    USGS Publications Warehouse

    2003-01-01

    This book represents the work of several authors who participated in the symposium entitled 'Multiple Stressor Effects in Relation to Declining Amphibian Populations' convened 16-17 April, 2002, in Pittsburgh, Pennsylvania. Declines of amphibian populations of varying severity have been observed for many years, and in the last 8 to 10 years considerable progress has been made in documenting the status and distribution of a range of amphibian species. Habitat alteration and destruction are likely linked to many amphibian declines, but a variety of other factors, both anthropogenic and natural, have been observed or proposed to have caused declines or extinctions of amphibian populations. Unfortunately, determining the environmental causes for the decline of many species has proven difficult. The goals of this symposium were three-fold. First, highlight ASTM's historic role in providing a forum for the standardization of amphibian toxicity test methods and the characterization of adverse effects potentially associated with chemical stressors. Second, demonstrate through case studies the current state of technical 'tools' available to biologists, ecologists, environmental scientists and natural resource professionals for assessing amphibian populations exposed to various environmental stressors. And third, characterize a process that brings a range of interdisciplinary technical and management tools to the tasks of causal analysis, especially as those relate to a multiple stressor risk assessment 'mind-set.' As part of the symposium, scientists and resource management professionals from diverse fields including ecotoxicology and chemistry, ecology and field biology, conservation biology, and natural resource management and policy contributed oral presentations and posters that addressed topics related to declining amphibian populations and the role that various stressors have in those losses. The papers contained in this publication reflect the commitment of ASTM

  12. Age related changes in age of starting to smoke.

    PubMed

    Weinkam, J J; Sterling, T D

    1990-01-01

    The Average Age of Starting to Smoke (AASS) has been reported to decline for younger birth cohorts. That apparent decline has been used to support a conclusion of an increase in smoking among younger individuals. However, in some cases the apparent decline is an artifact of the method of computation which arises when the quantity being averaged is related to a quantity used to classify subjects for comparison. In one other case, a second type of error arises because the distribution of smoking initiation with age changed in such a way that the proportion of individuals taking up smoking at older ages declined more rapidly than the proportion starting at younger ages. In fact, comparison of the 1970 National Health Interview Survey (NHIS) to the 1979/80 NHIS shows a uniform decrease in starting to smoke among teens and preteens. Examples are discussed which show that estimates of possible disease related factors actually experienced by a cohort are possible only if other suitable data are available for comparable representative sections of the population at different time periods and for different ages.

  13. Age related changes in age of starting to smoke.

    PubMed

    Weinkam, J J; Sterling, T D

    1990-01-01

    The Average Age of Starting to Smoke (AASS) has been reported to decline for younger birth cohorts. That apparent decline has been used to support a conclusion of an increase in smoking among younger individuals. However, in some cases the apparent decline is an artifact of the method of computation which arises when the quantity being averaged is related to a quantity used to classify subjects for comparison. In one other case, a second type of error arises because the distribution of smoking initiation with age changed in such a way that the proportion of individuals taking up smoking at older ages declined more rapidly than the proportion starting at younger ages. In fact, comparison of the 1970 National Health Interview Survey (NHIS) to the 1979/80 NHIS shows a uniform decrease in starting to smoke among teens and preteens. Examples are discussed which show that estimates of possible disease related factors actually experienced by a cohort are possible only if other suitable data are available for comparable representative sections of the population at different time periods and for different ages. PMID:2303843

  14. Is rising obesity causing a secular (age-independent) decline in testosterone among American men?

    PubMed

    Mazur, Allan; Westerman, Ronny; Mueller, Ulrich

    2013-01-01

    The testosterone of men in industrial societies peaks in their twenties and tends to decline with increasing age. Apart from this individual-level decline, there have been reports of a secular (age-independent population-level) decline in testosterone among American and Scandinavian men during the past few decades, possibly an indication of declining male reproductive health. It has been suggested that both declines in testosterone (individual-level and population-level) are due to increasing male obesity because men in industrial society tend to add body fat as they age, and overall rates of obesity are increasing. Using an unusually large and lengthy longitudinal dataset (991 US Air Force veterans examined in six cycles over 20 years), we investigate the relationship of obesity to individual and population-level declines in testosterone. Over twenty years of study, longitudinal decline in mean testosterone was at least twice what would be expected from cross-sectional estimates of the aging decline. Men who put on weight intensified their testosterone decline, some greatly so, but even among those who held their weight constant or lost weight during the study, mean testosterone declined 117 ng/dl (19%) over 20 years. We have not identified the reason for secular decline in testosterone, but we exclude increasing obesity as a sufficient or primary explanation, and we deny the supposition that men who avoid excessive weight will maintain their youthful levels of testosterone.

  15. 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

    2013-09-01

    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.

  16. A prospective study of decline in lung function in relation to welding emissions

    PubMed Central

    Christensen, Sigve W; Bonde, Jens Peter; Omland, Øyvind

    2008-01-01

    Background Numerous cross-sectional studies have reported reduced lung function among welders but limitations of exposure assessment and design preclude causal inference. The aim of this study was to investigate if long-term exposure to welding fume particulates accelerates the age-related decline in lung function. Methods Lung function was measured by spirometry in 1987 and 2004 among 68 steel welders and 32 non-welding production workers. The decline in forced expiratory volume (FEV1) was analysed in relation to cumulated exposure to fume particulates among welders during the follow-up period. Results Among smokers the decline in FEV1 through follow-up period was in average 150 ml larger among welders than non-welders while the difference was negligible among non-smokers. The results did not reach statistical significance and within welders the decline in lung function was not related to the cumulated welding particulate exposure during follow-up period Conclusion Long-term exposure to welding emissions may accelerate the age-related decline of lung function but at exposure levels in the range of 1.5 to 6.5 mg/m3 the average annual excess loss of FEV1 is unlikely to exceed 25 ml in smokers and 10 ml in non-smokers. PMID:18302754

  17. Age-dependent decline of nogo-a protein in the mouse cerebrum.

    PubMed

    Kumari, Anita; Thakur, M K

    2014-11-01

    Nogo-A, a myelin-associated neurite growth inhibitory protein, is implicated in synaptic plasticity. It binds to its receptor namely the Nogo-66 receptor1 (NgR1) and regulates filamentous (F) actin dynamics via small GTPases of the Rho family, RhoA kinase (ROCK), LimK and cofilin. These proteins are associated with the structural plasticity, one of the components of synaptic plasticity, which is known to decline with normal aging. So, the level of Nogo-A and its receptor NgR1 are likely to vary during normal brain aging. However, it is not clearly understood how the levels of Nogo-A and its receptor NgR1 change in the cerebrum during aging. Several studies show an age- and gender-dependent decline in synaptic plasticity. Therefore, the present study was planned to analyze the relative changes in the mRNA and protein levels of Nogo-A and NgR1 in both male and female mice cerebrum during normal aging. Western blot analysis has shown decrease in Nogo-A protein level during aging in both male and female mice cerebrum. This was further confirmed by immunofluorescence analysis. RT-PCR analysis of Nogo-A mRNA showed no significant difference in the above-mentioned groups. This was also supported by in situ hybridization. NgR1 protein and its mRNA expression levels showed no significant alteration with aging in the cerebrum of both male and female mice. Taken together, we speculate that the downregulation of Nogo-A protein might have a role in the altered synaptic plasticity during aging.

  18. New Clues to Age-Related Hearing Loss

    MedlinePlus

    ... gov/news/fullstory_161359.html New Clues to Age-Related Hearing Loss Older people's brains have a ... the brain's ability to process speech declines with age. For the study, Alessandro Presacco and colleagues divided ...

  19. Quantitative T2 mapping of white matter: applications for ageing and cognitive decline.

    PubMed

    Knight, Michael J; McCann, Bryony; Tsivos, Demitra; Dillon, Serena; Coulthard, Elizabeth; Kauppinen, Risto A

    2016-08-01

    In MRI, the coherence lifetime T2 is sensitive to the magnetic environment imposed by tissue microstructure and biochemistry in vivo. Here we explore the possibility that the use of T2 relaxometry may provide information complementary to that provided by diffusion tensor imaging (DTI) in ageing of healthy controls (HC), Alzheimer's disease (AD) and mild cognitive impairment (MCI). T2 and diffusion MRI metrics were quantified in HC and patients with MCI and mild AD using multi-echo MRI and DTI. We used tract-based spatial statistics (TBSS) to evaluate quantitative MRI parameters in white matter (WM). A prolonged T2 in WM was associated with AD, and able to distinguish AD from MCI, and AD from HC. Shorter WM T2 was associated with better cognition and younger age in general. In no case was a reduction in T2 associated with poorer cognition. We also applied principal component analysis, showing that WM volume changes independently of  T2, MRI diffusion indices and cognitive performance indices. Our data add to the evidence that age-related and AD-related decline in cognition is in part attributable to WM tissue state, and much less to WM quantity. These observations suggest that WM is involved in AD pathology, and that T2 relaxometry is a potential imaging modality for detecting and characterising WM in cognitive decline and dementia. PMID:27384985

  20. Quantitative T2 mapping of white matter: applications for ageing and cognitive decline

    NASA Astrophysics Data System (ADS)

    Knight, Michael J.; McCann, Bryony; Tsivos, Demitra; Dillon, Serena; Coulthard, Elizabeth; Kauppinen, Risto A.

    2016-08-01

    In MRI, the coherence lifetime T2 is sensitive to the magnetic environment imposed by tissue microstructure and biochemistry in vivo. Here we explore the possibility that the use of T2 relaxometry may provide information complementary to that provided by diffusion tensor imaging (DTI) in ageing of healthy controls (HC), Alzheimer’s disease (AD) and mild cognitive impairment (MCI). T2 and diffusion MRI metrics were quantified in HC and patients with MCI and mild AD using multi-echo MRI and DTI. We used tract-based spatial statistics (TBSS) to evaluate quantitative MRI parameters in white matter (WM). A prolonged T2 in WM was associated with AD, and able to distinguish AD from MCI, and AD from HC. Shorter WM T2 was associated with better cognition and younger age in general. In no case was a reduction in T2 associated with poorer cognition. We also applied principal component analysis, showing that WM volume changes independently of  T2, MRI diffusion indices and cognitive performance indices. Our data add to the evidence that age-related and AD-related decline in cognition is in part attributable to WM tissue state, and much less to WM quantity. These observations suggest that WM is involved in AD pathology, and that T2 relaxometry is a potential imaging modality for detecting and characterising WM in cognitive decline and dementia.

  1. Demographic and clinical characteristics related to cognitive decline in Alzheimer disease in China

    PubMed Central

    Peng, Dantao; Shi, Zhihong; Xu, Jun; Shen, Lu; Xiao, Shifu; Zhang, Nan; Li, Yi; Jiao, Jinsong; Wang, Yan-Jiang; Liu, Shuai; Zhang, Meilin; Wang, Meng; Liu, Shuling; Zhou, Yuying; Zhang, Xiao; Gu, Xiao-hua; Yang, Ce-ce; Wang, Yu; Jiao, Bin; Tang, Beisha; Wang, Jinhuan; Yu, Tao; Ji, Yong

    2016-01-01

    Abstract Alzheimer disease (AD) is the most frequent cause of dementia. AD diagnosis, progression, and treatment have not been analyzed nationwide in China. The primary aim of this study was to analyze demographic and clinical characteristics related to cognitive decline in AD patients treated at outpatient clinics in China. We performed a retrospective study of 1993 AD patients at 10 cognitive centers across 8 cities in China from March 2011 to October 2014. Of these, 891 patients were followed for more than 1 year. The mean age at diagnosis was 72.0 ± 10.0 years (range 38–96 years), and the mean age at onset of AD was 69.8 ± 9.5 years. Most patients (65.1%) had moderate to severe symptoms at the time of diagnosis, and mean Mini-Mental State Examination at diagnosis was 15.7 ± 7.7. AD patients showed significant cognitive decline at 12 months after diagnosis. Having more than 9 years of formal education was an independent risk factor related to rapid cognitive decline [odds ratio (OR) = 1.80; 95% confidence interval (95% CI): 1.11–2.91]. Early-onset AD patients experienced more rapid cognitive decline than late-onset patients (OR = 1.83; 95% CI: 1.09–3.06). Most AD patients in China had moderate to severe symptoms at the time of diagnosis and experienced significant cognitive decline within 1 year. Rapid cognitive decline in AD was related to having a higher educational level and younger age of onset. PMID:27367978

  2. A review of new insights on the association between hearing loss and cognitive decline in ageing.

    PubMed

    Fortunato, S; Forli, F; Guglielmi, V; De Corso, E; Paludetti, G; Berrettini, S; Fetoni, A R

    2016-06-01

    Age-related hearing loss (ARHL) has a multifactorial pathogenesis and it is an inevitable hearing impairment associated with reduction of communicative skills related to ageing. Increasing evidence has linked ARHL to more rapid progression of cognitive decline and incidental dementia. Many aspects of daily living of elderly people have been associated to hearing abilities, showing that hearing loss (HL) affects the quality of life, social relationships, motor skills, psychological aspects and function and morphology in specific brain areas. Epidemiological and clinical studies confirm the assumption of a relationship between these conditions. However, the mechanisms are still unclear and are reviewed herein. Long-term hearing deprivation of auditory inputs can impact cognitive performance by decreasing the quality of communication leading to social isolation and depression and facilitate dementia. On the contrary, the limited cognitive skills may reduce the cognitive resources available for auditory perception, increasing the effects of HL. In addition, hearing loss and cognitive decline may reflect a 'common cause' on the auditory pathway and brain. In fact, some pathogenetic factors are recongised in common microvascular disease factors such as diabetes, atherosclerosis and hypertension. Interdisciplinary efforts to investigate and address HL in the context of brain and cognitive ageing are needed. Surprisingly, few studies have been adressed on the effectiveness of hearing aids in changing the natural history of cognitive decline. Effective interventions with hearing aids or cochlear implant may improve social and emotional function, communication, cognitive function and positively impact quality of life. The aim of this review is to overview new insights on this challenging topic and provide new ideas for future research.

  3. A review of new insights on the association between hearing loss and cognitive decline in ageing.

    PubMed

    Fortunato, S; Forli, F; Guglielmi, V; De Corso, E; Paludetti, G; Berrettini, S; Fetoni, A R

    2016-06-01

    Age-related hearing loss (ARHL) has a multifactorial pathogenesis and it is an inevitable hearing impairment associated with reduction of communicative skills related to ageing. Increasing evidence has linked ARHL to more rapid progression of cognitive decline and incidental dementia. Many aspects of daily living of elderly people have been associated to hearing abilities, showing that hearing loss (HL) affects the quality of life, social relationships, motor skills, psychological aspects and function and morphology in specific brain areas. Epidemiological and clinical studies confirm the assumption of a relationship between these conditions. However, the mechanisms are still unclear and are reviewed herein. Long-term hearing deprivation of auditory inputs can impact cognitive performance by decreasing the quality of communication leading to social isolation and depression and facilitate dementia. On the contrary, the limited cognitive skills may reduce the cognitive resources available for auditory perception, increasing the effects of HL. In addition, hearing loss and cognitive decline may reflect a 'common cause' on the auditory pathway and brain. In fact, some pathogenetic factors are recongised in common microvascular disease factors such as diabetes, atherosclerosis and hypertension. Interdisciplinary efforts to investigate and address HL in the context of brain and cognitive ageing are needed. Surprisingly, few studies have been adressed on the effectiveness of hearing aids in changing the natural history of cognitive decline. Effective interventions with hearing aids or cochlear implant may improve social and emotional function, communication, cognitive function and positively impact quality of life. The aim of this review is to overview new insights on this challenging topic and provide new ideas for future research. PMID:27214827

  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. Imaging Phenotype of Occupational Endotoxin-Related Lung Function Decline

    PubMed Central

    Lai, Peggy S.; Hang, Jing-qing; Zhang, Feng-ying; Sun, J.; Zheng, Bu-Yong; Su, Li; Washko, George R.; Christiani, David C.

    2016-01-01

    Background: Although occupational exposures contribute to a significant proportion of obstructive lung disease, the phenotype of obstructive lung disease associated with work-related organic dust exposure independent of smoking remains poorly defined. Objective: We identified the relative contributions of smoking and occupational endotoxin exposure to parenchymal and airway remodeling as defined by quantitative computed tomography (CT). Methods: The Shanghai Textile Worker Study is a longitudinal study of endotoxin-exposed cotton workers and endotoxin-unexposed silk workers that was initiated in 1981. Spirometry, occupational endotoxin exposure, and smoking habits were assessed at 5-year intervals. High-resolution computed tomography (CT) was performed in 464 retired workers in 2011, along with quantitative lung densitometric and airway analysis. Results: Significant differences in all CT measures were noted across exposure groups. Occupational endotoxin exposure was associated with a decrease (–1.3%) in percent emphysema (LAAI-950), a 3.3-Hounsfield unit increase in 15th percentile density, an 18.1-g increase in lung mass, and a 2.3% increase in wall area percent. Current but not former smoking was associated with a similar CT phenotype. Changes in LAAI-950 were highly correlated with 15th percentile density (correlation –1.0). Lung mass was the only measure associated with forced expiratory volume in 1 sec (FEV1) decline, with each 10-g increase in lung mass associated with an additional loss (–6.1 mL) of FEV1 (p = 0.001) between 1981 and 2011. Conclusions: There are many similarities between the effects of occupational endotoxin exposure and those of tobacco smoke exposure on lung parenchyma and airway remodeling. The effects of occupational endotoxin exposure appear to persist even after the cessation of exposure. LAAI-950 may not be a reliable indicator of emphysema in subjects without spirometric impairment. Lung mass is a CT-based biomarker of

  6. Analysis of FEV1 decline in relatively healthy heavy smokers: implications of expressing changes in FEV1 in relative terms.

    PubMed

    Thomsen, Laura H; Dirksen, Asger; Shaker, Saher B; Skovgaard, Lene T; Dahlbäck, Magnus; Pedersen, Jesper H

    2014-02-01

    Progressive decline in lung function has been widely accepted as the hallmark of chronic obstructive pulmonary disease (COPD); however, recent evidence indicates that the rate of decline measured as decline in forced expiratory volume in one second (FEV1) is higher in mild to moderate COPD than in severe COPD. Usually changes in FEV1 are measured in ml that is "absolute"; however, changes can also be measured "relative" as a percentage of the actual FEV1. We hypothesize that relative measurements could be more appropriate than absolute measurements for describing changes in lung function. We analyzed data from 3,218 relatively healthy heavy smokers who participated in the Danish Lung Cancer Screening Trial. The influences of age, sex, height, body mass index, smoking, and severity of airflow limitation on FEV1 were analyzed in mixed effects models. In absolute terms those with the best lung function consistently showed the steepest decline, whereas in relative terms most fast decliners are found among those with low lung function. Measuring changes in relative terms implied statistically significant acceleration of decline with advancing age, smoking (pack-years) and severity of airflow limitation. Relative measurements may lead to a better understanding of changes in lung function. Smoking and severity of airflow limitation speed up the loss of lung function, and this emphasizes the importance of abstaining from smoking the sooner the better. Measuring changes in relative terms could have important implications for the interpretation of results from clinical trials where FEV1 is the primary outcome. DLCST; www.ClinicalTrials.org , registration number: NCT00496977.

  7. Development and Decline of Memory Functions in Normal, Pathological and Healthy Successful Aging

    PubMed Central

    Sanfratello, L.; Adair, J. C.; Knoefel, J. E.; Caprihan, A.; Stephen, J. M.

    2011-01-01

    Many neuroimaging studies of age-related memory decline interpret resultant differences in brain activation patterns in the elderly as reflecting a type of compensatory response or regression to a simpler state of brain organization. Here we review a series of our own studies which lead us to an alternative interpretation, and highlights a couple of potential confounds in the aging literature that may act to increase the variability of results within age groups and across laboratories. From our perspective, level of cognitive functioning achieved by a group of elderly is largely determined by the health of individuals within this group. Individuals with a history of hypertension, for example, are likely to have multiple white matter insults which compromise cognitive functioning, independent of aging processes. The health of the elderly group has not been well-documented in most previous studies and elderly participants are rarely excluded, or placed into a separate group, due to health-related problems. In addition, recent results show that white matter tracts within the frontal and temporal lobes, regions critical for higher cognitive functions, continue to mature well into the 4th decade of life. This suggests that a young age group may not be the best control group for understanding aging effects on the brain since development is ongoing within this age range. Therefore, we have added a middle-age group to our studies in order to better understand normal development across the lifespan as well as effects of pathology on cognitive functioning in the aging brain. PMID:21452018

  8. Age-dependent decline in fin regenerative capacity in the short-lived fish Nothobranchius furzeri

    PubMed Central

    Wendler, Sebastian; Hartmann, Nils; Hoppe, Beate; Englert, Christoph

    2015-01-01

    The potential to regenerate declines with age in a wide range of organisms. A popular model system to study the mechanisms of regeneration is the fin of teleost fish, which has the ability to fully regrow upon amputation. Here, we used the short-lived killifish Nothobranchius furzeri to analyse the impact of aging on fin regeneration in more detail. We observed that young fish were able to nearly completely (98%) regenerate their amputated caudal fins within 4 weeks, whereas middle-aged fish reached 78%, old fish 57% and very old fish 46% of their original fin size. The difference in growth rate between young and old fish was already significant at 3 days post amputation (dpa) and increased with time. We therefore hypothesized that early events are crucial for the age-related differences in regenerative capacity. Indeed, we could observe a higher percentage of proliferating cells in early regenerating fin tissue of young fish compared with aged fish and larger fractions of apoptotic cells in aged fish. Furthermore, young fish showed peak upregulation of several genes involved in fgf and wnt/β-catenin signalling at an earlier time point than old fish. Our findings suggest that regenerative processes are initiated earlier and that regeneration overall is more efficient in younger fish. PMID:26121607

  9. Age-dependent decline in fin regenerative capacity in the short-lived fish Nothobranchius furzeri.

    PubMed

    Wendler, Sebastian; Hartmann, Nils; Hoppe, Beate; Englert, Christoph

    2015-10-01

    The potential to regenerate declines with age in a wide range of organisms. A popular model system to study the mechanisms of regeneration is the fin of teleost fish, which has the ability to fully regrow upon amputation. Here, we used the short-lived killifish Nothobranchius furzeri to analyse the impact of aging on fin regeneration in more detail. We observed that young fish were able to nearly completely (98%) regenerate their amputated caudal fins within 4 weeks, whereas middle-aged fish reached 78%, old fish 57% and very old fish 46% of their original fin size. The difference in growth rate between young and old fish was already significant at 3 days post amputation (dpa) and increased with time. We therefore hypothesized that early events are crucial for the age-related differences in regenerative capacity. Indeed, we could observe a higher percentage of proliferating cells in early regenerating fin tissue of young fish compared with aged fish and larger fractions of apoptotic cells in aged fish. Furthermore, young fish showed peak upregulation of several genes involved in fgf and wnt/β-catenin signalling at an earlier time point than old fish. Our findings suggest that regenerative processes are initiated earlier and that regeneration overall is more efficient in younger fish. PMID:26121607

  10. Where the brain grows old: decline in anterior cingulate and medial prefrontal function with normal aging.

    PubMed

    Pardo, José V; Lee, Joel T; Sheikh, Sohail A; Surerus-Johnson, Christa; Shah, Hemant; Munch, Kristin R; Carlis, John V; Lewis, Scott M; Kuskowski, Michael A; Dysken, Maurice W

    2007-04-15

    Even healthy adults worry about declines in mental efficiency with aging. Subjective changes in mental flexibility, self-regulation, processing speed, and memory are often cited. We show here that focal decreases in brain activity occur with normal aging as measured with fluorodeoxyglucose and positron emission tomography. The largest declines localize to a medial network including the anterior cingulate/medial prefrontal cortex, dorsomedial thalamus, and sugenual cingulate/basal forebrain. Declining metabolism in this network correlates with declining cognitive function. The medial prefrontal metabolic changes with aging are similar in magnitude to the hypometabolism found in Mild Cognitive Impairment or Alzheimer's disease. These results converge with data from healthy elderly indicating dysfunction in the anterior attention system. The interaction of attention in the anterior cingulate cortex with memory in the medial temporal lobe may explain the global impairment that defines dementia. Despite the implications for an aging population, the neurophysiologic mechanisms of these metabolic decreases remain unknown. PMID:17321756

  11. Delaying aging and the aging-associated decline in protein homeostasis by inhibition of tryptophan degradation

    PubMed Central

    van der Goot, Annemieke T.; Zhu, Wentao; Vázquez-Manrique, Rafael P.; Seinstra, Renée I.; Dettmer, Katja; Michels, Helen; Farina, Francesca; Krijnen, Jasper; Melki, Ronald; Buijsman, Rogier C.; Ruiz Silva, Mariana; Thijssen, Karen L.; Kema, Ido P.; Neri, Christian; Oefner, Peter J.; Nollen, Ellen A. A.

    2012-01-01

    Toxicity of aggregation-prone proteins is thought to play an important role in aging and age-related neurological diseases like Parkinson and Alzheimer’s diseases. Here, we identify tryptophan 2,3-dioxygenase (tdo-2), the first enzyme in the kynurenine pathway of tryptophan degradation, as a metabolic regulator of age-related α-synuclein toxicity in a Caenorhabditis elegans model. Depletion of tdo-2 also suppresses toxicity of other heterologous aggregation-prone proteins, including amyloid-β and polyglutamine proteins, and endogenous metastable proteins that are sensors of normal protein homeostasis. This finding suggests that tdo-2 functions as a general regulator of protein homeostasis. Analysis of metabolite levels in C. elegans strains with mutations in enzymes that act downstream of tdo-2 indicates that this suppression of toxicity is independent of downstream metabolites in the kynurenine pathway. Depletion of tdo-2 increases tryptophan levels, and feeding worms with extra l-tryptophan also suppresses toxicity, suggesting that tdo-2 regulates proteotoxicity through tryptophan. Depletion of tdo-2 extends lifespan in these worms. Together, these results implicate tdo-2 as a metabolic switch of age-related protein homeostasis and lifespan. With TDO and Indoleamine 2,3-dioxygenase as evolutionarily conserved human orthologs of TDO-2, intervening with tryptophan metabolism may offer avenues to reducing proteotoxicity in aging and age-related diseases. PMID:22927396

  12. Long noncoding RNAs in aging and age-related diseases.

    PubMed

    Kour, Sukhleen; Rath, Pramod C

    2016-03-01

    Aging is the universal, intrinsic, genetically-controlled, evolutionarily-conserved and time-dependent intricate biological process characterised by the cumulative decline in the physiological functions and their coordination in an organism after the attainment of adulthood resulting in the imbalance of neurological, immunological and metabolic functions of the body. Various biological processes and mechanisms along with altered levels of mRNAs and proteins have been reported to be involved in the progression of aging. It is one of the major risk factors in the patho-physiology of various diseases and disorders. Recently, the discovery of pervasive transcription of a vast pool of heterogeneous regulatory noncoding RNAs (ncRNAs), including small ncRNAs (sncRNAs) and long ncRNAs (lncRNAs), in the mammalian genome have provided an alternative way to study and explore the missing links in the aging process, its mechanism(s) and related diseases in a whole new dimension. The involvement of small noncoding RNAs in aging and age-related diseases have been extensively studied and recently reviewed. However, lncRNAs, whose function is far less explored in relation to aging, have emerged as a class of major regulators of genomic functions. Here, we have described some examples of known as well as novel lncRNAs that have been implicated in the progression of the aging process and age-related diseases. This may further stimulate research on noncoding RNAs and the aging process.

  13. Long noncoding RNAs in aging and age-related diseases.

    PubMed

    Kour, Sukhleen; Rath, Pramod C

    2016-03-01

    Aging is the universal, intrinsic, genetically-controlled, evolutionarily-conserved and time-dependent intricate biological process characterised by the cumulative decline in the physiological functions and their coordination in an organism after the attainment of adulthood resulting in the imbalance of neurological, immunological and metabolic functions of the body. Various biological processes and mechanisms along with altered levels of mRNAs and proteins have been reported to be involved in the progression of aging. It is one of the major risk factors in the patho-physiology of various diseases and disorders. Recently, the discovery of pervasive transcription of a vast pool of heterogeneous regulatory noncoding RNAs (ncRNAs), including small ncRNAs (sncRNAs) and long ncRNAs (lncRNAs), in the mammalian genome have provided an alternative way to study and explore the missing links in the aging process, its mechanism(s) and related diseases in a whole new dimension. The involvement of small noncoding RNAs in aging and age-related diseases have been extensively studied and recently reviewed. However, lncRNAs, whose function is far less explored in relation to aging, have emerged as a class of major regulators of genomic functions. Here, we have described some examples of known as well as novel lncRNAs that have been implicated in the progression of the aging process and age-related diseases. This may further stimulate research on noncoding RNAs and the aging process. PMID:26655093

  14. Relation of neuropathology with cognitive decline among older persons without dementia

    PubMed Central

    Boyle, Patricia A.; Yu, Lei; Wilson, Robert S.; Schneider, Julie A.; Bennett, David A.

    2013-01-01

    Objective: Although it is now widely accepted that dementia has a long preclinical phase during which neuropathology accumulates and cognition declines, little is known about the relation of neuropathology with the longitudinal rate of change in cognition among older persons without dementia. We quantified the burden of the neuropathologies of the three most common causes of dementia [i.e., Alzheimer’s disease (AD), cerebrovascular disease (CVD), and Lewy body disease (LBD)] and examined their relation with cognitive decline in a large cohort of persons without dementia proximate to death. Methods: A total of 467 deceased participants without dementia from two longitudinal clinical-pathologic studies, Rush Memory and Aging Project and Religious Orders Study, completed a mean of 7 annual evaluations including 17 cognitive tests. Neuropathologic examinations provided quantitative measures of AD (i.e., amyloid load, tangle density), CVD (i.e., macroscopic infarcts, microinfarcts), and neocortical Lewy bodies. Random coefficient models were used to examine the relation of the neuropathologies with rates of global cognitive decline as well as decline in four specific cognitive systems. Results: At autopsy, 82% of persons without dementia had amyloid, 100% had tangles, 29% had macroscopic infarcts, 25% had microinfarcts, and 6% had neocortical Lewy bodies. Global cognition declined a mean of 0.034 unit per year (SE = 0.003, p < 0.001). In separate analyses, amyloid, tangles (p-values <0.001) and neocortical Lewy bodies (p = 0.015) were associated with an increased rate of global cognitive decline; macroscopic infarcts and microinfarcts were not. Further, when analyzed simultaneously, amyloid, tangles, and neocortical Lewy bodies remained associated with global cognitive decline (p-values <0.024). Finally, measures of AD were associated with decline in three of four systems, including episodic memory (i.e., tangles), semantic memory (i.e., amyloid and tangles), and

  15. Melatonin improves age-induced fertility decline and attenuates ovarian mitochondrial oxidative stress in mice

    PubMed Central

    Song, Chao; Peng, Wei; Yin, Songna; Zhao, Jiamin; Fu, Beibei; Zhang, Jingcheng; Mao, Tingchao; Wu, Haibo; Zhang, Yong

    2016-01-01

    Increasing evidence shows that melatonin protected against age-related mitochondrial oxidative damage. However, the protective effects of melatonin against ovarian aging has not been explored. Young Kunming females (aged 2–3 months) were fed with melatonin added to drinking water for 6 or 12 months (mo). We found that long-term (12 mo) melatonin treatment significantly reduced ovarian aging, as indicated by substantial increases in litter size, pool of follicles, and telomere length as well as oocyte quantity and quality. Melatonin treatment suppressed ovarian mitochondrial oxidative damage by decreasing mitochondrial reactive oxygen species (mROS) generation, inhibiting apoptosis, repressing collapse of mitochondrial membrane potential and preserving respiratory chain complex activities. Female mice fed with melatonin had enhanced mitochondrial antioxidant activities, thus reducing the risk of mitochondrial oxidative damage cause by free radicals. Notably, melatonin treatment enhanced SIRT3 activity but not the protein expression level, and increased the binding affinity of FoxO3a to the promoters of both superoxide dismutase 2 (SOD2) and catalase (CAT). In conclusion, melatonin exerted protection against aging-induced fertility decline and maintenance of mitochondrial redox balance. PMID:27731402

  16. Age-associated decline in mitochondrial respiration and electron transport in Drosophila melanogaster

    PubMed Central

    2005-01-01

    The principal objective of the present study was to identify specific alterations in mitochondrial respiratory functions during the aging process. Respiration rates and the activities of electron transport chain complexes were measured at various ages in mitochondria isolated from thoraces of the fruit fly, Drosophila melanogaster, which consist primarily of flight muscles. The rates of state 3 respiration (ADP-stimulated), RCRs (respiratory control ratios) and uncoupled respiration rates decreased significantly as a function of age, using either NAD+- or FAD-linked substrates; however, there were no differences in state 4 respiration (ADP-depleted) rates. There was also a significant age-related decline in the activity of cytochrome c oxidase (complex IV), but not of the other mitochondrial oxidoreductases examined. Exposure of mitochondria isolated from young flies to low doses of KCN or NaAz (sodium azide), complex IV inhibitors, decreased cytochrome c oxidase activity and increased the production of H2O2. Collectively, these results support the hypothesis that impairment of mitochondrial respiration may be a causal factor in the aging process, and that such impairment may result from and contribute to increased H2O2 production in vivo. PMID:15853766

  17. Physical activity and inflammation: effects on gray-matter volume and cognitive decline in aging.

    PubMed

    Papenberg, Goran; Ferencz, Beata; Mangialasche, Francesca; Mecocci, Patrizia; Cecchetti, Roberta; Kalpouzos, Grégoria; Fratiglioni, Laura; Bäckman, Lars

    2016-10-01

    Physical activity has been positively associated with gray-matter integrity. In contrast, pro-inflammatory cytokines seem to have negative effects on the aging brain and have been related to dementia. It was investigated whether an inactive lifestyle and high levels of inflammation resulted in smaller gray-matter volumes and predicted cognitive decline across 6 years in a population-based study of older adults (n = 414). Self-reported physical activity (fitness-enhancing, health-enhancing, inadequate) was linked to gray-matter volume, such that individuals with inadequate physical activity had the least gray matter. There were no overall associations between different pro-and anti-inflammatory markers (IL-1β, IL-6, IL-10, IL-12p40, IL-12p70, G-CSF, and TNF-α) and gray-matter integrity. However, persons with inadequate activity and high levels of the pro-inflammatory marker IL-12p40 had smaller volumes of lateral prefrontal cortex and hippocampus and declined more on the Mini-Mental State Examination test over 6 years compared with physically inactive individuals with low levels of IL-12p40 and to more physically active persons, irrespective of their levels of IL-12p40. These patterns of data suggested that inflammation was particularly detrimental in inactive older adults and may exacerbate the negative effects of physical inactivity on brain and cognition in old age. Hum Brain Mapp 37:3462-3473, 2016. © 2016 Wiley Periodicals, Inc.

  18. The SAT Score Decline: A Summary of Related Research.

    ERIC Educational Resources Information Center

    Breland, Hunter M.

    The available evidence pertaining to the decline in scores on the Scholastic Aptitude Test (SAT) and the American College Testing Program (ACT) is reviewed in terms of: the test, the test-taking population, the college bound population, the schools, and societal factors. The SAT score decline is described in both graphic and tabular form, and…

  19. Steeper declines in forest photosynthesis than respiration explain age-driven decreases in forest growth.

    PubMed

    Tang, Jianwu; Luyssaert, Sebastiaan; Richardson, Andrew D; Kutsch, Werner; Janssens, Ivan A

    2014-06-17

    The traditional view of forest dynamics originated by Kira and Shidei [Kira T, Shidei T (1967) Jap J Ecol 17:70-87] and Odum [Odum EP (1969) Science 164(3877):262-270] suggests a decline in net primary productivity (NPP) in aging forests due to stabilized gross primary productivity (GPP) and continuously increased autotrophic respiration (Ra). The validity of these trends in GPP and Ra is, however, very difficult to test because of the lack of long-term ecosystem-scale field observations of both GPP and Ra. Ryan and colleagues [Ryan MG, Binkley D, Fownes JH (1997) Ad Ecol Res 27:213-262] have proposed an alternative hypothesis drawn from site-specific results that aboveground respiration and belowground allocation decreased in aging forests. Here, we analyzed data from a recently assembled global database of carbon fluxes and show that the classical view of the mechanisms underlying the age-driven decline in forest NPP is incorrect and thus support Ryan's alternative hypothesis. Our results substantiate the age-driven decline in NPP, but in contrast to the traditional view, both GPP and Ra decline in aging boreal and temperate forests. We find that the decline in NPP in aging forests is primarily driven by GPP, which decreases more rapidly with increasing age than Ra does, but the ratio of NPP/GPP remains approximately constant within a biome. Our analytical models describing forest succession suggest that dynamic forest ecosystem models that follow the traditional paradigm need to be revisited.

  20. Declining plant nitrogen supply and carbon accumulation in ageing primary boreal forest ecosystems

    NASA Astrophysics Data System (ADS)

    Högberg, Mona N.; Yarwood, Stephanie A.; Trumbore, Susan; Högberg, Peter

    2016-04-01

    Boreal forest soils are commonly characterized by a low plant nitrogen (N) supply. A high tree below-ground allocation of carbon (C) to roots and soil microorganisms in response to the shortage of N may lead to high microbial immobilisation of N, thus aggravating the N limitation. We studied the N supply at a Swedish boreal forest ecosystem chronosequence created by new land rising out of the sea due to iso-static rebound. The youngest soils develop with meadows by the coast, followed by a zone of dinitrogen fixing alder trees, and primary boreal conifer forest on ground up to 560 years old. With increasing ecosystem age, the proportion of microbial C out of the total soil C pool from the youngest to the oldest coniferous ecosystem was constant (c. 1-1.5%), whereas immobilised N (microbial N out of total soil N) increased and approached the levels commonly observed in similar boreal coniferous forests (c. 6-7 %), whereas gross N mineralization declined. Simultaneously, plant foliar N % decreased and the natural abundance of N-15 in the soil increased. More specifically, the difference in N-15 between plant foliage and soil increased, which is related to greater retention of N-15 relative to N-14 by ectomycorrhizal fungi as N is taken up from the soil and some N is transferred to the plant host. In the conifer forest, where these changes were greatest, we found increased fungal biomass in the F- and H-horizons of the mor-layer, in which ectomycorrhizal fungi are known to dominate (the uppermost horizon with litter and moss is dominated by saprotrophic fungi). Hence, we propose that the decreasing N supply to the plants and the subsequent decline in plant production in ageing boreal forests is linked to high tree belowground C allocation to C limited ectomycorrhizal fungi (and other soil microorganisms), a strong sink for available soil N. Data on organic matter C-14 suggested that the largest input of recently fixed plant C occurred in the younger coniferous forest

  1. Preclinical Magnetic Resonance Imaging and Spectroscopy Studies of Memory, Aging, and Cognitive Decline

    PubMed Central

    Febo, Marcelo; Foster, Thomas C.

    2016-01-01

    Neuroimaging provides for non-invasive evaluation of brain structure and activity and has been employed to suggest possible mechanisms for cognitive aging in humans. However, these imaging procedures have limits in terms of defining cellular and molecular mechanisms. In contrast, investigations of cognitive aging in animal models have mostly utilized techniques that have offered insight on synaptic, cellular, genetic, and epigenetic mechanisms affecting memory. Studies employing magnetic resonance imaging and spectroscopy (MRI and MRS, respectively) in animal models have emerged as an integrative set of techniques bridging localized cellular/molecular phenomenon and broader in vivo neural network alterations. MRI methods are remarkably suited to longitudinal tracking of cognitive function over extended periods permitting examination of the trajectory of structural or activity related changes. Combined with molecular and electrophysiological tools to selectively drive activity within specific brain regions, recent studies have begun to unlock the meaning of fMRI signals in terms of the role of neural plasticity and types of neural activity that generate the signals. The techniques provide a unique opportunity to causally determine how memory-relevant synaptic activity is processed and how memories may be distributed or reconsolidated over time. The present review summarizes research employing animal MRI and MRS in the study of brain function, structure, and biochemistry, with a particular focus on age-related cognitive decline. PMID:27468264

  2. Preclinical Magnetic Resonance Imaging and Spectroscopy Studies of Memory, Aging, and Cognitive Decline.

    PubMed

    Febo, Marcelo; Foster, Thomas C

    2016-01-01

    Neuroimaging provides for non-invasive evaluation of brain structure and activity and has been employed to suggest possible mechanisms for cognitive aging in humans. However, these imaging procedures have limits in terms of defining cellular and molecular mechanisms. In contrast, investigations of cognitive aging in animal models have mostly utilized techniques that have offered insight on synaptic, cellular, genetic, and epigenetic mechanisms affecting memory. Studies employing magnetic resonance imaging and spectroscopy (MRI and MRS, respectively) in animal models have emerged as an integrative set of techniques bridging localized cellular/molecular phenomenon and broader in vivo neural network alterations. MRI methods are remarkably suited to longitudinal tracking of cognitive function over extended periods permitting examination of the trajectory of structural or activity related changes. Combined with molecular and electrophysiological tools to selectively drive activity within specific brain regions, recent studies have begun to unlock the meaning of fMRI signals in terms of the role of neural plasticity and types of neural activity that generate the signals. The techniques provide a unique opportunity to causally determine how memory-relevant synaptic activity is processed and how memories may be distributed or reconsolidated over time. The present review summarizes research employing animal MRI and MRS in the study of brain function, structure, and biochemistry, with a particular focus on age-related cognitive decline. PMID:27468264

  3. 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

  4. Forest stand structure, productivity, and age mediate climatic effects on aspen decline.

    PubMed

    Bell, David M; Bradford, John B; Lauenroth, William K

    2014-08-01

    Because forest stand structure, age, and productivity can mediate the impacts of climate on quaking aspen (Populus tremuloides) mortality, ignoring stand-scale factors limits inference on the drivers of recent sudden aspen decline. Using the proportion of aspen trees that were dead as an index of recent mortality at 841 forest inventory plots, we examined the relationship of this mortality index to forest structure and climate in the Rocky Mountains and Intermountain Western United States. We found that forest structure explained most of the patterns in mortality indices, but that variation in growing-season vapor pressure deficit and winter precipitation over the last 20 years was important. Mortality index sensitivity to precipitation was highest in forests where aspen exhibited high densities, relative basal areas, quadratic mean diameters, and productivities, whereas sensitivity to vapor pressure deficit was highest in young forest stands. These results indicate that the effects of drought on mortality may be mediated by forest stand development, competition with encroaching conifers, and physiological vulnerabilities of large trees to drought. By examining mortality index responses to both forest structure and climate, we show that forest succession cannot be ignored in studies attempting to understand the causes and consequences of sudden aspen decline.

  5. Forest stand structure, productivity, and age mediate climatic effects on aspen decline.

    PubMed

    Bell, David M; Bradford, John B; Lauenroth, William K

    2014-08-01

    Because forest stand structure, age, and productivity can mediate the impacts of climate on quaking aspen (Populus tremuloides) mortality, ignoring stand-scale factors limits inference on the drivers of recent sudden aspen decline. Using the proportion of aspen trees that were dead as an index of recent mortality at 841 forest inventory plots, we examined the relationship of this mortality index to forest structure and climate in the Rocky Mountains and Intermountain Western United States. We found that forest structure explained most of the patterns in mortality indices, but that variation in growing-season vapor pressure deficit and winter precipitation over the last 20 years was important. Mortality index sensitivity to precipitation was highest in forests where aspen exhibited high densities, relative basal areas, quadratic mean diameters, and productivities, whereas sensitivity to vapor pressure deficit was highest in young forest stands. These results indicate that the effects of drought on mortality may be mediated by forest stand development, competition with encroaching conifers, and physiological vulnerabilities of large trees to drought. By examining mortality index responses to both forest structure and climate, we show that forest succession cannot be ignored in studies attempting to understand the causes and consequences of sudden aspen decline. PMID:25230455

  6. Forest stand structure, productivity, and age mediate climatic effects on aspen decline

    USGS Publications Warehouse

    Bell, David M.; Bradford, John B.; Lauenroth, William K.

    2014-01-01

    Because forest stand structure, age, and productivity can mediate the impacts of climate on quaking aspen (Populus tremuloides) mortality, ignoring stand-scale factors limits inference on the drivers of recent sudden aspen decline. Using the proportion of aspen trees that were dead as an index of recent mortality at 841 forest inventory plots, we examined the relationship of this mortality index to forest structure and climate in the Rocky Mountains and Intermountain Western United States. We found that forest structure explained most of the patterns in mortality indices, but that variation in growing-season vapor pressure deficit and winter precipitation over the last 20 years was important. Mortality index sensitivity to precipitation was highest in forests where aspen exhibited high densities, relative basal areas, quadratic mean diameters, and productivities, whereas sensitivity to vapor pressure deficit was highest in young forest stands. These results indicate that the effects of drought on mortality may be mediated by forest stand development, competition with encroaching conifers, and physiological vulnerabilities of large trees to drought. By examining mortality index responses to both forest structure and climate, we show that forest succession cannot be ignored in studies attempting to understand the causes and consequences of sudden aspen decline.

  7. Recent decline in prostate cancer incidence in the United States, by age, stage, and Gleason score.

    PubMed

    Herget, Kimberly A; Patel, Darshan P; Hanson, Heidi A; Sweeney, Carol; Lowrance, William T

    2016-01-01

    Prostate cancer incidence is sensitive to screening practices, however the impact of recent screening recommendations from the United States Preventative Services Task Force on prostate cancer incidence by age, stage, race, and Gleason score is unknown. This study described the timing and magnitude of changes in prostate cancer incidence trends in the United States by month of diagnosis, and evaluated trends by age, Gleason score, and stage at diagnosis. We analyzed prostate cancer incidence trends using Surveillance, Epidemiology, and End Results (SEER) program data for men diagnosed with invasive prostate cancer from 2007 through 2012. JoinPoint analysis was used to detect changes in the rate of annual percent change (APC) in prostate cancer incidence for all diagnoses and by age, Gleason score, race, and stage. Prostate cancer incidence declined at an estimated -19.6% APC beginning May 2011. This decline was observed in all age groups. Low-grade tumors (Gleason score ≤6) showed a steeper decline (-29.1% APC) than high-grade tumors (Gleason score 8-10: -10.8% APC). Only stage I/II and stage III tumors saw declines (-24.2% and -16.7% APC, respectively). A sharp decline in prostate cancer incidence began before release of the United States Preventative Services Task Force October 2011 draft and May 2012 final screening recommendation. The greatest change occurred with incidence of low-grade tumors, although there is concern that some high-grade tumors may now go undetected.

  8. Diet and cognitive decline at middle age: the role of antioxidants.

    PubMed

    Nooyens, Astrid C J; Milder, Ivon E J; van Gelder, Boukje M; Bueno-de-Mesquita, H Bas; van Boxtel, Martin P J; Verschuren, W M Monique

    2015-05-14

    To assess the relationship between dietary intake of antioxidants (vitamin C, vitamin E, β-carotene, lutein, flavonoids and lignans) and cognitive decline at middle age, analyses were performed on data from the population based Doetinchem Cohort Study. Habitual diet and cognitive function were assessed twice with a 5-year interval in 2613 persons aged 43-70 year at baseline (1995-2002). Diet was assessed with a validated 178-item semi-quantitative FFQ. Cognitive function was assessed with a neuropsychological test battery, consisting of the 15 Words Learning Test, the Stroop Test, the Word Fluency test, and the Letter Digit Substitution Test. Scores on global cognitive function, memory, processing speed, and cognitive flexibility were calculated. In regression analyses, quintiles of antioxidant intake were associated with change in cognitive domain scores. Results showed that higher lignan intake was linearly associated with less decline in global cognitive function (P= 0.01), memory (P< 0.01) and processing speed (P= 0.04), with about two times less declines in the highest v. the lowest quintile. In the lowest quintile of vitamin E intake, decline in memory was twice as fast as in all higher quintiles (P< 0.01). Global cognitive decline in the highest lutein intake group was greater than in the lowest intake group (P< 0.05). Higher flavonoid intake was associated with greater decline in cognitive flexibility (P for trend = 0.04). Intakes of other antioxidants were not associated with cognitive decline. We conclude that within the range of a habitual dietary intake, higher intake of lignans is associated with less cognitive decline at middle age.

  9. The two faces of selective memory retrieval: Earlier decline of the beneficial than the detrimental effect with older age.

    PubMed

    Aslan, Alp; Schlichting, Andreas; John, Thomas; Bäuml, Karl-Heinz T

    2015-12-01

    Recent work with young adults has shown that, depending on study context access, selective memory retrieval can both impair and improve recall of other memories (Bäuml & Samenieh, 2010). Here, we investigated the 2 opposing effects of selective retrieval in older age. In Experiment 1, we examined 64 younger (20-35 years) and 64 older participants (above 60 years), and manipulated study context access using list-method directed forgetting. Whereas both age groups showed a detrimental effect of selective retrieval on to-be-remembered items, only younger but not older adults showed a beneficial effect on to-be-forgotten items. In Experiment 2, we examined 112 participants from a relatively wide age range (40-85 years), and manipulated study context access by varying the retention interval between study and test. Overall, a detrimental effect of selective retrieval arose when the retention interval was relatively short, but a beneficial effect when the retention interval was prolonged. Critically, the size of the beneficial but not the detrimental effect of retrieval decreased with age and this age-related decline was mediated by individuals' working memory capacity, as measured by the complex operation span task. Together, the results suggest an age-related dissociation in retrieval dynamics, indicating an earlier decline of the beneficial than the detrimental effect of selective retrieval with older age. PMID:26652723

  10. Lifelong bilingualism contributes to cognitive reserve against white matter integrity declines in aging.

    PubMed

    Gold, Brian T; Johnson, Nathan F; Powell, David K

    2013-11-01

    Recent evidence suggests that lifelong bilingualism may contribute to cognitive reserve (CR) in normal aging. However, there is currently no neuroimaging evidence to suggest that lifelong bilinguals can retain normal cognitive functioning in the face of age-related neurodegeneration. Here we explored this issue by comparing white matter (WM) integrity and gray matter (GM) volumetric patterns of older adult lifelong bilinguals (N=20) and monolinguals (N=20). The groups were matched on a range of relevant cognitive test scores and on the established CR variables of education, socioeconomic status and intelligence. Participants underwent high-resolution structural imaging for assessment of GM volume and diffusion tensor imaging (DTI) for assessment of WM integrity. Results indicated significantly lower microstructural integrity in the bilingual group in several WM tracts. In particular, compared to their monolingual peers, the bilingual group showed lower fractional anisotropy and/or higher radial diffusivity in the inferior longitudinal fasciculus/inferior fronto-occipital fasciculus bilaterally, the fornix, and multiple portions of the corpus callosum. There were no group differences in GM volume. Our results suggest that lifelong bilingualism contributes to CR against WM integrity declines in aging.

  11. Age-related cataract.

    PubMed

    Asbell, Penny A; Dualan, Ivo; Mindel, Joel; Brocks, Dan; Ahmad, Mehdi; Epstein, Seth

    Cataract, opacification of the lens, is one of the commonest causes of loss of useful vision, with an estimated 16 million people worldwide affected. Several risk factors have been identified in addition to increasing age--genetic composition, exposure to ultraviolet light, and diabetes. However, no method to halt the formation of a cataractous lens has been shown to be effective. Nevertheless, advances in surgical removal of cataracts, including small-incision surgery, use of viscoelastics, and the development of intraocular lenses, have made treatment very effective and visual recovery rapid in most cases. Despite these advances, cataract continues to be a leading public-health issue that will grow in importance as the population increases and life expectancy is extended worldwide. PMID:15708105

  12. Evidence of disease-related amphibian decline in Colorado

    USGS Publications Warehouse

    Muths, Erin; Corn, Paul Stephen; Pessier, Allan P.; Green, D. Earl

    2003-01-01

    The recent discovery of a pathogenic fungus (Batrachochytrium dendrobatidis) associated with declines of frogs in the American and Australian tropics, suggests that at least the proximate cause, may be known for many previously unexplained amphibian declines. We have monitored boreal toads in Colorado since 1991 at four sites using capturea??recapture of adults and counts of egg masses to examine the dynamics of this metapopulation. Numbers of male toads declined in 1996 and 1999 with annual survival rate averaging 78% from 1991 to 1994, 45% in 1995 and 3% between 1998 and 1999. Numbers of egg masses also declined. An etiological diagnosis of chytridiomycosis consistent with infections by the genus Batrachochytrium was made in six wild adult toads. Characteristic histomorphological features (i.e. intracellular location, shape of thalli, presence of discharge tubes and rhizoids) of chytrid organisms, and host tissue response (acanthosis and hyperkeratosis) were observed in individual toads. These characteristics were indistinguishable from previously reported mortality events associated with chytrid fungus. We also observed epizootiological features consistent with mortality events associated with chytrid fungus: an increase in the ratio of female:male toads captured, an apparent spread of mortalities within the metapopulation and mortalities restricted to post metamorphic animals. Eleven years of population data suggest that this metapopulation of toads is in danger of extinction, pathological and epizootiological evidence indicates that B. dendrobatidis has played a proximate role in this process

  13. Cognitive Decline and Oral Health in Middle-aged Adults in the ARIC Study

    PubMed Central

    Naorungroj, S.; Slade, G.D.; Beck, J.D.; Mosley, T.H.; Gottesman, R.F.; Alonso, A.; Heiss, G.

    2013-01-01

    Even before dementia becomes apparent, cognitive decline may contribute to deterioration in oral health. This cohort study of middle-aged adults evaluated associations of six-year change in cognitive function with oral health behaviors and conditions in the Atherosclerosis Risk in Communities (ARIC) study. Cognitive function was measured at study visits in 1990-1992 and 1996-1998 with three tests: (a) Delayed Word Recall (DWR), (b) Digit Symbol Substitution (DSS), and (c) Word Fluency (WF). Cognitive decline scores were computed as ‘studentized’ residuals of 1996-1998 scores regressed against 1990-1992 scores. In 1996-1998, 10,050 participants answered dental screening questions, and 5,878 of 8,782 dentate participants received a comprehensive oral examination. Multiple regression models used cognitive change to predict oral health behaviors and conditions with adjustment for covariates. In the fully adjusted models, greater decline in all three measures of cognitive function was associated with increased odds of complete tooth loss. Greater decline in DSS and WF scores was associated with infrequent toothbrushing. Decline in WF scores was also associated with higher plaque levels. In these middle-aged adults, six-year cognitive decline was modestly associated with less frequent toothbrushing, plaque deposit, and greater odds of edentulism, but not with other oral behaviors or diseases. PMID:23872988

  14. sAPPα Rescues Age-Linked Decline in Neural Progenitor Cell Proliferation

    PubMed Central

    Demars, Michael P.; Hollands, Carolyn; Zhao, Kai Da (Tommy); Lazarov, Orly

    2013-01-01

    Neurogenesis is thought to play a role in cognitive function and hippocampal plasticity. Previous studies suggest that neurogenesis declines with aging. However, the onset and mechanism of declined neurogenesis are not fully elucidated. Here we show that the major decline in neurogenesis takes place during adulthood, prior to aging. Decline in neurogenesis takes place in both the subgranular layer of the dentate gyrus and in the subventricular zone, and is primarily due to reduced number of fast-proliferating neural progenitor cells. Importantly, this decline can be rescued by intraventricular injection of recombinant soluble amyloid precursor protein (sAPPα) that regulates neural progenitor cell proliferation in the adult brain. The counterpart sAPPβ, a product of the amyloidogenic cleavage pathway of APP, fails to exhibit a proliferative effect in vitro and in vivo, in equimolar concentration to sAPPα. These observations suggest that adulthood is an appropriate time window for an intervention that upregulates neurogenesis, such as enhancement of sAPPα levels, for the prevention of declining brain plasticity and cognitive function. PMID:23683827

  15. Cognitive decline and oral health in middle-aged adults in the ARIC study.

    PubMed

    Naorungroj, S; Slade, G D; Beck, J D; Mosley, T H; Gottesman, R F; Alonso, A; Heiss, G

    2013-09-01

    Even before dementia becomes apparent, cognitive decline may contribute to deterioration in oral health. This cohort study of middle-aged adults evaluated associations of six-year change in cognitive function with oral health behaviors and conditions in the Atherosclerosis Risk in Communities (ARIC) study. Cognitive function was measured at study visits in 1990-1992 and 1996-1998 with three tests: (a) Delayed Word Recall (DWR), (b) Digit Symbol Substitution (DSS), and (c) Word Fluency (WF). Cognitive decline scores were computed as 'studentized' residuals of 1996-1998 scores regressed against 1990-1992 scores. In 1996-1998, 10,050 participants answered dental screening questions, and 5,878 of 8,782 dentate participants received a comprehensive oral examination. Multiple regression models used cognitive change to predict oral health behaviors and conditions with adjustment for covariates. In the fully adjusted models, greater decline in all three measures of cognitive function was associated with increased odds of complete tooth loss. Greater decline in DSS and WF scores was associated with infrequent toothbrushing. Decline in WF scores was also associated with higher plaque levels. In these middle-aged adults, six-year cognitive decline was modestly associated with less frequent toothbrushing, plaque deposit, and greater odds of edentulism, but not with other oral behaviors or diseases. PMID:23872988

  16. Physical activity and inflammation: effects on gray-matter volume and cognitive decline in aging.

    PubMed

    Papenberg, Goran; Ferencz, Beata; Mangialasche, Francesca; Mecocci, Patrizia; Cecchetti, Roberta; Kalpouzos, Grégoria; Fratiglioni, Laura; Bäckman, Lars

    2016-10-01

    Physical activity has been positively associated with gray-matter integrity. In contrast, pro-inflammatory cytokines seem to have negative effects on the aging brain and have been related to dementia. It was investigated whether an inactive lifestyle and high levels of inflammation resulted in smaller gray-matter volumes and predicted cognitive decline across 6 years in a population-based study of older adults (n = 414). Self-reported physical activity (fitness-enhancing, health-enhancing, inadequate) was linked to gray-matter volume, such that individuals with inadequate physical activity had the least gray matter. There were no overall associations between different pro-and anti-inflammatory markers (IL-1β, IL-6, IL-10, IL-12p40, IL-12p70, G-CSF, and TNF-α) and gray-matter integrity. However, persons with inadequate activity and high levels of the pro-inflammatory marker IL-12p40 had smaller volumes of lateral prefrontal cortex and hippocampus and declined more on the Mini-Mental State Examination test over 6 years compared with physically inactive individuals with low levels of IL-12p40 and to more physically active persons, irrespective of their levels of IL-12p40. These patterns of data suggested that inflammation was particularly detrimental in inactive older adults and may exacerbate the negative effects of physical inactivity on brain and cognition in old age. Hum Brain Mapp 37:3462-3473, 2016. © 2016 Wiley Periodicals, Inc. PMID:27159568

  17. Declines with Age in Childhood Asthma Symptoms and Health Care Use. An Adjustment for Evaluations

    PubMed Central

    Ko, Yi-An; Clark, Noreen M.

    2014-01-01

    Rationale: Asthma is a variable condition with an apparent tendency for a natural decline in asthma symptoms and health care use occurring as children age. As a result, asthma interventions using a pre-post design may overestimate the intervention effect when no proper control group is available. Objectives: Investigate patterns of natural decline over time with increasing age in asthma symptoms and health care use of children. Develop a statistical procedure that enables adjustment that accounts for expected declines in these outcomes and is useable when intervention evaluations must rely solely on pre-post data. Methods: Mixed-effects models with mixture distributions were used to describe the pattern of symptoms and health care use in 3,021 children aged 2 to 15 years in a combined sample from three controlled trials. An adaptive least squares estimation was used to account for overestimation of intervention effects and make adjustments for pre-post only data. Termed “Adjustment for Natural Declines in Asthma Outcomes (ANDAO),” the adjustment method uses bootstrap sampling to create control cohorts comparable to subjects in the intervention study from existing control subjects. ANDAO accounts for expected declines in outcomes and is beneficial when intervention evaluations must rely solely on pre-post data. Measurements and Main Results: Children under 10 years of age experienced 18% (95% confidence interval, 15–21%) fewer symptom days and 28% (95% confidence interval, 24–32%) fewer symptom nights with each additional year of age. The decline was less than 10% after age 10 years, depending on baseline asthma severity. Emergency department visits declined regardless of baseline symptom frequency (P = 0.02). The adjustment method corrected estimates to within 2.4% of true effects through simulations using control cohorts. Conclusions: Because of the declines in symptoms and health care use expected with increasing age of children with asthma, pre

  18. Confidant Relations of the Aged.

    ERIC Educational Resources Information Center

    Tigges, Leann M.; And Others

    The confidant relationship is a qualitatively distinct dimension of the emotional support system of the aged, yet the composition of the confidant network has been largely neglected in research on aging. Persons (N=940) 60 years of age and older were interviewed about their socio-environmental setting. From the enumeration of their relatives,…

  19. Accounting for Recent Declines in Employment Rates among Working-Aged Men and Women with Disabilities.

    ERIC Educational Resources Information Center

    Bound, John; Waidmann, Timothy

    2002-01-01

    During the 1990s, employment rates of people with disabilities fell and the number of working-age people receiving Social Security Disability Insurance (SSDI) benefits increased dramatically, Analysis of Current Population Survey and disability insurance data suggests that growth in the SSDI program accounts for much of the decline in employment…

  20. Replacement Migration: Is It a Solution to Declining and Ageing Populations?

    ERIC Educational Resources Information Center

    United Nations, New York, NY. Dept. of Economic and Social Affairs.

    The United Nations (UN) Population Division monitors fertility, mortality, and migration trends for all countries as a basis for producing the official UN population estimates and projections. Among recent demographic trends, two are prominent: (1) population decline and (2) population aging. Focusing on these two critical trends, a study…

  1. Declines with Age in Childhood Asthma Symptoms and Health Care Use: An Adjustment for Evaluations

    ERIC Educational Resources Information Center

    Ko, Yi-An; Song, Peter X. K.; Clark, Noreen M.

    2014-01-01

    Rationale: Asthma is a variable condition with an apparent tendency for a natural decline in asthma symptoms and health care use occurring as children age. As a result, asthma interventions using a pre-post design may overestimate the intervention effect when no proper control group is available. Objectives: Investigate patterns of natural decline…

  2. C-reactive protein and genetic variants and cognitive decline in old age: The PROSPER Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plasma concentrations of C-reactive protein (CRP), a marker of chronic inflammation, have been associated with cognitive impairment in old age. However, it is unknown whether CRP is causally linked to cognitive decline. Within the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) tri...

  3. Role of blood volume in the age-associated decline in peak oxygen uptake in humans.

    PubMed

    Ito, T; Takamata, A; Yaegashi, K; Itoh, T; Yoshida, T; Kawabata, T; Kimura, M; Morimoto, T

    2001-10-01

    It has been reported that maximal oxygen uptake (VO(2 max)) is linearly correlated with blood volume (BV) in young people and that there is a reduction in VO(2 max) with aging. To examine the involvement of BV in the reduction of VO(2 max), we used an incremental cycle ergometer protocol in a semi-recumbent position to determine the relationship between peak oxygen uptake (VO(2 peak)) and BV in older subjects (69.1 +/- 1.0 years; n = 22), then compared that relationship with that in young subjects (22.3 +/- 0.5 years; n = 31). In the present study, VO(2 peak) and BV were significantly lower in the older subjects, compared with those in the young subjects. A linear correlation was demonstrated between the VO(2 peak) and BV in both the older (r = 0.705; p < 0.001) and the young (r = 0.681; p < 0.001) subjects within the groups. However, an analysis of covariance with BV as a covariate revealed that VO(2 peak) at a given BV was smaller in the older subjects than in the young subjects (p < 0.001), i.e., graphically, the regression line determined for the older subjects showed a downward shift. The decreased peak heart rate as a result of aging (153 +/- 3 beats/min in the older vs. 189 +/- 2 beats/min in the young subjects) contributed partly to this downward shift. These results suggest that the BV is an important determinant factor for VO(2 peak), especially within an age group, and that the age-associated decline of VO(2 peak) is also, to a relatively larger degree, because of factors other than BV and heart rate.

  4. Role of body fat distribution in the decline in insulin sensitivity and glucose tolerance with age.

    PubMed

    Coon, P J; Rogus, E M; Drinkwater, D; Muller, D C; Goldberg, A P

    1992-10-01

    The relationships of body composition and physical fitness [maximal aerobic capacity (VO2max)] to the decline in insulin sensitivity with age were examined in healthy older (47-73 yr; n = 36) and young (19-36 yr; n = 13) men. In 18 older men with normal glucose tolerance (OGTT), glucose disposal rates (M) during hyperinsulinemic euglycemic clamps correlated negatively with the waist to hip ratio (WHR; r = -0.77; P < .001) and percent body fat (r = -0.46; P < 0.05) and positively with VO2max (r = 0.54; P < 0.05), but not with age. Similar relationships existed in the 36 older men with a spectrum of OGTT responses; however, only WHR was independently related to M (r2 = 0.32; P < 0.01). In the older men with normal OGTT, M (mean +/- SEM, 7.88 +/- 0.43 mg/kg fat-free mass.min) was not different from that in the young men (8.56 +/- 0.47; P = NS). Furthermore, in older and young men with normal OGTT matched for WHR, percent fat, or VO2max, glucose disposal was comparable at sequential 15-min intervals during the clamp and in its relationship to insulin concentrations at the tissue level (multicompartmental analysis). In contrast, despite higher steady state plasma insulin levels during the clamp, M was significantly lower in the older men with a higher WHR, greater percent fat, lower VO2max, or impaired OGTT. Thus, in healthy older men up to the age of 73 yr, insulin sensitivity and glucose tolerance are affected primarily by the regional body fat distribution, not age, obesity, or VO2max.

  5. Defensive Behavior against Noxious Heat Stimuli Is Declined with Aging Due to Decreased Pain-Associated Gene Expression in Drosophila

    PubMed Central

    Ghimire, Saurav; Kim, Man Su

    2015-01-01

    Aging is defined as a collective process that alters organism’s functional capacity and appearance over the course of life. Apart from an increase in susceptibility to many diseases, aging affects the cellular system that is responsible for decoding painful stimuli. Yet, aging-associated molecular mechanisms of pain perception remains elusive. Using Drosophila, we showed a decrease in temperature tolerance and a reduction in high temperature thermal avoidance with aging. Locomotor activity assay demonstrated that the age-dependent changes in heat nociception did not stem from the general decline in muscular activity. However, we identified pain-related gene expression alteration with aging. We anticipate that our findings would help opening a new window onto developing the optimal pain treatment for the elderly. PMID:25995829

  6. A Role for Identification in the Gradual Decline in the Pleasantness of Flavors With Age

    PubMed Central

    Smith, Eleanor

    2016-01-01

    Objectives: This study investigated a possible role for identification in the decline in flavor pleasantness with age. Methods: Two hundred sixty-four individuals aged from 16 to 85 years tasted 6 flavored drinks of varying identity and ease of identification, and rated each on pleasantness, a range of other characteristics and identified all flavors. Results: Using regression, firstly, pleasantness was inversely associated with age (β = −0.22, p < .01). Secondly, the decline in pleasantness with age was associated with poorer identification (β = 0.30, p < .01), lower perceptions of sweetness (β = 0.01, p < .01), lower strength of flavor (β = 0.00, p = .02), lower familiarity (β = 0.01, p < .01), and a lower frequency of usual drink consumption (β = 0.04, p < .01). Thirdly, improved identification with age was associated with increased drink familiarity (β =< 0.01, p < .01), coloration compared with no color (β = <0.06, p < .01), and correct compared with incorrect coloration (β = <0.27, p < .01). Discussion: These findings demonstrate a clear role for identification in the decline in flavor pleasantness with age. These findings thus provide clear evidence for a cognitive and perceptual element to these hedonic processes. Our findings suggest that likings for flavors in older individuals may be increased/maintained through the use of improved visual cues, easily recognizable foods, and/or identity labels. PMID:25975292

  7. Cognitive decline is associated with reduced surface GluR1 expression in the hippocampus of aged rats.

    PubMed

    Yang, Yuan-Jian; Chen, Hai-Bo; Wei, Bo; Wang, Wei; Zhou, Ping-Liang; Zhan, Jin-Qiong; Hu, Mao-Rong; Yan, Kun; Hu, Bin; Yu, Bin

    2015-03-30

    Individual differences in cognitive aging exist in humans and in rodent populations, yet the underlying mechanisms remain largely unclear. Activity-dependent delivery of GluR1-containing AMPA receptor (AMPARs) plays an essential role in hippocampal synaptic plasticity, learning and memory. We hypothesize that alterations of surface GluR1 expression in the hippocampus might correlate with age-related cognitive decline. To test this hypothesis, the present study evaluated the cognitive function of young adult and aged rats using Morris water maze. After the behavioral test, the surface expression of GluR1 protein in hippocampal CA1 region of rats was determined using Western blotting. The results showed that the surface expression of GluR1 in the hippocampus of aged rats that are cognitively impaired was much lower than that of young adults and aged rats with preserved cognitive abilities. The phosphorylation levels of GluR1 at Ser845 and Ser831 sites, which promote the synaptic delivery of GluR1, were also selectively decreased in the hippocampus of aged-impaired rats. Correlation analysis reveals that greater decrease in surface GluR1 expression was associated with worse behavioral performance. These results suggest that reduced surface GluR1 expression may contribute to cognitive decline that occurs in normal aging, and different pattern of surface GluR1 expression might be responsible for the individual differences in cognitive aging. PMID:25697598

  8. [Fibronectin, aging and related pathologies].

    PubMed

    Labat-Robert, J; Chevalier, X

    1991-01-01

    It could be demonstrated that plasma and tissue fibronectin (FN) increase with age. Some age dependent diseases as diabetes, osteoarthritis and Werner syndrome produce also an increase of tissue fibronectin biosynthesis. Plasma fibronectin decreases in diabetes and in breast cancer. Alternative splicing of the FN gene appears also to vary with age and in some related pathologies. Nutritional status and UV light also influence FN biosynthesis. It appears therefore that the determination of plasma FN and its isoforms as well as the study of tissue FN may be of interest for the study of chronological aging and related pathologies. PMID:1835421

  9. Biphasic Decline of β-Cell Function with Age in Euglycemic Non-Obese Diabetic (NOD) Mice Parallels Diabetes Onset

    PubMed Central

    Cechin, Sirlene R.; Lopez-Ocejo, Omar; Karpinsky-Semper, Darla; Buchwald, Peter

    2015-01-01

    A gradual decline in insulin response is known to precede the onset of type 1 diabetes (T1D). To track age-related changes in the β-cell function of non-obese diabetic (NOD) mice, the most commonly used animal model for T1D, and to establish differences between those who do and do not become hyperglycemic, we performed a long-term longitudinal oral glucose tolerance test (OGTT) study (10–42 weeks) in combination with immunofluorescence imaging of islet morphology and cell proliferation. We observed a clear biphasic decline in insulin secretion (AUC0–30min) even in euglycemic animals. A first phase (10–28 weeks) consisted of a relatively rapid decline and paralleled diabetes development in the same cohort of animals. This was followed by a second phase (29–42 weeks) during which insulin secretion declined much slower while no additional animals became diabetic. Blood glucose profiles showed a corresponding, but less pronounced change: the area under the concentration curve (AUC0–150min) increased with age, and fit with a bilinear model indicated a rate-change in the trendline around 28 weeks. In control NOD scids, no such changes were observed. Islet morphology also changed with age as islets become surrounded by mononuclear infiltrates, and, in all mice, islets with immune cell infiltration around them showed increased β-cell proliferation. In conclusion, insulin secretion declines in a biphasic manner in all NOD mice. This trend, as well as increased β-cell proliferation, is present even in the NODs that never become diabetic, whereas, it is absent in control NOD scid mice. PMID:26099053

  10. Preventive effects of Chlorella on cognitive decline in age-dependent dementia model mice.

    PubMed

    Nakashima, Yuya; Ohsawa, Ikuroh; Konishi, Fumiko; Hasegawa, Takashi; Kumamoto, Shoichiro; Suzuki, Yoshihiko; Ohta, Shigeo

    2009-10-30

    Oxidative stress is one of the major causes of age-dependent memory loss and cognitive decline. Cytotoxic aldehydes are derived from lipid peroxides and their accumulation may be responsible for age-dependent neurodegeneration, including Alzheimer's disease. Since aldehyde dehydrogenases detoxify such aldehydes, we constructed transgenic mice with mitochondrial aldehyde dehydrogenase 2 (ALDH2) activity deficiency (DAL101 mice) as an age-dependent dementia model. This model animal is age-dependently progressed by persistent oxidative stress, and thus enables us to investigate foods that prevent dementia. Since Chlorella, a kind of alga, exhibits various anti-oxidative effects, we investigated whether Chlorella has the potential to prevent age-dependent cognitive impairment. We fed Chlorella to DAL101 mice and investigated its effects on oxidative stress and the progression of cognitive decline using the Morris water-maze and object recognition tests. The diet with Chlorella tended to reduce oxidative stress and significantly prevented the decline of cognitive ability, as shown by both methods. Moreover, consumption of Chlorella decreased the number of activated astrocytes in the DAL101 brain. These findings suggest that the prolonged consumption of Chlorella has the potential to prevent the progression of cognitive impairment.

  11. 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.

  12. Circulating Growth Differentiation Factor 11/8 Levels Decline With Age

    PubMed Central

    Poggioli, Tommaso; Vujic, Ana; Yang, Peiguo; Macias-Trevino, Claudio; Uygur, Aysu; Loffredo, Francesco S.; Pancoast, James R.; Cho, Miook; Goldstein, Jill; Tandias, Rachel M.; Gonzalez, Emilia; Walker, Ryan G.; Thompson, Thomas B.; Wagers, Amy J.; Fong, Yick W.; Lee, Richard T.

    2016-01-01

    Rationale Growth differentiation factor 11 (GDF11) and GDF8 are members of the transforming growth factor-β superfamily sharing 89% protein sequence homology. We have previously shown that circulating GDF11 levels decrease with age in mice. However, a recent study by Egerman et al reported that GDF11/8 levels increase with age in mouse serum. Objective Here, we clarify the direction of change of circulating GDF11/8 levels with age and investigate the effects of GDF11 administration on the murine heart. Methods and Results We validated our previous finding that circulating levels of GDF11/8 decline with age in mice, rats, horses, and sheep. Furthermore, we showed by Western analysis that the apparent age-dependent increase in GDF11 levels, as reported by Egerman et al, is attributable to cross-reactivity of the anti-GDF11 antibody with immunoglobulin, which is known to increase with age. GDF11 administration in mice rapidly activated SMAD2 and SMAD3 signaling in myocardium in vivo and decreased cardiac mass in both young (2-month-old) and old (22-month-old) mice in a dose-dependent manner after only 9 days. Conclusions Our study confirms an age-dependent decline in serum GDF11/8 levels in multiple mammalian species and that exogenous GDF11 rapidly activates SMAD signaling and reduces cardiomyocyte size. Unraveling the molecular basis for the age-dependent decline in GDF11/8 could yield insight into age-dependent cardiac pathologies. PMID:26489925

  13. Symptoms and lung function decline in a middle-aged cohort of males and females in Australia

    PubMed Central

    Abramson, Michael J; Kaushik, Sonia; Benke, Geza P; Borg, Brigitte M; Smith, Catherine L; Dharmage, Shyamali C; Thompson, Bruce R

    2016-01-01

    Background The European Community Respiratory Health Survey is a major international study designed to assess lung health in adults. This Australian follow-up investigated changes in symptoms between sexes and the roles of asthma, smoking, age, sex, height, and change in body mass index (ΔBMI) on lung function decline (LFD), which is a major risk factor for chronic obstructive pulmonary disease (COPD). Methods LFD was measured as the rate of decline over time in FEV1 (mL/year) (ΔFEV1) and FVC (ΔFVC) between 1993 and 2013. Multiple linear regression was used to estimate associations between risk factors and LFD, separately for males and females. Multiple logistic regression was used to assess sex differences and changes in respiratory symptoms over time. Results In Melbourne, 318 subjects (53.8% females) participated. The prevalence of most respiratory symptoms had either remained relatively stable over 20 years or decreased (significantly so for wheeze). The exception was shortness of breath after activity, which had increased. Among the 262 subjects who completed spirometry, current smoking declined from 20.2% to 7.3%. Overall mean (± standard deviation) FEV1 declined by 23.1 (±17.1) and FVC by 22.9 (±20.2) mL/year. Predictors of ΔFEV1 in males were age, maternal smoking, and baseline FEV1; and in females they were age, ΔBMI, baseline FEV1, and pack-years in current smokers. Decline in FVC was predicted by baseline FVC, age, and ΔBMI in both sexes; however, baseline FVC predicted steeper decline in females than males. Conclusion Most respiratory symptoms remained stable or decreased over time in both sexes. Age, baseline lung function, and change in BMI were associated with the rate of decline in both sexes. However, obesity and personal smoking appear to put females at higher risk of LFD than males. Health promotion campaigns should particularly target females to prevent COPD. PMID:27307725

  14. Permanent personhood or meaningful decline? Toward a critical anthropology of successful aging.

    PubMed

    Lamb, Sarah

    2014-04-01

    The current North American successful aging movement offers a particular normative model of how to age well, one tied to specific notions of individualist personhood especially valued in North America emphasizing independence, productivity, self-maintenance, and the individual self as project. This successful aging paradigm, with its various incarnations as active, healthy and productive aging, has received little scrutiny as to its cultural assumptions. Drawing on fieldwork data with elders from both India and the United States, this article offers an analysis of cultural assumptions underlying the North American successful aging paradigm as represented in prevailing popular and scientific discourse on how to age well. Four key themes in this public successful aging discourse are examined: individual agency and control; maintaining productive activity; the value of independence and importance of avoiding dependence; and permanent personhood, a vision of the ideal person as not really aging at all in late life, but rather maintaining the self of one's earlier years. Although the majority of the (Boston-area, well-educated, financially privileged) US elders making up this study, and some of the most cosmopolitan Indians, embrace and are inspired by the ideals of the successful aging movement, others critique the prevailing successful aging model for insufficiently incorporating attention to and acceptance of the human realities of mortality and decline. Ultimately, the article argues that the vision offered by the dominant successful aging paradigm is not only a particular cultural and biopolitical model but, despite its inspirational elements, in some ways a counterproductive one. Successful aging discourse might do well to come to better terms with conditions of human transience and decline, so that not all situations of dependence, debility and even mortality in late life will be viewed and experienced as "failures" in living well.

  15. Oxidative stress induces the decline of brain EPO expression in aging rats.

    PubMed

    Li, Xu; Chen, Yubao; Shao, Siying; Tang, Qing; Chen, Weihai; Chen, Yi; Xu, Xiaoyu

    2016-10-01

    Brain Erythropoietin (EPO), an important neurotrophic factor and neuroprotective factor, was found to be associated with aging. Studies found EPO expression was significantly decreased in the hippocampus of aging rat compared with that of the youth. But mechanisms of the decline of the brain EPO during aging remain unclear. The present study utilized a d-galactose (d-gal)-induced aging model in which the inducement of aging was mainly oxidative injury, to explore underlying mechanisms for the decline of brain EPO in aging rats. d-gal-induced aging rats (2months) were simulated by subcutaneously injecting with d-gal at doses of 50mg·kg(-1), 150mg·kg(-1) and 250mg·kg(-1) daily for 8weeks while the control group received vehicle only. These groups were all compared with the aging rats (24months) which had received no other treatment. The cognitive impairment was assessed using Morris water maze (MWM) in the prepared models, and the amount of β-galactosidase, the lipid peroxidation product malondialdehyde (MDA) level and the superoxide dismutase (SOD) activity in the hippocampus was examined by assay kits. The levels of EPO, EPOR, p-JAK2 and hypoxia-inducible factor-2α (HIF-2α) in the hippocampus were detected by western blot. Additionally, the correlation coefficient between EPO/EPOR expression and MDA level was analyzed. The MWM test showed that compared to control group, the escape latency was significantly extended and the times of crossing the platform was decreased at the doses of 150mg·kg(-1) and 250mg·kg(-1) (p<0.05). Also, the amount of β-galactosidase and the MDA level in the hippocampus were significantly increased but the SOD activity was significantly decreased (p<0.05, 0.01 and 0.01, respectively). Similar to aging rats, the expressions of EPO, EPOR, p-JAK2, and HIF-2αin the brain of d-gal-treated rats were significantly decreased (p<0.05) at 150mg·kg(-1) and 250mg·kg(-1). Interestingly, negative correlations were found between EPOR (r=-0

  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. PMID:20623902

  17. Perception and Cognition in the Ageing Brain: A Brief Review of the Short- and Long-Term Links between Perceptual and Cognitive Decline

    PubMed Central

    Roberts, Katherine L.; Allen, Harriet A.

    2016-01-01

    Ageing is associated with declines in both perception and cognition. We review evidence for an interaction between perceptual and cognitive decline in old age. Impoverished perceptual input can increase the cognitive difficulty of tasks, while changes to cognitive strategies can compensate, to some extent, for impaired perception. While there is strong evidence from cross-sectional studies for a link between sensory acuity and cognitive performance in old age, there is not yet compelling evidence from longitudinal studies to suggest that poor perception causes cognitive decline, nor to demonstrate that correcting sensory impairment can improve cognition in the longer term. Most studies have focused on relatively simple measures of sensory (visual and auditory) acuity, but more complex measures of suprathreshold perceptual processes, such as temporal processing, can show a stronger link with cognition. The reviewed evidence underlines the importance of fully accounting for perceptual deficits when investigating cognitive decline in old age. PMID:26973514

  18. Perception and Cognition in the Ageing Brain: A Brief Review of the Short- and Long-Term Links between Perceptual and Cognitive Decline.

    PubMed

    Roberts, Katherine L; Allen, Harriet A

    2016-01-01

    Ageing is associated with declines in both perception and cognition. We review evidence for an interaction between perceptual and cognitive decline in old age. Impoverished perceptual input can increase the cognitive difficulty of tasks, while changes to cognitive strategies can compensate, to some extent, for impaired perception. While there is strong evidence from cross-sectional studies for a link between sensory acuity and cognitive performance in old age, there is not yet compelling evidence from longitudinal studies to suggest that poor perception causes cognitive decline, nor to demonstrate that correcting sensory impairment can improve cognition in the longer term. Most studies have focused on relatively simple measures of sensory (visual and auditory) acuity, but more complex measures of suprathreshold perceptual processes, such as temporal processing, can show a stronger link with cognition. The reviewed evidence underlines the importance of fully accounting for perceptual deficits when investigating cognitive decline in old age.

  19. Performances on a cognitive theory of mind task: specific decline or general cognitive deficits? Evidence from normal aging.

    PubMed

    Fliss, Rafika; Lemerre, Marion; Mollard, Audrey

    2016-06-01

    Compromised theory of mind (ToM) can be explained either by a failure to implement specific representational capacities (mental state representations) or by more general executive selection demands. In older adult populations, evidence supporting affected executive functioning and cognitive ToM in normal aging are reported. However, links between these two functions remain unclear. In the present paper, we address these shortcomings by using a specific task of ToM and classical executive tasks. We studied, using an original cognitive ToM task, the effect of age on ToM performances, in link with the progressive executive decline. 96 elderly participants were recruited. They were asked to perform a cognitive ToM task, and 5 executive tests (Stroop test and Hayling Sentence Completion Test to appreciate inhibitory process, Trail Making Test and Verbal Fluency for shifting assessment and backward span dedicated to estimate working memory capacity). The results show changes in cognitive ToM performance according to executive demands. Correlational studies indicate a significant relationship between ToM performance and the selected executive measures. Regression analyzes demonstrates that level of vocabulary and age as the best predictors of ToM performance. The results are consistent with the hypothesis that ToM deficits are related to age-related domain-general decline rather than as to a breakdown in specialized representational system. The implications of these findings for the nature of social cognition tests in normal aging are also discussed. PMID:27277154

  20. Performances on a cognitive theory of mind task: specific decline or general cognitive deficits? Evidence from normal aging.

    PubMed

    Fliss, Rafika; Lemerre, Marion; Mollard, Audrey

    2016-06-01

    Compromised theory of mind (ToM) can be explained either by a failure to implement specific representational capacities (mental state representations) or by more general executive selection demands. In older adult populations, evidence supporting affected executive functioning and cognitive ToM in normal aging are reported. However, links between these two functions remain unclear. In the present paper, we address these shortcomings by using a specific task of ToM and classical executive tasks. We studied, using an original cognitive ToM task, the effect of age on ToM performances, in link with the progressive executive decline. 96 elderly participants were recruited. They were asked to perform a cognitive ToM task, and 5 executive tests (Stroop test and Hayling Sentence Completion Test to appreciate inhibitory process, Trail Making Test and Verbal Fluency for shifting assessment and backward span dedicated to estimate working memory capacity). The results show changes in cognitive ToM performance according to executive demands. Correlational studies indicate a significant relationship between ToM performance and the selected executive measures. Regression analyzes demonstrates that level of vocabulary and age as the best predictors of ToM performance. The results are consistent with the hypothesis that ToM deficits are related to age-related domain-general decline rather than as to a breakdown in specialized representational system. The implications of these findings for the nature of social cognition tests in normal aging are also discussed.

  1. Aging and Autophagic Function Influences the Progressive Decline of Adult Drosophila Behaviors

    PubMed Central

    Kotzebue, Roxanne W.; Gonzalez, Arysa; Achal, Madhulika; Barekat, Ayeh; Finley, Kaelyn A.; Sparhawk, Jonathan M.; Robinson, James E.; Herr, Deron R.; Harris, Greg L.; Joiner, William J.; Finley, Kim D.

    2015-01-01

    Multiple neurological disorders are characterized by the abnormal accumulation of protein aggregates and the progressive impairment of complex behaviors. Our Drosophila studies demonstrate that middle-aged wild-type flies (WT, ~4-weeks) exhibit a marked accumulation of neural aggregates that is commensurate with the decline of the autophagy pathway. However, enhancing autophagy via neuronal over-expression of Atg8a (Atg8a-OE) reduces the age-dependent accumulation of aggregates. Here we assess basal locomotor activity profiles for single- and group-housed male and female WT flies and observed that only modest behavioral changes occurred by 4-weeks of age, with the noted exception of group-housed male flies. Male flies in same-sex social groups exhibit a progressive increase in nighttime activity. Infrared videos show aged group-housed males (4-weeks) are engaged in extensive bouts of courtship during periods of darkness, which is partly repressed during lighted conditions. Together, these nighttime courtship behaviors were nearly absent in young WT flies and aged Atg8a-OE flies. Previous studies have indicated a regulatory role for olfaction in male courtship partner choice. Coincidently, the mRNA expression profiles of several olfactory genes decline with age in WT flies; however, they are maintained in age-matched Atg8a-OE flies. Together, these results suggest that middle-aged male flies develop impairments in olfaction, which could contribute to the dysregulation of courtship behaviors during dark time periods. Combined, our results demonstrate that as Drosophila age, they develop early behavior defects that are coordinate with protein aggregate accumulation in the nervous system. In addition, the nighttime activity behavior is preserved when neuronal autophagy is maintained (Atg8a-OE flies). Thus, environmental or genetic factors that modify autophagic capacity could have a positive impact on neuronal aging and complex behaviors. PMID:26182057

  2. Galactic Globular Cluster Relative Ages

    NASA Astrophysics Data System (ADS)

    De Angeli, Francesca; Piotto, Giampaolo; Cassisi, Santi; Busso, Giorgia; Recio-Blanco, Alejandra; Salaris, Maurizio; Aparicio, Antonio; Rosenberg, Alfred

    2005-07-01

    We present accurate relative ages for a sample of 55 Galactic globular clusters. The ages have been obtained by measuring the difference between the horizontal branch and the turnoff in two internally photometrically homogeneous databases. The mutual consistency of the two data sets has been assessed by comparing the ages of 16 globular clusters in common between the two databases. We have also investigated the consistency of our relative age determination within the recent stellar model framework. All clusters with [Fe/H]<-1.7 are found to be old and coeval, with the possible exception of two objects, which are marginally younger. The age dispersion for the metal-poor clusters is 0.6 Gyr (rms), consistent with a null age dispersion. Intermediate-metallicity clusters (-1.7<[Fe/H]<-0.8) are on average 1.5 Gyr younger than the metal-poor ones, with an age dispersion of 1.0 Gyr (rms) and a total age range of ~3 Gyr. About 15% of the intermediate-metallicity clusters are coeval with the oldest clusters. All the clusters with [Fe/H]>-0.8 are ~1 Gyr younger than the most metal-poor ones, with a relatively small age dispersion, although the metal-rich sample is still too small to allow firmer conclusions. There is no correlation of the cluster age with the galactocentric distance. We briefly discuss the implication of these observational results for the formation history of the Galaxy. Based on observations with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555, and on observations made at the European Southern Observatory, La Silla, Chile, and with the Isaac Newton Group Telescopes.

  3. Relative value of diverse brain MRI and blood-based biomarkers for predicting cognitive decline in the elderly

    NASA Astrophysics Data System (ADS)

    Madsen, Sarah K.; Ver Steeg, Greg; Daianu, Madelaine; Mezher, Adam; Jahanshad, Neda; Nir, Talia M.; Hua, Xue; Gutman, Boris A.; Galstyan, Aram; Thompson, Paul M.

    2016-03-01

    Cognitive decline accompanies many debilitating illnesses, including Alzheimer's disease (AD). In old age, brain tissue loss also occurs along with cognitive decline. Although blood tests are easier to perform than brain MRI, few studies compare brain scans to standard blood tests to see which kinds of information best predict future decline. In 504 older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we first used linear regression to assess the relative value of different types of data to predict cognitive decline, including 196 blood panel biomarkers, 249 MRI biomarkers obtained from the FreeSurfer software, demographics, and the AD-risk gene APOE. A subset of MRI biomarkers was the strongest predictor. There was no specific blood marker that increased predictive accuracy on its own, we found that a novel unsupervised learning method, CorEx, captured weak correlations among blood markers, and the resulting clusters offered unique predictive power.

  4. Inflammation and interleukin-1 signaling network contribute to depressive symptoms but not cognitive decline in old age.

    PubMed

    van den Biggelaar, Anita H J; Gussekloo, Jacobijn; de Craen, Anton J M; Frölich, Marijke; Stek, Max L; van der Mast, Roos C; Westendorp, Rudi G J

    2007-07-01

    The association between inflammation and neuropsychiatric symptoms in old age is generally accepted but poorly understood. The purpose of this study was to examine whether inflammation precedes depressive symptoms and cognitive decline in old age, and to identify specific inflammatory pathways herein. We measured serum C-reactive protein (CRP) and lipopolysaccharide-induced production of Interleukin (IL)-1beta, IL-6, Tumor Necrosis Factor (TNF)-alpha, IL-1 receptor antagonist (ra), and IL-10 levels in 85-year-old participants free from neuropsychiatric symptoms at baseline (n=267). Participants were prospectively followed for depressive symptoms (Geriatric Depression Scale) and cognitive functioning (Mini Mental State Examination) from 85 to 90 years. Higher baseline CRP levels preceded accelerated increase in depressive symptoms (p<0.001). A higher production capacity of the pro-inflammatory cytokine IL-1beta preceded a greater increase of depressive symptoms (p=0.06), whereas that of its natural antagonist IL-1ra preceded a smaller increase of depressive symptoms (p=0.003). There was no relation of CRP, IL-1beta, and IL-1ra with cognitive decline. Our findings show that in old age inflammatory processes contribute to the development of depressive symptoms but not cognitive decline. A high innate IL-1ra to IL-1beta production capacity reflects a better ability to neutralize inflammation and may therefore protect against depressive symptoms. PMID:17350781

  5. Inhibition of CaMKK2 Reverses Age-Associated Decline in Bone Mass

    PubMed Central

    Pritchard, Zachary J.; Cary, Rachel L.; Yang, Chang; Novack, Deborah V.; Voor, Michael J.; Sankar, Uma

    2016-01-01

    Decline in bone formation is a major contributing factor to the loss of bone mass associated with aging. We previously showed that the genetic ablation of the tissue-restricted and multifunctional Ca2+/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) stimulates trabecular bone mass accrual, mainly by promoting anabolic pathways and inhibiting catabolic pathways of bone remodeling. In this study, we investigated whether inhibition of this kinase using its selective cell-permeable inhibitor STO-609 will stimulate bone formation in 32 week old male WT mice and reverse age-associated of decline in bone volume and strength. Tri-weekly intraperitoneal injections of saline or STO-609 (10 μM) were performed for six weeks followed by metabolic labeling with calcein and alizarin red. New bone formation was assessed by dynamic histomorphometry whereas micro-computed tomography was employed to measure trabecular bone volume, microarchitecture and femoral mid-shaft geometry. Cortical and trabecular bone biomechanical properties were assessed using three-point bending and punch compression methods respectively. Our results reveal that as they progress from 12 to 32 weeks of age, WT mice sustain a significant decline in trabecular bone volume, microarchitecture and strength as well as cortical bone strength. However, treatment of the 32 week old WT mice with STO-609 stimulated apposition of new bone and completely reversed the age-associated decrease in bone volume, quality, as well as trabecular and cortical bone strength. We also observed that regardless of age, male Camkk2−/− mice possessed significantly elevated trabecular bone volume, microarchitecture and compressive strength as well as cortical bone strength compared to age-matched WT mice, implying that the chronic loss of this kinase attenuates age-associated decline in bone mass. Further, whereas STO-609 treatment and/or the absence of CaMKK2 significantly enhanced the femoral midshaft geometry, the

  6. Distant functional connectivity for bimanual finger coordination declines with aging: an fMRI and SEM exploration.

    PubMed

    Kiyama, Sachiko; Kunimi, Mitsunobu; Iidaka, Tetsuya; Nakai, Toshiharu

    2014-01-01

    Although bimanual finger coordination is known to decline with aging, it still remains unclear how exactly the neural substrates underlying the coordination differ between young and elderly adults. The present study focused on: (1) characterization of the functional connectivity within the motor association cortex which is required for successful bimanual finger coordination, and (2) to elucidate upon its age-related decline. To address these objectives, we utilized functional magnetic resonance imaging (fMRI) in combination with structural equation modeling (SEM). This allowed us to compare functional connectivity models between young and elderly age groups during a visually guided bimanual finger movement task using both stable in-phase and complex anti-phase modes. Our SEM exploration of functional connectivity revealed significant age-related differences in connections surrounding the PMd in the dominant hemisphere. In the young group who generally displayed accurate behavior, the SEM model for the anti-phase mode exhibited significant connections from the dominant PMd to the non-dominant SPL, and from the dominant PMd to the dominant S1. However, the model for the elderly group's anti-phase mode in which task performance dropped, did not exhibit significant connections within the aforementioned regions. These results suggest that: (1) the dominant PMd acts as an intermediary to invoke intense intra- and inter-hemispheric connectivity with distant regions among the higher motor areas including the dominant S1 and the non-dominant SPL in order to achieve successful bimanual finger coordination, and (2) the distant connectivity among the higher motor areas declines with aging, whereas the local connectivity within the bilateral M1 is enhanced for the complex anti-phase mode. The latter may underlie the elderly's decreased performance in the complex anti-phase mode of the bimanual finger movement task.

  7. Exploring Experiences and Perceptions of Aging and Cognitive Decline Across Diverse Racial and Ethnic Groups

    PubMed Central

    Roberts, Lisa R.; Schuh, Holly; Sherzai, Dean; Belliard, Juan Carlos; Montgomery, Susanne B.

    2015-01-01

    Objective To explore how older adults from three prominent ethnoracial groups experience cognitive decline and aging. Method Semistructured key informant interviews (KIIs) and focus groups (FGs) were conducted with caregivers, experts, and older adults. Results (N = 75). Fifteen KIIs regarding cognitive aging issues were conducted among health care professionals and community-based agencies serving older adults. Eight FGs included family caregivers and physicians, and six FGs with Latino, African American, and White older adult community members. Major themes included (a) personal expectations about aging, (b) societal value of older adults, (c) model of care preferred, and (d) community concerns. An overarching theme was a sense of loss associated with aging; however, how this loss was experienced and dealt with varied. Discussion Distinct patterns of concerns and views are important to understand for the development of programs aimed at meeting the needs of diverse older adult community members to improve health outcomes. PMID:26925436

  8. Cognitive Decline and Reorganization of Functional Connectivity in Healthy Aging: The Pivotal Role of the Salience Network in the Prediction of Age and Cognitive Performances

    PubMed Central

    La Corte, Valentina; Sperduti, Marco; Malherbe, Caroline; Vialatte, François; Lion, Stéphanie; Gallarda, Thierry; Oppenheim, Catherine; Piolino, Pascale

    2016-01-01

    Normal aging is related to a decline in specific cognitive processes, in particular in executive functions and memory. In recent years a growing number of studies have focused on changes in brain functional connectivity related to cognitive aging. A common finding is the decreased connectivity within multiple resting state networks, including the default mode network (DMN) and the salience network. In this study, we measured resting state activity using fMRI and explored whether cognitive decline is related to altered functional connectivity. To this end we used a machine learning approach to classify young and old participants from functional connectivity data. The originality of the approach consists in the prediction of the performance and age of the subjects based on functional connectivity by using a machine learning approach. Our findings showed that the connectivity profile between specific networks predicts both the age of the subjects and their cognitive abilities. In particular, we report that the connectivity profiles between the salience and visual networks, and the salience and the anterior part of the DMN, were the features that best predicted the age. Moreover, independently of the age of the subject, connectivity between the salience network and various specific networks (i.e., visual, frontal) predicted episodic memory skills either based on a standard assessment or on an autobiographical memory task, and short-term memory binding. Finally, the connectivity between the salience and the frontal networks predicted inhibition and updating performance, but this link was no longer significant after removing the effect of age. Our findings confirm the crucial role of episodic memory and executive functions in cognitive aging and suggest a pivotal role of the salience network in neural reorganization in aging.

  9. Cognitive Decline and Reorganization of Functional Connectivity in Healthy Aging: The Pivotal Role of the Salience Network in the Prediction of Age and Cognitive Performances

    PubMed Central

    La Corte, Valentina; Sperduti, Marco; Malherbe, Caroline; Vialatte, François; Lion, Stéphanie; Gallarda, Thierry; Oppenheim, Catherine; Piolino, Pascale

    2016-01-01

    Normal aging is related to a decline in specific cognitive processes, in particular in executive functions and memory. In recent years a growing number of studies have focused on changes in brain functional connectivity related to cognitive aging. A common finding is the decreased connectivity within multiple resting state networks, including the default mode network (DMN) and the salience network. In this study, we measured resting state activity using fMRI and explored whether cognitive decline is related to altered functional connectivity. To this end we used a machine learning approach to classify young and old participants from functional connectivity data. The originality of the approach consists in the prediction of the performance and age of the subjects based on functional connectivity by using a machine learning approach. Our findings showed that the connectivity profile between specific networks predicts both the age of the subjects and their cognitive abilities. In particular, we report that the connectivity profiles between the salience and visual networks, and the salience and the anterior part of the DMN, were the features that best predicted the age. Moreover, independently of the age of the subject, connectivity between the salience network and various specific networks (i.e., visual, frontal) predicted episodic memory skills either based on a standard assessment or on an autobiographical memory task, and short-term memory binding. Finally, the connectivity between the salience and the frontal networks predicted inhibition and updating performance, but this link was no longer significant after removing the effect of age. Our findings confirm the crucial role of episodic memory and executive functions in cognitive aging and suggest a pivotal role of the salience network in neural reorganization in aging. PMID:27616991

  10. Cognitive Decline and Reorganization of Functional Connectivity in Healthy Aging: The Pivotal Role of the Salience Network in the Prediction of Age and Cognitive Performances.

    PubMed

    La Corte, Valentina; Sperduti, Marco; Malherbe, Caroline; Vialatte, François; Lion, Stéphanie; Gallarda, Thierry; Oppenheim, Catherine; Piolino, Pascale

    2016-01-01

    Normal aging is related to a decline in specific cognitive processes, in particular in executive functions and memory. In recent years a growing number of studies have focused on changes in brain functional connectivity related to cognitive aging. A common finding is the decreased connectivity within multiple resting state networks, including the default mode network (DMN) and the salience network. In this study, we measured resting state activity using fMRI and explored whether cognitive decline is related to altered functional connectivity. To this end we used a machine learning approach to classify young and old participants from functional connectivity data. The originality of the approach consists in the prediction of the performance and age of the subjects based on functional connectivity by using a machine learning approach. Our findings showed that the connectivity profile between specific networks predicts both the age of the subjects and their cognitive abilities. In particular, we report that the connectivity profiles between the salience and visual networks, and the salience and the anterior part of the DMN, were the features that best predicted the age. Moreover, independently of the age of the subject, connectivity between the salience network and various specific networks (i.e., visual, frontal) predicted episodic memory skills either based on a standard assessment or on an autobiographical memory task, and short-term memory binding. Finally, the connectivity between the salience and the frontal networks predicted inhibition and updating performance, but this link was no longer significant after removing the effect of age. Our findings confirm the crucial role of episodic memory and executive functions in cognitive aging and suggest a pivotal role of the salience network in neural reorganization in aging. PMID:27616991

  11. Aging: progressive decline in fitness due to the rising deleteriome adjusted by genetic, environmental, and stochastic processes.

    PubMed

    Gladyshev, Vadim N

    2016-08-01

    Different theories posit that aging is caused by molecular damage, genetic programs, continued development, hyperfunction, antagonistic pleiotropy alleles, mutations, trade-offs, incomplete repair, etc. Here, I discuss that these ideas can be conceptually unified as they capture particular facets of aging, while being incomplete. Their respective deleterious effects impact fitness at different levels of biological organization, adjusting progression through aging, rather than causing it. Living is associated with a myriad of deleterious processes, both random and deterministic, which are caused by imperfectness, exhibit cumulative properties, and represent the indirect effects of biological functions at all levels, from simple molecules to systems. From this, I derive the deleteriome, which encompasses cumulative deleterious age-related changes and represents the biological age. The organismal deleteriome consists of the deleteriomes of cells, organs, and systems, which change along roughly synchronized trajectories and may be assessed through biomarkers of aging. Aging is then a progressive decline in fitness due to the increasing deleteriome, adjusted by genetic, environmental, and stochastic processes. This model allows integration of diverse aging concepts, provides insights into the nature of aging, and suggests how lifespan may be adjusted during evolution and in experimental models. PMID:27060562

  12. Use of the Internet as a prevention tool against cognitive decline in normal aging

    PubMed Central

    Klimova, Blanka

    2016-01-01

    Recent demographic trends indicate that older people appear to be one of the fastest growing population groups worldwide. In the year 2000, people older than 65 years represented 12.4% of the population. This number is expected to rise to 19% by 2030, particularly in developed countries. Therefore, there is sustained effort at both national and international levels to prolong the active life of these people as long as possible. Since the present older generation at the age of 55 years is already digitally literate, the use of technologies is one of the solutions. The purpose of this study is to discuss the role of the Internet in the prevention of cognitive decline in normal aging. The author examines clinical studies that exploit the use of the Internet, including online training programs, in the prevention of cognitive decline in healthy older individuals. The findings of the clinical studies indicate that the use of the Internet, especially online cognitive training programs, may have a positive effect on the improvement of cognitive functions in healthy older adults. Nevertheless, larger sample longitudinal randomized controlled clinical trials aimed at the prevention of cognitive decline among healthy older adults are needed. PMID:27672317

  13. Use of the Internet as a prevention tool against cognitive decline in normal aging

    PubMed Central

    Klimova, Blanka

    2016-01-01

    Recent demographic trends indicate that older people appear to be one of the fastest growing population groups worldwide. In the year 2000, people older than 65 years represented 12.4% of the population. This number is expected to rise to 19% by 2030, particularly in developed countries. Therefore, there is sustained effort at both national and international levels to prolong the active life of these people as long as possible. Since the present older generation at the age of 55 years is already digitally literate, the use of technologies is one of the solutions. The purpose of this study is to discuss the role of the Internet in the prevention of cognitive decline in normal aging. The author examines clinical studies that exploit the use of the Internet, including online training programs, in the prevention of cognitive decline in healthy older individuals. The findings of the clinical studies indicate that the use of the Internet, especially online cognitive training programs, may have a positive effect on the improvement of cognitive functions in healthy older adults. Nevertheless, larger sample longitudinal randomized controlled clinical trials aimed at the prevention of cognitive decline among healthy older adults are needed.

  14. Enhanced defense against mitochondrial hydrogen peroxide attenuates age-associated cognition decline.

    PubMed

    Chen, Liuji; Na, Ren; Ran, Qitao

    2014-11-01

    Increased mitochondrial hydrogen peroxide (H2O2) is associated with Alzheimer's disease and brain aging. Peroxiredoxin 3 (Prdx3) is the key mitochondrial antioxidant defense enzyme in detoxifying H2O2. To investigate the importance of mitochondrial H2O2 in age-associated cognitive decline, we compared cognition between aged (17-19 months) APP transgenic mice and APP/Prdx3 double transgenic mice (dTG) and between old (24 months) wild-type mice and Prdx3 transgenic mice (TG). Compared with aged APP mice, aged dTG mice showed improved cognition that was correlated with reduced brain amyloid beta levels and decreased amyloid beta production. Old TG mice also showed significantly increased cognitive ability compared with old wild-type mice. Both aged dTG mice and old TG mice had reduced mitochondrial oxidative stress and increased mitochondrial function. Moreover, CREB signaling, a signaling pathway important for cognition was enhanced in both aged dTG mice and old TG mice. Thus, our results indicate that mitochondrial H2O2 is a key culprit of age-associated cognitive impairment, and that a reduction of mitochondrial H2O2 could improve cognition by maintaining mitochondrial health and enhancing CREB signaling.

  15. Exercise training from late middle age until senescence does not attenuate the declines in skeletal muscle aerobic function.

    PubMed

    Betik, Andrew C; Thomas, Melissa M; Wright, Kathryn J; Riel, Caitlin D; Hepple, Russell T

    2009-09-01

    We previously showed that 7 wk of treadmill exercise training in late-middle-aged rats can reverse the modest reductions in skeletal muscle aerobic function and enzyme activity relative to values in young adult rats (Exp Physiol 93: 863-871, 2008). The purpose of the present study was to determine whether extending this training program into senescence would attenuate the accelerated decline in the muscle aerobic machinery normally seen at this advanced age. For this purpose, 29-mo-old Fisher 344 Brown-Norway rats underwent 5 or 7 mo of treadmill exercise training. Training resulted in greater exercise capacity during an incremental treadmill exercise test and reduced percent body fat in 34- and 36-mo-old rats and improved survival. Despite these benefits at the whole body level, in situ muscle aerobic capacity and muscle mass were not greater in the trained groups at 34 mo or 36 mo of age. Similarly, the trained groups did not have higher activities of citrate synthase (CS) or Complex IV in homogenates of either the plantaris (fast twitch) or the soleus (slow twitch) muscles at either age. Finally, protein expression of CS (a marker of mitochondrial content) and peroxisome proliferator-activated receptor-gamma coactivator-1 (relating to the drive on mitochondrial biogenesis) were not higher in the trained groups. Therefore, although treadmill training from late middle age into senescence had significant benefits on running capacity, survival, and body fat, it did not prevent the declines in muscle mass, muscle aerobic capacity, or mitochondrial enzyme activities normally seen across this age, revealing a markedly diminished plasticity of the aerobic machinery in response to endurance exercise at advanced age.

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

    PubMed Central

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

    2015-01-01

    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

  17. 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

  18. 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.

  19. Amyloid burden, neuronal function, and cognitive decline in middle-aged adults at risk for Alzheimer's disease.

    PubMed

    Okonkwo, Ozioma C; Oh, Jennifer M; Koscik, Rebecca; Jonaitis, Erin; Cleary, Caitlin A; Dowling, N Maritza; Bendlin, Barbara B; Larue, Asenath; Hermann, Bruce P; Barnhart, Todd E; Murali, Dhanabalan; Rowley, Howard A; Carlsson, Cynthia M; Gallagher, Catherine L; Asthana, Sanjay; Sager, Mark A; Christian, Brad T; Johnson, Sterling C

    2014-04-01

    The relative influence of amyloid burden, neuronal structure and function, and prior cognitive performance on prospective memory decline among asymptomatic late middle-aged individuals at risk for Alzheimer's disease (AD) is currently unknown. We investigated this using longitudinal cognitive data from 122 middle-aged adults (21 "Decliners" and 101 "Stables") enrolled in the Wisconsin Registry for Alzheimer's Prevention who underwent multimodality neuroimaging [11C-Pittsburgh Compound B (PiB), 18F-fluorodeoxyglucose (FDG), and structural/functional magnetic resonance imaging (fMRI)] 5.7 ± 1.4 years (range = 2.9-8.9) after their baseline cognitive assessment. Covariate-adjusted regression analyses revealed that the only imaging measure that significantly distinguished Decliners from Stables (p = .027) was a Neuronal Function composite derived from FDG and fMRI. In contrast, several cognitive measures, especially those that tap episodic memory, significantly distinguished the groups (p's<.05). Complementary receiver operating characteristic curve analyses identified the Brief Visuospatial Memory Test-Revised (BVMT-R) Total (.82 ± .05, p < .001), the BVMT-R Delayed Recall (.73 ± .06, p = .001), and the Reading subtest from the Wide-Range Achievement Test-III (.72 ± .06, p = .002) as the top three measures that best discriminated the groups. These findings suggest that early memory test performance might serve a more clinically pivotal role in forecasting future cognitive course than is currently presumed.

  20. Default Mode Network Activity Predicts Early Memory Decline in Healthy Young Adults Aged 18-31.

    PubMed

    Nelson, Steven M; Savalia, Neil K; Fishell, Andrew K; Gilmore, Adrian W; Zou, Fan; Balota, David A; McDermott, Kathleen B

    2016-08-01

    Functional magnetic resonance imaging (fMRI) research conducted in healthy young adults is typically done with the assumption that this sample is largely homogeneous. However, studies from cognitive psychology suggest that long-term memory and attentional control begin to diminish in the third decade of life. Here, 100 participants between the ages of 18 and 31 learned Lithuanian translations of English words in an individual differences study using fMRI. Long-term memory ability was operationalized for each participant by deriving a memory score from 3 convergent measures. Age of participant predicted memory score in this cohort. In addition, degree of deactivation during initial encoding in a set of regions occurring largely in the default mode network (DMN) predicted both age and memory score. The current study demonstrates that early memory decline may partially be accounted for by failure to modulate activity in the DMN.

  1. Brain lesions and IQ: recovery versus decline depends on age of onset.

    PubMed

    Duval, Julie; Braun, Claude M J; Montour-Proulx, Isabelle; Daigneault, Sylvie; Rouleau, Isabelle; Bégin, Jean

    2008-06-01

    A growing literature suggests that early lesions are associated with poorer IQ outcome. Those studies covered a restricted age range in pediatric populations only and did not control for important moderator variables. The present investigation studied IQ change in brain-lesioned children and adults (age 0 to 84 years). Altogether, 725 cases with a documented unilateral focal lesion were gathered from hospital charts and from published cases in the literature, including 240 with repeated IQ testing. Multiple regression analyses isolated the contribution of age at lesion onset to IQ change. Important mediator variables included were lesion side, site, volume, etiology, and so on. An early lesion was significantly associated with poorer postlesion IQ in time and with decline of IQ in time. Later onset lesions were associated with better postlesion IQ and recovery in time. The so-called Kennard principle is refuted, with regard to IQ.

  2. Adverse environmental conditions influence age-related innate immune responsiveness

    PubMed Central

    May, Linda; van den Biggelaar, Anita HJ; van Bodegom, David; Meij, Hans J; de Craen, Anton JM; Amankwa, Joseph; Frölich, Marijke; Kuningas, Maris; Westendorp, Rudi GJ

    2009-01-01

    Background- The innate immune system plays an important role in the recognition and induction of protective responses against infectious pathogens, whilst there is increasing evidence for a role in mediating chronic inflammatory diseases at older age. Despite indications that environmental conditions can influence the senescence process of the adaptive immune system, it is not known whether the same holds true for the innate immune system. Therefore we studied whether age-related innate immune responses are similar or differ between populations living under very diverse environmental conditions. Methods- We compared cross-sectional age-related changes in ex vivo innate cytokine responses in a population living under affluent conditions in the Netherlands (age 20–68 years old, n = 304) and a population living under adverse environmental conditions in Ghana (age 23–95 years old, n = 562). Results- We found a significant decrease in LPS-induced Interleukin (IL)-10 and Tumor Necrosis Factor (TNF) production with age in the Dutch population. In Ghana a similar age-related decline in IL-10 responses to LPS, as well as to zymosan, or LPS plus zymosan, was observed. TNF production, however, did not show an age-associated decline, but increased significantly with age in response to co-stimulation with LPS and zymosan. Conclusion- We conclude that the decline in innate cytokine responses is an intrinsic ageing phenomenon, while pathogen exposure and/or selective survival drive pro-inflammatory responses under adverse living conditions. PMID:19480711

  3. [Age-related changes of the brain].

    PubMed

    Paltsyn, A A; Komissarova, S V

    2015-01-01

    The first morphological signs of aging of the brain are found in the white matter already at a young age (20-40 years), and later (40-50 years) in a gray matter. After the 40-50 years appear and in subsequently are becoming more pronounced functional manifestations of morphological changes: the weakening of sensory-motor and cognitive abilities. While in principle this dynamic of age-related changes is inevitable, the rate of their development to a large extent determined by the genetic characteristics and lifestyle of the individual. According to modem concepts age-related changes in the number of nerve cells are different in different parts of the brain. However, these changes are not large and are not the main cause of senile decline brain. The main processes that contribute to the degradation of the brain develop as in the bodies of neurons and in neuropil. In the bodies of neurons--it is a damage (usually decrease) of the level of expression of many genes, and especially of the genes determining cell communication. In neuropil: reduction in the number of synapses and the strength of synaptic connections, reduction in the number of dendritic spines and axonal buttons, reduction in the number and thickness of the dendritic branches, demyelination of axons. As the result of these events, it becomes a violation of the rate of formation and rebuilding neuronal circuits. It is deplete associative ability, brain plasticity, and memory. PMID:27116888

  4. 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…

  5. The Perimenopausal Aging Transition in the Female Rat Brain: Decline in Bioenergetic Systems and Synaptic Plasticity

    PubMed Central

    Yin, Fei; Yao, Jia; Sancheti, Harsh; Feng, Tao; Melcangi, Roberto C.; Morgan, Todd E.; Finch, Caleb E.; Pike, Christian J.; Mack, Wendy J.; Cadenas, Enrique; Brinton, Roberta D.

    2015-01-01

    The perimenopause is an aging transition unique to the female that leads to reproductive senescence which can be characterized by multiple neurological symptoms. To better understand potential underlying mechanisms of neurological symptoms of perimenopause, the current study determined genomic, biochemical, brain metabolic and electrophysiological transformations that occur during this transition using a rat model recapitulating fundamental characteristics of the human perimenopause. Gene expression analyses indicated two distinct aging programs: chronological and endocrine. A critical period emerged during the endocrine transition from regular to irregular cycling characterized by decline in bioenergetic gene expression, confirmed by deficits in FDG-PET brain metabolism, mitochondrial function, and long-term potentiation. Bioinformatic analysis predicted insulin/IGF1 and AMPK/PGC1α signaling pathways as upstream regulators. Onset of acyclicity was accompanied by a rise in genes required for fatty acid metabolism, inflammation, and mitochondrial function. Subsequent chronological aging resulted in decline of genes required for mitochondrial function and β-amyloid degradation. Emergence of glucose hypometabolism and impaired synaptic function in brain provide plausible mechanisms of neurological symptoms of perimenopause and may be predictive of later life vulnerability to hypometabolic conditions such as Alzheimer’s. PMID:25921624

  6. Adverse Vascular Risk is Related to Cognitive Decline in Older Adults

    PubMed Central

    Jefferson, Angela L.; Hohman, Timothy J.; Liu, Dandan; Haj-Hassan, Shereen; Gifford, Katherine A.; Benson, Elleena M.; Skinner, Jeannine S.; Lu, Zengqi; Sparling, Jamie; Sumner, Emily C.; Bell, Susan; Ruberg, Frederick L.

    2014-01-01

    Background Cardiovascular disease (CVD) and related risk factors are associated with Alzheimer’s disease (AD). This association is less well-defined in normal cognition (NC) or prodromal AD (mild cognitive impairment (MCI)). Objective Cross-sectionally and longitudinally relate a vascular risk index to cognitive outcomes among elders free of clinical dementia. Methods 3117 MCI (74±8 years, 56% female) and 6603 NC participants (72±8 years, 68% female) were drawn from the National Alzheimer’s Coordinating Center. A composite measure of vascular risk was defined using the Framingham Stroke Risk Profile (FSRP) score (i.e., age, systolic blood pressure, anti-hypertensive medication, diabetes, cigarette smoking, CVD history, atrial fibrillation). Ordinary linear regressions and generalized linear mixed models related baseline FSRP to cross-sectional and longitudinal cognitive outcomes, separately for NC and MCI, adjusting for age, sex, race, education, and follow-up time (in longitudinal models). Results In NC participants, increasing FSRP was related to worse baseline global cognition, information processing speed, and sequencing abilities (p-values<0.0001) and a worse longitudinal trajectory on all cognitive measures (p-values<0.0001). In MCI, increasing FSRP correlated with worse longitudinal delayed memory (p=0.004). In secondary models using an age-excluded FSRP score, associations persisted in NC participants for global cognition, naming, information processing speed, and sequencing abilities. Conclusions An adverse vascular risk profile is associated with worse cognitive trajectory, especially global cognition, naming, and information processing speed, among NC elders. Future studies are needed to understand how effective management of CVD and related risk factors can modify cognitive decline to identify the ideal timeframe for primary prevention implementation. PMID:25471188

  7. Hospital Admission Patterns in Children with CAH: Admission Rates and Adrenal Crises Decline with Age

    PubMed Central

    Rushworth, R. Louise; Falhammar, Henrik; Munns, Craig F.; Maguire, Ann M.; Torpy, David J.

    2016-01-01

    Objective. To examine patterns of hospitalisation for acute medical conditions in children with congenital adrenal hyperplasia (CAH). Design. A retrospective study of hospitalisation using administrative data. Setting. All hospitals in NSW, Australia. Patients. All patients admitted with CAH and a random sample of admissions in patients aged 0 to 18 years without adrenal insufficiency (AI). Main Outcome Measures. Admissions and comorbidities by age and sex. Results. Of 573 admissions for medical problems in CAH children, 286 (49.9%) were in males, and 236 (41.2%) had a principal diagnosis of CAH or had an adrenal crisis (AC). 37 (6.5%) ACs were recorded. An infection was found in 43.5% (n = 249) of the CAH patient admissions and 51.7% (n = 1613) of the non-AI group, p < 0.001. Children aged up to one year had the highest number of admissions (n = 149) and six ACs (four in males). There were 21 ACs recorded for children aged 1–5 years. Older CAH children had fewer admissions and fewer ACs. No in-hospital deaths were recorded. Conclusions. Admission for medical problems in CAH children declines with age. An AC was recorded in 6.5% of the admissions, with the majority of ACs occurring in the 1 to 5 years age group and there were no deaths. PMID:26880914

  8. Remedial Effects of Motivational Incentive on Declining Cognitive Control In Healthy Aging and Parkinson's Disease

    PubMed Central

    Harsay, Helga A.; Buitenweg, Jessika I. V.; Wijnen, Jasper G.; Guerreiro, Maria J. S.; Ridderinkhof, K. Richard

    2010-01-01

    The prospect of reward may provide a motivational incentive for optimizing goal-directed behavior. Animal work demonstrates that reward-processing networks and oculomotor-control networks in the brain are connected through the dorsal striatum, and that reward anticipation can improve oculomotor control via this nexus. Due perhaps to deterioration in dopaminergic striatal circuitry, goal-directed oculomotor control is subject to decline in healthy seniors, and even more in individuals with Parkinson's disease (PD). Here we examine whether healthy seniors and PD patients are able to utilize reward prospects to improve their impaired antisaccade performance. Results confirmed that oculomotor control declined in PD patients compared to healthy seniors, and in healthy seniors compared to young adults. However, the motivational incentive of reward expectation resulted in benefits in antisaccade performance in all groups alike. These findings speak against structural and non-modifiable decline in cognitive control functions, and emphasize the remedial potential of motivational incentive mechanisms in healthy as well as pathological aging. PMID:21060805

  9. Age-related atrial fibrosis.

    PubMed

    Gramley, Felix; Lorenzen, Johann; Knackstedt, Christian; Rana, Obaida R; Saygili, Erol; Frechen, Dirk; Stanzel, Sven; Pezzella, Francesco; Koellensperger, Eva; Weiss, Christian; Münzel, Thomas; Schauerte, Patrick

    2009-03-01

    Many age-related diseases are associated with, and may be promoted by, cardiac fibrosis. Transforming growth factor (TGF)-beta, hypoxia-induced factor (HIF), and the matrix metalloproteinase (MMP) system have been implicated in fibrogenesis. Thus, we investigated whether age is related to these systems and to atrial fibrosis. Right atrial appendages (RAA) obtained during heart surgery (n = 115) were grouped according to patients' age (<50 years, 51-60 years, 61-70 years, or >70 years). Echocardiographic ejection fractions (EF) and fibrosis using Sirius-red-stained histological sections were determined. TGF-beta was determined by quantitative RT-PCR and hypoxia-related factors [HIF1 alpha, the vascular endothelial growth factor (VEGF)-receptor, CD34 (a surrogate marker for microvessel density), the factor inhibiting HIF (FIH), and prolyl hydroxylase 3 (PHD 3)] were detected by immunostaining. MMP-2 and -9 activity were determined zymographically, and mRNA levels of their common tissue inhibitor TIMP-1 were determined by RT-PCR. Younger patients (<50 years) had significantly less fibrosis (10.1% +/- 4.4% vs 16.6% +/- 8.3%) than older individuals (>70 years). While HIF1 alpha, FIH, the VEGF-receptor, and CD34 were significantly elevated in the young, TGF-beta and PHD3 were suppressed in these patients. MMP-2 and -9 activity was found to be higher while TIMP-1 levels were lower in older patients. Statistical analysis proved age to be the only factor influencing fibrogenesis. With increasing age, RAAs develop significantly more fibrosis. An increase of fibrotic and decrease of hypoxic signalling and microvessel density, coupled with differential expression of MMPs and TIMP-1 favouring fibrosis may have helped promote atrial fibrogenesis. PMID:19234766

  10. Systematic review of the evidence relating FEV1 decline to giving up smoking

    PubMed Central

    2010-01-01

    Background The rate of forced expiratory volume in 1 second (FEV1) decline ("beta") is a marker of chronic obstructive pulmonary disease risk. The reduction in beta after quitting smoking is an upper limit for the reduction achievable from switching to novel nicotine delivery products. We review available evidence to estimate this reduction and quantify the relationship of smoking to beta. Methods Studies were identified, in healthy individuals or patients with respiratory disease, that provided data on beta over at least 2 years of follow-up, separately for those who gave up smoking and other smoking groups. Publications to June 2010 were considered. Independent beta estimates were derived for four main smoking groups: never smokers, ex-smokers (before baseline), quitters (during follow-up) and continuing smokers. Unweighted and inverse variance-weighted regression analyses compared betas in the smoking groups, and in continuing smokers by amount smoked, and estimated whether beta or beta differences between smoking groups varied by age, sex and other factors. Results Forty-seven studies had relevant data, 28 for both sexes and 19 for males. Sixteen studies started before 1970. Mean follow-up was 11 years. On the basis of weighted analysis of 303 betas for the four smoking groups, never smokers had a beta 10.8 mL/yr (95% confidence interval (CI), 8.9 to 12.8) less than continuing smokers. Betas for ex-smokers were 12.4 mL/yr (95% CI, 10.1 to 14.7) less than for continuing smokers, and for quitters, 8.5 mL/yr (95% CI, 5.6 to 11.4) less. These betas were similar to that for never smokers. In continuing smokers, beta increased 0.33 mL/yr per cigarette/day. Beta differences between continuing smokers and those who gave up were greater in patients with respiratory disease or with reduced baseline lung function, but were not clearly related to age or sex. Conclusion The available data have numerous limitations, but clearly show that continuing smokers have a beta that

  11. Age of onset as a moderator of cognitive decline in pediatric-onset multiple sclerosis.

    PubMed

    Hosseini, Banafsheh; Flora, David B; Banwell, Brenda L; Till, Christine

    2014-09-01

    Cognitive impairment is often reported in pediatric-onset multiple sclerosis (MS). Using serial cognitive data from 35 individuals with pediatric-onset MS, this study examined how age at disease-onset and proxies of cognitive reserve may impact cognitive maturation over the course of childhood and adolescence. Neuropsychological evaluations were conducted at baseline and up to four more assessments. Of the 35 participants, 7 completed only one assessment, 5 completed two assessments, 13 completed three assessments, 10 completed four or more assessments. Growth curve modeling was used to assess longitudinal trajectories on the Trail Making Test-Part B (TMT-B) and the Symbol Digit Modalities (SDMT; oral version) and to examine how age at disease onset, baseline Full Scale IQ, and social status may moderate rate of change on these measures. Mean number of evaluations completed per patient was 2.8. Younger age at disease onset was associated with a greater likelihood of cognitive decline on both the TMT-B (p=.001) and SDMT (p=.005). Baseline IQ and parental social status did not moderate any of the cognitive trajectories. Findings suggest that younger age at disease-onset increases the vulnerability for disrupted performance on measures of information processing, visual scanning, perceptual/motor speed, and working memory. Proxies of cognitive reserve did not protect against the progression of decline on these measures. Young patients with MS should be advised to seek follow-up cognitive evaluation to assess cognitive maturation and to screen for the potential late emergence of cognitive deficits. (JINS, 2014, 20, 1-9).

  12. Population declines of tuna and relatives depend on their speed of life.

    PubMed

    Juan-Jordá, M J; Mosqueira, I; Freire, J; Dulvy, N K

    2015-07-22

    Larger-bodied species in a wide range of taxonomic groups including mammals, fishes and birds tend to decline more steeply and are at greater risk of extinction. Yet, the diversity in life histories is governed not only by body size, but also by time-related traits. A key question is whether this size-dependency of vulnerability also holds, not just locally, but globally across a wider range of environments. We test the relative importance of size- and time-related life-history traits and fishing mortality in determining population declines and current exploitation status in tunas and their relatives. We use high-quality datasets of half a century of population trajectories combined with population-level fishing mortalities and life-history traits. Time-related traits (e.g. growth rate), rather than size-related traits (e.g. maximum size), better explain the extent and rate of declines and current exploitation status across tuna assemblages, after controlling for fishing mortality. Consequently, there is strong geographical patterning in population declines, such that populations with slower life histories (found at higher cooler latitudes) have declined most and more steeply and have a higher probability of being overfished than populations with faster life histories (found at tropical latitudes). Hence, the strong, temperature-driven, latitudinal gradients in life-history traits may underlie the global patterning of population declines, fisheries collapses and local extinctions.

  13. Population declines of tuna and relatives depend on their speed of life

    PubMed Central

    Juan-Jordá, M. J.; Mosqueira, I.; Freire, J.; Dulvy, N. K.

    2015-01-01

    Larger-bodied species in a wide range of taxonomic groups including mammals, fishes and birds tend to decline more steeply and are at greater risk of extinction. Yet, the diversity in life histories is governed not only by body size, but also by time-related traits. A key question is whether this size-dependency of vulnerability also holds, not just locally, but globally across a wider range of environments. We test the relative importance of size- and time-related life-history traits and fishing mortality in determining population declines and current exploitation status in tunas and their relatives. We use high-quality datasets of half a century of population trajectories combined with population-level fishing mortalities and life-history traits. Time-related traits (e.g. growth rate), rather than size-related traits (e.g. maximum size), better explain the extent and rate of declines and current exploitation status across tuna assemblages, after controlling for fishing mortality. Consequently, there is strong geographical patterning in population declines, such that populations with slower life histories (found at higher cooler latitudes) have declined most and more steeply and have a higher probability of being overfished than populations with faster life histories (found at tropical latitudes). Hence, the strong, temperature-driven, latitudinal gradients in life-history traits may underlie the global patterning of population declines, fisheries collapses and local extinctions. PMID:26156763

  14. Evolvability of an avian life history trait declines with father's age.

    PubMed

    Kim, S-Y; Drummond, H; Torres, R; Velando, A

    2011-02-01

    Studies of laboratory organisms have suggested that parental age affects the genetic variance of offspring traits. This effect can engender age-specific variance in genetic contributions to evolutionary change in heritable traits under directional selection, particularly in age-structured populations. Using long-term population data of the blue-footed booby (Sula nebouxii), we tested whether genetic variance of recruiting age varies with parental age. Using robust quantitative genetic models fitted to pedigree, we found a significant genotype-by-paternal age interaction for recruiting age. Genetic potential for adaptive change in recruiting age was greater in progeny of young (age 1-6 years) fathers (males: CV(A)=6.68; females: CV(A)=7.59) than those of middle age (7-9 years) fathers (males: CV(A) = 4.64; females: CV(A)=5.08) and old (10-14 years) fathers (CV(A)=0 for both sexes). Therefore, parental age dependence of heritable variance, in addition to age-related variation in survival and fecundity, should affect the strength of natural selection for evolutionary changes. Our results provide rare evidence for the influence of parental age on the evolutionary potential of a life history trait in a wild population.

  15. Evolvability of an avian life history trait declines with father's age.

    PubMed

    Kim, S-Y; Drummond, H; Torres, R; Velando, A

    2011-02-01

    Studies of laboratory organisms have suggested that parental age affects the genetic variance of offspring traits. This effect can engender age-specific variance in genetic contributions to evolutionary change in heritable traits under directional selection, particularly in age-structured populations. Using long-term population data of the blue-footed booby (Sula nebouxii), we tested whether genetic variance of recruiting age varies with parental age. Using robust quantitative genetic models fitted to pedigree, we found a significant genotype-by-paternal age interaction for recruiting age. Genetic potential for adaptive change in recruiting age was greater in progeny of young (age 1-6 years) fathers (males: CV(A)=6.68; females: CV(A)=7.59) than those of middle age (7-9 years) fathers (males: CV(A) = 4.64; females: CV(A)=5.08) and old (10-14 years) fathers (CV(A)=0 for both sexes). Therefore, parental age dependence of heritable variance, in addition to age-related variation in survival and fecundity, should affect the strength of natural selection for evolutionary changes. Our results provide rare evidence for the influence of parental age on the evolutionary potential of a life history trait in a wild population. PMID:21044208

  16. Birthdate and Performance: The Relative Age Effect.

    ERIC Educational Resources Information Center

    Barnsley, Roger H.

    The purpose of this paper is to consider the concept of "relative age" and to review recent research findings that have demonstrated that relative age is related to a variety of academic and athletic performance measures. The paper is divided into six parts: (1) the relative age concept; (2) relative age and achievement in sports; (3) relative age…

  17. 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.

  18. [Age-related macular degeneration].

    PubMed

    Garcia Layana, A

    1998-01-01

    Age-related macular degeneration (ARMD) is the leading cause of blindness in the occidental world. Patients suffering this process have an important reduction on their quality of life being handicapped to read, to write, to recognise faces of their friends, or even to watch the television. One of the main problems of that disease is the absence of an effective treatment able to revert the process. Laser treatment is only useful in a limited number of patients, and even in these cases recurrent lesions are frequent. These facts and the progressive ageing of our society establish the ARMD as one of the biggest aim of medical investigations for the next century, and currently is focus of attention in the most industrialised countries. One of the most promising pieces of research is focused in the investigation of the risk factors associated with the age-related macular degeneration, in order to achieve a prophylactic treatment avoiding its appearance. Diet elements such as fat ingestion or reduced antioxidant intakes are being investigated as some of these factors, what open a new possibility for a prophylactic treatment. Finally, research is looking for new therapeutic modalities such as selective radiotherapy in order to improve or maintain the vision of these patients.

  19. Age-dependent decline in learning and memory performances of WAG/Rij rat model of absence epilepsy

    PubMed Central

    2012-01-01

    Recent clinical studies revealed emotional and cognitive impairments associated with absence epilepsy. Preclinical research with genetic models of absence epilepsy however have primarily focused on dysfunctional emotional processes and paid relatively less attention to cognitive impairment. In order to bridge this gap, we investigated age-dependent changes in learning and memory performance, anxiety-like behavior, and locomotor activity of WAG/Rij rats (a valid model of generalized absence epilepsy) using passive avoidance, Morris water maze, elevated plus maze, and locomotor activity cage. We tested 5 month-old and 13 month-old WAG/Rij rats and compared their performance to age-matched Wistar rats. Results revealed a decline in emotional and spatial memory of WAG/Rij rats compared to age-matched Wistar rats only at 13 months of age. Importantly, there were no significant differences between WAG/Rij and Wistar rats in terms of anxiety-like behavior and locomotor activity at either age. Results pointed at age-dependent learning and memory deficits in the WAG/Rij rat model of absence epilepsy. PMID:22998946

  20. Glutamatergic treatment strategies for age-related memory disorders.

    PubMed

    Müller, W E; Scheuer, K; Stoll, S

    1994-01-01

    Age-related changes of N-methyl-D-aspartate (NMDA) receptors have been found in cortical areas and in the hippocampus of many species. On the basis of a variety of experimental observations it has been suggested that the decrease of NMDA receptor density might be one of the causative factors of the cognitive decline with aging. Based on these findings several strategies have been developed to improve cognition by compensating the NMDA receptor deficits in aging. The most promising approaches are the indirect activation of glutamatergic neurotransmission by agonists of the glycine site or the restoration of the age-related deficit of receptor density by several nootropics. PMID:7997073

  1. Social life histories: jackdaw dominance increases with age, terminally declines and shortens lifespan.

    PubMed

    Verhulst, Simon; Geerdink, Moniek; Salomons, H Martijn; Boonekamp, Jelle J

    2014-09-22

    Behaviour may contribute to changes in fitness prospects with age, for example through effects of age-dependent social dominance on resource access. Older individuals often have higher dominance rank, which may reflect a longer lifespan of dominants and/or an increase in social dominance with age. In the latter case, increasing dominance could mitigate physiological senescence. We studied the social careers of free-living jackdaws over a 12 year period, and found that: (i) larger males attained higher ranks, (ii) social rank increased with age within individuals, and (iii) high-ranked individuals had shorter lifespan suggesting that maintaining or achieving high rank and associated benefits comes at a cost. Lastly, (iv) social rank declined substantially in the last year an individual was observed in the colony, and through its effect on resource access this may accelerate senescence. We suggest that behaviour affecting the ability to secure resources is integral to the senescence process via resource effects on somatic state, where behaviour may include not only social dominance, but also learning, memory, perception and (sexual) signalling. Studying behavioural effects on senescence via somatic state may be most effective in the wild, where there is competition for resources, which is usually avoided in laboratory conditions.

  2. Cohorts based on Decade of Death: No Evidence for Secular Trends Favoring Later Cohorts in Cognitive Aging and Terminal Decline in the AHEAD Study

    PubMed Central

    Hülür, Gizem; Infurna, Frank J.; Ram, Nilam; Gerstorf, Denis

    2012-01-01

    Studies of birth-year cohorts examined over the same age range often report secular trends favoring later-born cohorts, who are cognitively fitter and show less steep cognitive declines than earlier-born cohorts. However, there is initial evidence that those advantages of later-born cohorts do not carry into the last years of life, suggesting that pervasive mortality-related processes minimize differences that were apparent earlier in life. Elaborating this work from an alternative perspective on cohort differences, we compared rates of cognitive aging and terminal decline in episodic memory between cohorts based on the year participants had died, earlier (between 1993 and 1999) or later in historical time (between 2000 and 2010). Specifically, we compared trajectories of cognitive decline in two death-year cohorts of participants in the Asset and Health Dynamics among the Oldest Old (AHEAD) Study that were matched on age at death and education and controlled for a variety of additional covariates. Results revealed little evidence of secular trends favoring later cohorts. To the contrary, the cohort that died in the 2000s showed a less favorable trajectory of age-related memory decline than the cohort who died in the 1990s. In examinations of change in relation to time-to-death, the cohort dying in the 2000s experienced even steeper terminal declines than the cohort dying in the 1990s. We suggest that secular increases in “manufacturing” survival may exacerbate age- and mortality-related cognitive declines among the oldest old. PMID:23046001

  3. 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

  4. Canonical Nlrp3 inflammasome links systemic low grade inflammation to functional decline in aging

    PubMed Central

    Youm, Yun-Hee; Grant, Ryan W.; McCabe, Laura R.; Albarado, Diana C.; Nguyen, Kim Yen; Ravussin, Anthony; Pistell, Paul; Newman, Susan; Carter, Renee; Laque, Amanda; Münzberg, Heike; Rosen, Clifford J.; Ingram, Donald K.; Salbaum, J. Michael; Dixit, Vishwa Deep

    2014-01-01

    SUMMARY Despite a wealth of clinical data showing an association between inflammation and degenerative disorders in elderly, the immune sensors that causally link systemic inflammation to aging remain unclear. Here we detail a mechanism that the Nlrp3 inflammasome controls systemic low grade age-related ‘sterile’ inflammation in both periphery and brain independently of the non-canonical caspase-11 inflammasome. Ablation of Nlrp3 inflammasome protected mice from age-related increases in the innate immune activation, alterations in CNS transcriptome and astrogliosis. Consistent with the hypothesis that systemic low grade inflammation promotes age-related degenerative changes, the deficient Nlrp3 inflammasome mediated caspase-1 activity improved glycemic control and attenuated bone loss and thymic demise. Notably, IL-1 mediated only Nlrp3 inflammasome dependent improvement in cognitive function and motor performance in aged mice. These studies reveal Nlrp3 inflammasome as an upstream target that controls age-related inflammation and offer innovative therapeutic strategy to lower Nlrp3 activity to delay multiple age-related chronic diseases. PMID:24093676

  5. Amyloid burden, neuronal function, and cognitive decline in middle-aged adults at risk for Alzheimer’s disease

    PubMed Central

    Okonkwo, Ozioma C.; Oh, Jennifer M.; Koscik, Rebecca; Jonaitis, Erin; Cleary, Caitlin A.; Dowling, N. Maritza; Bendlin, Barbara B.; LaRue, Asenath; Hermann, Bruce P.; Barnhart, Todd E.; Murali, Dhanabalan; Rowley, Howard A.; Carlsson, Cynthia M.; Gallagher, Catherine L.; Asthana, Sanjay; Sager, Mark A.; Christian, Brad T.; Johnson, Sterling C.

    2014-01-01

    The relative influence of amyloid burden, neuronal structure and function, and prior cognitive performance on prospective memory decline among asymptomatic late middle-aged individuals at risk for Alzheimer’s disease (AD) is currently unknown. We investigated this using longitudinal cognitive data from 122 middle-aged adults (21 “Decliners” and 101 “Stables”) enrolled in the Wisconsin Registry for Alzheimer’s Prevention who underwent multimodality neuroimaging (11C-Pittsburgh Compound B (PiB), 18F-fluorodeoxyglucose (FDG), and structural/functional MRI) 5.7±1.4 years (range=2.9–8.9) after their baseline cognitive assessment. Covariate-adjusted regression analyses revealed that the only imaging measure that significantly distinguished Decliners from Stables (p=.027) was a Neuronal Function composite derived from FDG and fMRI. In contrast, several cognitive measures, especially those that tap episodic memory, significantly distinguished the groups (p’s < .05). Complementary receiver operating characteristic curve analyses identified the Brief Visuospatial Memory Test-Revised (BVMT-R) Total (.82±.05, p<.001), the BVMT-R Delayed Recall (.73±.06, p=.001), and the Reading subtest from the Wide-Range Achievement Test-III (.72±.06, p=.002) as the top three measures that best discriminated the groups. These findings suggest that early memory test performance might serve a more clinically-pivotal role in forecasting future cognitive course than is currently presumed. PMID:24621494

  6. Effects of assistive technology on functional decline in people aging with a disability.

    PubMed

    Wilson, Dorothy J; Mitchell, Judith M; Kemp, Bryan J; Adkins, Rodney H; Mann, William

    2009-01-01

    This study used a randomized control group design to investigate the impact of an assistive technology and home modification intervention on function for individuals who are aging with a disability. There were 91 participants with polio, rheumatoid arthritis, cerebral palsy, spinal cord injury, stroke, and other impairments. Outcome data were collected at 12 and 24 months through in-home interviews using the Older Americans Resources and Services Instrument (OARS) and the Functional Independence Measure (FIM), and through monthly telephone contact on the hours of in-home care, hospitalizations, and acquisition of AT. The treatment group received an in-home evaluation of their equipment and home modification needs. All recommended AT and home modifications were provided and paid for in full or in part by the study. The control group received the standard community-available health care. A significant "group by time" interaction for the FIM suggested a slower decline in function for the treatment group over 2 years. Further analyses found that the treatment group was more likely to use equipment to maintain independence vs. personal assistance. This study supports the value of assistive technology for adults aging with a disability and suggests that it be provided earlier in the aging process. PMID:20066887

  7. APOE and BDNF polymorphisms moderate amyloid β-related cognitive decline in preclinical Alzheimer's disease

    PubMed Central

    Lim, Y Y; Villemagne, V L; Laws, S M; Pietrzak, R H; Snyder, P J; Ames, D; Ellis, K A; Harrington, K; Rembach, A; Martins, R N; Rowe, C C; Masters, C L; Maruff, P

    2015-01-01

    Accumulation of β-amyloid (Aβ) in the brain is associated with memory decline in healthy individuals as a prelude to Alzheimer's disease (AD). Genetic factors may moderate this decline. We examined the role of apolipoprotein E (ɛ4 carrier[ɛ4+], ɛ4 non-carrier[ɛ4−]) and brain-derived neurotrophic factor (BDNFVal/Val, BDNFMet) in the extent to which they moderate Aβ-related memory decline. Healthy adults (n=333, Mage=70 years) enrolled in the Australian Imaging, Biomarkers and Lifestyle study underwent Aβ neuroimaging. Neuropsychological assessments were conducted at baseline, 18-, 36- and 54-month follow-ups. Aβ positron emission tomography neuroimaging was used to classify participants as Aβ− or Aβ+. Relative to Aβ−ɛ4−, Aβ+ɛ4+ individuals showed significantly faster rates of cognitive decline over 54 months across all domains (d=0.40–1.22), while Aβ+ɛ4− individuals showed significantly faster decline only on verbal episodic memory (EM). There were no differences in rates of cognitive change between Aβ−ɛ4− and Aβ−ɛ4+ groups. Among Aβ+ individuals, ɛ4+/BDNFMet participants showed a significantly faster rate of decline on verbal and visual EM, and language over 54 months compared with ɛ4−/BDNFVal/Val participants (d=0.90–1.02). At least two genetic loci affect the rate of Aβ-related cognitive decline. Aβ+ɛ4+/BDNFMet individuals can expect to show clinically significant memory impairment after 3 years, whereas Aβ+ɛ4+/BDNFVal/Val individuals can expect a similar degree of impairment after 10 years. Little decline over 54 months was observed in the Aβ− and Aβ+ ɛ4− groups, irrespective of BDNF status. These data raise important prognostic issues in managing preclinical AD, and should be considered in designing secondary preventative clinical trials. PMID:25288138

  8. Cognitive decline is mediated by gray matter changes during middle age.

    PubMed

    Ferreira, Daniel; Molina, Yaiza; Machado, Alejandra; Westman, Eric; Wahlund, Lars-Olof; Nieto, Antonieta; Correia, Rut; Junqué, Carme; Díaz-Flores, Lucio; Barroso, José

    2014-05-01

    The present theoretical framework of Alzheimer's disease proposes that pathophysiological changes occur 10-20 years before the diagnosis of dementia. We addressed the question of how age-related changes in gray matter mediate the cognitive performance during middle age. Eighty-two participants (40-50 years, ±2) were assessed with a comprehensive neuropsychological battery covering a broad spectrum of cognitive domains and components. Mediation effects were studied with hierarchical regression and bootstrapping analysis. Results showed that more vulnerable cognitive components were related to executive functioning and in a lesser degree to processing speed. Age-related differences in gray matter mainly involved the frontal lobes. Moreover, age-related differences in visuoconstructive, visuospatial functions, reaction time, and mental flexibility and executive control were mediated by several gray matter regions. It is important to increase the knowledge of the impact of brain changes on cognitive function during middle age. To define the early stages of the aging process may allow early detection of pathologic changes and therapeutic interventions.

  9. Later developments: molecular keys to age-related memory impairment.

    PubMed

    Barad, Mark

    2003-01-01

    Age-related memory impairment, a cognitive decline not clearly related to any gross pathology, is progressive and widespread in the population, although not universal. While the mechanisms of learning and memory remain incompletely understood, the study of their molecular mechanisms is already yielding promising approaches toward therapy for such "normal" declines in the efficiency of learning. This review presents the rationale and results for two such approaches. One approach, partial inhibition of the type IV cAMP specific phosphodiesterase, appears to act indirectly. Although little evidence supports an age-related decline in this system, considerable evidence indicates that this approach can facilitate the transition from short-term to long-term memory and thus counterbalance defects in long-term memory, which may be due to other causes. A second approach, inhibition of l-type voltage gated calcium channels (LVGCCs) may be a specific corrective for a molecular pathology of aging, as substantial evidence indicates that an ongoing increase occurs throughout the lifespan in the density of these channels in hippocampal pyramidal cells, with a concomitant reduction in cellular excitability. Because LVGCCs are also crucial to extinction, a paradigm of inhibitory learning, age-related memory impairment may be an unfortunate side effect of a developmental process necessary to the maturation of the ability to suppress inappropriate behavior, an interpretation consistent with the antagonistic pleiotropy theory of aging.

  10. Age-Related Changes in Visual Pseudoneglect

    ERIC Educational Resources Information Center

    Schmitz, Remy; Peigneux, Philippe

    2011-01-01

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

  11. Ergothioneine levels in an elderly population decrease with age and incidence of cognitive decline; a risk factor for neurodegeneration?

    PubMed

    Cheah, Irwin K; Feng, Lei; Tang, Richard M Y; Lim, Keith H C; Halliwell, Barry

    2016-09-01

    Ergothioneine (ET), a naturally occurring thione, can accumulate in the human body at high concentrations from diet. Following absorption via a specific transporter, OCTN1, ET may accumulate preferentially in tissues predisposed to higher levels of oxidative stress and inflammation. Given its potential cytoprotective effects, we examined how ET levels change with age. We found that whole blood ET levels in elderly individuals decline significantly beyond 60 years of age. Additionally, a subset of these subjects with mild cognitive impairment had significantly lower plasma ET levels compared with age-matched subjects. This decline suggests that deficiency in ET may be a risk factor, predisposing individuals to neurodegenerative diseases. PMID:27444382

  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. Dietary patterns and cognitive decline in an Australian study of ageing.

    PubMed

    Gardener, S L; Rainey-Smith, S R; Barnes, M B; Sohrabi, H R; Weinborn, M; Lim, Y Y; Harrington, K; Taddei, K; Gu, Y; Rembach, A; Szoeke, C; Ellis, K A; Masters, C L; Macaulay, S L; Rowe, C C; Ames, D; Keogh, J B; Scarmeas, N; Martins, R N

    2015-07-01

    The aim of this paper was to investigate the association of three well-recognised dietary patterns with cognitive change over a 3-year period. Five hundred and twenty-seven healthy participants from the Australian Imaging, Biomarkers and Lifestyle study of ageing completed the Cancer Council of Victoria food frequency questionnaire at baseline and underwent a comprehensive neuropsychological assessment at baseline, 18 and 36 months follow-up. Individual neuropsychological test scores were used to construct composite scores for six cognitive domains and a global cognitive score. Based on self-reported consumption, scores for three dietary patterns, (1) Australian-style Mediterranean diet (AusMeDi), (2) western diet and (3) prudent diet were generated for each individual. Linear mixed model analyses were conducted to examine the relationship between diet scores and cognitive change in each cognitive domain and for the global score. Higher baseline adherence to the AusMeDi was associated with better performance in the executive function cognitive domain after 36 months in apolipoprotein E (APOE) ɛ4 allele carriers (P<0.01). Higher baseline western diet adherence was associated with greater cognitive decline after 36 months in the visuospatial cognitive domain in APOE ɛ4 allele non-carriers (P<0.01). All other results were not significant. Our findings in this well-characterised Australian cohort indicate that adherence to a healthy diet is important to reduce risk for cognitive decline, with the converse being true for the western diet. Executive function and visuospatial functioning appear to be particularly susceptible to the influence of diet.

  14. Leg strength declines with advancing age despite habitual endurance exercise in active older adults.

    PubMed

    Marcell, Taylor J; Hawkins, Steven A; Wiswell, Robert A

    2014-02-01

    Age-associated loss of muscle mass (sarcopenia) and strength (dynapenia) is associated with a loss of independence that contributes to falls, fractures, and nursing home admissions, whereas regular physical activity has been suggested to offset these losses. The purpose of this study was to evaluate the effect of habitual endurance exercise on muscle mass and strength in active older adults. A longitudinal analysis of muscle strength (≈4.8 years apart) was performed on 59 men (age at start of study: 58.6 ± 7.3 years) and 35 women (56.9 ± 8.2 years) who used endurance running as their primary mode of exercise. There were no changes in fat-free mass although body fat increased minimally (1.0-1.5%). Training volume (km·wk, d·wk) decreased in both the men and women. There was a significant loss of both isometric knee extension (≈5% per year) and knee flexion (≈3.6% per year) strength in both the men and women. However, there was no significant change in either isokinetic concentric or eccentric torque of the knee extensors. Our data demonstrated a significant decline in isometric knee extensor and knee flexor strength although there were no changes in body mass in this group of very active older men and women. Our data support newer exercise guidelines for older Americans suggesting resistance training be an integral component of a fitness program and that running alone was not sufficient to prevent the loss in muscle strength (dynapenia) with aging.

  15. The Declining Relative Status of Black Women Workers, 1980-2002

    ERIC Educational Resources Information Center

    Dozier, Raine

    2010-01-01

    During the 1980s and 1990s, industrial restructuring led to a marked increase in wage inequality. Women, however, were not as negatively affected by declining manufacturing employment because their pay was relatively low within the industry, and their already high representation in the service sector provided access to newly created opportunities.…

  16. Age-related differences in multiple task monitoring.

    PubMed

    Todorov, Ivo; Del Missier, Fabio; Mäntylä, Timo

    2014-01-01

    Coordinating multiple tasks with narrow deadlines is particularly challenging for older adults because of age related decline in cognitive control functions. We tested the hypothesis that multiple task performance reflects age- and gender-related differences in executive functioning and spatial ability. Young and older adults completed a multitasking session with four monitoring tasks as well as separate tasks measuring executive functioning and spatial ability. For both age groups, men exceeded women in multitasking, measured as monitoring accuracy. Individual differences in executive functioning and spatial ability were independent predictors of young adults' monitoring accuracy, but only spatial ability was related to sex differences. For older adults, age and executive functioning, but not spatial ability, predicted multitasking performance. These results suggest that executive functions contribute to multiple task performance across the adult life span and that reliance on spatial skills for coordinating deadlines is modulated by age.

  17. Age-Related Differences in Multiple Task Monitoring

    PubMed Central

    Todorov, Ivo; Del Missier, Fabio; Mäntylä, Timo

    2014-01-01

    Coordinating multiple tasks with narrow deadlines is particularly challenging for older adults because of age related decline in cognitive control functions. We tested the hypothesis that multiple task performance reflects age- and gender-related differences in executive functioning and spatial ability. Young and older adults completed a multitasking session with four monitoring tasks as well as separate tasks measuring executive functioning and spatial ability. For both age groups, men exceeded women in multitasking, measured as monitoring accuracy. Individual differences in executive functioning and spatial ability were independent predictors of young adults' monitoring accuracy, but only spatial ability was related to sex differences. For older adults, age and executive functioning, but not spatial ability, predicted multitasking performance. These results suggest that executive functions contribute to multiple task performance across the adult life span and that reliance on spatial skills for coordinating deadlines is modulated by age. PMID:25215609

  18. Declining well yields related to depth in fractured rocks - Use of an exponential equation

    SciTech Connect

    Page, R.W. )

    1993-03-01

    In southwestern Nevada County, where most wells are drilled into granitic or metamorphic rocks, well yields were found to decrease with increasing well depth. Data from that report indicated that declining well yields in the area probably could be approximated by an exponential equation. The purpose of this report is to demonstrate that an exponential equation can be used to approximate declining well yields related to depth in hard-rock areas of granitic and metamorphic rocks in the western foothills of the Sierra Nevada. The scope includes applying this equation to data from southwestern Nevada County, California.

  19. Decline of Phosphotransfer and Substrate Supply Metabolic Circuits Hinders ATP Cycling in Aging Myocardium.

    PubMed

    Nemutlu, Emirhan; Gupta, Anu; Zhang, Song; Viqar, Maria; Holmuhamedov, Ekhson; Terzic, Andre; Jahangir, Arshad; Dzeja, Petras

    2015-01-01

    Integration of mitochondria with cytosolic ATP-consuming/ATP-sensing and substrate supply processes is critical for muscle bioenergetics and electrical activity. Whether age-dependent muscle weakness and increased electrical instability depends on perturbations in cellular energetic circuits is unknown. To define energetic remodeling of aged atrial myocardium we tracked dynamics of ATP synthesis-utilization, substrate supply, and phosphotransfer circuits through adenylate kinase (AK), creatine kinase (CK), and glycolytic/glycogenolytic pathways using 18O stable isotope-based phosphometabolomic technology. Samples of intact atrial myocardium from adult and aged rats were subjected to 18O-labeling procedure at resting basal state, and analyzed using the 18O-assisted HPLC-GC/MS technique. Characteristics for aging atria were lower inorganic phosphate Pi[18O], γ-ATP[18O], β-ADP[18O], and creatine phosphate CrP[18O] 18O-labeling rates indicating diminished ATP utilization-synthesis and AK and CK phosphotransfer fluxes. Shift in dynamics of glycolytic phosphotransfer was reflected in the diminished G6P[18O] turnover with relatively constant glycogenolytic flux or G1P[18O] 18O-labeling. Labeling of G3P[18O], an indicator of G3P-shuttle activity and substrate supply to mitochondria, was depressed in aged myocardium. Aged atrial myocardium displayed reduced incorporation of 18O into second (18O2), third (18O3), and fourth (18O4) positions of Pi[18O] and a lower Pi[18O]/γ-ATP[18 O]-labeling ratio, indicating delayed energetic communication and ATP cycling between mitochondria and cellular ATPases. Adrenergic stress alleviated diminished CK flux, AK catalyzed β-ATP turnover and energetic communication in aging atria. Thus, 18O-assisted phosphometabolomics uncovered simultaneous phosphotransfer through AK, CK, and glycolytic pathways and G3P substrate shuttle deficits hindering energetic communication and ATP cycling, which may underlie energetic vulnerability of aging

  20. Decline of Phosphotransfer and Substrate Supply Metabolic Circuits Hinders ATP Cycling in Aging Myocardium.

    PubMed

    Nemutlu, Emirhan; Gupta, Anu; Zhang, Song; Viqar, Maria; Holmuhamedov, Ekhson; Terzic, Andre; Jahangir, Arshad; Dzeja, Petras

    2015-01-01

    Integration of mitochondria with cytosolic ATP-consuming/ATP-sensing and substrate supply processes is critical for muscle bioenergetics and electrical activity. Whether age-dependent muscle weakness and increased electrical instability depends on perturbations in cellular energetic circuits is unknown. To define energetic remodeling of aged atrial myocardium we tracked dynamics of ATP synthesis-utilization, substrate supply, and phosphotransfer circuits through adenylate kinase (AK), creatine kinase (CK), and glycolytic/glycogenolytic pathways using 18O stable isotope-based phosphometabolomic technology. Samples of intact atrial myocardium from adult and aged rats were subjected to 18O-labeling procedure at resting basal state, and analyzed using the 18O-assisted HPLC-GC/MS technique. Characteristics for aging atria were lower inorganic phosphate Pi[18O], γ-ATP[18O], β-ADP[18O], and creatine phosphate CrP[18O] 18O-labeling rates indicating diminished ATP utilization-synthesis and AK and CK phosphotransfer fluxes. Shift in dynamics of glycolytic phosphotransfer was reflected in the diminished G6P[18O] turnover with relatively constant glycogenolytic flux or G1P[18O] 18O-labeling. Labeling of G3P[18O], an indicator of G3P-shuttle activity and substrate supply to mitochondria, was depressed in aged myocardium. Aged atrial myocardium displayed reduced incorporation of 18O into second (18O2), third (18O3), and fourth (18O4) positions of Pi[18O] and a lower Pi[18O]/γ-ATP[18 O]-labeling ratio, indicating delayed energetic communication and ATP cycling between mitochondria and cellular ATPases. Adrenergic stress alleviated diminished CK flux, AK catalyzed β-ATP turnover and energetic communication in aging atria. Thus, 18O-assisted phosphometabolomics uncovered simultaneous phosphotransfer through AK, CK, and glycolytic pathways and G3P substrate shuttle deficits hindering energetic communication and ATP cycling, which may underlie energetic vulnerability of aging

  1. The Association of Levels of and Decline in Grip Strength in Old Age with Trajectories of Life Course Occupational Position

    PubMed Central

    Fritzell, Johan; Hoffmann, Rasmus

    2016-01-01

    Background The study of the influence of life course occupational position (OP) on health in old age demands analysis of time patterns in both OP and health. We study associations between life course time patterns of OP and decline in grip strength in old age. Methods We analyze 5 waves from the Survey of Health Ageing and Retirement in Europe (n = 5108, ages 65–90). We use a pattern-mixture latent growth model to predict the level and decline in grip strength in old age by trajectory of life course OP. We extend and generalize the structured regression approach to establish the explanatory power of different life course models for both the level and decline of grip strength. Results Grip strength declined linearly by 0.70 kg (95% CI -0.74;-0.66) for men and 0.42 kg (95% CI -0.45;-0.39) for women per year. The level of men’s grip strength can best be explained by a critical period during midlife, with those exposed to low OP during this period having 1.67 kg (95% CI -2.33;-1.00) less grip strength. These differences remain constant over age. For women, no association between OP and levels of or decline in grip strength was found. Conclusions Men’s OP in midlife seems to be a critical period for the level of grip strength in old age. Inequalities remain constant over age. The integration of the structured regression approach and latent growth modelling offers new possibilities for life course epidemiology. PMID:27232696

  2. A TOMM40 poly-T variant modulates gene expression and is associated with vocabulary ability and decline in nonpathologic aging.

    PubMed

    Payton, A; Sindrewicz, P; Pessoa, V; Platt, H; Horan, M; Ollier, W; Bubb, V J; Pendleton, N; Quinn, J P

    2016-03-01

    The Translocase of Outer Mitochondrial Membrane 40 Homolog and Apolipoprotein E (TOMM40-APOE) locus has been associated with a number of age-related phenotypes in humans including nonpathologic cognitive aging, late-onset Alzheimer's disease, and longevity. Here, we investigate the influence of the TOMM40 intron 6 poly-T variant (rs10524523) on TOMM40 gene expression and cognitive abilities and decline in a cohort of 1613 community-dwelling elderly volunteers who had been followed for changes in cognitive functioning over a period of 14 years (range = 12-18 years). We showed that the shorter length poly-T variants were found to act as a repressor of luciferase gene expression in reporter gene constructs. Expression was reduced to approximately half of that observed for the very long variant. We further observed that the shorter poly-T variant was significantly associated with reduced vocabulary ability and a slower rate of vocabulary decline with age compared to the very long poly-T variants. No significant associations were observed for memory, fluid intelligence or processing speed, although the direction of effect, where the short variant was correlated with reduced ability and slower rate of decline was observed for all tests. Our results indicate that the poly-T variant has the ability to interact with transcription machinery and differentially modulate reporter gene expression and influence vocabulary ability and decline with age.

  3. Involuntary Capture and Voluntary Reorienting of Attention Decline in Middle-Aged and Old Participants.

    PubMed

    Correa-Jaraba, Kenia S; Cid-Fernández, Susana; Lindín, Mónica; Díaz, Fernando

    2016-01-01

    The main aim of this study was to examine the effects of aging on event-related brain potentials (ERPs) associated with the automatic detection of unattended infrequent deviant and novel auditory stimuli (Mismatch Negativity, MMN) and with the orienting to these stimuli (P3a component), as well as the effects on ERPs associated with reorienting to relevant visual stimuli (Reorienting Negativity, RON). Participants were divided into three age groups: (1) Young: 21-29 years old; (2) Middle-aged: 51-64 years old; and (3) Old: 65-84 years old. They performed an auditory-visual distraction-attention task in which they were asked to attend to visual stimuli (Go, NoGo) and to ignore auditory stimuli (S: standard, D: deviant, N: novel). Reaction times (RTs) to Go visual stimuli were longer in old and middle-aged than in young participants. In addition, in all three age groups, longer RTs were found when Go visual stimuli were preceded by novel relative to deviant and standard auditory stimuli, indicating a distraction effect provoked by novel stimuli. ERP components were identified in the Novel minus Standard (N-S) and Deviant minus Standard (D-S) difference waveforms. In the N-S condition, MMN latency was significantly longer in middle-aged and old participants than in young participants, indicating a slowing of automatic detection of changes. The following results were observed in both difference waveforms: (1) the P3a component comprised two consecutive phases in all three age groups-an early-P3a (e-P3a) that may reflect the orienting response toward the irrelevant stimulation and a late-P3a (l-P3a) that may be a correlate of subsequent evaluation of the infrequent unexpected novel or deviant stimuli; (2) the e-P3a, l-P3a, and RON latencies were significantly longer in the Middle-aged and Old groups than in the Young group, indicating delay in the orienting response to and the subsequent evaluation of unattended auditory stimuli, and in the reorienting of attention to

  4. Involuntary Capture and Voluntary Reorienting of Attention Decline in Middle-Aged and Old Participants

    PubMed Central

    Correa-Jaraba, Kenia S.; Cid-Fernández, Susana; Lindín, Mónica; Díaz, Fernando

    2016-01-01

    The main aim of this study was to examine the effects of aging on event-related brain potentials (ERPs) associated with the automatic detection of unattended infrequent deviant and novel auditory stimuli (Mismatch Negativity, MMN) and with the orienting to these stimuli (P3a component), as well as the effects on ERPs associated with reorienting to relevant visual stimuli (Reorienting Negativity, RON). Participants were divided into three age groups: (1) Young: 21–29 years old; (2) Middle-aged: 51–64 years old; and (3) Old: 65–84 years old. They performed an auditory-visual distraction-attention task in which they were asked to attend to visual stimuli (Go, NoGo) and to ignore auditory stimuli (S: standard, D: deviant, N: novel). Reaction times (RTs) to Go visual stimuli were longer in old and middle-aged than in young participants. In addition, in all three age groups, longer RTs were found when Go visual stimuli were preceded by novel relative to deviant and standard auditory stimuli, indicating a distraction effect provoked by novel stimuli. ERP components were identified in the Novel minus Standard (N-S) and Deviant minus Standard (D-S) difference waveforms. In the N-S condition, MMN latency was significantly longer in middle-aged and old participants than in young participants, indicating a slowing of automatic detection of changes. The following results were observed in both difference waveforms: (1) the P3a component comprised two consecutive phases in all three age groups—an early-P3a (e-P3a) that may reflect the orienting response toward the irrelevant stimulation and a late-P3a (l-P3a) that may be a correlate of subsequent evaluation of the infrequent unexpected novel or deviant stimuli; (2) the e-P3a, l-P3a, and RON latencies were significantly longer in the Middle-aged and Old groups than in the Young group, indicating delay in the orienting response to and the subsequent evaluation of unattended auditory stimuli, and in the reorienting of

  5. Risk Factors for Late-Life Cognitive Decline and Variation with Age and Sex in the Sydney Memory and Ageing Study

    PubMed Central

    Lipnicki, Darren M.; Sachdev, Perminder S.; Crawford, John; Reppermund, Simone; Kochan, Nicole A.; Trollor, Julian N.; Draper, Brian; Slavin, Melissa J.; Kang, Kristan; Lux, Ora; Mather, Karen A.; Brodaty, Henry

    2013-01-01

    Introduction An aging population brings increasing burdens and costs to individuals and society arising from late-life cognitive decline, the causes of which are unclear. We aimed to identify factors predicting late-life cognitive decline. Methods Participants were 889 community-dwelling 70–90-year-olds from the Sydney Memory and Ageing Study with comprehensive neuropsychological assessments at baseline and a 2-year follow-up and initially without dementia. Cognitive decline was considered as incident mild cognitive impairment (MCI) or dementia, as well as decreases in attention/processing speed, executive function, memory, and global cognition. Associations with baseline demographic, lifestyle, health and medical factors were determined. Results All cognitive measures showed decline and 14% of participants developed incident MCI or dementia. Across all participants, risk factors for decline included older age and poorer smelling ability most prominently, but also more education, history of depression, being male, higher homocysteine, coronary artery disease, arthritis, low health status, and stroke. Protective factors included marriage, kidney disease, and antidepressant use. For some of these factors the association varied with age or differed between men and women. Additional risk and protective factors that were strictly age- and/or sex-dependent were also identified. We found salient population attributable risks (8.7–49.5%) for older age, being male or unmarried, poor smelling ability, coronary artery disease, arthritis, stroke, and high homocysteine. Discussion Preventing or treating conditions typically associated with aging might reduce population-wide late-life cognitive decline. Interventions tailored to particular age and sex groups may offer further benefits. PMID:23799051

  6. Pathophysiology of ageing, longevity and age related diseases

    PubMed Central

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

    2007-01-01

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

  7. Declining fertility in England and Wales as a major cause of the twentieth century decline in mortality. The role of changing family size and age structure in infectious disease mortality in infancy.

    PubMed

    Reves, R

    1985-07-01

    The decline in infectious disease mortality in England and Wales beginning about 1880 has been attributed to improved nutrition, hygiene, and sanitation. Such an explanation does not adequately explain the lack of improvement in infant and diarrheal disease mortality before 1900 nor the abrupt subsequent decline. A hypothesis was proposed that the decline in fertility rate was a major cause of the decline in infant mortality by raising the median age at infection. The hypothesis could only be tested indirectly. A review of morbidity data demonstrates the importance of family characteristics on the median age at infection for measles, pertussis, and common respiratory illness. The association of parity with infectious disease mortality supports the hypothesis. A method was developed for estimating the change in birth order distribution resulting from declining fertility. Using 1949-1950 data, it was shown that declining fertility could account for at least a 24% decline in postneonatal mortality due to bronchitis and pneumonia. Age-specific measles mortality rates are consistent, with an increase in age at infection. Declining fertility appears to have played a major role in the decline in infectious disease mortality in England and Wales by increasing the median age at infection.

  8. Overcoming Age-Related Differences

    ERIC Educational Resources Information Center

    Agullo, Gloria Luque

    2006-01-01

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

  9. Early age-related changes in episodic memory retrieval as revealed by event-related potentials.

    PubMed

    Guillaume, Cécile; Clochon, Patrice; Denise, Pierre; Rauchs, Géraldine; Guillery-Girard, Bérengère; Eustache, Francis; Desgranges, Béatrice

    2009-01-28

    Familiarity is better preserved than recollection in ageing. The age at which changes first occur and the slope of the subsequent decline, however, remain unclear. In this study, we investigated changes in episodic memory, by using event-related potentials (ERPs) in young (m=24), middle-aged (m=58) and older (m=70) adults. Although behavioural performance did not change before the age of 65 years, changes in ERP correlates were already present in the middle-aged adults. The ERP correlates of recollection and monitoring processes were the first to be affected by ageing, with a linear decrease as age increased. Conversely, the ERP correlate of familiarity remained unchanged, at least up to the age of 65 years. These results suggest a differential time course for the age effects on episodic retrieval. PMID:19104457

  10. Incident Subjective Cognitive Decline Does Not Predict Mortality in the Elderly – Results from the Longitudinal German Study on Ageing, Cognition, and Dementia (AgeCoDe)

    PubMed Central

    Roehr, Susanne; Luck, Tobias; Heser, Kathrin; Fuchs, Angela; Ernst, Annette; Wiese, Birgitt; Werle, Jochen; Bickel, Horst; Brettschneider, Christian; Koppara, Alexander; Pentzek, Michael; Lange, Carolin; Prokein, Jana; Weyerer, Siegfried; Mösch, Edelgard; König, Hans-Helmut; Maier, Wolfgang; Scherer, Martin

    2016-01-01

    Objective Subjective cognitive decline (SCD) might represent the first symptomatic representation of Alzheimer’s disease (AD), which is associated with increased mortality. Only few studies, however, have analyzed the association of SCD and mortality, and if so, based on prevalent cases. Thus, we investigated incident SCD in memory and mortality. Methods Data were derived from the German AgeCoDe study, a prospective longitudinal study on the epidemiology of mild cognitive impairment (MCI) and dementia in primary care patients over 75 years covering an observation period of 7.5 years. We used univariate and multivariate Cox regression analyses to examine the relationship of SCD and mortality. Further, we estimated survival times by the Kaplan Meier method and case-fatality rates with regard to SCD. Results Among 971 individuals without objective cognitive impairment, 233 (24.0%) incidentally expressed SCD at follow-up I. Incident SCD was not significantly associated with increased mortality in the univariate (HR = 1.0, 95% confidence interval = 0.8–1.3, p = .90) as well as in the multivariate analysis (HR = 0.9, 95% confidence interval = 0.7–1.2, p = .40). The same applied for SCD in relation to concerns. Mean survival time with SCD was 8.0 years (SD = 0.1) after onset. Conclusion Incident SCD in memory in individuals with unimpaired cognitive performance does not predict mortality. The main reason might be that SCD does not ultimately lead into future cognitive decline in any case. However, as prevalence studies suggest, subjectively perceived decline in non-memory cognitive domains might be associated with increased mortality. Future studies may address mortality in such other cognitive domains of SCD in incident cases. PMID:26766555

  11. Decline in relative abundance of bottlenose dolphins exposed to long-term disturbance.

    PubMed

    Bejder, Lars; Samuels, Amy; Whitehead, Hal; Gales, Nick; Mann, Janet; Connor, Richard; Heithaus, Mike; Watson-Capps, Jana; Flaherty, Cindy; Krützen, Michael

    2006-12-01

    Studies evaluating effects of human activity on wildlife typically emphasize short-term behavioral responses from which it is difficult to infer biological significance or formulate plans to mitigate harmful impacts. Based on decades of detailed behavioral records, we evaluated long-term impacts of vessel activity on bottlenose dolphins (Tursiops sp.) in Shark Bay, Australia. We compared dolphin abundance within adjacent 36-km2 tourism and control sites, over three consecutive 4.5-year periods wherein research activity was relatively constant but tourism levels increased from zero, to one, to two dolphin-watching operators. A nonlinear logistic model demonstrated that there was no difference in dolphin abundance between periods with no tourism and periods in which one operator offered tours. As the number of tour operators increased to two, there was a significant average decline in dolphin abundance (14.9%; 95% CI=-20.8 to -8.23), approximating a decline of one per seven individuals. Concurrently, within the control site, the average increase in dolphin abundance was not significant (8.5%; 95% CI=-4.0 to +16.7). Given the substantially greater presence and proximity of tour vessels to dolphins relative to research vessels, tour-vessel activity contributed more to declining dolphin numbers within the tourism site than research vessels. Although this trend may not jeopardize the large, genetically diverse dolphin population of Shark Bay, the decline is unlikely to be sustainable for local dolphin tourism. A similar decline would be devastating for small, closed, resident, or endangered cetacean populations. The substantial effect of tour vessels on dolphin abundance in a region of low-level tourism calls into question the presumption that dolphin-watching tourism is benign.

  12. 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...

  13. Physiological neuronal decline in healthy aging human brain - An in vivo study with MRI and short echo-time whole-brain (1)H MR spectroscopic imaging.

    PubMed

    Ding, Xiao-Qi; Maudsley, Andrew A; Sabati, Mohammad; Sheriff, Sulaiman; Schmitz, Birte; Schütze, Martin; Bronzlik, Paul; Kahl, Kai G; Lanfermann, Heinrich

    2016-08-15

    Knowledge of physiological aging in healthy human brain is increasingly important for neuroscientific research and clinical diagnosis. To investigate neuronal decline in normal aging brain eighty-one healthy subjects aged between 20 and 70years were studied with MRI and whole-brain (1)H MR spectroscopic imaging. Concentrations of brain metabolites N-acetyl-aspartate (NAA), choline (Cho), total creatine (tCr), myo-inositol (mI), and glutamine+glutamate (Glx) in ratios to internal water, and the fractional volumes of brain tissue were estimated simultaneously in eight cerebral lobes and in cerebellum. Results demonstrated that an age-related decrease in gray matter volume was the largest contribution to changes in brain volume. Both lobar NAA and the fractional volume of gray matter (FVGM) decreased with age in all cerebral lobes, indicating that the decreased NAA was predominantly associated with decreased gray matter volume and neuronal density or metabolic activity. In cerebral white matter Cho, tCr, and mI increased with age in association with increased fractional volume, showing altered cellular membrane turn-over, energy metabolism, and glial activity in human aging white matter. In cerebellum tCr increased while brain tissue volume decreased with age, showing difference to cerebral aging. The observed age-related metabolic and microstructural variations suggest that physiological neuronal decline in aging human brain is associated with a reduction of gray matter volume and neuronal density, in combination with cellular aging in white matter indicated by microstructural alterations and altered energy metabolism in the cerebellum. PMID:27164326

  14. Physiological neuronal decline in healthy aging human brain - An in vivo study with MRI and short echo-time whole-brain (1)H MR spectroscopic imaging.

    PubMed

    Ding, Xiao-Qi; Maudsley, Andrew A; Sabati, Mohammad; Sheriff, Sulaiman; Schmitz, Birte; Schütze, Martin; Bronzlik, Paul; Kahl, Kai G; Lanfermann, Heinrich

    2016-08-15

    Knowledge of physiological aging in healthy human brain is increasingly important for neuroscientific research and clinical diagnosis. To investigate neuronal decline in normal aging brain eighty-one healthy subjects aged between 20 and 70years were studied with MRI and whole-brain (1)H MR spectroscopic imaging. Concentrations of brain metabolites N-acetyl-aspartate (NAA), choline (Cho), total creatine (tCr), myo-inositol (mI), and glutamine+glutamate (Glx) in ratios to internal water, and the fractional volumes of brain tissue were estimated simultaneously in eight cerebral lobes and in cerebellum. Results demonstrated that an age-related decrease in gray matter volume was the largest contribution to changes in brain volume. Both lobar NAA and the fractional volume of gray matter (FVGM) decreased with age in all cerebral lobes, indicating that the decreased NAA was predominantly associated with decreased gray matter volume and neuronal density or metabolic activity. In cerebral white matter Cho, tCr, and mI increased with age in association with increased fractional volume, showing altered cellular membrane turn-over, energy metabolism, and glial activity in human aging white matter. In cerebellum tCr increased while brain tissue volume decreased with age, showing difference to cerebral aging. The observed age-related metabolic and microstructural variations suggest that physiological neuronal decline in aging human brain is associated with a reduction of gray matter volume and neuronal density, in combination with cellular aging in white matter indicated by microstructural alterations and altered energy metabolism in the cerebellum.

  15. Decline in Cognitive Function and Risk of Elder Self-Neglect: Finding from the Chicago Health Aging Project

    PubMed Central

    Dong, XinQi; Simon, Melissa A.; Wilson, Robert S.; Mendes de Leon, Carlos F.; Rajan, K. Bharat; Evans, Denis A.

    2010-01-01

    Objectives This study aimed to examine the longitudinal association between decline in cognitive function and risk of elder self-neglect in a community-dwelling population. Design Prospective population-based study Setting Geographically-defined community in Chicago. Participants Community-dwelling subjects reported to the social services agency from 1993–2005 for self-neglect who also participated in the Chicago Health Aging Project (CHAP). Of the 5,519 participants in the Chicago Health Aging Project, 1,017 were reported to social services agency for suspected elder self-neglect from 1993–2005. Measurements Reported elder self-neglect was identified by social services agency. The primary predictor was decline in cognitive function assessed using the Mini-Mental State Examination (MMSE), the Symbol Digit Modalities Test (Executive Function), and both immediate and delayed recall of the East Boston Memory Test (Episodic Memory). An index of global cognitive function scores was derived by averaging z-scores of all tests. Outcome of interest was elder self-neglect. Logistic and linear regression models were used to assess these longitudinal associations. Results After adjusting for potential confounding factors, decline in global cognitive function, MMSE or episodic memory was not independently associated with increased risk of reported and confirmed elder self-neglect. Decline in executive function was associated with increased risk of reported and confirmed elder self-neglect. Decline in global cognitive function was associated with increased risk of greater self-neglect severity (PE=0.76, SE=0.31, p=0.014). Conclusion Decline in executive function was associated with increased risk of reported and confirmed elder self-neglect. Decline in global cognitive function was associated with increased risk of greater self-neglect severity. PMID:21143438

  16. Telomere length variations in aging and age-related diseases.

    PubMed

    Rizvi, Saliha; Raza, Syed Tasleem; Mahdi, Farzana

    2014-01-01

    Telomeres are gene sequences present at chromosomal ends and are responsible for maintaining genome integrity. Telomere length is maximum at birth and decreases progressively with advancing age and thus is considered as a biomarker of chronological aging. This age associated decrease in the length of telomere is linked to various ageing associated diseases like diabetes, hypertension, Alzheimer's disease, cancer etc. and their associated complications. Telomere length is a result of combined effect of oxidative stress, inflammation and repeated cell replication on it, and thus forming an association between telomere length and chronological aging and related diseases. Thus, decrease in telomere length was found to be important in determining both, the variations in longevity and age-related diseases in an individual. Ongoing and progressive research in the field of telomere length dynamics has proved that aging and age-related diseases apart from having a synergistic effect on telomere length were also found to effect telomere length independently also. Here a short description about telomere length variations and its association with human aging and age-related diseases is reviewed.

  17. Trajectories of memory decline in preclinical Alzheimer's disease: results from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of ageing.

    PubMed

    Pietrzak, Robert H; Lim, Yen Ying; Ames, David; Harrington, Karra; Restrepo, Carolina; Martins, Ralph N; Rembach, Alan; Laws, Simon M; Masters, Colin L; Villemagne, Victor L; Rowe, Christopher C; Maruff, Paul

    2015-03-01

    Memory changes in preclinical Alzheimer's disease (AD) are often characterized by heterogenous trajectories. However, data regarding the nature and determinants of predominant trajectories of memory changes in preclinical AD are lacking. We analyzed data from 333 cognitively healthy older adults who participated in a multicenter prospective cohort study with baseline and 18-, 36-, and 54-month follow-up assessments. Latent growth mixture modeling revealed 3 predominant trajectories of memory change: a below average, subtly declining memory trajectory (30.9%); a below average, rapidly declining memory trajectory (3.6%); and an above average, stable memory trajectory (65.5%). Compared with the stable memory trajectory, high Αβ (relative risk ratio [RRR] = 2.1), and lower Mini-Mental State Examination (RRR = 0.6) and full-scale IQ (RRR = 0.9) scores were independently associated with the subtly declining memory trajectory; and high Αβ (RRR = 8.3), APOE ε4 carriage (RRR = 6.1), and greater subjective memory impairment (RRR = 1.2) were independently associated with the rapidly declining memory trajectory. Compared with the subtly declining memory trajectory group, APOE ε4 carriage (RRR = 8.4), and subjective memory complaints (RRR = 1.2) were associated with a rapidly declining memory trajectory. These results suggest that the preclinical phase of AD may be characterized by 2 predominant trajectories of memory decline that have common (e.g., high Αβ) and unique (e.g., APOE ε4 genotype) determinants. PMID:25585532

  18. Longitudinal decline of leukocyte telomere length in old age and the association with sex and genetic risk

    PubMed Central

    Berglund, Kari; Reynolds, Chandra A.; Ploner, Alexander; Gerritsen, Lotte; Hovatta, Iiris; Pedersen, Nancy L.; Hägg, Sara

    2016-01-01

    Telomeres are DNA-protein structures at the ends of chromosomes. Leukocyte telomere length (LTL) shortening has been associated with advanced age. However, most studies use cross-sectional data, hence, the aim of our study was to model longitudinal trajectories of LTL attrition across 20 years at old age. Assessments of LTL were done by qPCR in SATSA (Swedish Adoption/Twin Study of Aging; N=636 individuals). Cross-sectional and longitudinal associations with age were estimated, the latter using latent growth curve analysis. A genetic risk score (GRS) for LTL was further assessed and included in the models. We confirmed an inverse cross-sectional association of LTL with age (B=−0.0022 T/S-ratio; 95% CI: −0.0035, −0.0009, p-value=0.0008). Longitudinal LTL analyses adjusted for sex (1598 samples; ≤5 measurements) suggested modest average decline until 69 years of age but accelerating decline after 69 years, with significant inter-individual variation. Women had on average ∼6% T/S-ratio units longer LTL at baseline, and inclusion of the GRS improved the model where four risk alleles was equivalent to the effect size difference between the sexes. In this cohort of old individuals, baseline LTL varied with age, sex and genetic background. The rate of change of LTL accelerated with age and varied considerably between individuals. PMID:27391763

  19. Longitudinal decline of leukocyte telomere length in old age and the association with sex and genetic risk.

    PubMed

    Berglund, Kari; Reynolds, Chandra A; Ploner, Alexander; Gerritsen, Lotte; Hovatta, Iiris; Pedersen, Nancy L; Hägg, Sara

    2016-07-01

    Telomeres are DNA-protein structures at the ends of chromosomes. Leukocyte telomere length (LTL) shortening has been associated with advanced age. However, most studies use cross-sectional data, hence, the aim of our study was to model longitudinal trajectories of LTL attrition across 20 years at old age. Assessments of LTL were done by qPCR in SATSA (Swedish Adoption/Twin Study of Aging; N=636 individuals). Cross-sectional and longitudinal associations with age were estimated, the latter using latent growth curve analysis. A genetic risk score (GRS) for LTL was further assessed and included in the models. We confirmed an inverse cross-sectional association of LTL with age (B=-0.0022 T/S-ratio; 95% CI: -0.0035, -0.0009, p-value=0.0008). Longitudinal LTL analyses adjusted for sex (1598 samples; ≤5 measurements) suggested modest average decline until 69 years of age but accelerating decline after 69 years, with significant inter-individual variation. Women had on average ~6% T/S-ratio units longer LTL at baseline, and inclusion of the GRS improved the model where four risk alleles was equivalent to the effect size difference between the sexes. In this cohort of old individuals, baseline LTL varied with age, sex and genetic background. The rate of change of LTL accelerated with age and varied considerably between individuals. PMID:27391763

  20. Longitudinal decline of leukocyte telomere length in old age and the association with sex and genetic risk.

    PubMed

    Berglund, Kari; Reynolds, Chandra A; Ploner, Alexander; Gerritsen, Lotte; Hovatta, Iiris; Pedersen, Nancy L; Hägg, Sara

    2016-07-01

    Telomeres are DNA-protein structures at the ends of chromosomes. Leukocyte telomere length (LTL) shortening has been associated with advanced age. However, most studies use cross-sectional data, hence, the aim of our study was to model longitudinal trajectories of LTL attrition across 20 years at old age. Assessments of LTL were done by qPCR in SATSA (Swedish Adoption/Twin Study of Aging; N=636 individuals). Cross-sectional and longitudinal associations with age were estimated, the latter using latent growth curve analysis. A genetic risk score (GRS) for LTL was further assessed and included in the models. We confirmed an inverse cross-sectional association of LTL with age (B=-0.0022 T/S-ratio; 95% CI: -0.0035, -0.0009, p-value=0.0008). Longitudinal LTL analyses adjusted for sex (1598 samples; ≤5 measurements) suggested modest average decline until 69 years of age but accelerating decline after 69 years, with significant inter-individual variation. Women had on average ~6% T/S-ratio units longer LTL at baseline, and inclusion of the GRS improved the model where four risk alleles was equivalent to the effect size difference between the sexes. In this cohort of old individuals, baseline LTL varied with age, sex and genetic background. The rate of change of LTL accelerated with age and varied considerably between individuals.

  1. Relational learning and transitive expression in aging and amnesia.

    PubMed

    Ryan, Jennifer D; D'Angelo, Maria C; Kamino, Daphne; Ostreicher, Melanie; Moses, Sandra N; Rosenbaum, R Shayna

    2016-02-01

    Aging has been associated with a decline in relational memory, which is critically supported by the hippocampus. By adapting the transitivity paradigm (Bunsey and Eichenbaum (1996) Nature 379:255-257), which traditionally has been used in nonhuman animal research, this work examined the extent to which aging is accompanied by deficits in relational learning and flexible expression of relational information. Older adults' performance was additionally contrasted with that of amnesic case DA to understand the critical contributions of the medial temporal lobe, and specifically, the hippocampus, which endures structural and functional changes in healthy aging. Participants were required to select the correct choice item (B versus Y) based on the presented sample item (e.g., A). Pairwise relations must be learned (A->B, B->C, C->D) so that ultimately, the correct relations can be inferred when presented with a novel probe item (A->C?Z?). Participants completed four conditions of transitivity that varied in terms of the degree to which the stimuli and the relations among them were known pre-experimentally. Younger adults, older adults, and DA performed similarly when the condition employed all pre-experimentally known, semantic, relations. Older adults and DA were less accurate than younger adults when all to-be-learned relations were arbitrary. However, accuracy improved for older adults when they could use pre-experimentally known pairwise relations to express understanding of arbitrary relations as indexed through inference judgments. DA could not learn arbitrary relations nor use existing knowledge to support novel inferences. These results suggest that while aging has often been associated with an emerging decline in hippocampal function, prior knowledge can be used to support novel inferences. However, in case DA, significant damage to the hippocampus likely impaired his ability to learn novel relations, while additional damage to ventromedial prefrontal and

  2. Do testosterone declines during the transition to marriage and fatherhood relate to men's sexual behavior? Evidence from the Philippines.

    PubMed

    Gettler, Lee T; McDade, Thomas W; Agustin, Sonny S; Feranil, Alan B; Kuzawa, Christopher W

    2013-11-01

    Testosterone (T) is thought to help facilitate trade-offs between mating and parenting in humans. Across diverse cultural settings married men and fathers have lower T than other men and couples' sexual activity often declines during the first years of marriage and after having children. It is unknown whether these behavioral and hormonal changes are related. Here we use longitudinal data from a large study in the Philippines (n=433) to test this model. We show that among unmarried non-fathers at baseline (n=153; age: 21.5 ± 0.3 years) who became newly married new fathers by follow-up (4.5 years later), those who experienced less pronounced longitudinal declines in T reported more frequent intercourse with their partners at follow-up (p<0.01) compared to men with larger declines in T. Controlling for duration of marriage, findings were similar for men transitioning from unmarried to married (without children) (p<0.05). Men who remained unmarried and childless throughout the study period did not show similar T-sexual activity outcomes. Among newly married new fathers, subjects who had frequent intercourse both before and after the transition to married fatherhood had more modest declines in T compared to peers who had less frequent sex (p<0.001). Our findings are generally consistent with theoretical expectations and cross-species empirical observations regarding the role of T in male life history trade-offs, particularly in species with bi-parental care, and add to evidence that T and sexual activity have bidirectional relationships in human males.

  3. 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…

  4. Age-related aspects of addiction

    PubMed Central

    Koechl, Birgit; Unger, Annemarie; Fischer, Gabriele

    2013-01-01

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

  5. Aging related changes in determinants of muscle force generating capacity: a comparison of muscle aging in men and male rodents.

    PubMed

    Ballak, Sam B; Degens, Hans; de Haan, Arnold; Jaspers, Richard T

    2014-03-01

    Human aging is associated with a progressive decline in skeletal muscle mass and force generating capacity, however the exact mechanisms underlying these changes are not fully understood. Rodents models have often been used to enhance our understanding of mechanisms of age-related changes in human skeletal muscle. However, to what extent age-related alterations in determinants of muscle force generating capacity observed in rodents resemble those in humans has not been considered thoroughly. This review compares the effect of aging on muscle force generating determinants (muscle mass, fiber size, fiber number, fiber type distribution and muscle specific tension), in men and male rodents at similar relative age. It appears that muscle aging in male F344*BN rat resembles that in men most; 32-35-month-old rats exhibit similar signs of muscle weakness to those of 70-80-yr-old men, and the decline in 36-38-month-old rats is similar to that in men aged over 80 yrs. For male C57BL/6 mice, age-related decline in muscle force generating capacity seems to occur only at higher relative age than in men. We conclude that the effects on determinants of muscle force differ between species as well as within species, but qualitatively show the same pattern as that observed in men.

  6. Enjoyment of life and declining physical function at older ages: a longitudinal cohort study

    PubMed Central

    Steptoe, Andrew; de Oliveira, Cesar; Demakakos, Panayotes; Zaninotto, Paola

    2014-01-01

    Background: Positive affective well-being (i.e., feelings of happiness and enjoyment) has been associated with longer survival and reduced incidence of serious illness. Our objective was to discover whether enjoyment of life also predicted a reduced risk of functional impairment over an 8-year period in a large population sample. Methods: We carried out a prospective analysis involving 3199 men and women aged 60 years or older from the English Longitudinal Study of Ageing. Enjoyment of life was assessed by questionnaire. Outcomes were impairment in 2 or more activities of daily living and changes in gait speed on a walking test. Covariates included sociodemographic factors, baseline health, depressive symptoms, impairment of mobility and health behaviours. Results: Two or more impaired activities of daily living developed among 4.4%, 11.7% and 16.8% of participants in the high, medium and low enjoyment-of-life tertiles, respectively. After adjustment for covariates, the odds of impaired activities of daily living developing were 1.83 (95% confidence interval 1.13–2.96) in the low compared with high tertile. Gait speed after 8 years was also related to baseline enjoyment of life after adjustment for gait speed and other covariates at baseline (p < 0.001). We obtained similar results when we limited analyses to participants younger than 70 years at baseline. Interpretation: This is an observational study, so causal conclusions cannot be drawn. But our results provide evidence that reduced enjoyment of life may be related to the future disability and mobility of older people. PMID:24446463

  7. Epigenetic modification of PKMζ rescues aging-related cognitive impairment.

    PubMed

    Chen, Chen; Meng, Shi-Qiu; Xue, Yan-Xue; Han, Ying; Sun, Cheng-Yu; Deng, Jia-Hui; Chen, Na; Bao, Yan-Ping; Zhang, Fei-Long; Cao, Lin-Lin; Zhu, Wei-Guo; Shi, Jie; Song, Wei-Hong; Lu, Lin

    2016-03-01

    Cognition is impacted by aging. However, the mechanisms that underlie aging-associated cognitive impairment are unclear. Here we showed that cognitive decline in aged rats was associated with changes in DNA methylation of protein kinase Mζ (PKMζ) in the prelimbic cortex (PrL). PKMζ is a crucial molecule involved in the maintenance of long-term memory. Using different behavioral models, we confirmed that aged rats exhibited cognitive impairment in memory retention test 24 h after training, and overexpression of PKMζ in the PrL rescued cognitive impairment in aged rats. After fear conditioning, the protein levels of PKMζ and the membrane expression of GluR2 increased in the PrL in young and adult rats but not in aged rats, and the levels of methylated PKMζ DNA in the PrL decreased in all age groups, whereas the levels of unmethylated PKMζ DNA increased only in young and adult rats. We also found that environmentally enriched housing reversed the hypermethylation of PKMζ and restored cognitive performance in aged rats. Inactivation of PKMζ prevented the potentiating effects of environmental enrichment on memory retention in aged rats. These results indicated that PKMζ might be a potential target for the treatment of aging-related cognitive impairment, suggesting a potential therapeutic avenue.

  8. Epigenetic modification of PKMζ rescues aging-related cognitive impairment

    PubMed Central

    Chen, Chen; Meng, Shi-Qiu; Xue, Yan-Xue; Han, Ying; Sun, Cheng-Yu; Deng, Jia-Hui; Chen, Na; Bao, Yan-Ping; Zhang, Fei-Long; Cao, Lin-Lin; Zhu, Wei-Guo; Shi, Jie; Song, Wei-Hong; Lu, Lin

    2016-01-01

    Cognition is impacted by aging. However, the mechanisms that underlie aging-associated cognitive impairment are unclear. Here we showed that cognitive decline in aged rats was associated with changes in DNA methylation of protein kinase Mζ (PKMζ) in the prelimbic cortex (PrL). PKMζ is a crucial molecule involved in the maintenance of long-term memory. Using different behavioral models, we confirmed that aged rats exhibited cognitive impairment in memory retention test 24 h after training, and overexpression of PKMζ in the PrL rescued cognitive impairment in aged rats. After fear conditioning, the protein levels of PKMζ and the membrane expression of GluR2 increased in the PrL in young and adult rats but not in aged rats, and the levels of methylated PKMζ DNA in the PrL decreased in all age groups, whereas the levels of unmethylated PKMζ DNA increased only in young and adult rats. We also found that environmentally enriched housing reversed the hypermethylation of PKMζ and restored cognitive performance in aged rats. Inactivation of PKMζ prevented the potentiating effects of environmental enrichment on memory retention in aged rats. These results indicated that PKMζ might be a potential target for the treatment of aging-related cognitive impairment, suggesting a potential therapeutic avenue. PMID:26926225

  9. Extending the Lee-Carter method to model the rotation of age patterns of mortality-decline for long-term projection

    PubMed Central

    Li, Nan; Lee, Ronald; Gerland, Patrick

    2015-01-01

    In developed countries, mortality decline is decelerating at younger ages and accelerating at old ages, which we call a “rotation”. We expect that this rotation will also occur in developing countries as they attain high life expectancies. But the rotation is subtle and has proved difficult to handle in mortality models that include all age groups. Without taking it into account, however, long-term mortality projections will produce questionable results. Here we simplify the problem by focusing on the relative magnitude of death rates at two ages, 0 and 15–19, while making assumptions about changes in rates of decline at other ages. We extend the Lee-Carter method to incorporate this subtle rotation in projection. We suggest that the extended Lee-Carter method could provide plausible projections of the age pattern of mortality for populations that currently have very high life expectancies as well as others. Detailed examples are given using data from Japan and the US. PMID:23904392

  10. A decline in PABPN1 induces progressive muscle weakness in oculopharyngeal muscle dystrophy and in muscle aging.

    PubMed

    Anvar, Seyed Yahya; Raz, Yotam; Verway, Nisha; van der Sluijs, Barbara; Venema, Andrea; Goeman, Jelle J; Vissing, John; van der Maarel, Silvère M; 't Hoen, Peter A C; van Engelen, Baziel G M; Raz, Vered

    2013-06-01

    Oculopharyngeal muscular dystrophy (OPMD) is caused by trinucleotide repeat expansion mutations in Poly(A) binding protein 1 (PABPN1). PABPN1 is a regulator of mRNA stability and is ubiquitously expressed. Here we investigated how symptoms in OPMD initiate only at midlife and why a subset of skeletal muscles is predominantly affected. Genome-wide RNA expression profiles from Vastus lateralis muscles human carriers of expanded-PABPN1 at pre-symptomatic and symptomatic stages were compared with healthy controls. Major expression changes were found to be associated with age rather than with expression of expanded-PABPN1, instead transcriptomes of OPMD and elderly muscles were significantly similar (P<0.05). Using k-means clustering we identified age-dependent trends in both OPMD and controls, but trends were often accelerated in OPMD. We report an age-regulated decline in PABPN1 levels in Vastus lateralis muscles from the fifth decade. In concurrence with severe muscle degeneration in OPMD, the decline in PABPN1 accelerated in OPMD and was specific to skeletal muscles. Reduced PABPN1 levels (30% to 60%) in muscle cells induced myogenic defects and morphological signatures of cellular aging in proportion to PABPN1 expression levels. We suggest that PABPN1 levels regulate muscle cell aging and OPMD represents an accelerated muscle aging disorder.

  11. Immunology of age-related macular degeneration

    PubMed Central

    Ambati, Jayakrishna; Atkinson, John P.; Gelfand, Bradley D.

    2014-01-01

    Age-related macular degeneration (AMD) is a leading cause of blindness in aged individuals. Recent advances have highlighted the essential role of immune processes in the development, progression and treatment of AMD. In this Review we discuss recent discoveries related to the immunological aspects of AMD pathogenesis. We outline the diverse immune cell types, inflammatory activators and pathways that are involved. Finally, we discuss the future of inflammation-directed therapeutics to treat AMD in the growing aged population. PMID:23702979

  12. Leadership instability in hospitals: the influence of Board-CEO relations and organizational growth and decline.

    PubMed

    Alexander, J A; Fennell, M L; Halpern, M T

    1993-03-01

    This study tested whether leadership instability--a systemic pattern of frequent succession in the top management position of an organization--was associated with sociopolitical structures that define the relationship between the board and chief executive officer (CEO), controlling for temporal patterns of the organizational life-cycle stage. In organizations that are not profit maximizing and subject to considerable uncertainty, such governance properties were hypothesized to affect leadership instability independent of organizational growth or decline. Results of regression analyses demonstrate strong main effects of board-CEO relations, net of the impact of organizational life cycle, on leadership instability.

  13. On the definition of age-related norms for visual function testing.

    PubMed

    Johnson, M A; Choy, D

    1987-04-15

    Cross-sectional psychophysical and electrophysiologic studies of aging indicate that visual function declines only slightly or not at all until age 50-60, at which time the decline in visual function rapidly accelerates. This accelerated loss of function may reflect an increased rate of natural cellular degradation, or it may reflect an increased proportion of subclinical pathology in the presumed normal older population. This paper provides a critical review of the changes in visual function that occur with age. The results of this review have implications for both the definition of age-matched control groups and for early detection of age-related pathology.

  14. Age-related priming effects in social judgments.

    PubMed

    Hess, T M; McGee, K A; Woodburn, S M; Bolstad, C A

    1998-03-01

    Two experiments investigated adult age differences in the impact of previously activated (and thus easily accessible) trait-related information on judgments about people. The authors hypothesized that age-related declines in the efficiency of controlled processing mechanisms during adulthood would be associated with increased susceptibility to judgment biases associated with such information. In each study, different-aged adults made impression judgments about a target, and assimilation of these judgments to trait constructs activated in a previous, unrelated task were examined. Consistent with the authors' hypotheses, older adults were likely to form impressions that were biased toward the primed trait constructs. In contrast, younger adults exhibited greater awareness of the primed information and were more likely to correct for its perceived influence, especially when distinctive contextual cues regarding the source of the primes were available. PMID:9533195

  15. Clinical predictors of cognitive decline in patients with mild cognitive impairment: the Chongqing aging study.

    PubMed

    Li, Ling; Wang, Yanjiang; Yan, Jiachuan; Chen, Yang; Zhou, Rui; Yi, Xu; Shi, Qianqian; Zhou, Huadong

    2012-07-01

    Mild cognitive impairment (MCI) is considered as the early stage of dementia which currently has no effective treatments. Reducing progression of cognitive decline at the MCI stage could be an important strategy for preventing conversion to dementia. The goal of this work was to screen for clinical predictors indicating the prognosis of MCI comprehensively; therefore, we assumed vascular risk factors (VRFs), carotid stenosis, and white matter changes (WMC) to be independent predictors. A total of 257 patients with MCI underwent collection of VRF information, neuropsychological evaluation, computed tomography angiography (CTA) to investigate carotid stenosis, and magnetic resonance imaging (MRI) to identify severity of WMC. After a 3-year follow-up period, the neuropsychological evaluation, CTA, and MRI were repeated to assess the progression of cognitive decline, carotid stenosis, and WMC. The conversion rate from MCI to dementia was 11.65% per year, and the conversion rate from MCI to Alzheimer's disease was 7.05% per year in our cohort. Cognitive decline (in terms of changes in Mini Mental State Examination scores) was associated with diabetes mellitus (p = 0.004), baseline WMC severity (p < 0.001), baseline carotid stenosis (p < 0.001), and WMC severity change (p < 0.001). Besides, diabetes, baseline WMC severity, baseline moderate-to-severe carotid stenosis, and carotid stenosis change during follow-up were predictors of conversion from MCI to dementia. Given the potential clinical predictors, our findings could imply that controlling blood glucose, removing carotid stenosis, and improving cerebral perfusion could be effective measures to delay cognitive decline in patients with MCI and prevent conversion from MCI to dementia. PMID:22186849

  16. Age Related Changes in Autonomic Functions

    PubMed Central

    Amir, Mohammed; Pakhare, Abhijit; Rathi, Preeti; Chaudhary, Lalita

    2016-01-01

    Introduction Autonomic Nervous System (ANS) imbalance may trigger or enhance pathology in different organ systems that varies in different age groups hence objective of present study was to evaluate association of different Age-groups with autonomic functions. Materials and Methods A cross-sectional study was conducted in 62 healthy volunteers in Department of Physiology LLRM Medical College Meerut, India. Volunteers were divided into three groups as younger (15-45 years), middle (45-60) and elder age (above 60), Autonomic functions were tested in three domains viz. Cardio-vagal, adrenergic and sudomotor functions. Numerical data was summarized as mean and standard deviation and categorical data as count and percentage. ANOVA and Chi-square test were used to find difference among groups, p<0.05 was considered statistically significant. Results Mean ± standard deviation OHT(Orthostatic Hypotension Test) among of younger, middle and elder age groups were 8.80±2.28, 13.40±4.64 and 21.82±6.04 respectively which represent decrease in sympathetic functions with age (p<0.001). Cardio-vagal or parasympathetic responses indicated by DBT (Deep Breathing Test) Valsalva and 30:15 ratio of HR response to standing tests has shown statistically significant (p<0.001) decrease in mean response with increasing age. Sudomotor response appeared normal in younger and middle group but was interrupted in more than half of elderly people (p<0.001). Conclusion Sympathetic responses & para-sympathetic responses have shown the significant decline with increasing age group. Sudomotor responses were partially interrupted in elderly age group. PMID:27134865

  17. Microsurgeons do better--tactile training might prevent the age-dependent decline of the sensibility of the hand.

    PubMed

    Schmauss, Daniel; Megerle, Kai; Weinzierl, Andrea; Agua, Kariem; Cerny, Michael; Schmauss, Verena; Lohmeyer, Joern A; Machens, Hans-Guenther; Erne, Holger

    2015-12-01

    Recent data demonstrate that the normal sensibility of the hand seems to be age-dependent with the best values in the third decade and a consecutive deterioration afterwards. However, it is not clear if long-term tactile training might prevent this age-dependent decline. We evaluated sensibility of the hand in 125 surgeons aged between 26 and 75 years who perform microsurgical operations, thereby undergoing regular tactile training. We examined sensibility of the radial digital nerve of the index finger (N3) and the ulnar digital nerve of the small finger (N10) using static and moving two-point discrimination (2PD) tests and compared the results to 154 age-matched individuals without specific long-term tactile training. We found significantly lower static and moving 2PD values for the sixth, seventh, and eighth decade of life in the microsurgery group compared to the control group (p < 0.05). This study demonstrates that long-term tactile training might prevent the known age-dependent decline of the sensibility of the hand.

  18. 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.

  19. Age-related preferences and age weighting health benefits.

    PubMed

    Tsuchiya, A

    1999-01-01

    This paper deals with the relevance of age in the paradigm of quality adjusted life years (QALYs). The first section outlines two rationales for incorporating age weights into QALYs. One of them is based on efficiency concerns; and the other on equity concerns. Both of these are theoretical constructs. The main purpose of this paper is to examine the extent of published empirical support for such age weighting. The second section is a brief survey of nine empirical studies that elicited age-related preferences from the general public. Six of these quantified the strength of the preferences, and these are discussed in more detail in the third section. The analysis distinguishes three kinds of age-related preference: productivity ageism, utilitarian ageism and egalitarian ageism. The relationship between them and their relevance to the two different rationales for age weighting are then explored. It is concluded that, although there is strong prima facie evidence of public support for both types of age weighting, the empirical evidence to support any particular set of weights is at present weak. PMID:10048783

  20. DNA damage and repair in telomeres: relation to aging.

    PubMed Central

    Kruk, P A; Rampino, N J; Bohr, V A

    1995-01-01

    We have established a method for the detection of DNA damage and its repair in human telomeres, the natural ends of chromosomes which are necessary for replication and critical for chromosomal stability. We find that ultraviolet light-induced pyrimidine dimers in telomeric DNA are repaired less efficiently than endogenous genes but more efficiently than inactive, noncoding regions. We have also measured telomeric length, telomeric DNA damage, and its repair in relation to the progression of aging. Telomeres are shorter in fibroblasts from an old donor compared to fibroblasts from a young donor, shortest in cells from a patient with the progeroid disorder Werner syndrome, and relatively long in fibroblasts from a patient with Alzheimer disease. Telomeric DNA repair efficiency is lower in cells from an old donor than in cells from a young donor, normal in Alzheimer cells, and slightly lower in Werner cells. It is possible that this decline in telomeric repair with aging is of functional significance to an age-related decline in genomic stability. Images Fig. 1 Fig. 2 PMID:7816828

  1. Baseline white matter microstructural integrity is not related to cognitive decline after 5 years: The RUN DMC study.

    PubMed

    van Uden, I W M; van der Holst, H M; Schaapsmeerders, P; Tuladhar, A M; van Norden, A G W; de Laat, K F; Norris, D G; Claassen, J A H R; van Dijk, E J; Richard, E; Kessels, R P C; de Leeuw, F-E

    2015-12-01

    •DTI can provide information on microstructural white matter integrity.•White matter microstructural integrity is not related to cognitive decline in SVD.•These results are in contrast with cross-sectional findings.•Other factors than white matter microstructural damage underlie this cognitive decline.

  2. Automated Semantic Indices Related to Cognitive Function and Rate of Cognitive Decline

    PubMed Central

    Pakhomov, Serguei V.S.; Hemmy, Laura S.; Lim, Kelvin O.

    2012-01-01

    The objective of our study is to introduce a fully automated, computational linguistic technique to quantify semantic relations between words generated on a standard semantic verbal fluency test and to determine its cognitive and clinical correlates. Cognitive differences between patients with Alzheimer’s disease and mild cognitive impairment are evident in their performance on the semantic verbal fluency test. In addition to the semantic verbal fluency test score, several other performance characteristics sensitive to disease status and predictive of future cognitive decline have been defined in terms of words generated from semantically related categories (clustering) and shifting between categories (switching). However, the traditional assessment of clustering and switching has been performed manually in a qualitative fashion resulting in subjective scoring with limited reproducibility and scalability. Our approach uses word definitions and hierarchical relations between the words in WordNet®, a large electronic lexical database, to quantify the degree of semantic similarity and relatedness between words. We investigated the novel semantic fluency indices of mean cumulative similarity and relatedness between all pairs of words regardless of their order, and mean sequential similarity and relatedness between pairs of adjacent words in a sample of patients with clinically diagnosed probable (n=55) or possible (n=27) Alzheimer’s disease or mild cognitive impairment (n=31). The semantic fluency indices differed significantly between the diagnostic groups, and were strongly associated with neuropsychological tests of executive function, as well as the rate of global cognitive decline. Our results suggest that word meanings and relations between words shared across individuals and computationally modeled via WordNet and large text corpora provide the necessary context to account for the variability in language-based behavior and relate it to cognitive dysfunction

  3. Declining Effectiveness of Herpes Zoster Vaccine in Adults Aged ≥60 Years.

    PubMed

    Tseng, Hung Fu; Harpaz, Rafael; Luo, Yi; Hales, Craig M; Sy, Lina S; Tartof, Sara Y; Bialek, Stephanie; Hechter, Rulin C; Jacobsen, Steven J

    2016-06-15

    Understanding long-term effectiveness of herpes zoster (HZ) vaccine is critical for determining vaccine policy. 176 078 members of Kaiser Permanente ≥60 years vaccinated with HZ vaccine and three matched unvaccinated members were included. Hazard ratios and 95% confidence intervals (CIs) associated with vaccination at each year following vaccination were estimated by Cox regression model. The effectiveness of HZ vaccine decreased from 68.7% (95% CI, 66.3%-70.9%) in the first year to 4.2% (95% CI, -24.0% to 25.9%) in the eighth year. This rapid decline in effectiveness of HZ vaccine suggests that a revaccination strategy may be needed, if feasible.

  4. Incentive relativity in middle aged rats.

    PubMed

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

    2014-01-24

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

  5. Functional Decline in Children Undergoing Selective Dorsal Rhizotomy after Age 10

    ERIC Educational Resources Information Center

    MacWilliams, Bruce A.; Johnson, Barbara A.; Shuckra, Amy L.; D'Astous, Jacques L.

    2011-01-01

    Aim: To compare function and gait in a group of children older than most children who received selective dorsal rhizotomy (SDR) with age- and function-matched peers who received either orthopedic surgery or no surgical intervention. Method: A retrospective study examined ambulatory children with diplegic cerebral palsy, aged between 10 years and…

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

    ClinicalTrials.gov

    2016-08-16

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

  7. Curcumin, inflammation, ageing and age-related diseases.

    PubMed

    Sikora, E; Scapagnini, Giovanni; Barbagallo, Mario

    2010-01-17

    A Symposium regarding the Pathophysiology of Successful and Unsuccessful Ageing was held in Palermo, Italy between April 7 and 8th 2009. Here the lecture by Sikora with some input from the chairpersons Scapagnini and Barbagallo is summarized. Ageing is manifested by the decreasing health status and increasing probability to acquire age-related disease such as cancer, Alzheimer's disease, atherosclerosis, metabolic disorders and others. They are likely caused by low grade inflammation driven by oxygen stress and manifested by the increased level of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-alpha, encoded by genes activated by the transcription factor NF-kappaB. It is believed that ageing is plastic and can be slowed down by caloric restriction as well as by some nutraceuticals. Accordingly, slowing down ageing and postponing the onset of age-related diseases might be achieved by blocking the NF-kappaB-dependent inflammation. In this review we consider the possibility of the spice curcumin, a powerful antioxidant and anti-inflammatory agent possibly capable of improving the health status of the elderly.

  8. Reproductive Performance of a Declining Forest Passerine in Relation to Environmental and Social Factors: Implications for Species Conservation

    PubMed Central

    Grendelmeier, Alex; Arlettaz, Raphaël; Gerber, Michael; Pasinelli, Gilberto

    2015-01-01

    Identifying factors influencing a species' ecological niche and demography is a prerequisite for species conservation. However, our understanding of the interplay between demographic rates and biotic/abiotic factors is still poor for most species of conservation concern. We evaluated relevance of eight hypotheses relating to timing of breeding, temporal nest exposure, nest concealment, topography, tree structure, predation risk and disturbance, density dependence and weather for explaining variation in reproductive performance of the declining wood warbler Phylloscopus sibilatrix in northern Switzerland. Reproductive performance was monitored with cameras at 136 nests from 2010 to 2012 and was associated to temporal exposure, timing of breeding and concealment of nests. Daily nest survival was positively related to the number of grass and sedge tussocks, nest concealment and nest age. Clutch size and number of fledglings decreased, the later in the season a nest was initiated. Nest survival over an average nesting period of 31 days was 46.9 ± 0.07% (mean ± SE), daily nest survival rate was 0.976 ± 0.002. As for many ground-breeding birds, nest predation was the principal cause of nest failure, accounting for 79% of all nest losses. Conservation measures should aim at increasing the area of relatively homogenous forest stands featuring suitable habitats characterized by abundant and accessible grass and sedge tussocks. In managed forests, such conditions can be found in stands of middle age (i.e. pole wood) with little to no shrub layer. PMID:26172954

  9. Reproductive Performance of a Declining Forest Passerine in Relation to Environmental and Social Factors: Implications for Species Conservation.

    PubMed

    Grendelmeier, Alex; Arlettaz, Raphaël; Gerber, Michael; Pasinelli, Gilberto

    2015-01-01

    Identifying factors influencing a species' ecological niche and demography is a prerequisite for species conservation. However, our understanding of the interplay between demographic rates and biotic/abiotic factors is still poor for most species of conservation concern. We evaluated relevance of eight hypotheses relating to timing of breeding, temporal nest exposure, nest concealment, topography, tree structure, predation risk and disturbance, density dependence and weather for explaining variation in reproductive performance of the declining wood warbler Phylloscopus sibilatrix in northern Switzerland. Reproductive performance was monitored with cameras at 136 nests from 2010 to 2012 and was associated to temporal exposure, timing of breeding and concealment of nests. Daily nest survival was positively related to the number of grass and sedge tussocks, nest concealment and nest age. Clutch size and number of fledglings decreased, the later in the season a nest was initiated. Nest survival over an average nesting period of 31 days was 46.9 ± 0.07% (mean ± SE), daily nest survival rate was 0.976 ± 0.002. As for many ground-breeding birds, nest predation was the principal cause of nest failure, accounting for 79% of all nest losses. Conservation measures should aim at increasing the area of relatively homogenous forest stands featuring suitable habitats characterized by abundant and accessible grass and sedge tussocks. In managed forests, such conditions can be found in stands of middle age (i.e. pole wood) with little to no shrub layer.

  10. Association of Apolipoprotein E-e4 and Dementia Declines with Age

    PubMed Central

    Valerio, Daniel; Raventos, Henriette; Schmeidler, James; Beeri, Michal S.; Villalobos, Lara Mora; Bolaños, Patricia; Carrión-Baralt, José R.; Fornaguera, Jaime; Silverman, Jeremy M.

    2014-01-01

    Objective To study the association of dementia with APOE-e4 and its interaction with age in a nonagenarian Costa Ricans (N-sample) and a general elderly contrast group (GE-sample). Methods In both case-control studies, participants were cognitively intact or demented. The N-sample (N=112) was at least age 90; the GE-sample (N=98) was at least age 65. Results Dementia and APOE-e4 were not significantly associated in the N-sample, but were in the GE-sample. There was a significant interaction of age with APOE-e4 in the N-sample, but not in the GE-sample. Descriptively dividing the N-sample at the median (age 93) showed a group interaction: APOE-e4 was more associated with dementia in the younger N-sample than in the older N-sample, where six of seven APOE-e4 carriers were cognitively intact. Conclusions The results support the reduction in association of APOE-e4 with dementia in extreme old age, consistent with a survivor effect model for successful cognitive aging. PMID:24731780

  11. Genetic and pharmacological evidence that G2019S LRRK2 confers a hyperkinetic phenotype, resistant to motor decline associated with aging

    PubMed Central

    Longo, Francesco; Russo, Isabella; Shimshek, Derya R.; Greggio, Elisa; Morari, Michele

    2014-01-01

    The leucine-rich repeat kinase 2 mutation G2019S in the kinase-domain is the most common genetic cause of Parkinson's disease. To investigate the impact of the G2019S mutation on motor activity in vivo, a longitudinal phenotyping approach was developed in knock-in (KI) mice bearing this kinase-enhancing mutation. Two cohorts of G2019S KI mice and wild-type littermates (WT) were subjected to behavioral tests, specific for akinesia, bradykinesia and overall gait ability, at different ages (3, 6, 10, 15 and 19 months). The motor performance of G2019S KI mice remained stable up to the age of 19 months and did not show the typical age-related decline in immobility time and stepping activity of WT. Several lines of evidence suggest that enhanced LRRK2 kinase activity is the main contributor to the observed hyperkinetic phenotype of G2019S KI mice: i) KI mice carrying a LRRK2 kinase-dead mutation (D1994S KD) showed a similar progressive motor decline as WT; ii) two LRRK2 kinase inhibitors, H-1152 and Nov-LRRK2-11, acutely reversed the hyperkinetic phenotype of G2019S KI mice, while being ineffective in WT or D1994S KD animals. LRRK2 target engagement in vivo was further substantiated by reduction of LRRK2 phosphorylation at Ser935 in the striatum and cortex at efficacious doses of Nov-LRRK2-11, and in the striatum at efficacious doses of H-1152. In summary, expression of the G2019S mutation in the mouse LRRK2 gene confers a hyperkinetic phenotype that is resistant to age-related motor decline, likely via enhancement of LRRK2 kinase activity. This study provides an in vivo model to investigate the effects of LRRK2 inhibitors on motor function. PMID:25107341

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2015-12-01

    Aging is a risk factor for several of the world's most prevalent diseases, including neurodegenerative disorders, cancer, cardiovascular disease and metabolic disease. Although our understanding of the molecular pathways that contribute to the aging process and age-related disease is progressing through the use of model organisms, how to apply this knowledge in the clinic is less clear. In September, Nature Medicine, in collaboration with the Volkswagen Foundation, hosted a conference at the beautiful Herrenhausen Palace in Hannover, Germany with the goal of broadening our understanding of the aging process and its meaning as a 'risk factor' in disease. Here, several of the speakers at that conference answer questions posed by Nature Medicine. PMID:26646495

  14. Language in the aging brain: the network dynamics of cognitive decline and preservation.

    PubMed

    Shafto, Meredith A; Tyler, Lorraine K

    2014-10-31

    Language is a crucial and complex lifelong faculty, underpinned by dynamic interactions within and between specialized brain networks. Whereas normal aging impairs specific aspects of language production, most core language processes are robust to brain aging. We review recent behavioral and neuroimaging evidence showing that language systems remain largely stable across the life span and that both younger and older adults depend on dynamic neural responses to linguistic demands. Although some aspects of network dynamics change with age, there is no consistent evidence that core language processes are underpinned by different neural networks in younger and older adults.

  15. Endocrine alterations and signaling changes associated with declining ovarian function and advanced biological aging in follicle-stimulating hormone receptor haploinsufficient mice.

    PubMed

    Danilovich, Natalia; Javeshghani, Danesh; Xing, Weirong; Sairam, M Ram

    2002-08-01

    Reproductive aging in female mammals is characterized by a progressive decline in fertility due to loss of follicles and reduced ovarian steroidogenesis. In this study we examined some of the endocrine and signaling parameters that might contribute to a decrease in ovulation and reproductive performance of mice with haploinsufficiency of the FSH receptor (FSH-R). For this purpose we compared ovarian changes and hormone levels in FSH-R heterozygous (+/-) and wild-type mice of different ages (3, 7, and 12 mo). Hormone-induced ovulations in immature and 3-mo-old +/- mice were consistently lower. The number of corpora lutea (CL) were lower at 3 and 7 mo, and none were present in 1-yr-old +/- females. The plasma steroid and gonadotropin levels exhibited changes associated with typical ovarian aging. Plasma FSH and LH levels were higher in 7-mo-old +/- mice, but FSH levels continued to rise in both genotypes by 1 yr. Serum estradiol and progesterone were lower in +/- mice at all ages, and testosterone was several-fold higher in 7-mo-old and 1-yr-old +/- mice. Inhibin alpha (Western blot) appeared to be lower in +/- ovaries at all ages. FSH-R (FSH* binding) declined steadily from 3 mo and reaching the lowest point at 1 yr. LH receptor (LH* binding) was high in the 1-yr-old ovary, and expression was localized in the stroma and interstitial cells. Our findings demonstrate that haploinsufficiency of the FSH-R gene could cause premature exhaustion of the gonadal reserves previously noted in these mice. This is accompanied by age-related changes in the hypothalamic-pituitary axis. As these features in our FSH-R +/- mice resemble reproductive failure occurring in middle-age women, further studies in this model might provide useful insights into the mechanisms underlying ovarian aging.

  16. Decline and Decadence in Iraq and Syria after the Age of Avicenna?

    PubMed Central

    Joosse, N. Peter; Pormann, Peter E.

    2010-01-01

    Summary 'Abd al-Laṭīf al-Baghdādī's (d. 1231) work Book of the Two Pieces ofAdvice (Kitāb al Nasīḥatayn) challenges the idea that Islamic medicine declined after the twelfth century AD. Moreover, it offers some interesting insights into the social history of medicine. 'Abd al-Laṭīf advocated using the framework of Greek medical epistemology to criticize the rationalist physicians of his day; he argued that female and itinerant practitioners, relying on experience, were superior to some rationalists. He lambasted contemporaneous medical education because it put too much faith in a restricted number of textbooks such as the Canon by Ibn Sīnā (Avicenna, d. 1037) or imperfect abridgments. PMID:20632731

  17. Alpha-Synuclein Levels in Blood Plasma Decline with Healthy Aging

    PubMed Central

    Koehler, Niklas K. U.; Stransky, Elke; Meyer, Mirjam; Gaertner, Susanne; Shing, Mona; Schnaidt, Martina; Celej, Maria S.; Jovin, Thomas M.; Leyhe, Thomas; Laske, Christoph; Batra, Anil; Buchkremer, Gerhard; Fallgatter, Andreas J.; Wernet, Dorothee; Richartz-Salzburger, Elke

    2015-01-01

    There is unequivocal evidence that alpha-synuclein plays a pivotal pathophysiological role in neurodegenerative diseases, and in particular in synucleinopathies. These disorders present with a variable extent of cognitive impairment and alpha-synuclein is being explored as a biomarker in CSF, blood serum and plasma. Considering key events of aging that include proteostasis, alpha-synuclein may not only be useful as a marker for differential diagnosis but also for aging per se. To explore this hypothesis, we developed a highly specific ELISA to measure alpha-synuclein. In healthy males plasma alpha-synuclein levels correlated strongly with age, revealing much lower concentrations in older (avg. 58.1 years) compared to younger (avg. 27.6 years) individuals. This difference between the age groups was enhanced after acidification of the plasmas (p<0.0001), possibly reflecting a decrease of alpha-synuclein-antibody complexes or chaperone activity in older individuals. Our results support the concept that alpha-synuclein homeostasis may be impaired early on, possibly due to disturbance of the proteostasis network, a key component of healthy aging. Thus, alpha-synuclein may be a novel biomarker of aging, a factor that should be considered when analyzing its presence in biological specimens. PMID:25844871

  18. Ambrosia fungi in the insect-fungi symbiosis in relation to cork oak decline.

    PubMed

    Henriques, Joana; Inácio, Maria Lurdes; Sousa, Edmundo

    2006-09-01

    Ambrosia fungi live associated with beetles (Scolytidae and Platypodidae) in host trees and act as a food source for the insects. The symbiotic relation is important to the colonizing strategies of host trees by beetles. Ambrosia fungi are dimorphic: they grow as ambrosial form and as mycelium. The fungi are highly specialized, adapted to a specific beetle and to the biotope where they both live. In addition other fungi have been found such as tree pathogenic fungi that may play a role in insects host colonization success. Saprophytic fungi are also present in insects galleries. These may decompose cellulose and/or be antagonistic to other less beneficial fungi. This paper summarizes the importance of ambrosia fungi and the interaction with insects and hosts. The possibility of the transport of pathogenic fungi by Platypus cylindrus to cork oak thus contributing for its decline is discussed.

  19. Relative age effect in Japanese male athletes.

    PubMed

    Nakata, Hiroki; Sakamoto, Kiwako

    2011-10-01

    The present study investigated the relative age effect, a biased distribution of elite athletes' birthdates, in Japanese male athletes. Japan applies a unique annual-age grouping for sport and education, which is from April 1 to March 31 of the following year. A total of 4,318 male athletes was evaluated from 12 sports: baseball, soccer, basketball, volleyball, handball, golf, horse racing, rugby, American football, sumo, Ekiden (track and field in long distance), and badminton. They played in the top level of Japanese leagues for each sport in 2010. The distribution of the birth dates was examined in each sport and showed significant relative age effect in baseball, soccer, volleyball, Ekiden, basketball, sumo, and horse racing, but not in all sports. The findings suggest that although the school year in Japan starts on April 1, significant relative age effects are observed in some sporting events. PMID:22185072

  20. Relative age effect in Japanese male athletes.

    PubMed

    Nakata, Hiroki; Sakamoto, Kiwako

    2011-10-01

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

  1. Age related microsatellite instability in T cells from healthy individuals.

    PubMed

    Krichevsky, Svetlana; Pawelec, Graham; Gural, Alexander; Effros, Rita B; Globerson, Amiela; Yehuda, Dina Ben; Yehuda, Arie Ben

    2004-04-01

    Many immune functions decline with age and may jeopardize the elderly, as illustrated, for example by the significantly higher mortality rate from influenza in old age. Although innate and humoral immunity are affected by aging, it is the T cell compartment, which manifests most alterations. The mechanisms behind these alterations are still unclear, and several explanations have been offered including thymic involution and Telomere attrition leading to cell senescence. Age related accumulation of mutations has been documented and could serve as an additional mechanism of T cell dysfunction. One effective repair mechanism capable of rectifying errors in DNA replications is the mismatch repair (MMR) system. We previously reported a comparative examination of individual DNA samples from blood cells obtained at 10 year intervals from young and old subjects. We showed significantly higher rates of microsatellite instability (MSI), an indicator of MMR dysfunction in older subjects, compared to young. In the present study we confirm this result, using direct automated sequencing and in addition, we demonstrate that as CD8 lymphocytes from aged individuals, undergo repeated population doublings (PDs) in culture, they develop MSI. CD4 clones that also undergo repeated PDs in culture develop significant MSI as well. Elucidation of this previously unexplored facet of lymphocyte dynamics in relation to aging may help identify novel mechanisms of immunosenescence and pathways that could serve as targets for interventions to restore immune function.

  2. Heterochromatin-Mediated Association of Achiasmate Homologs Declines With Age When Cohesion Is Compromised

    PubMed Central

    Subramanian, Vijayalakshmi V.; Bickel, Sharon E.

    2009-01-01

    Normally, meiotic crossovers in conjunction with sister-chromatid cohesion establish a physical connection between homologs that is required for their accurate segregation during the first meiotic division. However, in some organisms an alternative mechanism ensures the proper segregation of bivalents that fail to recombine. In Drosophila oocytes, accurate segregation of achiasmate homologs depends on pairing that is mediated by their centromere-proximal heterochromatin. Our previous work uncovered an unexpected link between sister-chromatid cohesion and the fidelity of achiasmate segregation when Drosophila oocytes are experimentally aged. Here we show that a weak mutation in the meiotic cohesion protein ORD coupled with a reduction in centromere-proximal heterochromatin causes achiasmate chromosomes to missegregate with increased frequency when oocytes undergo aging. If ORD activity is more severely disrupted, achiasmate chromosomes with the normal amount of pericentric heterochromatin exhibit increased nondisjunction when oocytes age. Significantly, even in the absence of aging, a weak ord allele reduces heterochromatin-mediated pairing of achiasmate chromosomes. Our data suggest that sister-chromatid cohesion proteins not only maintain the association of chiasmate homologs but also play a role in promoting the physical association of achiasmate homologs in Drosophila oocytes. In addition, our data support the model that deterioration of meiotic cohesion during the aging process compromises the segregation of achiasmate as well as chiasmate bivalents. PMID:19204374

  3. CANTAB object recognition and language tests to detect aging cognitive decline: an exploratory comparative study

    PubMed Central

    Cabral Soares, Fernanda; de Oliveira, Thaís Cristina Galdino; de Macedo, Liliane Dias e Dias; Tomás, Alessandra Mendonça; Picanço-Diniz, Domingos Luiz Wanderley; Bento-Torres, João; Bento-Torres, Natáli Valim Oliver; Picanço-Diniz, Cristovam Wanderley

    2015-01-01

    Objective The recognition of the limits between normal and pathological aging is essential to start preventive actions. The aim of this paper is to compare the Cambridge Neuropsychological Test Automated Battery (CANTAB) and language tests to distinguish subtle differences in cognitive performances in two different age groups, namely young adults and elderly cognitively normal subjects. Method We selected 29 young adults (29.9±1.06 years) and 31 older adults (74.1±1.15 years) matched by educational level (years of schooling). All subjects underwent a general assessment and a battery of neuropsychological tests, including the Mini Mental State Examination, visuospatial learning, and memory tasks from CANTAB and language tests. Cluster and discriminant analysis were applied to all neuropsychological test results to distinguish possible subgroups inside each age group. Results Significant differences in the performance of aged and young adults were detected in both language and visuospatial memory tests. Intragroup cluster and discriminant analysis revealed that CANTAB, as compared to language tests, was able to detect subtle but significant differences between the subjects. Conclusion Based on these findings, we concluded that, as compared to language tests, large-scale application of automated visuospatial tests to assess learning and memory might increase our ability to discern the limits between normal and pathological aging. PMID:25565785

  4. 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

    2016-08-01

    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. PMID:27444019

  5. Adaptation to Low Vision Caused by Age-Related Macular Degeneration: A Case Study

    ERIC Educational Resources Information Center

    Smith, Theresa Marie

    2008-01-01

    One in eight Americans aged 65 and older has an eye disease resulting in low vision, and more women than men are visually impaired, mainly because women live longer. Age-related visual impairments are an indicator of a decline in activities of daily living and self-help skills. The top eye conditions that affect older adults are macular…

  6. Aging Labels: The Decline of Control and the Fall of Self-Esteem.

    ERIC Educational Resources Information Center

    Rodin, Judith; Langer, Ellen

    1980-01-01

    Describes studies that investigate how labeling and stigmatization of the elderly might contribute to behavior that would confirm prevalent stereotypes of old age and lead to lowered self esteem and diminished feelings of control. Also discusses suggested strategies for social change. (Author/GC)

  7. Effects of Assistive Technology on Functional Decline in People Aging with a Disability

    ERIC Educational Resources Information Center

    Wilson, Dorothy J.; Mitchell, Judith M.; Kemp, Bryan J.; Adkins, Rodney H.; Mann, William

    2009-01-01

    This study used a randomized control group design to investigate the impact of an assistive technology and home modification intervention on function for individuals who are aging with a disability. There were 91 participants with polio, rheumatoid arthritis, cerebral palsy, spinal cord injury, stroke, and other impairments. Outcome data were…

  8. Cohort Differences in Cognitive Aging and Terminal Decline in the Seattle Longitudinal Study

    ERIC Educational Resources Information Center

    Gerstorf, Denis; Ram, Nilam; Hoppmann, Christiane; Willis, Sherry L.; Schaie, K. Warner

    2011-01-01

    Life span researchers have long been interested in how and why fundamental aspects of human ontogeny differ between cohorts of people who have lived through different historical epochs. When examined at the same age, later born cohorts are often cognitively and physically fitter than earlier born cohorts. Less is known, however, about cohort…

  9. Role of forkhead box protein A3 in age-associated metabolic decline

    PubMed Central

    Ma, Xinran; Xu, Lingyan; Gavrilova, Oksana; Mueller, Elisabetta

    2014-01-01

    Aging is associated with increased adiposity and diminished thermogenesis, but the critical transcription factors influencing these metabolic changes late in life are poorly understood. We recently demonstrated that the winged helix factor forkhead box protein A3 (Foxa3) regulates the expansion of visceral adipose tissue in high-fat diet regimens; however, whether Foxa3 also contributes to the increase in adiposity and the decrease in brown fat activity observed during the normal aging process is currently unknown. Here we report that during aging, levels of Foxa3 are significantly and selectively up-regulated in brown and inguinal white fat depots, and that midage Foxa3-null mice have increased white fat browning and thermogenic capacity, decreased adipose tissue expansion, improved insulin sensitivity, and increased longevity. Foxa3 gain-of-function and loss-of-function studies in inguinal adipose depots demonstrated a cell-autonomous function for Foxa3 in white fat tissue browning. Furthermore, our analysis revealed that the mechanisms of Foxa3 modulation of brown fat gene programs involve the suppression of peroxisome proliferator activated receptor γ coactivtor 1 α (PGC1α) levels through interference with cAMP responsive element binding protein 1-mediated transcriptional regulation of the PGC1α promoter. Overall, our data demonstrate a role for Foxa3 in energy expenditure and in age-associated metabolic disorders. PMID:25225406

  10. Aging-dependent decline of IL-10 producing B cells coincides with production of antinuclear antibodies but not rheumatoid factors.

    PubMed

    van der Geest, Kornelis S M; Lorencetti, Pedro G; Abdulahad, Wayel H; Horst, Gerda; Huitema, Minke; Roozendaal, Caroline; Kroesen, Bart-Jan; Brouwer, Elisabeth; Boots, Annemieke M H

    2016-03-01

    Aging is associated with development of autoimmunity. Loss of B cell tolerance in the elderly is suggested by an increased prevalence of anti-nuclear antibodies (ANAs) and rheumatoid factors (RFs). Accumulating evidence indicates that B cells also impact autoimmunity via secretion of cytokines. So far, few studies have directly assessed the effect of aging on the latter B cell function. Here, we determined if and how human aging influences the production of cytokines by B cells. In a cross-sectional study, we found that absolute numbers of circulating B cells were similar in 31 young (ages 19-39) and 73 old (age ≥ 60) individuals. Numbers of transitional B cells (CD19(+)CD27(-)CD38(High)CD24(High)) were decreased in old individuals, whereas numbers of naive and memory B cell subsets were comparable in young and old individuals. Short-term in vitro stimulation of whole blood samples revealed that numbers of B cells capable of producing TNF-α were similar in young and old individuals. In contrast, B cells capable of IL-10 production were decreased in old subjects. This decline of IL-10(+) B cells was observed in old individuals that were ANA positive, and in those that were negative for both ANAs and RFs. However, IL-10(+) B cells were remarkably well retained in the circulation of old subjects that were RF positive. Thus, pro-inflammatory TNF-α(+) B cells are retained in the elderly, whereas IL-10(+) B cells generally decline. In addition, our findings indicate that IL-10(+) B cells may differentially impact the development of ANAs and RFs in the elderly.

  11. Gender Relations and Applied Research on Aging

    ERIC Educational Resources Information Center

    Calasanti, Toni

    2010-01-01

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

  12. [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.

  13. Relational learning and transitive expression in aging and amnesia

    PubMed Central

    D'Angelo, Maria C.; Kamino, Daphne; Ostreicher, Melanie; Moses, Sandra N.; Rosenbaum, R. Shayna

    2016-01-01

    ABSTRACT Aging has been associated with a decline in relational memory, which is critically supported by the hippocampus. By adapting the transitivity paradigm (Bunsey and Eichenbaum (1996) Nature 379:255‐257), which traditionally has been used in nonhuman animal research, this work examined the extent to which aging is accompanied by deficits in relational learning and flexible expression of relational information. Older adults' performance was additionally contrasted with that of amnesic case DA to understand the critical contributions of the medial temporal lobe, and specifically, the hippocampus, which endures structural and functional changes in healthy aging. Participants were required to select the correct choice item (B versus Y) based on the presented sample item (e.g., A). Pairwise relations must be learned (A‐>B, B‐>C, C‐>D) so that ultimately, the correct relations can be inferred when presented with a novel probe item (A‐>C?Z?). Participants completed four conditions of transitivity that varied in terms of the degree to which the stimuli and the relations among them were known pre‐experimentally. Younger adults, older adults, and DA performed similarly when the condition employed all pre‐experimentally known, semantic, relations. Older adults and DA were less accurate than younger adults when all to‐be‐learned relations were arbitrary. However, accuracy improved for older adults when they could use pre‐experimentally known pairwise relations to express understanding of arbitrary relations as indexed through inference judgments. DA could not learn arbitrary relations nor use existing knowledge to support novel inferences. These results suggest that while aging has often been associated with an emerging decline in hippocampal function, prior knowledge can be used to support novel inferences. However, in case DA, significant damage to the hippocampus likely impaired his ability to learn novel relations, while additional damage to

  14. Calibrating the Decline Rate - Peak Luminosity Relation for Type Ia Supernovae

    NASA Astrophysics Data System (ADS)

    Rust, Bert W.; Pruzhinskaya, Maria V.; Thijsse, Barend J.

    2015-08-01

    The correlation between peak luminosity and rate of decline in luminosity for Type I supernovae was first studied by B. W. Rust [Ph.D. thesis, Univ. of Illinois (1974) ORNL-4953] and Yu. P. Pskovskii [Sov. Astron., 21 (1977) 675] in the 1970s. Their work was little-noted until Phillips rediscovered the correlation in 1993 [ApJ, 413 (1993) L105] and attempted to derive a calibration relation using a difference quotient approximation Δm15(B) to the decline rate after peak luminosity Mmax(B). Numerical differentiation of data containing measuring errors is a notoriously unstable calculation, but Δm15(B) remains the parameter of choice for most calibration methods developed since 1993. To succeed, it should be computed from good functional fits to the lightcurves, but most workers never exhibit their fits. In the few instances where they have, the fits are not very good. Some of the 9 supernovae in the Phillips study required extinction corrections in their estimates of the Mmax(B), and so were not appropriate for establishing a calibration relation. Although the relative uncertainties in his Δm15(B) estimates were comparable to those in his Mmax(B) estimates, he nevertheless used simple linear regression of the latter on the former, rather than major-axis regression (total least squares) which would have been more appropriate.Here we determine some new calibration relations using a sample of nearby "pure" supernovae suggested by M. V. Pruzhinskaya [Astron. Lett., 37 (2011) 663]. Their parent galaxies are all in the NED collection, with good distance estimates obtained by several different methods. We fit each lightcurve with an optimal regression spline obtained by B. J. Thijsse's spline2 [Comp. in Sci. & Eng., 10 (2008) 49]. The fits, which explain more that 99% of the variance in each case, are better than anything heretofore obtained by stretching "template" lightcurves or fitting combinations of standard lightcurves. We use the fits to compute estimates of

  15. 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

  16. Learning to bypass the central bottleneck: declining automaticity with advancing age.

    PubMed

    Maquestiaux, François; Laguë-Beauvais, Maude; Ruthruff, Eric; Hartley, Alan; Bherer, Louis

    2010-03-01

    Does advancing age reduce the ability to bypass the central bottleneck through task automatization? To answer this question, the authors asked 12 older adults and 20 young adults to first learn to perform an auditory-vocal task (low vs. high pitch) in 6 single-task sessions. Their dual-task performance was then assessed with a psychological refractory period paradigm, in which the highly practiced auditory-vocal task was presented as Task 2, along with an unpracticed visual-manual Task 1. Converging evidence indicated qualitative differences in dual-task performance with age: Whereas the vast majority of young adults bypassed the bottleneck, at most 1 of the 12 older adults was able to do so. Older adults are either reluctant to bypass the bottleneck (as a matter of strategy) or have lost the ability to automatize task performance. PMID:20230138

  17. Olfactory selection of Plantago lanceolata by snails declines with seedling age

    PubMed Central

    Hanley, M. E.; Girling, R. D.; Felix, A. E.; Olliff, E. D.; Newland, P. L.; Poppy, G. M.

    2013-01-01

    Background and Aims Despite recent recognition that (1) plant–herbivore interactions during the establishment phase, (2) ontogenetic shifts in resource allocation and (3) herbivore response to plant volatile release are each pivotal to a comprehensive understanding of plant defence, no study has examined how herbivore olfactory response varies during seedling ontogeny. Methods Using a Y-tube olfactometer we examined snail (Helix aspersa) olfactory response to pellets derived from macerated Plantago lanceolata plants harvested at 1, 2, 3, 4, 5, 6 and 8 weeks of age to test the hypothesis that olfactory selection of plants by a generalist herbivore varies with plant age. Plant volatiles were collected for 10 min using solid-phase microextraction technique on 1- and 8-week-old P. lanceolata pellets and analysed by gas chromatography coupled with a mass spectrometer. Key Results Selection of P. lanceolata was strongly negatively correlated with increasing age; pellets derived from 1-week-old seedlings were three times more likely to be selected as those from 8-week-old plants. Comparison of plant selection experiments with plant volatile profiles from GC/MS suggests that patterns of olfactory selection may be linked to ontogenetic shifts in concentrations of green leaf volatiles and ethanol (and its hydrolysis derivatives). Conclusions Although confirmatory of predictions made by contemporary plant defence theory, this is the first study to elucidate a link between seedling age and olfactory selection by herbivores. As a consequence, this study provides a new perspective on the ontogenetic expression of seedling defence, and the role of seedling herbivores, particularly terrestrial molluscs, as selective agents in temperate plant communities. PMID:23380239

  18. Complexity of human gait pattern at different ages assessed using multiscale entropy: From development to decline.

    PubMed

    Bisi, M C; Stagni, R

    2016-06-01

    Multiscale entropy (MSE) has been applied in biomechanics to evaluate gait stability during human gait and was found to be a promising method for evaluating fall risk in elderly and/or pathologic subjects. The hypothesis of this work is that gait complexity is a relevant parameter of gait development during life, decreasing from immature to mature gait and then increasing again during old age. In order to verify this hypothesis, MSE was applied on trunk acceleration data collected during gait of subjects of different ages: toddlers at the onset of walking, pre-scholar and scholar children, adolescents, young adults, adults and elderlies. MSE was estimated by calculating sample entropy (SEN) on raw unfiltered data of L5 acceleration along the three axes, using values of τ ranging from 1 to 6. In addition, other performance parameters (cadence, stride time variability and harmonic ratio) were evaluated. The results followed the hypothesized trend when MSE was applied on the vertical and/or anteroposterior axis of trunk acceleration: an age effect was found and adult SEN values were significantly different from children ones. From young adults to elderlies a slight increase in SEN values was shown although not statistically significant. While performance gait parameters showed adolescent gait similar to the one of adults, SEN highlighted that their gait maturation is not complete yet. In conclusion, present results suggest that the complexity of gait, evaluated on the sagittal plane, can be used as a characterizing parameter of the maturation of gait control. PMID:27264400

  19. Phospholipase A2 – nexus of aging, oxidative stress, neuronal excitability, and functional decline of the aging nervous system? Insights from a snail model system of neuronal aging and age-associated memory impairment

    PubMed Central

    Hermann, Petra M.; Watson, Shawn N.; Wildering, Willem C.

    2014-01-01

    The aging brain undergoes a range of changes varying from subtle structural and physiological changes causing only minor functional decline under healthy normal aging conditions, to severe cognitive or neurological impairment associated with extensive loss of neurons and circuits due to age-associated neurodegenerative disease conditions. Understanding how biological aging processes affect the brain and how they contribute to the onset and progress of age-associated neurodegenerative diseases is a core research goal in contemporary neuroscience. This review focuses on the idea that changes in intrinsic neuronal electrical excitability associated with (per)oxidation of membrane lipids and activation of phospholipase A2 (PLA2) enzymes are an important mechanism of learning and memory failure under normal aging conditions. Specifically, in the context of this special issue on the biology of cognitive aging we portray the opportunities offered by the identifiable neurons and behaviorally characterized neural circuits of the freshwater snail Lymnaea stagnalis in neuronal aging research and recapitulate recent insights indicating a key role of lipid peroxidation-induced PLA2 as instruments of aging, oxidative stress and inflammation in age-associated neuronal and memory impairment in this model system. The findings are discussed in view of accumulating evidence suggesting involvement of analogous mechanisms in the etiology of age-associated dysfunction and disease of the human and mammalian brain. PMID:25538730

  20. Developmental Origin of Oligodendrocyte Lineage Cells Determines Response to Demyelination and Susceptibility to Age-Associated Functional Decline

    PubMed Central

    Crawford, Abbe H.; Tripathi, Richa B.; Richardson, William D.; Franklin, Robin J.M.

    2016-01-01

    Summary Oligodendrocyte progenitors (OPs) arise from distinct ventral and dorsal domains within the ventricular germinal zones of the embryonic CNS. The functional significance, if any, of these different populations is not known. Using dual-color reporter mice to distinguish ventrally and dorsally derived OPs, we show that, in response to focal demyelination of the young adult spinal cord or corpus callosum, dorsally derived OPs undergo enhanced proliferation, recruitment, and differentiation as compared with their ventral counterparts, making a proportionally larger contribution to remyelination. However, with increasing age (up to 13 months), the dorsally derived OPs become less able to differentiate into mature oligodendrocytes. Comparison of dorsally and ventrally derived OPs in culture revealed inherent differences in their migration and differentiation capacities. Therefore, the responsiveness of OPs to demyelination, their contribution to remyelination, and their susceptibility to age-associated functional decline are markedly dependent on their developmental site of origin in the developing neural tube. PMID:27149850

  1. Difference in tenderness and pH decline between water buffalo meat and beef during postmortem aging.

    PubMed

    Neath, K E; Del Barrio, A N; Lapitan, R M; Herrera, J R V; Cruz, L C; Fujihara, T; Muroya, S; Chikuni, K; Hirabayashi, M; Kanai, Y

    2007-03-01

    The objective of this research was to determine the difference in tenderness and some characteristics of water buffalo meat and beef during postmortem aging. Five female crossbred water-buffalo (Philippine Carabao×Bulgarian Murrah) and five female crossbred cattle (Brahman×Philippine Native), were finished on the same diet for 6 months and slaughtered at 30 months of age. The muscle pH was measured at 40min, 3h, 7h, 24h, and 48h postmortem. Longissimus thoracis (LT) and semimembranosus (SM) muscles were excised at 2d postmortem, and shear force was measured at 2, 4, 7, and 14d postmortem. Glycogen and lactate concentrations were determined from 0, 2, and 4d LT samples, and myosin heavy chain type of buffalo and cattle LT was determined by ELISA methods. Myofibrillar protein degradation was also observed by SDS-PAGE and Western blotting of fast-type troponin T. Results showed that the buffalo meat had significantly lower shear force values compared to beef for LT and SM muscles, which was supported by a difference in troponin T degradation. Postmortem pH decline of buffalo meat was significantly slower than that of beef, which was confirmed by lactic acid concentrations, but was not explained by glycogen content. In addition, there was no significant difference in the ratio of slow to fast type muscle fibers in buffalo and cattle, indicating that myosin heavy chain type was not responsible for the difference in pH decline and tenderness between the buffalo meat and beef. This study demonstrated that the tenderness of water buffalo meat was superior to that of Brahman beef, which may have been due to the difference in pH decline and the subsequent effect on muscle protease activity.

  2. Spatio-Temporal Variation in Age Structure and Abundance of the Endangered Snail Kite: Pooling across Regions Masks a Declining and Aging Population

    PubMed Central

    Kendall, William L.; Fletcher, Robert J.; Kitchens, Wiley M.

    2016-01-01

    While variation in age structure over time and space has long been considered important for population dynamics and conservation, reliable estimates of such spatio-temporal variation in age structure have been elusive for wild vertebrate populations. This limitation has arisen because of problems of imperfect detection, the potential for temporary emigration impacting assessments of age structure, and limited information on age. However, identifying patterns in age structure is important for making reliable predictions of both short- and long-term dynamics of populations of conservation concern. Using a multistate superpopulation estimator, we estimated region-specific abundance and age structure (the proportion of individuals within each age class) of a highly endangered population of snail kites for two separate regions in Florida over 17 years (1997–2013). We find that in the southern region of the snail kite—a region known to be critical for the long-term persistence of the species—the population has declined significantly since 1997, and during this time, it has increasingly become dominated by older snail kites (> 12 years old). In contrast, in the northern region—a region historically thought to serve primarily as drought refugia—the population has increased significantly since 2007 and age structure is more evenly distributed among age classes. Given that snail kites show senescence at approximately 13 years of age, where individuals suffer higher mortality rates and lower breeding rates, these results reveal an alarming trend for the southern region. Our work illustrates the importance of accounting for spatial structure when assessing changes in abundance and age distribution and the need for monitoring of age structure in imperiled species. PMID:27681854

  3. Audience Design and Social Relations in Aging.

    PubMed

    Keller-Cohen, Deborah

    2015-10-01

    This study asks two questions: (1) Do older adults modify their language based on age of the listener (audience design)? (2) Does social contact affect audience design in older adults? Older adults (n = 34; mean age = 82) engaged in an instructions task with two fictive listeners (a child and an adult) to test these questions. Results show that older adults used a greater total number of propositions and rapport-building devices and a lower type-token ratio when giving instructions to the child compared to the adult listener. Adults with more social interactions used more propositions when talking to a child. In addition, satisfaction with interactions was significantly positively related to task-tracking devices and negatively related to rapport-building devices by older adults. These results suggest that audience design and social relations are worth further study in language maintenance in older age. PMID:25651591

  4. Age-related impairment of mesenchymal progenitor cell function.

    PubMed

    Stolzing, Alexandra; Scutt, Andrew

    2006-06-01

    In most mesenchymal tissues a subcompartment of multipotent progenitor cells is responsible for the maintenance and repair of the tissue following trauma. With increasing age, the ability of tissues to repair themselves is diminished, which may be due to reduced functional capacity of the progenitor cells. The purpose of this study was to investigate the effect of aging on rat mesenchymal progenitor cells. Mesenchymal progenitor cells were isolated from Wistar rats aged 3, 7, 12 and 56 weeks. Viability, capacity for differentiation and cellular aging were examined. Cells from the oldest group accumulated raised levels of oxidized proteins and lipids and showed decreased levels of antioxidative enzyme activity. This was reflected in decreased fibroblast colony-forming unit (CFU-f) numbers, increased levels of apoptosis and reduced proliferation and potential for differentiation. These data suggest that the reduced ability to maintain mesenchymal tissue homeostasis in aged mammals is not purely due to a decline in progenitor cells numbers but also to a loss of progenitor functionality due to the accumulation of oxidative damage, which may in turn be a causative factor in a number of age-related pathologies such as arthritis, tendinosis and osteoporosis.

  5. Substantial effects of apolipoprotein E ε4 on memory decline in very old age: longitudinal findings from a population-based sample.

    PubMed

    Praetorius, Marcus; Thorvaldsson, Valgeir; Hassing, Linda B; Johansson, Boo

    2013-12-01

    We examined associations between the apolipoprotein E (APOE) ε4 allele and levels of performance and rates of change in cognition in late life taking incident dementia into account. The sample consisted of 482 nondemented individuals, aged 80 years and older at baseline, drawn from the OCTO twin study. A battery of 10 cognitive tests was administered at 5 occasions with measurements intervals of 2 years. We fitted hierarchical linear models with time specified as time to death and controlled for baseline age, sex, education, stroke, cardiovascular disease, hypertension, diabetes, and incident dementia. The ε4 allele was significantly associated with lower levels of performance or steeper rate of decline in all 7 memory tests. Largest effect sizes were found in tests of delayed recall and recognition memory. The effects of the APOE ε4 allele were, however, reduced to a nonsignificant level in all tests except 1 after accounting for incident dementia. The findings support the notion that the APOE ε4 allele is associated with substantial memory decline in very old age, but as expected, the effect is largely related to incident dementia.

  6. Cognitive performance and age-related changes in the hippocampal proteome

    PubMed Central

    Freeman, Willard M.; VanGuilder, Heather D.; Bennett, Colleen; Sonntag, William E.

    2008-01-01

    Declining cognitive performance is associated with increasing age, even in the absence of overt pathological processes. We and others have reported that declining cognitive performance is associated with age-related changes in brain glucose utilization, long-term potentiation and paired-pulse facilitation, protein expression, neurotransmitter levels, and trophic factors. However, it is unclear whether these changes are causes or symptoms of the underlying alterations in dendritic and synaptic morphology that occur with age. In this study, we examined the hippocampal proteome for age- and cognition-associated changes in behaviorally stratified young and old rats, using 2-DIGE and MS/MS-MS. Comparison of old cognitively intact with old cognitively impaired animals revealed additional changes that would not have been detected otherwise. Interestingly, not all age-related changes in protein expression were associated with cognitive decline, and distinct differences in protein expression were found when comparing old cognitively intact with old cognitively impaired rats. A large number of protein changes with age were related to the glycolysis/gluconeogenesis pathway. In total, the proteomic changes suggest that age-related alterations act synergistically with other perturbations to result in cognitive decline. This study also demonstrates the importance of examining behaviorally-defined animals in proteomic studies, as comparison of young to old animals regardless of behavioral performance would have failed to detect many cognitive impairment-specific protein expression changes evident when behavioral stratification data was used. PMID:19135133

  7. Age-related hair pigment loss.

    PubMed

    Tobin, Desmond J

    2015-01-01

    Humans are social animals that communicate disproportionately via potent genetic signals imbued in the skin and hair, including racial, ethnic, health, gender, and age status. For the vast majority of us, age-related hair pigment loss becomes the inescapable signal of our disappearing youth. The hair follicle (HF) pigmentary unit is a wonderful tissue for studying mechanisms generally regulating aging, often before this becomes evident elsewhere in the body. Given that follicular melanocytes (unlike those in the epidermis) are regulated by the hair growth cycle, this cycle is likely to impact the process of aging in the HF pigmentary unit. The formal identification of melanocyte stem cells in the mouse skin has spurred a flurry of reports on the potential involvement of melanocyte stem cell depletion in hair graying (i.e., canities). Caution is recommended, however, against simple extrapolation of murine data to humans. Regardless, hair graying in both species is likely to involve an age-related imbalance in the tissue's oxidative stress handling that will impact not only melanogenesis but also melanocyte stem cell and melanocyte homeostasis and survival. There is some emerging evidence that the HF pigmentary unit may have regenerative potential, even after it has begun to produce white hair fibers. It may therefore be feasible to develop strategies to modulate some aging-associated changes to maintain melanin production for longer. PMID:26370651

  8. Phylogeny of Aging and Related Phenoptotic Phenomena.

    PubMed

    Libertini, G

    2015-12-01

    The interpretation of aging as adaptive, i.e. as a phenomenon genetically determined and modulated, and with an evolutionary advantage, implies that aging, as any physiologic mechanism, must have phylogenetic connections with similar phenomena. This review tries to find the phylogenetic connections between vertebrate aging and some related phenomena in other species, especially within those phenomena defined as phenoptotic, i.e. involving the death of one or more individuals for the benefit of other individuals. In particular, the aim of the work is to highlight and analyze similarities and connections, in the mechanisms and in the evolutionary causes, between: (i) proapoptosis in prokaryotes and apoptosis in unicellular eukaryotes; (ii) apoptosis in unicellular and multicellular eukaryotes; (iii) aging in yeast and in vertebrates; and (iv) the critical importance of the DNA subtelomeric segment in unicellular and multicellular eukaryotes. In short, there is strong evidence that vertebrate aging has clear similarities and connections with phenomena present in organisms with simpler organization. These phylogenetic connections are a necessary element for the sustainability of the thesis of aging explained as an adaptive phenomenon, and, on the contrary, are incompatible with the opposite view of aging as being due to the accumulation of random damages of various kinds.

  9. Phylogeny of Aging and Related Phenoptotic Phenomena.

    PubMed

    Libertini, G

    2015-12-01

    The interpretation of aging as adaptive, i.e. as a phenomenon genetically determined and modulated, and with an evolutionary advantage, implies that aging, as any physiologic mechanism, must have phylogenetic connections with similar phenomena. This review tries to find the phylogenetic connections between vertebrate aging and some related phenomena in other species, especially within those phenomena defined as phenoptotic, i.e. involving the death of one or more individuals for the benefit of other individuals. In particular, the aim of the work is to highlight and analyze similarities and connections, in the mechanisms and in the evolutionary causes, between: (i) proapoptosis in prokaryotes and apoptosis in unicellular eukaryotes; (ii) apoptosis in unicellular and multicellular eukaryotes; (iii) aging in yeast and in vertebrates; and (iv) the critical importance of the DNA subtelomeric segment in unicellular and multicellular eukaryotes. In short, there is strong evidence that vertebrate aging has clear similarities and connections with phenomena present in organisms with simpler organization. These phylogenetic connections are a necessary element for the sustainability of the thesis of aging explained as an adaptive phenomenon, and, on the contrary, are incompatible with the opposite view of aging as being due to the accumulation of random damages of various kinds. PMID:26638678

  10. Work related injury among aging women.

    PubMed

    Harrison, Tracie; Legarde, Brittany; Kim, Sunhun; Walker, Janiece; Blozis, Shelley; Umberson, Debra

    2013-02-01

    This article reports the experiences of women aged 55 to 75 with mobility impairments who attributed aspects of their limitations to workplace injuries and provides insight into worker's compensation policies. The study sample includes Mexican American (MA) and non-Hispanic White (NHW) women aged 55 to 75 who participated in a 4-year ethnographic study of disablement. Ninety-two of the 122 participants in the study attributed aspects of their functional limitations to employment, and their experiences were analyzed using data from 354 meetings. Using Lipscomb and colleagues' conceptual model of work and health disparities, the women's experiences were grouped into three categories according to type of injury, assistance gained, and the consequences of a workplace injury; the results have broad implications for policies that influence aging outcomes. Workplace injuries causing permanent functional limitations compound the effects of age and gender on employment outcomes. Policies addressing health disparities should consider work related influences. PMID:23528432

  11. Work Related Injury among Aging Women

    PubMed Central

    LeGarde, Brittany; Kim, SungHun; Walker, Janiece; Blozis, Shelley; Umberson, Debra

    2013-01-01

    This article reports the experiences of women age 55 to 75 with mobility impairments who attributed aspects of their limitations to workplace injuries and provides insight into worker’s compensation policies. The study sample includes Mexican American and non-Hispanic White women ages 55–75 who participated in a 4-year ethnographic study of disablement. Ninety-two of the 122 participants in the study attributed aspects of their functional limitations to employment, and their experiences were analyzed using data from 354 meetings. Using Lipscomb and colleagues’ conceptual model of work and health disparities, the women’s experiences were grouped into three categories according to type of injury, assistance gained, and the consequences of a workplace injury; the results have broad implications for policies that influence aging outcomes. Workplace injuries causing permanent functional limitations compound the effects of age and gender on employment outcomes. Policies addressing health disparities should consider work related influences. PMID:23528432

  12. Reduced writing and reading speed and age-related changes in verbal fluency tasks.

    PubMed

    Rodríguez-Aranda, Claudia

    2003-05-01

    The present study examined the influence of age-related decline in psychomotor speed on verbal fluency tasks. Reading speed, handwriting speed, written fluency, oral fluency, vocabulary, and years of formal education were measured in a sample of healthy volunteers (N=101) ranging in age from 20 to 88 years. Multiple regression analyses revealed that reading and handwriting speed strongly predicted verbal fluency performance. These measures, together with vocabulary skills and mental status, were significant predictors of performance on the fluency tasks. Present results suggest that decrement in verbal fluency performance in the aged may, at least partially, be due to reduced psychomotor speed rather than to decline in linguistic or cognitive functions.

  13. Respiratory training as strategy to prevent cognitive decline in aging: a randomized controlled trial

    PubMed Central

    Ferreira, Leandro; Tanaka, Kátia; Santos-Galduróz, Ruth Ferreira; Galduróz, José Carlos Fernandes

    2015-01-01

    Background Inadequate oxygenation may cause lesions and brain atrophy during aging. Studies show a positive association between pulmonary function and the cognitive performance of individuals from middle age on. Objective To investigate the effect of aerobic physical exercises and respiratory training on the blood oxygenation, pulmonary functions, and cognition of the elderly. Design This was a randomized and controlled trial with three parallel groups. A total of 195 community-dwelling elderly were assessed for eligibility; only n=102 were included and allocated into the three groups, but after 6 months, n=68 were analyzed in the final sample. Participants were randomized into a social interaction group (the control group), an aerobic exercise group (the “walking” group), or a respiratory training group (the “breathing” group). The main outcome measures were the Wechsler Adult Intelligence Scale, Wechsler Memory Scale, Wisconsin Card Sorting Test, respiratory muscular strength, cirtometry (thoracic–abdominal circumference); oxygen saturation in arterial blood (SpO2), and hemogram. Results No differences were observed for any of the blood parameters. Aerobic exercise and respiratory training were effective in improving the pulmonary parameters. Better cognitive performance was observed for the breathing group as regards abstraction and mental flexibility. The walking group remained stable in the cognitive performance of most of the tests, except attention. The control group presented worst performance in mental manipulation of information, abstraction, mental flexibility, and attention. Conclusion Our results showed that both the walking and breathing groups presented improvement of pulmonary function. However, only the breathing group showed improved cognitive function (abstraction, mental flexibility). The improvement in cognitive functions cannot be explained by blood parameters, such as SpO2, erythrocytes, hemoglobin, and hematocrit. PMID:25848235

  14. What Causes the Age Decline in Reports of Being Bullied at School? Towards a Developmental Analysis of the Risks of Being Bullied.

    ERIC Educational Resources Information Center

    Smith, Peter K.; Moody, Janet C.; Madsen, Kirsten C.

    1999-01-01

    Interviews with 48 participants aged 7-8, 9-10, 11-12, and 13-14 and with 159 aged 5-6, 9-10, 15-16, and 18-29 showed that younger children have different definitions of bullying and lack social and assertiveness skills, which may explain the age decline in bullying reports. (SK)

  15. 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

  16. Long term determinants of functional decline of mobility: an 11-year follow-up of 5464 adults of late middle aged and elderly.

    PubMed

    Lêng, Chhian Hūi; Wang, Jung-Der

    2013-01-01

    This confirmatory study aims at investigating the long term determinants of mobility limitation among late middle aged and elderly in a physically less active population. Five thousand four hundred and sixty-four participants aged 50-97 in 1996 enrolled the Taiwan Longitudinal Study on Aging (TLSA) for four waves of interview during 11 years. Social and health-related determinants were collected in each interview. Mobility limitation was enquired level of difficulty in eight movement tasks, including lifting 11kg weight, squatting, running 20-30m, standing for 15min, walking 200-300m, climbing up two to three floors, raising arms up and grasping with fingers. According to the mixed models with repeated measurements, more frequent gardening and longer time for each exercise predicted subsequent better mobility function in Taiwanese elderly while controlling demographics and current comorbidities. The protective effect of gardening was robust in all models. Frequent alcohol consumption was harmful to future mobility function, but less as harmful when participants aged. Besides, the depression-related somatic complaints were predictive to future mobility limitation among those without limitation at baseline. It shall be worthy to explore the dosage as well as the mechanism of these protective factors, especially the most significant but the least explored factor, gardening. Additionally, efforts should be made to understand the relationship between depression-related somatic complaints and mobility decline and so as the relevant interventions. PMID:23608344

  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. 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,…

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

    PubMed

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

    2013-07-01

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

  20. 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.

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

    PubMed

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

    2016-09-01

    Fall prevention technologies have the potential to improve the lives of older adults. Because of the multisensory nature of human balance control, sensory therapies, including some involving tactile and auditory noise, are being explored that might reduce increased balance variability due to typical age-related sensory declines. Auditory white noise has previously been shown to reduce postural sway variability in healthy young adults. In the present experiment, we examined this treatment in young adults and typically aging older adults. We measured postural sway of healthy young adults and adults over the age of 65 years during silence and auditory white noise, with and without vision. Our results show reduced postural sway variability in young and older adults with auditory noise, even in the absence of vision. We show that vision and noise can reduce sway variability for both feedback-based and exploratory balance processes. In addition, we show changes with auditory noise in nonlinear patterns of sway in older adults that reflect what is more typical of young adults, and these changes did not interfere with the typical random walk behavior of sway. Our results suggest that auditory noise might be valuable for therapeutic and rehabilitative purposes in older adults with typical age-related balance variability. PMID:27495013

  2. Net aboveground biomass declines of four major forest types with forest ageing and climate change in western Canada's boreal forests.

    PubMed

    Chen, Han Y H; Luo, Yong

    2015-10-01

    Biomass change of the world's forests is critical to the global carbon cycle. Despite storing nearly half of global forest carbon, the boreal biome of diverse forest types and ages is a poorly understood component of the carbon cycle. Using data from 871 permanent plots in the western boreal forest of Canada, we examined net annual aboveground biomass change (ΔAGB) of four major forest types between 1958 and 2011. We found that ΔAGB was higher for deciduous broadleaf (DEC) (1.44 Mg ha(-1)  year(-1) , 95% Bayesian confidence interval (CI), 1.22-1.68) and early-successional coniferous forests (ESC) (1.42, CI, 1.30-1.56) than mixed forests (MIX) (0.80, CI, 0.50-1.11) and late-successional coniferous (LSC) forests (0.62, CI, 0.39-0.88). ΔAGB declined with forest age as well as calendar year. After accounting for the effects of forest age, ΔAGB declined by 0.035, 0.021, 0.032 and 0.069 Mg ha(-1)  year(-1) per calendar year in DEC, ESC, MIX and LSC forests, respectively. The ΔAGB declines resulted from increased tree mortality and reduced growth in all forest types except DEC, in which a large biomass loss from mortality was accompanied with a small increase in growth. With every degree of annual temperature increase, ΔAGB decreased by 1.00, 0.20, 0.55 and 1.07 Mg ha(-1)  year(-1) in DEC, ESC, MIX and LSC forests, respectively. With every cm decrease of annual climatic moisture availability, ΔAGB decreased 0.030, 0.045 and 0.17 Mg ha(-1)  year(-1) in ESC, MIX and LSC forests, but changed little in DEC forests. Our results suggest that persistent warming and decreasing water availability have profound negative effects on forest biomass in the boreal forests of western Canada. Furthermore, our results indicate that forest responses to climate change are strongly dependent on forest composition with late-successional coniferous forests being most vulnerable to climate changes in terms of aboveground biomass.

  3. Statistical physics of age related macular degeneration

    NASA Astrophysics Data System (ADS)

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

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

  4. Age-related changes in human vestibulo-ocular and optokinetic reflexes: Pseudorandom rotation tests

    NASA Technical Reports Server (NTRS)

    Peterka, R. J.; Black, F. O.; Schoenhoff, M. B.

    1989-01-01

    The dynamic response properties of horizontal vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) were characterized in 216 human subjects ranging in age from 7 to 81 years. The object of this cross-sectional study was to determine the effects of aging on VOR and OKR reflex dynamics, and to identify the distributions of parameters which describe VOR and OKR responses to pseudorandom stimuli in a putatively normal population. In general, VOR and OKR response parameters changed in a manner consistent with declining function with increasing age. For the VOR this was reflected in declining response amplitudes, although the magnitude of the decline was small relative to the variability of the data. For the OKR the lag time of the response, probably associated with the time required for visual information processing, increased linearly with age at a rate of about 1 ms per year.

  5. The age of astronomy-related organizations

    NASA Astrophysics Data System (ADS)

    Heck, A.

    1999-03-01

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

  6. Oxygen isotope in archaeological bioapatites from India: Implications to climate change and decline of Bronze Age Harappan civilization.

    PubMed

    Sarkar, Anindya; Mukherjee, Arati Deshpande; Bera, M K; Das, B; Juyal, Navin; Morthekai, P; Deshpande, R D; Shinde, V S; Rao, L S

    2016-01-01

    The antiquity and decline of the Bronze Age Harappan civilization in the Indus-Ghaggar-Hakra river valleys is an enigma in archaeology. Weakening of the monsoon after ~5 ka BP (and droughts throughout the Asia) is a strong contender for the Harappan collapse, although controversy exists about the synchroneity of climate change and collapse of civilization. One reason for this controversy is lack of a continuous record of cultural levels and palaeomonsoon change in close proximity. We report a high resolution oxygen isotope (δ(18)O) record of animal teeth-bone phosphates from an archaeological trench itself at Bhirrana, NW India, preserving all cultural levels of this civilization. Bhirrana was part of a high concentration of settlements along the dried up mythical Vedic river valley 'Saraswati', an extension of Ghaggar river in the Thar desert. Isotope and archaeological data suggest that the pre-Harappans started inhabiting this area along the mighty Ghaggar-Hakra rivers fed by intensified monsoon from 9 to 7 ka BP. The monsoon monotonically declined after 7 ka yet the settlements continued to survive from early to mature Harappan time. Our study suggests that other cause like change in subsistence strategy by shifting crop patterns rather than climate change was responsible for Harappan collapse. PMID:27222033

  7. Oxygen isotope in archaeological bioapatites from India: Implications to climate change and decline of Bronze Age Harappan civilization.

    PubMed

    Sarkar, Anindya; Mukherjee, Arati Deshpande; Bera, M K; Das, B; Juyal, Navin; Morthekai, P; Deshpande, R D; Shinde, V S; Rao, L S

    2016-01-01

    The antiquity and decline of the Bronze Age Harappan civilization in the Indus-Ghaggar-Hakra river valleys is an enigma in archaeology. Weakening of the monsoon after ~5 ka BP (and droughts throughout the Asia) is a strong contender for the Harappan collapse, although controversy exists about the synchroneity of climate change and collapse of civilization. One reason for this controversy is lack of a continuous record of cultural levels and palaeomonsoon change in close proximity. We report a high resolution oxygen isotope (δ(18)O) record of animal teeth-bone phosphates from an archaeological trench itself at Bhirrana, NW India, preserving all cultural levels of this civilization. Bhirrana was part of a high concentration of settlements along the dried up mythical Vedic river valley 'Saraswati', an extension of Ghaggar river in the Thar desert. Isotope and archaeological data suggest that the pre-Harappans started inhabiting this area along the mighty Ghaggar-Hakra rivers fed by intensified monsoon from 9 to 7 ka BP. The monsoon monotonically declined after 7 ka yet the settlements continued to survive from early to mature Harappan time. Our study suggests that other cause like change in subsistence strategy by shifting crop patterns rather than climate change was responsible for Harappan collapse.

  8. Oxygen isotope in archaeological bioapatites from India: Implications to climate change and decline of Bronze Age Harappan civilization

    PubMed Central

    Sarkar, Anindya; Mukherjee, Arati Deshpande; Bera, M. K.; Das, B.; Juyal, Navin; Morthekai, P.; Deshpande, R. D.; Shinde, V. S.; Rao, L. S.

    2016-01-01

    The antiquity and decline of the Bronze Age Harappan civilization in the Indus-Ghaggar-Hakra river valleys is an enigma in archaeology. Weakening of the monsoon after ~5 ka BP (and droughts throughout the Asia) is a strong contender for the Harappan collapse, although controversy exists about the synchroneity of climate change and collapse of civilization. One reason for this controversy is lack of a continuous record of cultural levels and palaeomonsoon change in close proximity. We report a high resolution oxygen isotope (δ18O) record of animal teeth-bone phosphates from an archaeological trench itself at Bhirrana, NW India, preserving all cultural levels of this civilization. Bhirrana was part of a high concentration of settlements along the dried up mythical Vedic river valley ‘Saraswati’, an extension of Ghaggar river in the Thar desert. Isotope and archaeological data suggest that the pre-Harappans started inhabiting this area along the mighty Ghaggar-Hakra rivers fed by intensified monsoon from 9 to 7 ka BP. The monsoon monotonically declined after 7 ka yet the settlements continued to survive from early to mature Harappan time. Our study suggests that other cause like change in subsistence strategy by shifting crop patterns rather than climate change was responsible for Harappan collapse. PMID:27222033

  9. Multi-modal imaging predicts memory performance in normal aging and cognitive decline.

    PubMed

    Walhovd, K B; Fjell, A M; Dale, A M; McEvoy, L K; Brewer, J; Karow, D S; Salmon, D P; Fennema-Notestine, C

    2010-07-01

    This study (n=161) related morphometric MR imaging, FDG-PET and APOE genotype to memory scores in normal controls (NC), mild cognitive impairment (MCI) and Alzheimer's disease (AD). Stepwise regression analyses focused on morphometric and metabolic characteristics of the episodic memory network: hippocampus, entorhinal, parahippocampal, retrosplenial, posterior cingulate, precuneus, inferior parietal, and lateral orbitofrontal cortices. In NC, hippocampal metabolism predicted learning; entorhinal metabolism predicted recognition; and hippocampal metabolism predicted recall. In MCI, thickness of the entorhinal and precuneus cortices predicted learning, while parahippocampal metabolism predicted recognition. In AD, posterior cingulate cortical thickness predicted learning, while APOE genotype predicted recognition. In the total sample, hippocampal volume and metabolism, cortical thickness of the precuneus, and inferior parietal metabolism predicted learning; hippocampal volume and metabolism, parahippocampal thickness and APOE genotype predicted recognition. Imaging methods appear complementary and differentially sensitive to memory in health and disease. Medial temporal and parietal metabolism and morphometry best explained memory variance. Medial temporal characteristics were related to learning, recall and recognition, while parietal structures only predicted learning.

  10. The Neural Consequences of Age-Related Hearing Loss.

    PubMed

    Peelle, Jonathan E; Wingfield, Arthur

    2016-07-01

    During hearing, acoustic signals travel up the ascending auditory pathway from the cochlea to auditory cortex; efferent connections provide descending feedback. In human listeners, although auditory and cognitive processing have sometimes been viewed as separate domains, a growing body of work suggests they are intimately coupled. Here, we review the effects of hearing loss on neural systems supporting spoken language comprehension, beginning with age-related physiological decline. We suggest that listeners recruit domain general executive systems to maintain successful communication when the auditory signal is degraded, but that this compensatory processing has behavioral consequences: even relatively mild levels of hearing loss can lead to cascading cognitive effects that impact perception, comprehension, and memory, leading to increased listening effort during speech comprehension. PMID:27262177

  11. The Neural Consequences of Age-Related Hearing Loss.

    PubMed

    Peelle, Jonathan E; Wingfield, Arthur

    2016-07-01

    During hearing, acoustic signals travel up the ascending auditory pathway from the cochlea to auditory cortex; efferent connections provide descending feedback. In human listeners, although auditory and cognitive processing have sometimes been viewed as separate domains, a growing body of work suggests they are intimately coupled. Here, we review the effects of hearing loss on neural systems supporting spoken language comprehension, beginning with age-related physiological decline. We suggest that listeners recruit domain general executive systems to maintain successful communication when the auditory signal is degraded, but that this compensatory processing has behavioral consequences: even relatively mild levels of hearing loss can lead to cascading cognitive effects that impact perception, comprehension, and memory, leading to increased listening effort during speech comprehension.

  12. Neuropharmacology of depression in aging and age-related diseases.

    PubMed

    Gareri, Pietro; De Fazio, Pasquale; De Sarro, Giovambattista

    2002-02-01

    Depression in the elderly is nowadays a predominant health care problem, mainly due to the progressive aging of the population. It results from psychosocial stress, polypathology, as well as some biochemical changes which occur in the aged brain and can lead to cognitive impairments, increased symptoms from medical illness, higher utilization of health care services and increased rates of suicide and non-suicide mortality. Depression may be also caused by a various number of drugs currently administered; this is remarkable especially in elderly people, where polypathology is often associated with polypharmacotherapy. However, the pathogenesis of geriatric depression is not well understood; major depression may arise from dysfunction of the limbic-hypothalamic-pituitary-adrenal axis. Some clinical observations also suggest that striato-frontal dysfunction is associated with late life depression. A number of hypotheses have been made, focusing that mood disturbances are probably linked to a disturbed central metabolism of monoamines 5-hydroxytryptamine, noradrenaline and dopamine; however most of this knowledge is derived from animal models. Parkinson's and Alzheimer's diseases are age-related diseases associated to decreased activity or brain lesions in the orbital frontal cortex and basal ganglia. These observations lead to the hypothesis that the dysfunction of one or more of the cortical basal ganglia-thalamic neuronal loops are involved in the pathophysiology of primary and secondary depression. This dysfunction may be mediated by decreased serotonin release and probably, also by reduction in serotonin receptors. Development of novel approaches such as dynamic brain imaging methods, together with indirect knowledge coming from the effects of new antidepressants, will increase the understanding of neurochemistry of depression in old age. PMID:12039452

  13. Age-dependent decline in density of human nerve and spinal ganglia neurons expressing the α3 isoform of Na/K-ATPase.

    PubMed

    Romanovsky, D; Mrak, R E; Dobretsov, M

    2015-12-01

    Ambulatory instability and falls are a major source of morbidity in the elderly. Age-related loss of tendon reflexes is a major contributing factor to this morbidity, and deterioration of the afferent limb of the stretch reflex is a potential contributing factor to such age-dependent loss of tendon reflexes. To evaluate this, we assessed the number and distribution of muscle spindle afferent fibers in human sacral spinal ganglia (S1) and tibial nerve samples obtained at autopsy, using immunohistochemical staining for the α3 isoform of Na(+), K(+)-ATPase (α3NKA), a marker of muscle spindle afferents. Across all age groups, an average of 26 ± 4% of myelinated fibers of tibial nerve and 17 ± 2% of ganglion neuronal profiles were α3NKA-positive (n = 8 per group). Subject age explained 85% of the variability in these counts. The relative frequency of α3NKA-labeled fibers/neurons starts to decline during the 5th decade of life, approaching half that of young adult values in 65-year-old subjects. At all ages, α3NKA-positive neurons were among the largest of spinal ganglia neurons. However, as compared to younger subjects, the population of α3NKA-positive neurons from advanced-age subjects showed diminished numbers of large (both moderately and strongly labeled), and medium-sized (strongly labeled) profiles. Considering the critical significance of ion transport by NKA for neuronal activity, our data suggest that functional impairment and, also, most likely atrophy and/or degeneration of muscle spindle afferents, are mechanisms underlying loss of tendon reflexes with age. The larger and more strongly α3NKA-expressing spindle afferents appear to be proportionally more vulnerable. PMID:26386295

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

    PubMed

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

    2010-09-01

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

  15. Age-related changes in conventional road versus off-road triathlon performance.

    PubMed

    Lepers, Romuald; Stapley, Paul J

    2011-08-01

    The aims of this study were: (i) to analyze age-related declines in swimming, cycling, and running performances for road-based and off-road triathlons, and (ii) to compare age-related changes in these three disciplines between road-based and off-road triathlons. Swimming, cycling, running and total time performances of the top five males between 20 and 70 years of age (in 5-year intervals) were analyzed for short distance road-based (1.5 km swim, 40 km cycle, and 10 km run) and off-road (1.5 km swim, 30 km mountain bike, and 11 km trail run) triathlons at the 2009 World Championships. Independently of age, there was a lesser age-related decline in cycling performance (P < 0.01) compared to running and swimming for road-based triathlon. In contrast, age-related decline did not differ between the three locomotion modes for off-road triathlon. With advancing age, the performance decline was less pronounced (P < 0.01) for road-based than for off-road triathlon in swimming (≥65 years), cycling (≥50 years), running (≥60 years), and total event (≥55 years) times, respectively. These results suggest that the rate of the decline in performance for off-road triathlon is greater than for road-based triathlon, indicating that the type of discipline (road vs. mountain bike cycling and road vs. trail running) exerts an important influence on the magnitude of the age-associated changes in triathlon performance.

  16. [Epidemiology of age related macular degeneration].

    PubMed

    Leveziel, N; Delcourt, C; Zerbib, J; Dollfus, H; Kaplan, J; Benlian, P; Coscas, G; Souied, E H; Soubrane, G

    2009-06-01

    Age-related macular degeneration (ARMD) is a multifactorial and polygenic disease and is the main cause of vision loss in developed countries. The environmental factors of ARMD can modify prevalence and incidence of this disease. This article is a review of the main environmental factors currently recognized as at risk or protective factor for ARMD. Modification of these factors is of crucial importance because it could delay the onset of exudative or atrophic forms of the disease. PMID:19515460

  17. Controlled processes account for age-related decrease in episodic memory.

    PubMed

    Vanderaspoilden, Valérie; Adam, Stéphane; der Linden, Martial Van; Morais, José

    2007-05-01

    A decrease in controlled processes has been proposed to be responsible for age-related episodic memory decline. We used the Process Dissociation Procedure, a method that attempts to estimate the contribution of controlled and automatic processes to cognitive performance, and entered both estimates in regression analyses. Results indicate that only controlled processes explained a great part of the age-related variance in a word recall task, especially when little environmental support was offered. PMID:16860766

  18. Age-Related Loss of Muscle Mass and Strength

    PubMed Central

    Goldspink, Geoffrey

    2012-01-01

    Age-related muscle wasting and increased frailty are major socioeconomic as well as medical problems. In the quest to extend quality of life it is important to increase the strength of elderly people sufficiently so they can carry out everyday tasks and to prevent them falling and breaking bones that are brittle due to osteoporosis. Muscles generate the mechanical strain that contributes to the maintenance of other musculoskeletal tissues, and a vicious circle is established as muscle loss results in bone loss and weakening of tendons. Molecular and proteomic approaches now provide strategies for preventing age-related muscle wasting. Here, attention is paid to the role of the GH/IGF-1 axis and the special role of the IGFI-Ec (mechano growth factor/MGF) which is derived from the IGF-I gene by alternative splicing. During aging MGF levels decline but when administered MGF activates the muscle satellite (stem) cells that “kick start” local muscle repair and induces hypertrophy. PMID:22506111

  19. Physics of Age Related Macular Degeneration

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon

    2009-11-01

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

  20. Differential Trajectories of Age-Related Changes in Components of Executive and Memory Processes

    PubMed Central

    Goh, Joshua O.; An, Yang; Resnick, Susan M.

    2012-01-01

    Several studies have demonstrated age-related declines in general executive function and memory. In this study, we examined cross-sectional and longitudinal age effects in more specific cognitive processes that constitute executive function and memory. We postulated that, whereas some components of executive and memory functions would show age differences and longitudinal declines, other specific abilities would be maintained or even improve with repeated testing. In a sample of individuals ≥55 years old from the Baltimore Longitudinal Study of Aging, we found longitudinal declines in inhibition, manipulation, semantic retrieval, phonological retrieval, s