Age-Related Decline in Anticipatory Motor Planning and Its Relation to Cognitive and Motor Skill Proficiency

PubMed Central

Stöckel, Tino; Wunsch, Kathrin; Hughes, Charmayne M. L.

2017-01-01

Anticipatory motor planning abilities mature as children grow older, develop throughout childhood and are likely to be stable till the late sixties. In the seventh decade of life, motor planning performance dramatically declines, with anticipatory motor planning abilities falling to levels of those exhibited by children. At present, the processes enabling successful anticipatory motor planning in general, as do the cognitive processes mediating these age-related changes, remain elusive. Thus, the aim of the present study was (a) to identify cognitive and motor functions that are most affected by normal aging and (b) to elucidate key (cognitive and motor) factors that are critical for successful motor planning performance in young (n = 40, mean age = 23.1 ± 2.6 years) and older adults (n = 37, mean age = 73.5 ± 7.1 years). Results indicate that normal aging is associated with a marked decline in all aspects of cognitive and motor functioning tested. However, age-related declines were more apparent for fine motor dexterity, processing speed and cognitive flexibility. Furthermore, up to 64% of the variance in motor planning performance across age groups could be explained by the cognitive functions processing speed, response planning and cognitive flexibility. It can be postulated that anticipatory motor planning abilities are strongly influenced by cognitive control processes, which seem to be key mechanisms to compensate for age-related decline. These findings support the general therapeutic and preventive value of cognitive-motor training programs to reduce adverse effects associated with high age. PMID:28928653

Female age-related fertility decline. Committee Opinion No. 589.

PubMed

2014-03-01

The fecundity of women decreases gradually but significantly beginning approximately at age 32 years and decreases more rapidly after age 37 years. Education and enhanced awareness of the effect of age on fertility are essential in counseling the patient who desires pregnancy. Given the anticipated age-related decline in fertility, the increased incidence of disorders that impair fertility, and the higher risk of pregnancy loss, women older than 35 years should receive an expedited evaluation and undergo treatment after 6 months of failed attempts to conceive or earlier, if clinically indicated. In women older than 40 years, more immediate evaluation and treatment are warranted.

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).…

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

Female age-related fertility decline. Committee Opinion No. 589.

PubMed

2014-03-01

The fecundity of women decreases gradually but significantly beginning approximately at age 32 years and decreases more rapidly after age 37 years. Education and enhanced awareness of the effect of age on fertility are essential in counseling the patient who desires pregnancy. Given the anticipated age-related decline in fertility, the increased incidence of disorders that impair fertility, and the higher risk of pregnancy loss, women older than 35 years should receive an expedited evaluation and undergo treatment after 6 months of failed attempts to conceive or earlier, if clinically indicated. In women older than 40 years, more immediate evaluation and treatment are warranted. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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

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

Associations between cognitively stimulating leisure activities, cognitive function and age-related cognitive decline.

PubMed

Ferreira, Nicola; Owen, Adrian; Mohan, Anita; Corbett, Anne; Ballard, Clive

2015-04-01

Emerging literature suggests that lifestyle factors may play an important role in reducing age-related cognitive decline. There have, however, been few studies investigating the role of cognitively stimulating leisure activities in maintaining cognitive health. This study sought to identify changes in cognitive performance with age and to investigate associations of cognitive performance with several key cognitively stimulating leisure activities. Over 65,000 participants provided demographic and lifestyle information and completed tests of grammatical reasoning, spatial working memory, verbal working memory and episodic memory. Regression analyses suggested that frequency of engaging in Sudoku or similar puzzles was significantly positively associated with grammatical reasoning, spatial working memory and episodic memory scores. Furthermore, for participants aged under 65 years, frequency of playing non-cognitive training computer games was also positively associated with performance in the same cognitive domains. The results also suggest that grammatical reasoning and episodic memory are particularly vulnerable to age-related decline. Further investigation to determine the potential benefits of participating in Sudoku puzzles and non-cognitive computer games is indicated, particularly as they are associated with grammatical reasoning and episodic memory, cognitive domains found to be strongly associated with age-related cognitive decline. Results of this study have implications for developing improved guidance for the public regarding the potential value of cognitively stimulating leisure activities. The results also suggest that grammatical reasoning and episodic memory should be targeted in developing appropriate outcome measures to assess efficacy of future interventions, and in developing cognitive training programmes to prevent or delay cognitive decline. Copyright © 2014 John Wiley & Sons, Ltd.

Young and Older Adults’ Beliefs about Effective Ways to Mitigate Age-Related Memory Decline

PubMed Central

Horhota, Michelle; Lineweaver, Tara; Ositelu, Monique; Summers, Kristi; Hertzog, Christopher

2013-01-01

This study investigated whether young and older adults vary in their beliefs about the impact of various mitigating factors on age-related memory decline. Eighty young (ages 18–23) and eighty older (ages 60–82) participants reported their beliefs about their own memory abilities and the strategies that they use in their everyday lives to attempt to control their memory. Participants also reported their beliefs about memory change with age for hypothetical target individuals who were described as using (or not using) various means to mitigate memory decline. There were no age differences in personal beliefs about control over current or future memory ability. However, the two age groups differed in the types of strategies they used in their everyday life to control their memory. Young adults were more likely to use internal memory strategies, whereas older adults were more likely to focus on cognitive exercise and maintaining physical health as ways to optimize their memory ability. There were no age differences in rated memory change across the life span in hypothetical individuals. Both young and older adults perceived strategies related to improving physical and cognitive health as effective means of mitigating memory loss with age, whereas internal memory strategies were perceived as less effective means for controlling age-related memory decline. PMID:22082012

Young and older adults' beliefs about effective ways to mitigate age-related memory decline.

PubMed

Horhota, Michelle; Lineweaver, Tara; Ositelu, Monique; Summers, Kristi; Hertzog, Christopher

2012-06-01

This study investigated whether young and older adults vary in their beliefs about the impact of various mitigating factors on age-related memory decline. Eighty young (ages 18-23) and 80 older (ages 60-82) participants reported their beliefs about their own memory abilities and the strategies that they use in their everyday lives to attempt to control their memory. Participants also reported their beliefs about memory change with age for hypothetical target individuals who were described as using (or not using) various means to mitigate memory decline. There were no age differences in personal beliefs about control over current or future memory ability. However, the two age groups differed in the types of strategies they used in their everyday life to control their memory. Young adults were more likely to use internal memory strategies, whereas older adults were more likely to focus on cognitive exercise and maintaining physical health as ways to optimize their memory ability. There were no age differences in rated memory change across the life span in hypothetical individuals. Both young and older adults perceived strategies related to improving physical and cognitive health as effective means of mitigating memory loss with age, whereas internal memory strategies were perceived as less effective means for controlling age-related memory decline. PsycINFO Database Record (c) 2012 APA, all rights reserved

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

Subcortical volumetric changes across the adult lifespan: subregional thalamic atrophy accounts for age-related sensorimotor performance declines.

PubMed

Serbruyns, Leen; Leunissen, Inge; Huysmans, Toon; Cuypers, Koen; Meesen, Raf L; van Ruitenbeek, Peter; Sijbers, Jan; Swinnen, Stephan P

2015-04-01

Even though declines in sensorimotor performance during healthy aging have been documented extensively, its underlying neural mechanisms remain unclear. Here, we explored whether age-related subcortical atrophy plays a role in sensorimotor performance declines, and particularly during bimanual manipulative performance (Purdue Pegboard Test). The thalamus, putamen, caudate and pallidum of 91 participants across the adult lifespan (ages 20-79 years) were automatically segmented. In addition to studying age-related changes in the global volume of each subcortical structure, local deformations within these structures, indicative of subregional volume changes, were assessed by means of recently developed shape analyses. Results showed widespread age-related global and subregional atrophy, as well as some notable subregional expansion. Even though global atrophy failed to explain the observed performance declines with aging, shape analyses indicated that atrophy in left and right thalamic subregions, specifically subserving connectivity with the premotor, primary motor and somatosensory cortical areas, mediated the relation between aging and performance decline. It is concluded that subregional volume assessment by means of shape analyses offers a sensitive tool with high anatomical resolution in the search for specific age-related associations between brain structure and behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

Age-related Decline of Abiotic Stress Tolerance in Young Drosophila melanogaster Adults.

PubMed

Colinet, Hervé; Chertemps, Thomas; Boulogne, Isabelle; Siaussat, David

2016-12-01

Stress tolerance generally declines with age as a result of functional senescence. Age-dependent alteration of stress tolerance can also occur in early adult life. In Drosophila melanogaster, evidence of such a decline in young adults has only been reported for thermotolerance. It is not known whether early adult life entails a general stress tolerance reduction and whether the response is peculiar to thermal traits. The present work was designed to investigate whether newly eclosed D melanogaster adults present a high tolerance to a range of biotic and abiotic insults. We found that tolerance to most of the abiotic stressors tested (desiccation, paraquat, hydrogen peroxide, deltamethrin, and malathion) was high in newly eclosed adults before dramatically declining over the next days of adult life. No clear age-related pattern was found for resistance to biotic stress (septic or fungal infection) and starvation. These results suggest that newly eclosed adults present a culminating level of tolerance to extrinsic stress which is likely unrelated to immune process. We argue that stress tolerance variation at very young age is likely a residual attribute from the previous life stage (ontogenetic carryover) or a feature related to the posteclosion development. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Age-Related Decline of Wrist Position Sense and its Relationship to Specific Physical Training.

PubMed

Van de Winckel, Ann; Tseng, Yu-Ting; Chantigian, Daniel; Lorant, Kaitlyn; Zarandi, Zinat; Buchanan, Jeffrey; Zeffiro, Thomas A; Larson, Mia; Olson-Kellogg, Becky; Konczak, Jürgen; Keller-Ross, Manda L

2017-01-01

Perception of limb and body positions is known as proprioception. Sensory feedback, especially from proprioceptive receptors, is essential for motor control. Aging is associated with a decline in position sense at proximal joints, but there is inconclusive evidence of distal joints being equally affected by aging. In addition, there is initial evidence that physical activity attenuates age-related decline in proprioception. Our objectives were, first, to establish wrist proprioceptive acuity in a large group of seniors and compare their perception to young adults, and second, to determine if specific types of training or regular physical activity are associated with preserved wrist proprioception. We recruited community-dwelling seniors ( n = 107, mean age, 70 ± 5 years, range, 65-84 years) without cognitive decline (Mini Mental State Examination-brief version ≥13/16) and young adult students ( n = 51, mean age, 20 ± 1 years, range, 19-26 years). Participants performed contralateral and ipsilateral wrist position sense matching tasks with a bimanual wrist manipulandum to a 15° flexion reference position. Systematic error or proprioceptive bias was computed as the mean difference between matched and reference position. The respective standard deviation over five trials constituted a measure of random error or proprioceptive precision . Current levels of physical activity and previous sport, musical, or dance training were obtained through a questionnaire. We employed longitudinal mixed effects linear models to calculate the effects of trial number, sex, type of matching task and age on wrist proprioceptive bias and precision. The main results were that relative proprioceptive bias was greater in older when compared to young adults (mean difference: 36% ipsilateral, 88% contralateral, p < 0.01). Proprioceptive precision for contralateral but not for ipsilateral matching was smaller in older than in young adults (mean difference: 38% contralateral, p < 0

Age-Related Decline of Wrist Position Sense and its Relationship to Specific Physical Training

PubMed Central

Van de Winckel, Ann; Tseng, Yu-Ting; Chantigian, Daniel; Lorant, Kaitlyn; Zarandi, Zinat; Buchanan, Jeffrey; Zeffiro, Thomas A.; Larson, Mia; Olson-Kellogg, Becky; Konczak, Jürgen; Keller-Ross, Manda L.

2017-01-01

Perception of limb and body positions is known as proprioception. Sensory feedback, especially from proprioceptive receptors, is essential for motor control. Aging is associated with a decline in position sense at proximal joints, but there is inconclusive evidence of distal joints being equally affected by aging. In addition, there is initial evidence that physical activity attenuates age-related decline in proprioception. Our objectives were, first, to establish wrist proprioceptive acuity in a large group of seniors and compare their perception to young adults, and second, to determine if specific types of training or regular physical activity are associated with preserved wrist proprioception. We recruited community-dwelling seniors (n = 107, mean age, 70 ± 5 years, range, 65–84 years) without cognitive decline (Mini Mental State Examination-brief version ≥13/16) and young adult students (n = 51, mean age, 20 ± 1 years, range, 19–26 years). Participants performed contralateral and ipsilateral wrist position sense matching tasks with a bimanual wrist manipulandum to a 15° flexion reference position. Systematic error or proprioceptive bias was computed as the mean difference between matched and reference position. The respective standard deviation over five trials constituted a measure of random error or proprioceptive precision. Current levels of physical activity and previous sport, musical, or dance training were obtained through a questionnaire. We employed longitudinal mixed effects linear models to calculate the effects of trial number, sex, type of matching task and age on wrist proprioceptive bias and precision. The main results were that relative proprioceptive bias was greater in older when compared to young adults (mean difference: 36% ipsilateral, 88% contralateral, p < 0.01). Proprioceptive precision for contralateral but not for ipsilateral matching was smaller in older than in young adults (mean difference: 38% contralateral, p < 0

Visual function and cognitive speed of processing mediate age-related decline in memory span and fluid intelligence

PubMed Central

Clay, Olivio J.; Edwards, Jerri D.; Ross, Lesley A.; Okonkwo, Ozioma; Wadley, Virginia G.; Roth, David L.; Ball, Karlene K.

2010-01-01

Objectives: To evaluate the relationship between sensory and cognitive decline, particularly with respect to speed of processing, memory span, and fluid intelligence. Additionally, the common cause, sensory degradation and speed of processing hypotheses were compared. Methods: Structural equation modeling was used to investigate the complex relationships among age-related decrements in these areas. Results: Cross-sectional data analyses included 842 older adult participants (M = 73 years). After accounting for age-related declines in vision and processing speed, the direct associations between age and memory span and between age and fluid intelligence were nonsignificant. Older age was associated with visual decline, which was associated with slower speed of processing, which in turn was associated with greater cognitive deficits. Discussion: The findings support both the sensory degradation and speed of processing accounts of age-related cognitive decline. Further, the findings highlight positive aspects of normal cognitive aging in that older age may not be associated with a loss of fluid intelligence if visual sensory functioning and processing speed can be maintained. PMID:19436063

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

PubMed Central

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

2013-01-01

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

Age-related decline in mitochondrial DNA copy number in isolated human pancreatic islets.

PubMed

Cree, L M; Patel, S K; Pyle, A; Lynn, S; Turnbull, D M; Chinnery, P F; Walker, M

2008-08-01

Pancreatic beta cell function has been shown to decline with age in man. Depletion of mitochondrial DNA (mtDNA) copy number is associated with impaired insulin secretion in pancreatic beta cell lines, and decreased mtDNA copy number has been observed with age in skeletal muscle in man. We investigated whether mtDNA copy number decreases with age in human pancreatic beta cells, which might in turn contribute to the age-related decline in insulin secretory capacity. We quantified mtDNA copy number in isolated human islet preparations from 15 pancreas donors aged between 17 and 75 years. Islets (n = 20) were individually hand-picked and pooled from each donor isolate for the quantification of mtDNA copy number and deleted mtDNA (%), which were determined using real-time PCR methods. There was a significant negative correlation between mtDNA copy number and islet donor age (r = -0.53, p = 0.044). mtDNA copy number was significantly decreased in islet preparations from donors aged > or =50 years (n = 8) compared with those aged <50 years (n = 7) (median [interquartile range]: 418 [236-503] vs 596 [554-729] mtDNA copy number/diploid genome; p = 0.032). None of the islet preparations harboured high levels of deleted mtDNA affecting the major arc. Given the correlation between mtDNA content and respiratory chain activity, the age-related decrease in mtDNA copy number that we observed in human pancreatic islet preparations may contribute to the age-dependent decline in pancreatic beta cell insulin secretory capacity.

Trajectories of age-related cognitive decline and potential associated factors of cognitive function in senior citizens of Beijing.

PubMed

Li, He; Lv, Chenlong; Zhang, Ting; Chen, Kewei; Chen, Chuansheng; Gai, Guozhong; Hu, Liangping; Wang, Yongyan; Zhang, Zhanjun

2014-01-01

With a longer life expectancy and an increased prevalence of neurodegenerative diseases, investigations on trajectories of cognitive aging have become exciting and promising. This study aimed to estimate the patterns of age-related cognitive decline and the potential associated factors of cognitive function in community-dwelling residents of Beijing, China. In this study, 1248 older adults aged 52-88 years [including 175 mild cognitive impairment (MCI) subjects] completed a battery of neuropsychological scales. The personal information, including demographic information, medical history, eating habits, lifestyle regularity and leisure activities, was also collected. All cognitive function exhibited an agerelated decline in normal volunteers. Piece-wise linear fitting results suggested that performance on the Auditory Verbal Learning Test remained stable until 58 years of age and continued to decline thereafter. The decline in processing speed and executive function began during the early 50's. Scores on visual-spatial and language tests declined after 66 years of age. The decline stage of the general mental status ranged from 63 to 70 years of age. However, the MCI group did not exhibit an obvious age-related decline in most cognitive tests. Multivariate linear regression analyses indicated that education, gender, leisure activities, diabetes and eating habits were associated with cognitive abilities. These results indicated various trajectories of age-related decline across multiple cognitive domains. We also found different patterns of agerelated cognitive decline between MCI and normal elderly. These findings could help improve the guidance of cognitive intervention program and have implications for public policy issues.

CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism.

PubMed

Camacho-Pereira, Juliana; Tarragó, Mariana G; Chini, Claudia C S; Nin, Veronica; Escande, Carlos; Warner, Gina M; Puranik, Amrutesh S; Schoon, Renee A; Reid, Joel M; Galina, Antonio; Chini, Eduardo N

2016-06-14

Nicotinamide adenine dinucleotide (NAD) levels decrease during aging and are involved in age-related metabolic decline. To date, the mechanism responsible for the age-related reduction in NAD has not been elucidated. Here we demonstrate that expression and activity of the NADase CD38 increase with aging and that CD38 is required for the age-related NAD decline and mitochondrial dysfunction via a pathway mediated at least in part by regulation of SIRT3 activity. We also identified CD38 as the main enzyme involved in the degradation of the NAD precursor nicotinamide mononucleotide (NMN) in vivo, indicating that CD38 has a key role in the modulation of NAD-replacement therapy for aging and metabolic diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Age-related testosterone decline in a Brazilian cohort of healthy military men.

PubMed

Nardozza Júnior, Archimedes; Szelbracikowski, Sergio dos Santos; Nardi, Aguinaldo Cesar; Almeida, Jose Carlos de

2011-01-01

Androgen decline in the aging man has become a topic of increasing clinical relevance worldwide, as the reduction in testosterone levels has been reported to be accompanied by loss of muscle mass, accumulation of central adiposity, impaired mobility and increase risk of bone fractures. Although well-established in studies conducted in developed countries, progressive decline in serum testosterone levels with age has been poorly investigated in Brazil. To determine the pattern of blood testosterone concentrations decline with age in a cohort of Brazilian healthy military men. We retrospectively reviewed data on serum testosterone measurements of healthy individuals that had undergone a routine check-up at the Military Biology Institute. Blood samples were obtained early in the morning, and total testosterone concentration was determined using a commercial chemoluminescent immunoassay. Mean values were analyzed in five age groups: ≤ 40, 41 to 50, 51 to 60, 61 to 70, and > 70 years. Mean total testosterone levels. 1,623 subjects were included in the analysis; mean age was 57 years (24 to 87), and mean testosterone level was 575.5 ng/dL (25.0 to 1308.0 ng/dL). The evaluation of age-related changes in total testosterone levels revealed a progressive reduction in serum levels of this hormone with increasing age. Testosterone levels below 300 ng/dL were reported in 321 participants, a prevalence of nearly 20% in the study population. In agreement with other findings, a reduction of total testosterone levels with age was reported for healthy Brazilian men.

Age Differences in Brain Activity during Emotion Processing: Reflections of Age-Related Decline or Increased Emotion Regulation?

PubMed Central

Nashiro, Kaoru; Sakaki, Michiko; Mather, Mara

2012-01-01

Despite the fact that physical health and cognitive abilities decline with aging, the ability to regulate emotion remains stable and in some aspects improves across the adult life span. Older adults also show a positivity effect in their attention and memory, with diminished processing of negative stimuli relative to positive stimuli compared with younger adults. The current paper reviews functional magnetic resonance imaging studies investigating age-related differences in emotional processing and discusses how this evidence relates to two opposing theoretical accounts of older adults’ positivity effect. The aging-brain model [Cacioppo et al. in: Social Neuroscience: Toward Understanding the Underpinnings of the Social Mind. New York, Oxford University Press, 2011] proposes that older adults’ positivity effect is a consequence of age-related decline in the amygdala, whereas the cognitive control hypothesis [Kryla-Lighthall and Mather in: Handbook of Theories of Aging, ed 2. New York, Springer, 2009; Mather and Carstensen: Trends Cogn Sci 2005;9:496–502; Mather and Knight: Psychol Aging 2005;20:554–570] argues that the positivity effect is a result of older adults’ greater focus on regulating emotion. Based on evidence for structural and functional preservation of the amygdala in older adults and findings that older adults show greater prefrontal cortex activity than younger adults while engaging in emotion-processing tasks, we argue that the cognitive control hypothesis is a more likely explanation for older adults’ positivity effect than the aging-brain model. PMID:21691052

Age differences in brain activity during emotion processing: reflections of age-related decline or increased emotion regulation?

PubMed

Nashiro, Kaoru; Sakaki, Michiko; Mather, Mara

2012-01-01

Despite the fact that physical health and cognitive abilities decline with aging, the ability to regulate emotion remains stable and in some aspects improves across the adult life span. Older adults also show a positivity effect in their attention and memory, with diminished processing of negative stimuli relative to positive stimuli compared with younger adults. The current paper reviews functional magnetic resonance imaging studies investigating age-related differences in emotional processing and discusses how this evidence relates to two opposing theoretical accounts of older adults' positivity effect. The aging-brain model [Cacioppo et al. in: Social Neuroscience: Toward Understanding the Underpinnings of the Social Mind. New York, Oxford University Press, 2011] proposes that older adults' positivity effect is a consequence of age-related decline in the amygdala, whereas the cognitive control hypothesis [Kryla-Lighthall and Mather in: Handbook of Theories of Aging, ed 2. New York, Springer, 2009; Mather and Carstensen: Trends Cogn Sci 2005;9:496-502; Mather and Knight: Psychol Aging 2005;20:554-570] argues that the positivity effect is a result of older adults' greater focus on regulating emotion. Based on evidence for structural and functional preservation of the amygdala in older adults and findings that older adults show greater prefrontal cortex activity than younger adults while engaging in emotion-processing tasks, we argue that the cognitive control hypothesis is a more likely explanation for older adults' positivity effect than the aging-brain model. Copyright © 2011 S. Karger AG, Basel.

Age-related Decline in Case-Marker Processing and its Relation to Working Memory Capacity.

PubMed

Sung, Jee Eun

2017-09-01

Purposes of the current study were to investigate whether age-related decline emerged in a case-marker assignment task (CMAT) and to explore the relationship between working-memory (WM) capacity and case-marker processing. A total of 121 individuals participated in the study with 62 younger adults and 59 elderly adults. All were administered a CMAT that consisted of active and passive constructions with canonical and noncanonical word-order conditions. A composite measure of WM tasks served as an index of participants' WM capacity. The older group performed worse than the younger group, and the noncanonical word order elicited worse performance than the canonical condition. The older group demonstrated greater difficulty in case-marker processing under the canonical condition and passive construction. Regression results revealed that age, education, and sentence type were the best predictors to account for performance on the CMAT. The canonicity of word order and passive construction were critical factors related to decline in abilities in a case-marker assignment. The combination of age, education, and sentence type factors accounted for overall performance on case-marker processing. Results indicated the crucial necessity to find a cognitively and linguistically demanding condition that elicits aging effects most efficiently, considering language-specific syntactic features. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

Age-related annual decline of lung function in patients with COPD.

PubMed

Kim, Soo Jung; Lee, Jinwoo; Park, Young Sik; Lee, Chang-Hoon; Yoon, Ho Il; Lee, Sang-Min; Yim, Jae-Joon; Kim, Young Whan; Han, Sung Koo; Yoo, Chul-Gyu

2016-01-01

According to the Fletcher-Peto curve, rate of decline in forced expiratory volume in 1-second (FEV1) accelerates as age increases. However, recent studies have not demonstrated that the rate of FEV1 decline accelerates with age among COPD patients. The objective of the study is to evaluate annual rate of FEV1 decline as age increases among COPD patients. In this retrospective cohort study, we enrolled COPD patients who were followed up at two tertiary care university hospitals from January 2000 to August 2013. COPD was defined as post-bronchodilator (BD) FEV1/forced vital capacity (FVC) of <0.7. All participants had more than two spirometries, including BD response. Age groups were categorized as follows: below versus above median age or four quartiles. A total of 518 participants (94.2% male; median age, 67 years; range, 42-90 years) were included. Mean absolute and predictive values of post-BD FEV1 were 1.57±0.62 L and 52.53%±18.29%, respectively. Distribution of Global initiative for Chronic Obstructive Lung Disease groups did not show statistical differences between age groups categorized by two different criteria. After grouping the population by age quartiles, the rate of FEV1 decline was faster among older patients than younger ones whether expressed as absolute value (-10.60±5.57 mL/year, -15.84±6.01 mL/year, -18.63±5.53 mL/year, 32.94±6.01 mL/year, respectively; P=0.048) or predicted value (-0.34%±0.19%/year, -0.53%±0.21%/year, -0.62%±0.19%/year, -1.26%±0.21%/year, respectively, P=0.010). As suggested conceptually by the Fletcher-Peto curve, annual FEV1 decline among COPD patients is accelerated among older patients than younger ones.

Visual Search Load Effects on Age-Related Cognitive Decline: Evidence From the Yakumo Longitudinal Study.

PubMed

Hatta, Takeshi; Kato, Kimiko; Hotta, Chie; Higashikawa, Mari; Iwahara, Akihiko; Hatta, Taketoshi; Hatta, Junko; Fujiwara, Kazumi; Nagahara, Naoko; Ito, Emi; Hamajima, Nobuyuki

2017-01-01

The validity of Bucur and Madden's (2010) proposal that an age-related decline is particularly pronounced in executive function measures rather than in elementary perceptual speed measures was examined via the Yakumo Study longitudinal database. Their proposal suggests that cognitive load differentially affects cognitive abilities in older adults. To address their proposal, linear regression coefficients of 104 participants were calculated individually for the digit cancellation task 1 (D-CAT1), where participants search for a given single digit, and the D-CAT3, where they search for 3 digits simultaneously. Therefore, it can be conjectured that the D-CAT1 represents primarily elementary perceptual speed and low-visual search load task. whereas the D-CAT3 represents primarily executive function and high-visual search load task. Regression coefficients from age 65 to 75 for the D-CAT3 showed a significantly steeper decline than that for the D-CAT1, and a large number of participants showed this tendency. These results support the proposal by Brcur and Madden (2010) and suggest that the degree of cognitive load affects age-related cognitive decline.

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

PubMed

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

2018-05-07

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

Evaluating Alzheimer's disease biomarkers as mediators of age-related cognitive decline.

PubMed

Hohman, Timothy J; Tommet, Doug; Marks, Shawn; Contreras, Joey; Jones, Rich; Mungas, Dan

2017-10-01

Age-related changes in cognition are partially mediated by the presence of neuropathology and neurodegeneration. This manuscript evaluates the degree to which biomarkers of Alzheimer's disease, (AD) neuropathology and longitudinal changes in brain structure, account for age-related differences in cognition. Data from the AD Neuroimaging Initiative (n = 1012) were analyzed, including individuals with normal cognition and mild cognitive impairment. Parallel process mixed effects regression models characterized longitudinal trajectories of cognitive variables and time-varying changes in brain volumes. Baseline age was associated with both memory and executive function at baseline (p's < 0.001) and change in memory and executive function performances over time (p's < 0.05). After adjusting for clinical diagnosis, baseline, and longitudinal changes in brain volume, and baseline levels of cerebrospinal fluid biomarkers, age effects on change in episodic memory and executive function were fully attenuated, age effects on baseline memory were substantially attenuated, but an association remained between age and baseline executive function. Results support previous studies that show that age effects on cognitive decline are fully mediated by disease and neurodegeneration variables but also show domain-specific age effects on baseline cognition, specifically an age pathway to executive function that is independent of brain and disease pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Biological age and sex-related declines in physical activity during adolescence.

PubMed

Cairney, John; Veldhuizen, Scott; Kwan, Matthew; Hay, John; Faught, Brent E

2014-04-01

Sex differences in the rate of decline in physical activity (PA) are most pronounced during adolescence. However, once boys and girls are aligned on biological age, sex differences in the patterns of PA become attenuated. The aim of this study was to test whether biological maturation can account for sex differences in participation in PA over time from late childhood to early adolescence. A prospective cohort of children (N = 2100; 1064 boys) was followed from ages 11 to 14 yr, with repeated assessments of PA and anthropometry. Self-reported participation in organized and free play activities was used to track participation in PA. Biological age was measured using an estimate of years to attainment of peak height velocity. Mixed-effects models were used to test whether controlling for biological age attenuates the effect of chronological age and sex on PA. As expected, the rate of decline in participation in PA was greater for girls than for boys (B = -1.18, P < 0.01). In multivariable analyses, adjusting for biological age completely attenuated the effect of sex and chronological age for participation in free play activities, but not for participation in organized play. Overall, biological age was a stronger predictor of participation than chronological age. The effect of biological age on sex by chronological age differences may be specific to certain types of PA participation. Given the importance of maturation to participation in activity, it is suggested that public health strategies target biological not chronological age to prevent declines in PA during adolescence particularly when promoting habitual or lifestyle activity.

A novel approach to rapidly prevent age-related cognitive decline

PubMed Central

Adlard, Paul A; Sedjahtera, Amelia; Gunawan, Lydia; Bray, Lisa; Hare, Dominic; Lear, Jessica; Doble, Philip; Bush, Ashley I; Finkelstein, David I; Cherny, Robert A

2014-01-01

The loss of cognitive function is a pervasive and often debilitating feature of the aging process for which there are no effective therapeutics. We hypothesized that a novel metal chaperone (PBT2; Prana Biotechnology, Parkville, Victoria, Australia) would enhance cognition in aged rodents. We show here that PBT2 rapidly improves the performance of aged C57Bl/6 mice in the Morris water maze, concomitant with increases in dendritic spine density, hippocampal neuron number and markers of neurogenesis. There were also increased levels of specific glutamate receptors (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-d-aspartate), the glutamate transporter (VGLUT1) and glutamate itself. Markers of synaptic plasticity [calmodulin-dependent protein kinase II (CaMKII) and phosphorylated CaMKII, CREB, synaptophysin] were also increased following PBT2 treatment. We also demonstrate that PBT2 treatment results in a subregion-specific increase in hippocampal zinc, which is increasingly recognized as a potent neuromodulator. These data demonstrate that metal chaperones are a novel approach to the treatment of age-related cognitive decline. PMID:24305557

HIV/HCV Co-infection, Liver Disease Progression, and Age-Related IGF-1 Decline.

PubMed

Quinn, Jeffrey; Astemborski, Jacquie; Mehta, Shruti H; Kirk, Gregory D; Thomas, David L; Balagopal, Ashwin

2017-01-01

We have previously reported that persons co-infected with HIV and hepatitis C virus (HCV) had liver disease stages similar to HIV-uninfected individuals who were approximately 10 years older. Insulin-like growth factor 1(IGF-1) levels have long been known to decline with advancing age in humans and non-humans alike. We examined whether HIV infection affects the expected decline in IGF-1 in persons with chronic hepatitis C virus (HCV) infection and if that alteration in IGF-1 decline contributes to the link between HIV, aging, and liver disease progression. A total of 553 individuals with HCV infection were studied from the AIDS Linked to the Intravenous Experience (ALIVE) cohort for whom more than 10 years of follow-up was available. Serum IGF-1 levels were determined by ELISA and evaluated according to baseline characteristics and over time by HIV status and liver disease progression. Linear regression with generalized estimating equations was used to determine whether IGF-1 decline over time was independently associated with liver disease progression. Baseline IGF-1 levels were strongly associated with age ( P < 0.0001) but not with gender or HIV infection. Levels of IGF-1 declined at a rate of -1.75 ng/mL each year in HCV mono-infected individuals and at a rate of -1.23 ng/mL each year in HIV/HCV co-infected individuals ( P < 0.05). In a multivariable linear regression model, progression of liver fibrosis was associated with HIV infection and age, as well as with a slower rate of IGF-1 decline ( P = 0.001); however, the rate of IGF-1 decline did not alter the strength of the associations between HIV, liver disease, and age. The normal decline in IGF-1 levels with age was attenuated in HIV/HCV co-infected individuals compared to those with HCV mono-infection, and slower IGF-1 decline was independently associated with liver disease progression.

Alzheimer's disease and age-related memory decline (preclinical).

PubMed

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

2011-08-01

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 and 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 and 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

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

Raspberry differentially improves age-related declines in psychomotor function dependent on baseline motor ability

USDA-ARS?s Scientific Manuscript database

Among older adults, falls are a leading cause of distress, pain, injury, loss of confidence, and ultimately, loss of independence and death. Previous studies in our laboratory have demonstrated that berry supplementation improves the age-related declines in balance, muscle strength, and coordination...

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

PubMed

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

2017-01-01

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

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. Copyright 2010 Elsevier B.V. All rights reserved.

Food for thought: the role of appetitive peptides in age-related cognitive decline.

PubMed

Fadel, Jim R; Jolivalt, Corinne G; Reagan, Lawrence P

2013-06-01

Through their well described actions in the hypothalamus, appetitive peptides such as insulin, orexin and leptin are recognized as important regulators of food intake, body weight and body composition. Beyond these metabolic activities, these peptides also are critically involved in a wide variety of activities ranging from modulation of immune and neuroendocrine function to addictive behaviors and reproduction. The neurological activities of insulin, orexin and leptin also include facilitation of hippocampal synaptic plasticity and enhancement of cognitive performance. While patients with metabolic disorders such as obesity and diabetes have greater risk of developing cognitive deficits, dementia and Alzheimer's disease (AD), the underlying mechanisms that are responsible for, or contribute to, age-related cognitive decline are poorly understood. In view of the importance of these peptides in metabolic disorders, it is not surprising that there is a greater focus on their potential role in cognitive deficits associated with aging. The goal of this review is to describe the evidence from clinical and pre-clinical studies implicating insulin, orexin and leptin in the etiology and progression of age-related cognitive decline. Collectively, these studies support the hypothesis that leptin and insulin resistance, concepts normally associated with the hypothalamus, are also applicable to the hippocampus. Copyright © 2013 Elsevier B.V. All rights reserved.

Seafood Types and Age-Related Cognitive Decline in the Women’s Health Study

PubMed Central

2013-01-01

Background. Seafood consumption may prevent age-related cognitive decline. However, benefits may vary by nutrient contents in different seafood types. We examined associations between total seafood consumption and cognitive decline and whether these associations differ by seafood types. Methods. We conducted a prospective cohort study of 5,988 women (mean age, 72 years) from the Women’s Health Study who self-reported seafood intake at Women’s Health Study baseline and also participated in telephone assessments of general cognition, verbal memory, and category fluency administered 5.6 years after Women’s Health Study baseline and 2 and 4 years thereafter. Primary outcomes were standardized composite scores of global cognition and verbal memory. Results. After adjusting for potential confounders, different amounts of total seafood consumption were not associated with changes in global cognition (p = .56) or verbal memory (p = .29). Considering seafood types, however, compared with women consuming less than once-weekly tuna or dark-meat finfish, those with once-weekly or higher consumption had significantly better verbal memory (0.079 standard units; p < .01) after 4 years—a difference comparable to that for women 2.1 years apart in age. There was also a statistically nonsignificant suggestion of better global cognition (p = .13) with once-weekly or higher tuna or dark-meat fish consumption. No significant associations were observed for light-meat finfish or shellfish. Conclusions. The relation of seafood to cognition may depend on the types consumed. Total consumption levels of seafood were unrelated to cognitive change. However, consumption of tuna and dark-meat fish once weekly or higher was associated with lower decline in verbal memory for a period of 4 years. PMID:23554464

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

PubMed Central

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

2015-01-01

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

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.

β-Secretase inhibitor GRL-8234 rescues age-related cognitive decline in APP transgenic mice

PubMed Central

Chang, Wan-Pin; Huang, Xiangping; Downs, Deborah; Cirrito, John R.; Koelsch, Gerald; Holtzman, David M.; Ghosh, Arun K.; Tang, Jordan

2011-01-01

Alzheimer disease is intimately linked to an excess amount of amyloid-β (Aβ) in the brain. Thus, therapeutic inhibition of Aβ production is an attractive clinical approach to treat this disease. Here we provide the first direct experimental evidence that the treatment of Tg2576 transgenic mice with an inhibitor of β-secretase, GRL-8234, rescues the age-related cognitive decline. We demonstrated that the injected GRL-8234 effectively enters the brain and rapidly decreases soluble Aβ in the brain of Tg2576 mice. The rescue of cognition, which was observed only after long-term inhibitor treatment ranging from 5 to 7.5 mo, was associated with a decrease of brain amyloid-β plaque load. We also found no accumulation of amyloid-β precursor protein after several months of inhibitor treatment. These observations substantiate the idea that Aβ accumulation plays a major role in the cognitive decline of Tg2576 mice and support the concept of Aβ reduction therapy as a treatment of AD.—Chang, W.-P., Huang, X., Downs, D., Cirrito, J. R., Koelsch, G., Holtzman, D. M. Ghosh, A. K., Tang, J. β-Secretase inhibitor GRL-8234 rescues age-related cognitive decline in APP transgenic mice. PMID:21059748

Haploinsufficiency of myostatin protects against aging-related declines in muscle function and enhances the longevity of mice.

PubMed

Mendias, Christopher L; Bakhurin, Konstantin I; Gumucio, Jonathan P; Shallal-Ayzin, Mark V; Davis, Carol S; Faulkner, John A

2015-08-01

The molecular mechanisms behind aging-related declines in muscle function are not well understood, but the growth factor myostatin (MSTN) appears to play an important role in this process. Additionally, epidemiological studies have identified a positive correlation between skeletal muscle mass and longevity. Given the role of myostatin in regulating muscle size, and the correlation between muscle mass and longevity, we tested the hypotheses that the deficiency of myostatin would protect oldest-old mice (28-30 months old) from an aging-related loss in muscle size and contractility, and would extend the maximum lifespan of mice. We found that MSTN(+/-) and MSTN(-/-) mice were protected from aging-related declines in muscle mass and contractility. While no differences were detected between MSTN(+/+) and MSTN(-/-) mice, MSTN(+/-) mice had an approximately 15% increase in maximal lifespan. These results suggest that targeting myostatin may protect against aging-related changes in skeletal muscle and contribute to enhanced longevity. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Protective Effects of Foods Containing Flavonoids on Age-Related Cognitive Decline.

PubMed

Gildawie, Kelsea R; Galli, Rachel L; Shukitt-Hale, Barbara; Carey, Amanda N

2018-06-01

Evidence suggests that flavonoids, polyphenolic compounds found in many plant-derived foods, such as berries, may allay cognitive impairment. We review recent research exploring the protective effects of flavonoids on age-related cognitive decline and neurodegenerative disorders in humans and animals. We also address the mechanisms by which flavonoids may exert their effects and promising avenues of future research. Flavonoids have been found to decrease neuroinflammation, reduce oxidative stress, and mediate neuroplasticity in animal models of neurodegeneration and aging. Injecting flavonoids encased in metal nanoparticles may further enhance the efficacy of flavonoids. Animal studies also demonstrate that flavonoid supplementation may alleviate neurodegenerative cognitive and memory impairments. Limited human studies, however, demonstrate the need for further clinical research investigating flavonoids. Flavonoid supplementation, as well as dietary modification to include whole foods high in flavonoids, may provide therapeutic potential for aging individuals experiencing cognitive deficits resulting from neurodegeneration.

Age-Related Skeletal Muscle Decline Is Similar in HIV-Infected and Uninfected Individuals

PubMed Central

Yarasheski, Kevin E.; Scherzer, Rebecca; Kotler, Donald P.; Dobs, Adrian S.; Tien, Phyllis C.; Lewis, Cora E.; Kronmal, Richard A.; Heymsfield, Steven B.; Bacchetti, Peter

2011-01-01

Background. Skeletal muscle (SM) mass decreases with advanced age and with disease in HIV infection. It is unknown whether age-related muscle loss is accelerated in the current era of antiretroviral therapy and which factors might contribute to muscle loss among HIV-infected adults. We hypothesized that muscle mass would be lower and decline faster in HIV-infected adults than in similar-aged controls. Methods. Whole-body 1H-magnetic resonance imaging was used to quantify regional and total SM in 399 HIV-infected and 204 control men and women at baseline and 5 years later. Multivariable regression identified associated factors. Results. At baseline and Year 5, total SM was lower in HIV-infected than control men. HIV-infected women were similar to control women at both time points. After adjusting for demographics, lifestyle factors, and total adipose tissue, HIV infection was associated with lower Year 5 SM in men and higher SM in women compared with controls. Average overall 5-year change in total SM was small and age related, but rate of change was similar in HIV-infected and control men and women. CD4 count and efavirenz use in HIV-infected participants were associated with increasing SM, whereas age and stavudine use were associated with decreasing SM. Conclusions. Muscle mass was lower in HIV-infected men compared with controls, whereas HIV-infected women had slightly higher SM than control women after multivariable adjustment. We found evidence against substantially faster SM decline in HIV infected versus similar-aged controls. SM gain was associated with increasing CD4 count, whereas stavudine use may contribute to SM loss. PMID:21310810

Age-related skeletal muscle decline is similar in HIV-infected and uninfected individuals.

PubMed

Yarasheski, Kevin E; Scherzer, Rebecca; Kotler, Donald P; Dobs, Adrian S; Tien, Phyllis C; Lewis, Cora E; Kronmal, Richard A; Heymsfield, Steven B; Bacchetti, Peter; Grunfeld, Carl

2011-03-01

Skeletal muscle (SM) mass decreases with advanced age and with disease in HIV infection. It is unknown whether age-related muscle loss is accelerated in the current era of antiretroviral therapy and which factors might contribute to muscle loss among HIV-infected adults. We hypothesized that muscle mass would be lower and decline faster in HIV-infected adults than in similar-aged controls. Whole-body (1)H-magnetic resonance imaging was used to quantify regional and total SM in 399 HIV-infected and 204 control men and women at baseline and 5 years later. Multivariable regression identified associated factors. At baseline and Year 5, total SM was lower in HIV-infected than control men. HIV-infected women were similar to control women at both time points. After adjusting for demographics, lifestyle factors, and total adipose tissue, HIV infection was associated with lower Year 5 SM in men and higher SM in women compared with controls. Average overall 5-year change in total SM was small and age related, but rate of change was similar in HIV-infected and control men and women. CD4 count and efavirenz use in HIV-infected participants were associated with increasing SM, whereas age and stavudine use were associated with decreasing SM. Muscle mass was lower in HIV-infected men compared with controls, whereas HIV-infected women had slightly higher SM than control women after multivariable adjustment. We found evidence against substantially faster SM decline in HIV infected versus similar-aged controls. SM gain was associated with increasing CD4 count, whereas stavudine use may contribute to SM loss.

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

PubMed

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

2017-06-01

Correlations in activity across disparate brain regions during rest reveal functional networks in the brain. Although previous studies largely agree that there is an age-related decline in the "default mode network," how age affects other resting-state networks, such as emotion-related networks, is still controversial. Here we used a dual-regression approach to investigate age-related alterations in resting-state networks. The results revealed age-related disruptions in functional connectivity in all 5 identified cognitive networks, namely the default mode network, cognitive-auditory, cognitive-speech (or speech-related somatosensory), and right and left frontoparietal networks, whereas such age effects were not observed in the 3 identified emotion networks. In addition, we observed age-related decline in functional connectivity in 3 visual and 3 motor/visuospatial networks. Older adults showed greater functional connectivity in regions outside 4 out of the 5 identified cognitive networks, consistent with the dedifferentiation effect previously observed in task-based functional magnetic resonance imaging studies. Both reduced within-network connectivity and increased out-of-network connectivity were correlated with poor cognitive performance, providing potential biomarkers for cognitive aging. Copyright © 2017 Elsevier Inc. All rights reserved.

MIND diet slows cognitive decline with aging.

PubMed

Morris, Martha Clare; Tangney, Christy C; Wang, Yamin; Sacks, Frank M; Barnes, Lisa L; Bennett, David A; Aggarwal, Neelum T

2015-09-01

The Mediterranean and dash diets have been shown to slow cognitive decline; however, neither diet is specific to the nutrition literature on dementia prevention. We devised the Mediterranean-Dietary Approach to Systolic Hypertension (DASH) diet intervention for neurodegenerative delay (MIND) diet score that specifically captures dietary components shown to be neuroprotective and related it to change in cognition over an average 4.7 years among 960 participants of the Memory and Aging Project. In adjusted mixed models, the MIND score was positively associated with slower decline in global cognitive score (β = 0.0092; P < .0001) and with each of five cognitive domains. The difference in decline rates for being in the top tertile of MIND diet scores versus the lowest was equivalent to being 7.5 years younger in age. The study findings suggest that the MIND diet substantially slows cognitive decline with age. Replication of these findings in a dietary intervention trial would be required to verify its relevance to brain health. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

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…

Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline.

PubMed

Yurko-Mauro, Karin; McCarthy, Deanna; Rom, Dror; Nelson, Edward B; Ryan, Alan S; Blackwell, Andrew; Salem, Norman; Stedman, Mary

2010-11-01

Docosahexaenoic acid (DHA) plays an important role in neural function. Decreases in plasma DHA are associated with cognitive decline in healthy elderly adults and in patients with Alzheimer's disease. Higher DHA intake is inversely correlated with relative risk of Alzheimer's disease. The potential benefits of DHA supplementation in age-related cognitive decline (ARCD) have not been fully examined. Determine effects of DHA administration on improving cognitive functions in healthy older adults with ARCD. Randomized, double-blind, placebo-controlled, clinical study was conducted at 19 U.S. clinical sites. A total of 485 healthy subjects, aged ≥55 with Mini-Mental State Examination >26 and a Logical Memory (Wechsler Memory Scale III) baseline score ≥1 standard deviation below younger adults, were randomly assigned to 900 mg/d of DHA orally or matching placebo for 24 weeks. The primary outcome was the CANTAB Paired Associate Learning (PAL), a visuospatial learning and episodic memory test. Intention-to-treat analysis demonstrated significantly fewer PAL six pattern errors with DHA versus placebo at 24 weeks (difference score, -1.63 ± 0.76 [-3.1, -0.14, 95% CI], P = .03). DHA supplementation was also associated with improved immediate and delayed Verbal Recognition Memory scores (P < .02), but not working memory or executive function tests. Plasma DHA levels doubled and correlated with improved PAL scores (P < .02) in the DHA group. DHA was well tolerated with no reported treatment-related serious adverse events. Twenty-four week supplementation with 900 mg/d DHA improved learning and memory function in ARCD and is a beneficial supplement that supports cognitive health with aging. Clinicaltrials.gov, Identifier: NCT0027813. Copyright © 2010 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Age-related Effects on Word Recognition: Reliance on Cognitive Control Systems with Structural Declines in Speech-responsive Cortex

PubMed Central

Walczak, Adam; Ahlstrom, Jayne; Denslow, Stewart; Horwitz, Amy; Dubno, Judy R.

2008-01-01

Speech recognition can be difficult and effortful for older adults, even for those with normal hearing. Declining frontal lobe cognitive control has been hypothesized to cause age-related speech recognition problems. This study examined age-related changes in frontal lobe function for 15 clinically normal hearing adults (21–75 years) when they performed a word recognition task that was made challenging by decreasing word intelligibility. Although there were no age-related changes in word recognition, there were age-related changes in the degree of activity within left middle frontal gyrus (MFG) and anterior cingulate (ACC) regions during word recognition. Older adults engaged left MFG and ACC regions when words were most intelligible compared to younger adults who engaged these regions when words were least intelligible. Declining gray matter volume within temporal lobe regions responsive to word intelligibility significantly predicted left MFG activity, even after controlling for total gray matter volume, suggesting that declining structural integrity of brain regions responsive to speech leads to the recruitment of frontal regions when words are easily understood. Electronic supplementary material The online version of this article (doi:10.1007/s10162-008-0113-3) contains supplementary material, which is available to authorized users. PMID:18274825

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

PubMed

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

2012-12-01

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

Perceptions of oocyte banking from women intending to circumvent age-related fertility decline.

PubMed

de Groot, Marije; Dancet, Eline; Repping, Sjoerd; Goddijn, Mariette; Stoop, Dominic; van der Veen, Fulco; Gerrits, Trudie

2016-12-01

Women can now opt to bank their oocytes with the intention of increasing their chances of achieving a pregnancy after their fertility has declined. This exploratory study aimed to gain insight into how women, considering oocyte banking to circumvent age-related fertility decline, perceive this intervention. We conducted a qualitative study in a Dutch university medical center and held in-depth interviews with women on the waiting list for oocyte banking. We recorded the interviews, transcribed them verbatim and used thematic analysis. All women were financially independent and lived in single-person urban households. They opted for oocyte banking because they wished to share parenthood with a future partner rather than becoming a single parent. This strong desire was key in their interpretation of all aspects of the intervention. Women set aside information about the limited success rates and potential risks, as they were optimistic about their own prognosis, thought that the chances for success were equally likely as the chances it would fail, and because of "anticipatory regret". They perceived oocyte banking as a "helping hand" to achieve shared parenthood. Although women found the costs of the intervention high, they were willing to invest their money to increase their chances for shared parenthood. Oocyte banking allows women to circumvent age-related fertility decline. The prospect of potential shared parenthood overrules the perceived health risks and burden. Health professionals should take this into account when informing potential users of oocyte banking. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

Metabolic syndrome but not obesity measures are risk factors for accelerated age-related glomerular filtration rate decline in the general population.

PubMed

Stefansson, Vidar T N; Schei, Jørgen; Solbu, Marit D; Jenssen, Trond G; Melsom, Toralf; Eriksen, Bjørn O

2018-05-01

Rapid age-related glomerular filtration rate (GFR) decline increases the risk of end-stage renal disease, and a low GFR increases the risk of mortality and cardiovascular disease. High body mass index and the metabolic syndrome are well-known risk factors for patients with advanced chronic kidney disease, but their role in accelerating age-related GFR decline independent of cardiovascular disease, hypertension and diabetes is not adequately understood. We studied body mass index, waist circumference, waist-hip ratio and metabolic syndrome as risk factors for accelerated GFR decline in 1261 middle-aged people representative of the general population without diabetes, cardiovascular disease or kidney disease. GFR was measured as iohexol clearance at baseline and repeated after a median of 5.6 years. Metabolic syndrome was defined as fulfilling three out of five criteria, based on waist circumference, blood pressure, glucose, high-density lipoprotein cholesterol and triglycerides. The mean GFR decline rate was 0.95 ml/min/year. Neither the body mass index, waist circumference nor waist-hip ratio predicted statistically significant changes in age-related GFR decline, but individuals with baseline metabolic syndrome had a significant mean of 0.30 ml/min/year faster decline than individuals without metabolic syndrome in a multivariable adjusted linear regression model. This association was mainly driven by the triglyceride criterion of metabolic syndrome, which was associated with a significant 0.36 ml/min/year faster decline when analyzed separately. Results differed significantly when GFR was estimated using creatinine and/or cystatin C. Thus, metabolic syndrome, but not the body mass index, waist circumference or waist-hip ratio, is an independent risk factor for accelerated age-related GFR decline in the general population. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

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…

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

Characterizing age-related decline of recognition memory and brain activation profile in mice.

PubMed

Belblidia, Hassina; Leger, Marianne; Abdelmalek, Abdelouadoud; Quiedeville, Anne; Calocer, Floriane; Boulouard, Michel; Jozet-Alves, Christelle; Freret, Thomas; Schumann-Bard, Pascale

2018-06-01

Episodic memory decline is one of the earlier deficits occurring during normal aging in humans. The question of spatial versus non-spatial sensitivity to age-related memory decline is of importance for a full understanding of these changes. Here, we characterized the effect of normal aging on both non-spatial (object) and spatial (object location) memory performances as well as on associated neuronal activation in mice. Novel-object (NOR) and object-location (OLR) recognition tests, respectively assessing the identity and spatial features of object memory, were examined at different ages. We show that memory performances in both tests were altered by aging as early as 15 months of age: NOR memory was partially impaired whereas OLR memory was found to be fully disrupted at 15 months of age. Brain activation profiles were assessed for both tests using immunohistochemical detection of c-Fos (neuronal activation marker) in 3and 15 month-old mice. Normal performances in NOR task by 3 month-old mice were associated to an activation of the hippocampus and a trend towards an activation in the perirhinal cortex, in a way that did significantly differ with 15 month-old mice. During OLR task, brain activation took place in the hippocampus in 3 month-old but not significantly in 15 month-old mice, which were fully impaired at this task. These differential alterations of the object- and object-location recognition memory may be linked to differential alteration of the neuronal networks supporting these tasks. Copyright © 2018 Elsevier Inc. All rights reserved.

Age-related cognitive decline coincides with accelerated volume loss of the dorsal but not ventral hippocampus in mice.

PubMed

Reichel, J M; Bedenk, B T; Czisch, M; Wotjak, C T

2017-01-01

Even in the absence of neurodegenerative diseases, progressing age often coincides with cognitive decline and morphological changes. However, longitudinal studies that directly link these two processes are missing. In this proof-of-concept study we therefore performed repeated within-subject testing of healthy male R26R mice in a spatial learning task in combination with manganese-enhanced volumetric MRI analyses at the ages of 8, 16, and 24 months. We grouped the mice into good and poor performers (n = 6, each), based on their spatial learning abilities at the age of 24 months. Using this stratification, we failed to detect a priori volume differences, but observed a significant decrease in total hippocampal volume over time for both groups. Interestingly, this volume decrease was specific for the dorsal hippocampus and significantly accelerated in poor performers between 16 and 24 months of age. This is the first time that individual changes in hippocampal volume were traced alongside cognitive performance within the same subjects over 1½ years. Our study points to a causal link between volume loss of the dorsal hippocampus and cognitive impairments. In addition, it suggests accelerated degenerative processes rather than a priori volume differences as determining trajectories of age-related cognitive decline. Despite the relatively small sample sizes, the strong behavioral and moderate morphological alterations demonstrate the general feasibility of longitudinal studies of age-related decline in cognition and hippocampus integrity. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

Age-related declines in the swallowing muscle strength of men and women aged 20-89 years: A cross-sectional study on tongue pressure and jaw-opening force in 980 subjects.

PubMed

Hara, Koji; Tohara, Haruka; Kobayashi, Kenichiro; Yamaguchi, Kohei; Yoshimi, Kanako; Nakane, Ayako; Minakuchi, Shunsuke

2018-05-31

Swallowing muscle strength weakens with aging. Although numerous studies have investigated tongue pressure (TP) changes with age, studies on jaw-opening force (JOF), an indicator of suprahyoid muscle strength, are lacking. We investigated differences between age-related declines in TP and JOF in a cross-sectional study of 980 healthy and independent participants (379 men, 601 women) without dysphagia. Hand grip strength (HGS), TP, and JOF were compared among decade-based age groups in multiple comparison analyses with post-hoc tests and effect size calculated. Participants were divided into adult (20 s-50 s) and elderly groups (60 s-80 s); within each group, Pearson correlations between age and muscle strength indices were evaluated. TP started to significantly decline in the 60 s and 50 s for men and women (p < .01, medium effect size and p < .05, small effect size, respectively); HGS also declined at these ages (men: p < .01, women: p < .01, medium effect size). JOF started to significantly decline in men in their 80 s (p < .01, large effect size), but remained unchanged in women. In the elderly group, all measurements declined with age more sharply in men (HGS: r = -0.56, TP: r = -0.63, JOF: r = -0.13) than in women (HGS: r = -0.38, TP: r = -0.49, JOF: r = -0.003). TP declined more steeply than did JOF. Thus, the age related-decline in TP was similar to that of the HGS, but not the JOF. The results reveal that different patterns exist in the age-related decline in swallowing muscle strength, and suggest that maintenance of JOF might contribute to safe swallowing in healthy elderly individuals. Copyright © 2018 Elsevier B.V. All rights reserved.

The therapeutic potential of metabolic hormones in the treatment of age-related cognitive decline and Alzheimer’s disease

PubMed Central

Grizzanti, John; Lee, Hyoung-Gon; Camins, Antoni; Pallas, Merce; Casadesus, Gemma

2017-01-01

Aging leads to a number of physiological alterations, specifically changes in circulating hormone levels, increases in fat deposition, decreases in metabolism, changes in inflammatory responses, and reductions in growth factors. These progressive changes in physiology and metabolism are exacerbated by modern culture and Western diet and give rise to diseases such as obesity, metabolic syndrome, and type 2 (non–insulin-dependent) diabetes (T2D). These age and lifestyle-related metabolic diseases are often accompanied by insulin and leptin resistance, as well as aberrant amylin production and signaling. Many of these alterations in hormone production and signaling are directly influenced by an increase in both oxidative stress and inflammation. Importantly, changes in hormone production and signaling have direct effects on brain function and the development of age-related neurologic disorders. Therefore, this review aims to present evidence on the effects that diet and metabolic disease have on age-related cognitive decline and the development of cognitive diseases, particularly Alzheimer disease. This review will focus on the metabolic hormones insulin, leptin, and amylin and their role in cognitive decline, as well as the therapeutic potential of these hormones in treating cognitive disease. Future investigations targeting the long-term effects of insulin and leptin treatment may reveal evidence to reduce risk of cognitive decline and Alzheimer disease. PMID:27923524

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.

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

The importance of age-related decline in forest NPP for modeling regional carbon balances.

PubMed

Zaehle, Sönke; Sitch, Stephen; Prentice, I Colin; Liski, Jari; Cramer, Wolfgang; Erhard, Markus; Hickler, Thomas; Smith, Benjamin

2006-08-01

We show the implications of the commonly observed age-related decline in aboveground productivity of forests, and hence forest age structure, on the carbon dynamics of European forests in response to historical changes in environmental conditions. Size-dependent carbon allocation in trees to counteract increasing hydraulic resistance with tree height has been hypothesized to be responsible for this decline. Incorporated into a global terrestrial biosphere model (the Lund-Potsdam-Jena model, LPJ), this hypothesis improves the simulated increase in biomass with stand age. Application of the advanced model, including a generic representation of forest management in even-aged stands, for 77 European provinces shows that model-based estimates of biomass development with age compare favorably with inventory-based estimates for different tree species. Model estimates of biomass densities on province and country levels, and trends in growth increment along an annual mean temperature gradient are in broad agreement with inventory data. However, the level of agreement between modeled and inventory-based estimates varies markedly between countries and provinces. The model is able to reproduce the present-day age structure of forests and the ratio of biomass removals to increment on a European scale based on observed changes in climate, atmospheric CO2 concentration, forest area, and wood demand between 1948 and 2000. Vegetation in European forests is modeled to sequester carbon at a rate of 100 Tg C/yr, which corresponds well to forest inventory-based estimates.

Mouse forepaw lumbrical muscles are resistant to age-related declines in force production.

PubMed

Russell, Katelyn A; Ng, Rainer; Faulkner, John A; Claflin, Dennis R; Mendias, Christopher L

2015-05-01

A progressive loss of skeletal muscle mass and force generating capacity occurs with aging. Mice are commonly used in the study of aging-associated changes in muscle size and strength, with most models of aging demonstrating 15-35% reductions in muscle mass, cross-sectional area (CSA), maximum isometric force production (Po) and specific force (sPo), which is Po/CSA. The lumbrical muscle of the mouse forepaw is exceptionally small, with corresponding short diffusion distances that make it ideal for in vitro pharmacological studies and measurements of contractile properties. However, the aging-associated changes in lumbrical function have not previously been reported. To address this, we tested the hypothesis that compared to adult (12month old) mice, the forepaw lumbrical muscles of old (30month old) mice exhibit aging-related declines in size and force production similar to those observed in larger limb muscles. We found that the forepaw lumbricals were composed exclusively of fibers with type II myosin heavy chain isoforms, and that the muscles accumulated connective tissue with aging. There were no differences in the number of fibers per whole-muscle cross-section or in muscle fiber CSA. The whole muscle CSA in old mice was increased by 17%, but the total CSA of all muscle fibers in a whole-muscle cross-section was not different. No difference in Po was observed, and while sPo normalized to total muscle CSA was decreased in old mice by 22%, normalizing Po by the total muscle fiber CSA resulted in no difference in sPo. Combined, these results indicate that forepaw lumbrical muscles from 30month old mice are largely protected from the aging-associated declines in size and force production that are typically observed in larger limb muscles. Copyright © 2015 Elsevier Inc. All rights reserved.

Functional neuroimaging of normal aging: Declining brain, adapting brain.

PubMed

Sugiura, Motoaki

2016-09-01

Early functional neuroimaging research on normal aging brain has been dominated by the interest in cognitive decline. In this framework the age-related compensatory recruitment of prefrontal cortex, in terms of executive system or reduced lateralization, has been established. Further details on these compensatory mechanisms and the findings reflecting cognitive decline, however, remain the matter of intensive investigations. Studies in another framework where age-related neural alteration is considered adaptation to the environmental change are recently burgeoning and appear largely categorized into three domains. The age-related increase in activation of the sensorimotor network may reflect the alteration of the peripheral sensorimotor systems. The increased susceptibility of the network for the mental-state inference to the socioemotional significance may be explained by the age-related motivational shift due to the altered social perception. The age-related change in activation of the self-referential network may be relevant to the focused positive self-concept of elderly driven by a similar motivational shift. Across the domains, the concept of the self and internal model may provide the theoretical bases of this adaptation framework. These two frameworks complement each other to provide a comprehensive view of the normal aging brain. Copyright © 2016 Elsevier B.V. All rights reserved.

Age-related islet inflammation marks the proliferative decline of pancreatic beta-cells in zebrafish

PubMed Central

Tsakmaki, Anastasia; Mousavy Gharavy, S Neda; Murawala, Priyanka; Konantz, Judith; Birke, Sarah; Hodson, David J; Rutter, Guy A; Bewick, Gavin A

2018-01-01

The pancreatic islet, a cellular community harboring the insulin-producing beta-cells, is known to undergo age-related alterations. However, only a handful of signals associated with aging have been identified. By comparing beta-cells from younger and older zebrafish, here we show that the aging islets exhibit signs of chronic inflammation. These include recruitment of tnfα-expressing macrophages and the activation of NF-kB signaling in beta-cells. Using a transgenic reporter, we show that NF-kB activity is undetectable in juvenile beta-cells, whereas cells from older fish exhibit heterogeneous NF-kB activity. We link this heterogeneity to differences in gene expression and proliferation. Beta-cells with high NF-kB signaling proliferate significantly less compared to their neighbors with low activity. The NF-kB signalinghi cells also exhibit premature upregulation of socs2, an age-related gene that inhibits beta-cell proliferation. Together, our results show that NF-kB activity marks the asynchronous decline in beta-cell proliferation with advancing age. PMID:29624168

Systemic Regulation of the Age-Related Decline of Pancreatic β-Cell Replication

PubMed Central

Salpeter, Seth J.; Khalaileh, Abed; Weinberg-Corem, Noa; Ziv, Oren; Glaser, Benjamin; Dor, Yuval

2013-01-01

The frequency of pancreatic β-cell replication declines dramatically with age, potentially contributing to the increased risk of type 2 diabetes in old age. Previous studies have shown the involvement of cell-autonomous factors in this phenomenon, particularly the decline of polycomb genes and accumulation of p16/INK4A. Here, we demonstrate that a systemic factor found in the circulation of young mice is able to increase the proliferation rate of old pancreatic β-cells. Old mice parabiosed to young mice have increased β-cell replication compared with unjoined old mice or old mice parabiosed to old mice. In addition, we demonstrate that old β-cells transplanted into young recipients have increased replication rate compared with cells transplanted into old recipients; conversely, young β-cells transplanted into old mice decrease their replication rate compared with young cells transplanted into young recipients. The expression of p16/INK4A mRNA did not change in heterochronic parabiosis, suggesting the involvement of other pathways. We conclude that systemic factors contribute to the replicative decline of old pancreatic β-cells. PMID:23630298

Quality of life attenuates age-related decline in functional status of older adults.

PubMed

Palgi, Yuval; Shrira, Amit; Zaslavsky, Oleg

2015-08-01

In the present study, we aimed to examine the total and moderating effects of needs-satisfaction-driven quality-of-life (QoL) measure on age-related change in functional status. Participants in the Survey of Health and Retirement in Europe (N = 18,781 at Wave 1) completed a measure of QoL (CASP-12) at baseline and reported their functional status across subsequent three waves using activities of daily living (ADL), instrumental activities of daily living (IADL), and functional limitation indices. Growth-curve model estimates revealed that aged individuals with lower QoL scores at baseline had a steeper increase in disability deficits accumulation and functional limitation progression than their counterparts with a higher sense of QoL. The effects were more pronounced in ADL and IADL disability scales in which QoL moderated both linear and quadratic age-related changes. Higher QoL attenuates processes of functional decline in late adulthood. Practitioners may seek strategies for improving and enhancing patients' QoL, as its salutary effects diffuse beyond psychological experience and include long-term effects on physical functioning.

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

PubMed

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

2016-03-01

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

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. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Rates of decline in Alzheimer disease decrease with age.

PubMed

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

2012-01-01

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

Functional brain imaging of episodic memory decline in ageing.

PubMed

Nyberg, L

2017-01-01

The episodic long-term memory system supports remembering of events. It is considered to be the most age-sensitive system, with an average onset of decline around 60 years of age. However, there is marked interindividual variability, such that some individuals show faster than average change and others show no or very little change. This variability may be related to the risk of developing dementia, with elevated risk for individuals with accelerated episodic memory decline. Brain imaging with functional magnetic resonance imaging (MRI) of blood oxygen level-dependent (BOLD) signalling or positron emission tomography (PET) has been used to reveal the brain bases of declining episodic memory in ageing. Several studies have demonstrated a link between age-related episodic memory decline and the hippocampus during active mnemonic processing, which is further supported by studies of hippocampal functional connectivity in the resting state. The hippocampus interacts with anterior and posterior neocortical regions to support episodic memory, and alterations in hippocampus-neocortex connectivity have been shown to contribute to impaired episodic memory. Multimodal MRI studies and more recently hybrid MRI/PET studies allow consideration of various factors that can influence the association between the hippocampal BOLD signal and memory performance. These include neurovascular factors, grey and white matter structural alterations, dopaminergic neurotransmission, amyloid-Β and glucose metabolism. Knowledge about the brain bases of episodic memory decline can guide interventions to strengthen memory in older adults, particularly in those with an elevated risk of developing dementia, with promising results for combinations of cognitive and physical stimulation. © 2016 The Association for the Publication of the Journal of Internal Medicine.

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…

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.

The Tyrosine Phosphatase STEP Is Involved in Age-Related Memory Decline.

PubMed

Castonguay, David; Dufort-Gervais, Julien; Ménard, Caroline; Chatterjee, Manavi; Quirion, Rémi; Bontempi, Bruno; Schneider, Jay S; Arnsten, Amy F T; Nairn, Angus C; Norris, Christopher M; Ferland, Guylaine; Bézard, Erwan; Gaudreau, Pierrette; Lombroso, Paul J; Brouillette, Jonathan

2018-04-02

Cognitive disabilities that occur with age represent a growing and expensive health problem. Age-associated memory deficits are observed across many species, but the underlying molecular mechanisms remain to be fully identified. Here, we report elevations in the levels and activity of the striatal-enriched phosphatase (STEP) in the hippocampus of aged memory-impaired mice and rats, in aged rhesus monkeys, and in people diagnosed with amnestic mild cognitive impairment (aMCI). The accumulation of STEP with aging is related to dysfunction of the ubiquitin-proteasome system that normally leads to the degradation of STEP. Higher level of active STEP is linked to enhanced dephosphorylation of its substrates GluN2B and ERK1/2, CREB inactivation, and a decrease in total levels of GluN2B and brain-derived neurotrophic factor (BDNF). These molecular events are reversed in aged STEP knockout and heterozygous mice, which perform similarly to young control mice in the Morris water maze (MWM) and Y-maze tasks. In addition, administration of the STEP inhibitor TC-2153 to old rats significantly improved performance in a delayed alternation T-maze memory task. In contrast, viral-mediated STEP overexpression in the hippocampus is sufficient to induce memory impairment in the MWM and Y-maze tests, and these cognitive deficits are reversed by STEP inhibition. In old LOU/C/Jall rats, a model of healthy aging with preserved memory capacities, levels of STEP and GluN2B are stable, and phosphorylation of GluN2B and ERK1/2 is unaltered. Altogether, these data suggest that elevated levels of STEP that appear with advancing age in several species contribute to the cognitive declines associated with aging. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Declining fertility with age].

PubMed

Lourdel, Emmanuelle; Merviel, Philippe; Cabry-Goubet, Rosalie; Brzakowski, Mélanie

2010-06-20

The will to be a mother at a late age has become a real problem of society for many reasons, first and foremost because of efficient birth control, long studies and second matrimonies. In front of these still young women but quite "old" for maternity, practitioners specialized in medically assisted procreation (MAP) are often helpless, specially because most of the patients think that the MAP will be able to cure the natural decline of fertility. However, MAP's procedures cannot correct the decrease of pregnancies' rates and the increase of spontaneous miscarriages linked with the age. One of the first aims of consulting-physicians should be to give patients proper advice about fertility decline, so that women could run their life, aware of these facts.

Association between age associated cognitive decline and health related quality of life among Iranian older individuals.

PubMed

Kazazi, Leila; Foroughan, Mahshid; Nejati, Vahid; Shati, Mohsen

2018-04-01

Age associated cognitive decline or normal cognitive aging is related with lower levels of functioning in real life, and may interfere with maintaining independence and health related quality of life (HRQL). In this study, health related quality of life and cognitive function in community-dwelling older adults were evaluated with the aim of exploring the association between them by adjusting for potential confounders. This cross-sectional study, was implemented on 425 community-dwelling older adults aged 60 and over, between August 2016 and October 2016 in health centers of the municipality of Tehran, Iran, using Mini Mental State Examination (MMSE) to assess cognitive function and Short Form-36 scales (SF-36) to assess HRQL. The relation between HRQL and cognitive function was evaluated by Pearson's correlation coefficient, and the impact of cognitive function on HRQL adjusted for potential confounders was estimated by linear regression model. All analyses were done using SPSS, version 22.0. A positive significant correlation between cognitive function and quality of life (r=0.434; p<0.001) and its dimensions was observed. Two variables of educational level (B=2.704; 95% CI: 2.09 to 3.30; p<0.001) and depression (B=2.554; 95% CI: 2.00 to 3.10; p<0.001) were assumed as potential confounder by changing effect measure after entering the model. After adjusting for potential confounders in regression model, the association between MMSE scores and quality of life persisted (B=2.417; 95% CI: 1.86 to 2.96; p<0.001). The results indicate that cognitive function was associated with HRQL in older adults with age associated cognitive function. Two variables of educational level and depression can affect the relation between cognitive decline and HRQL.

Protective Role of Recent and Past Long-Term Physical Activity on Age-Related Cognitive Decline: The Moderating Effect of Sex.

PubMed

Lopez-Fontana, Iréné; Castanier, Carole; Le Scanff, Christine; Perrot, Alexandra

2018-06-13

This study aimed to investigate if the impact of both recent and long-term physical activity on age-related cognitive decline would be modified by sex. One-hundred thirty-five men (N = 67) and women (N = 68) aged 18 to 80 years completed the Modifiable Activity Questionnaire and the Historical Leisure Activity Questionnaire. A composite score of cognitive functions was computed from five experimental tasks. Hierarchical regression analyses performed to test the moderating effect of recent physical activity on age-cognition relationship had not revealed significant result regardless of sex. Conversely, past long-term physical activity was found to slow down the age-related cognitive decline among women (β = 0.22, p = .03), but not men. The findings support a lifecourse approach in identifying determinants of cognitive aging and the importance of taking into account the moderating role of sex. This article presented potential explanations for these moderators and future avenues to explore.

Brain Network Changes and Memory Decline in Aging

PubMed Central

Beason-Held, Lori L.; Hohman, Timothy J.; Venkatraman, Vijay; An, Yang; Resnick, Susan M.

2016-01-01

One theory of age-related cognitive decline proposes that changes within the default mode network (DMN) of the brain impact the ability to successfully perform cognitive operations. To investigate this theory, we examined functional covariance within brain networks using regional cerebral blood flow data, measured by 15O-water PET, from 99 participants (mean baseline age 68.6 ±7.5) in the Baltimore Longitudinal Study of Aging collected over a 7.4 year period. The sample was divided in tertiles based on longitudinal performance on a verbal recognition memory task administered during scanning, and functional covariance was compared between the upper (improvers) and lower (decliners) tertile groups. The DMN and verbal memory networks (VMN) were then examined during the verbal memory scan condition. For each network, group differences in node-to-network coherence and individual node-to-node covariance relationships were assessed at baseline and in change over time. Compared with improvers, decliners showed differences in node-to-network coherence and in node-to-node relationships in the DMN but not the VMN during verbal memory. These DMN differences reflected greater covariance with better task performance at baseline and both increasing and declining covariance with declining task performance over time for decliners. When examined during the resting state alone, the direction of change in DMN covariance was similar to that seen during task performance, but node-to-node relationships differed from those observed during the task condition. These results suggest that disengagement of DMN components during task performance is not essential for successful cognitive performance as previously proposed. Instead, a proper balance in network processes may be needed to support optimal task performance. PMID:27319002

Evidence for age-associated cognitive decline from Internet game scores.

PubMed

Geyer, Jason; Insel, Philip; Farzin, Faraz; Sternberg, Daniel; Hardy, Joseph L; Scanlon, Michael; Mungas, Dan; Kramer, Joel; Mackin, R Scott; Weiner, Michael W

2015-06-01

Lumosity's Memory Match (LMM) is an online game requiring visual working memory. Change in LMM scores may be associated with individual differences in age-related changes in working memory. Effects of age and time on LMM learning and forgetting rates were estimated using data from 1890 game sessions for users aged 40 to 79 years. There were significant effects of age on baseline LMM scores (β = -.31, standard error or SE = .02, P < .0001) and lower learning rates (β = -.0066, SE = .0008, P < .0001). A sample size of 202 subjects/arm was estimated for a 1-year study for subjects in the lower quartile of game performance. Online memory games have the potential to identify age-related decline in cognition and to identify subjects at risk for cognitive decline with smaller sample sizes and lower cost than traditional recruitment methods.

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

PubMed Central

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

2008-01-01

Supplemental choline in the maternal diet produces a lasting enhancement in memory in offspring that resists age-related decline and is accompanied by neuroanatomical, neurophysiological and neurochemical changes in the hippocampus. The present study was designed to examine: 1) if prenatal choline supplementation alters behaviors that contribute to risk or resilience in cognitive aging, and 2) whether, at old age (25 months), prenatally choline supplemented rats show evidence of preserved hippocampal plasticity. A longitudinal design was used to look at exploration of an open field, with and without objects, at 1 and 24 months of age in male and female rats whose mothers were fed a diet supplemented with choline (SUP; 5 mg/kg choline chloride) or not supplemented (CON; 1.1 mg/kg choline chloride) on embryonic days 12–17. Aging caused a significant decline in open field exploration that was more pronounced in males but interest in novel objects was maintained in both sexes. Prenatal choline supplementation attenuated, but did not prevent age-related decline in exploration in males and increased object exploration in young females. Following behavioral assessment, rats were euthanized to assess markers of hippocampal plasticity. Aged SUP males and females had more newly proliferated cells in the hippocampal dentate gyrus and protein levels of vascular-endothelial growth factor (VEGF) and neurotrophin-3 (NT-3) were significantly elevated in female SUP rats in comparison to all other groups. Taken together, these findings provide the first evidence that prenatal cholinesupplementation causes changes in exploratory behaviors over the lifespan and preserves some features of hippocampal plasticity that can be seen even at 2 years of age. PMID:18786518

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.

Events Associated with Early Age-Related Decline in Adventitious Rooting Competence of Eucalyptus globulus Labill.

PubMed

Aumond, Márcio L; de Araujo, Artur T; de Oliveira Junkes, Camila F; de Almeida, Márcia R; Matsuura, Hélio N; de Costa, Fernanda; Fett-Neto, Arthur G

2017-01-01

The development of adventitious roots is affected by several factors, including the age of the cutting donor plant, which negatively affects rooting capacity. Eucalyptus globulus quickly loses rooting capacity of cuttings as the donor plant ages, although the molecular and biochemical mechanisms behind this process are still unclear. To better understand the bases of rooting competence loss in E. globulus , the time required for a significant decline in rhizogenic ability without exogenous auxin was determined in microcuttings derived from donor plants of different ages after sowing. Tip cuttings of donor plants were severed before and after loss of rooting competence of microcuttings to test the hypothesis that auxin and carbohydrate homeostasis regulate rooting competence decline. There were no significant changes in concentration of carbohydrates, flavonoids, or proteins before and after the loss of rooting capacity. Peroxidase (EC 1.11.1.7) total activity increased with loss of rooting competence. Auxin concentration showed the opposite pattern. In good agreement, TAA1 , a key gene in auxin biosynthesis, had lower expression after loss of rooting capacity. The same applied to the auxin receptor gene TIR1 , suggesting reduced auxin sensitivity. On the other hand, genes associated with auxin response repression ( TPL , IAA12 ) or with the action of cytokinins, the rhizogenesis inhibitor-related ARR1 , showed higher expression in plants with lower rooting competence. Taken together, data suggest that age negatively affects E. globulus rooting by a combination of factors. Decreased endogenous auxin concentration, possibly caused by less biosynthesis, lower auxin sensitivity, higher expression of genes inhibiting auxin action, as well as of genes related to the action of cytokinins, appear to play roles in this process.

Events Associated with Early Age-Related Decline in Adventitious Rooting Competence of Eucalyptus globulus Labill

PubMed Central

Aumond, Márcio L.; de Araujo, Artur T.; de Oliveira Junkes, Camila F.; de Almeida, Márcia R.; Matsuura, Hélio N.; de Costa, Fernanda; Fett-Neto, Arthur G.

2017-01-01

The development of adventitious roots is affected by several factors, including the age of the cutting donor plant, which negatively affects rooting capacity. Eucalyptus globulus quickly loses rooting capacity of cuttings as the donor plant ages, although the molecular and biochemical mechanisms behind this process are still unclear. To better understand the bases of rooting competence loss in E. globulus, the time required for a significant decline in rhizogenic ability without exogenous auxin was determined in microcuttings derived from donor plants of different ages after sowing. Tip cuttings of donor plants were severed before and after loss of rooting competence of microcuttings to test the hypothesis that auxin and carbohydrate homeostasis regulate rooting competence decline. There were no significant changes in concentration of carbohydrates, flavonoids, or proteins before and after the loss of rooting capacity. Peroxidase (EC 1.11.1.7) total activity increased with loss of rooting competence. Auxin concentration showed the opposite pattern. In good agreement, TAA1, a key gene in auxin biosynthesis, had lower expression after loss of rooting capacity. The same applied to the auxin receptor gene TIR1, suggesting reduced auxin sensitivity. On the other hand, genes associated with auxin response repression (TPL, IAA12) or with the action of cytokinins, the rhizogenesis inhibitor-related ARR1, showed higher expression in plants with lower rooting competence. Taken together, data suggest that age negatively affects E. globulus rooting by a combination of factors. Decreased endogenous auxin concentration, possibly caused by less biosynthesis, lower auxin sensitivity, higher expression of genes inhibiting auxin action, as well as of genes related to the action of cytokinins, appear to play roles in this process. PMID:29067033

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

PubMed

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

2017-06-01

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

Insulin-like growth factor-1 is a mediator of age-related decline of bone health status in men.

PubMed

Chin, Kok-Yong; Ima-Nirwana, Soelaiman; Mohamed, Isa Naina; Hanapi Johari, Mohamad; Ahmad, Fairus; Mohamed Ramli, Elvy Suhana; Wan Ngah, Wan Zurinah

2014-06-01

The role of insulin-like growth factor-1 (IGF-1) in bone health in men is debatable. This study aimed to determine whether IGF-1 is a mediator in age-related decline of bone health status measured by calcaneal speed of sound (SOS) in Malaysian men. The study recruited 279 Chinese and Malay men. Their demographic data, weight, height, calcaneal SOS were taken and fasting blood was collected for total testosterone, sex-hormone binding globulin and IGF-1 assays. The associations between the studied variables were assessed using multiple linear regression (MLR) analysis. Mediator analysis was performed using Sobel test. There was a significant and parallel decrease of IGF-1 and SOS with age (p < 0.05). Serum IGF-1 was significantly and positively associated with SOS (p < 0.05) but after further adjustment for age, the significance was lost (p > 0.05). The strength of the association between age and SOS decreased after adjusting for IGF-1 level but it remained significant (p < 0.05). Sobel test revealed that IGF-1 was a significant partial mediator in the relationship between age and SOS (z = -4.3). Serum IGF-1 is a partial mediator in the age-related decline of bone health in men as determined by calcaneal ultrasound. A prospective study should be performed to validate this relationship.

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

PubMed

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

2016-02-01

Aging is associated with decreased neurogenesis in the hippocampus and diminished hippocampus-dependent cognitive functions. Expression of bone morphogenetic protein 4 (BMP4) increases with age by more than 10-fold in the mouse dentate gyrus while levels of the BMP inhibitor, noggin, decrease. This results in a profound 30-fold increase in phosphorylated-SMAD1/5/8, the effector of canonical BMP signaling. Just as observed in mice, a profound increase in expression of BMP4 is observed in the dentate gyrus of humans with no known cognitive abnormalities. Inhibition of BMP signaling either by overexpression of noggin or transgenic manipulation not only increases neurogenesis in aging mice, but remarkably, is associated with a rescue of cognitive deficits to levels comparable to young mice. Additive benefits are observed when combining inhibition of BMP signaling and environmental enrichment. These findings indicate that increased BMP signaling contributes significantly to impairments in neurogenesis and to cognitive decline associated with aging, and identify this pathway as a potential druggable target for reversing age-related changes in cognition. Copyright © 2016 Elsevier Inc. All rights reserved.

Aging in the Brain: New Roles of Epigenetics in Cognitive Decline.

PubMed

Barter, Jolie D; Foster, Thomas C

2018-06-01

Gene expression in the aging brain depends on transcription signals generated by senescent physiology, interacting with genetic and epigenetic programs. In turn, environmental factors influence epigenetic mechanisms, such that an epigenetic-environmental link may contribute to the accumulation of cellular damage, susceptibility or resilience to stressors, and variability in the trajectory of age-related cognitive decline. Epigenetic mechanisms, DNA methylation and histone modifications, alter chromatin structure and the accessibility of DNA. Furthermore, small non-coding RNA, termed microRNA (miRNA) bind to messenger RNA (mRNA) to regulate translation. In this review, we examine key questions concerning epigenetic mechanisms in regulating the expression of genes associated with brain aging and age-related cognitive decline. In addition, we highlight the interaction of epigenetics with senescent physiology and environmental factors in regulating transcription.

Linking Cognitive and Visual Perceptual Decline in Healthy Aging: The Information Degradation Hypothesis

PubMed Central

Monge, Zachary A.; Madden, David J.

2016-01-01

Several hypotheses attempt to explain the relation between cognitive and perceptual decline in aging (e.g., common-cause, sensory deprivation, cognitive load on perception, information degradation). Unfortunately, the majority of past studies examining this association have used correlational analyses, not allowing for these hypotheses to be tested sufficiently. This correlational issue is especially relevant for the information degradation hypothesis, which states that degraded perceptual signal inputs, resulting from either age-related neurobiological processes (e.g., retinal degeneration) or experimental manipulations (e.g., reduced visual contrast), lead to errors in perceptual processing, which in turn may affect non-perceptual, higher-order cognitive processes. Even though the majority of studies examining the relation between age-related cognitive and perceptual decline have been correlational, we reviewed several studies demonstrating that visual manipulations affect both younger and older adults’ cognitive performance, supporting the information degradation hypothesis and contradicting implications of other hypotheses (e.g., common-cause, sensory deprivation, cognitive load on perception). The reviewed evidence indicates the necessity to further examine the information degradation hypothesis in order to identify mechanisms underlying age-related cognitive decline. PMID:27484869

Selective decline of Nogo mRNA in the aging brain.

PubMed

Trifunovski, Alexandra; Josephson, Anna; Bickford, Paula C; Olson, Lars; Brené, Stefan

2006-06-26

The Nogo system has recently been implicated not only in regeneration but also in modulating plasticity. One reason for declining memory functions in aging may be altered plasticity in the aged hippocampus and cortex cerebri. Therefore, we have examined the levels of mRNA encoding Nogo, OMgp and MAG, as well as the receptor components NgR, Lingo-1 and Troy in cortex and hippocampus of young (4 months), middle aged (16 months) and old (24 months) Fisher 344 rats. No significant changes of receptor components or the ligands OMgp or MAG were observed. Nogo mRNA, however, was significantly decreased in hippocampal subregions of aged animals. The specific decrease of Nogo mRNA levels in hippocampus and possibly cortex cerebri may relate to age-dependent decline of brain plasticity.

Aging children of long-lived parents experience slower cognitive decline.

PubMed

Dutta, Ambarish; Henley, William; Robine, Jean-Marie; Llewellyn, David; Langa, Kenneth M; Wallace, Robert B; Melzer, David

2014-10-01

Parental longevity confers lower risks for some age-related diseases in offspring. We tested the association between parental longevity and late-life cognitive decline or dementia. Data were from the Health and Retirement Study (HRS), a US national sample. Biennial cognitive assessment (Telephone Interview of Cognitive Status-Modified [TICS-m]) occurred for ages 64 years or older in 1996 through 2008 (maximum, 79 years), including physician-diagnosed memory disorder. Offspring were categorized into parental longevity groups based on gender-specific distributional cut points. Model covariates included race, respondents' education, and income status during childhood and adulthood. Offspring groups did not differ on TICS-m scores at baseline. During follow-up, offspring of two long-lived parents experienced 40% slower rates of TICS-m decline than those with no long-lived parents (95% confidence interval, 12-72; P=.003; n=4731). Increased parental longevity was also associated with lower risk of physician-diagnosed memory disorder. Estimates did not change after controlling for environmental variables. Parental longevity is associated inversely with cognitive decline and self-reported diagnosed memory disorders in aging offspring. Parental longevity may be a valuable trait for identifying early biomarkers for resistance to cognitive decline in aging. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

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

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

PubMed

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

2017-03-01

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

Patterns of brain atrophy associated with episodic memory and semantic fluency decline in aging.

PubMed

Pelletier, Amandine; Bernard, Charlotte; Dilharreguy, Bixente; Helmer, Catherine; Le Goff, Melanie; Chanraud, Sandra; Dartigues, Jean-François; Allard, Michèle; Amieva, Hélène; Catheline, Gwénaëlle

2017-03-09

The cerebral substratum of age-related cognitive decline was evaluated in an elderly-cohort followed for 12 years (n=306). Participants, free of dementia, received neuropsychological assessments every two years and an MRI exam at baseline and four years later. Cognitive decline was evaluated on two broadly used tests to detect dementia: the Free and Cued Selective Reminding Test (FCSRT), a verbal episodic memory task, and the Isaacs Set Test (IST), a semantic fluency task. Using voxel-based approach, the relationship between cognitive decline with 1/ baseline grey matter volumes and 2/ grey matter volume loss between the two scans was explored. Baseline volumes analysis revealed that FCSRT and IST declines were both associated with lower volumes of the medial temporal region. Volumes loss analysis confirmed that both declines are related to medial temporal lobe atrophy and revealed that FCSRT decline was specifically associated with atrophy of the posterior cingulate cortex whereas IST decline was specifically related to temporal pole atrophy. These results suggest that cognitive decline across aging is firstly related to structural modifications of the medial temporal lobe, followed by an atrophy in the posterior midline structures for episodic memory and an atrophy of the temporal pole for semantic fluency.

Age-related cognitive decline as a function of daytime testing.

PubMed

Puiu, Andrei Alexandru

2017-05-01

The current study investigates the effects of age, cognitive load, optimal time-of-day testing, and irrelevant background noise suppression on mental processing. One hundred and seventy-eight young (M = 22.97 years) and 114 old adults (M = 56.38 years) were assessed for implicit learning and speed of information processing under irrelevant sound interference early during daytime (7AM-2.30PM) or in the afternoons (3PM-midnight). No direct effect of irrelevant speech effect was found on implicit learning. An optimal time of testing per age group was identified according to the ability to suppress irrelevant auditory information. If no semantic meaning was derived from the sound conditions, irrelevant sound was easily inhibited leaving no room for declined cognitive performance. This suggests an intact phonological inhibition in older adults and a further circumvention of the phonological loop. However, when difficulty was increased, a widened performance gap between young and old people could be observed. Education modulated difficult performance irrespective of age. With increasing age, task demand fulfillment becomes a function of a limited time mechanism. If extraneous time is not adapted to cognitive skills and performance, higher order processing cannot be reached, rendering older adults slower than their younger counterparts.

Genetic Contributions to Age-Related Decline in Executive Function: A 10-Year Longitudinal Study of COMT and BDNF Polymorphisms

PubMed Central

Erickson, Kirk I.; Kim, Jennifer S.; Suever, Barbara L.; Voss, Michelle W.; Francis, B. Magnus; Kramer, Arthur F.

2008-01-01

Genetic variability in the dopaminergic and neurotrophic systems could contribute to age-related impairments in executive control and memory function. In this study we examined whether genetic polymorphisms for catechol-O-methyltransferase (COMT) and brain-derived neurotrophic factor (BDNF) were related to the trajectory of cognitive decline occurring over a 10-year period in older adults. A single nucleotide polymorphism in the COMT (Val158/108Met) gene affects the concentration of dopamine in the prefrontal cortex. In addition, a Val/Met substitution in the pro-domain for BDNF (Val66Met) affects the regulated secretion and trafficking of BDNF with Met carriers showing reduced secretion and poorer cognitive function. We found that impairments over the 10-year span on a task-switching paradigm did not vary as a function of the COMT polymorphism. However, for the BDNF polymorphism the Met carriers performed worse than Val homozygotes at the first testing session but only the Val homozygotes demonstrated a significant reduction in performance over the 10-year span. Our results argue that the COMT polymorphism does not affect the trajectory of age-related executive control decline, whereas the Val/Val polymorphism for BDNF may promote faster rates of cognitive decay in old age. These results are discussed in relation to the role of BDNF in senescence and the transforming impact of the Met allele on cognitive function in old age. PMID:18958211

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

PubMed

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

2017-06-01

Mounting evidence indicates that serum cholesterol and other risk factors for cardiovascular disease intensify normative trajectories of age-related cognitive decline. However, the neural mechanisms by which this occurs remain largely unknown. To understand the impact of cholesterol on brain networks, we applied graph theory to resting-state fMRI in a large sample of early- to mid-life Veterans (N = 206, Mean age  = 32). A network emerged (centered on the banks of the superior temporal sulcus) that evidenced age-related decoupling (i.e., decreased network connectivity with age), but only in participants with clinically-elevated total cholesterol (≥180 mg/dL). Crucially, decoupling in this network corresponded to greater day-to-day disability and mediated age-related declines in psychomotor speed. Finally, examination of network organization revealed a pattern of age-related dedifferentiation for the banks of the superior temporal sulcus, again present only with higher cholesterol. More specifically, age was related to decreasing within-module communication (indexed by Within-Module Degree Z-Score) and increasing between-module communication (indexed by Participation Coefficient), but only in participants with clinically-elevated cholesterol. Follow-up analyses indicated that all findings were driven by low-density lipoprotein (LDL) levels, rather than high-density lipoprotein (HDL) or triglycerides, which is interesting as LDL levels have been linked to increased risk for cardiovascular disease, whereas HDL levels appear inversely related to such disease. These findings provide novel insight into the deleterious effects of cholesterol on brain health and suggest that cholesterol accelerates the impact of age on neural trajectories by disrupting connectivity in circuits implicated in integrative processes and behavioral control. Hum Brain Mapp 38:3249-3261, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

PubMed

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

2013-09-01

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

Predictive neuromechanical simulations indicate why walking performance declines with ageing.

PubMed

Song, Seungmoon; Geyer, Hartmut

2018-04-01

Although the natural decline in walking performance with ageing affects the quality of life of a growing elderly population, its physiological origins remain unknown. By using predictive neuromechanical simulations of human walking with age-related neuro-musculo-skeletal changes, we find evidence that the loss of muscle strength and muscle contraction speed dominantly contribute to the reduced walking economy and speed. The findings imply that focusing on recovering these muscular changes may be the only effective way to improve performance in elderly walking. More generally, the work is of interest for investigating the physiological causes of altered gait due to age, injury and disorders. Healthy elderly people walk slower and energetically less efficiently than young adults. This decline in walking performance lowers the quality of life for a growing ageing population, and understanding its physiological origin is critical for devising interventions that can delay or revert it. However, the origin of the decline in walking performance remains unknown, as ageing produces a range of physiological changes whose individual effects on gait are difficult to separate in experiments with human subjects. Here we use a predictive neuromechanical model to separately address the effects of common age-related changes to the skeletal, muscular and nervous systems. We find in computer simulations of this model that the combined changes produce gait consistent with elderly walking and that mainly the loss of muscle strength and mass reduces energy efficiency. In addition, we find that the slower preferred walking speed of elderly people emerges in the simulations when adapting to muscle fatigue, again mainly caused by muscle-related changes. The results suggest that a focus on recovering these muscular changes may be the only effective way to improve performance in elderly walking. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

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

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

PubMed Central

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

2013-01-01

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 side 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. PMID:23624491

Age-associated power decline from running, jumping, and throwing male masters world records.

PubMed

Gava, Paolo; Kern, Helmut; Carraro, Ugo

2015-01-01

BACKGROUND/STUDY CONTEXT: The capacity to perform everyday tasks is directly related to the muscular power the body can develop (see Appendix). The age-related loss of power is a fact, but the characterization or the rate of muscle power loss remains an open issue. Data useful to study the decline of the skeletal muscles power are largely available from sources other than medical tests, e.g., from track and field competitions of Masters athletes. The aim of our study is to identify the age-related decline trend of the power developed by the athletes in carrying out the track and field events. Absolute male world records of 16 events were collected along with world records of male Masters categories. Performance was normalized with respect to the absolute record; the performance of various age groups is consequently represented by a number ranging from 1 (world absolute records) to 0 (null performance). The performance of a jumping event is transformed into a parameter proportional to the power developed by the athletes: the displacement of the center of gravity of the athlete. Throwing events are further normalized for the decreasing weight of the implements with the increasing age of the Masters athletes. Most track and field events show a linear decline to 70 years. The annual rate of power decline for all the events (running, throwing, and jumping), using a simplified synthesis, is 1.25% per year. The events that involve mostly upper limbs (shot put, javelin throw) show a higher rate of decline (1.4% per year) compared to those where the lower limbs are mostly involved (long jump 1.1%, track events 0.6-0.7% per year). This analysis of muscle power decline is only partially in line with the results of works based on clinical tests. A clarification of the reasons for such discrepancy may provide clinically significant information. Human power decline in Masters athletes was analyzed, adopting a coherent approach based on an extended database. Skeletal muscle power

Aging and the shape of cognitive change before death: terminal decline or terminal drop?

PubMed

MacDonald, Stuart W S; Hultsch, David F; Dixon, Roger A

2011-05-01

Relative to typical age-related cognitive decrements, the terms "terminal decline" and "terminal drop" refer to the phenomenon of increased cognitive decline in proximity to death. Given that these terms are not necessarily synonymous, we examined the important theoretical distinction between the two alternative trajectories or shapes of changes they imply. We used 12-year (5-wave) data from the Victoria Longitudinal Study to directly test whether pre-death cognitive decrements follow a terminal decline (generally gradual) or a terminal drop (more abrupt) shape. Pre-death trajectories of cognitive decline for n=265 decedents (Mage = 72.67 years, SD = 6.44) were examined separately for 5 key cognitive constructs (verbal speed, working memory, episodic memory, semantic memory, and crystallized ability). Several classes of linear mixed models evaluated whether cognitive decline increased per additional year closer to death. Findings indicated that the shape of pre-death cognitive change was predominantly characterized by decline that is steeper as compared with typical aging-related change, but still best described as slow and steady decline, especially as compared with precipitous drop. The present findings suggest that terminal decline and terminal drop trajectories may not be mutually exclusive but could rather reflect distinct developmental trajectories within the same individual.

Music to my ears: Age-related decline in musical and facial emotion recognition.

PubMed

Sutcliffe, Ryan; Rendell, Peter G; Henry, Julie D; Bailey, Phoebe E; Ruffman, Ted

2017-12-01

We investigated young-old differences in emotion recognition using music and face stimuli and tested explanatory hypotheses regarding older adults' typically worse emotion recognition. In Experiment 1, young and older adults labeled emotions in an established set of faces, and in classical piano stimuli that we pilot-tested on other young and older adults. Older adults were worse at detecting anger, sadness, fear, and happiness in music. Performance on the music and face emotion tasks was not correlated for either age group. Because musical expressions of fear were not equated for age groups in the pilot study of Experiment 1, we conducted a second experiment in which we created a novel set of music stimuli that included more accessible musical styles, and which we again pilot-tested on young and older adults. In this pilot study, all musical emotions were identified similarly by young and older adults. In Experiment 2, participants also made age estimations in another set of faces to examine whether potential relations between the face and music emotion tasks would be shared with the age estimation task. Older adults did worse in each of the tasks, and had specific difficulty recognizing happy, sad, peaceful, angry, and fearful music clips. Older adults' difficulties in each of the 3 tasks-music emotion, face emotion, and face age-were not correlated with each other. General cognitive decline did not appear to explain our results as increasing age predicted emotion performance even after fluid IQ was controlled for within the older adult group. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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.

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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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

PubMed

Lipnicki, Darren M; Crawford, John D; Dutta, Rajib; Thalamuthu, Anbupalam; Kochan, Nicole A; Andrews, Gavin; Lima-Costa, M Fernanda; Castro-Costa, Erico; Brayne, Carol; Matthews, Fiona E; Stephan, Blossom C M; Lipton, Richard B; Katz, Mindy J; Ritchie, Karen; Scali, Jacqueline; Ancelin, Marie-Laure; Scarmeas, Nikolaos; Yannakoulia, Mary; Dardiotis, Efthimios; Lam, Linda C W; Wong, Candy H Y; Fung, Ada W T; Guaita, Antonio; Vaccaro, Roberta; Davin, Annalisa; Kim, Ki Woong; Han, Ji Won; Kim, Tae Hui; Anstey, Kaarin J; Cherbuin, Nicolas; Butterworth, Peter; Scazufca, Marcia; Kumagai, Shuzo; Chen, Sanmei; Narazaki, Kenji; Ng, Tze Pin; Gao, Qi; Reppermund, Simone; Brodaty, Henry; Lobo, Antonio; Lopez-Anton, Raúl; Santabárbara, Javier; Sachdev, Perminder S

2017-03-01

The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (APOE*4) carrier status were associated with decline. We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54-105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2-16 assessment waves (median = 3) and a follow-up duration of 2-15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval [CI] [-0.35, -0.16], p < 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI [-0.10, -0.03], p = 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (p = 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI [-0.28, -0.12], p < 0.001) than for whites (-0.09 SD/decade, 95% CI [-0.16, -0.02], p = 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0.023 SD/decade, 95% CI [0.011, 0.035], p

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2018-03-01

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

Age-related reduction in microcolumnar structure correlates with cognitive decline in ventral but not dorsal area 46 of the rhesus monkey.

PubMed

Cruz, L; Roe, D L; Urbanc, B; Inglis, A; Stanley, H E; Rosene, D L

2009-02-18

The age-related decline in cognitive function that is observed in normal aging monkeys and humans occurs without significant loss of cortical neurons. This suggests that cognitive impairment results from subtle, sub-lethal changes in the cortex. Recently, changes in the structural coherence in mini- or microcolumns without loss of neurons have been linked to loss of function. Here we use a density map method to quantify microcolumnar structure in both banks of the sulcus principalis (prefrontal cortical area 46) of 16 (ventral) and 19 (dorsal) behaviorally tested female rhesus monkeys from 6 to 33 years of age. While total neuronal density does not change with age in either of these banks, there is a significant age-related reduction in the strength of microcolumns in both regions on the order of 40%. This likely reflects a subtle but definite loss of organization in the structure of the cortical microcolumn. The reduction in strength in ventral area 46 correlates with cognitive impairments in learning and memory while the reduction in dorsal area 46 does not. This result is congruent with published data attributing cognitive functions to ventral area 46 that are similar to our particular cognitive battery which does not optimally tap cognitive functions attributed to dorsal area 46. While the exact mechanisms underlying this loss of microcolumnar organization remain to be determined, it is plausible that they reflect age-related alterations in dendritic and/or axonal organization which alter connectivity and may contribute to age-related declines in cognitive performance.

Aging and the Shape of Cognitive Change Before Death: Terminal Decline Or Terminal Drop?

PubMed Central

Hultsch, David F.; Dixon, Roger A.

2011-01-01

Objectives. Relative to typical age-related cognitive decrements, the terms “terminal decline” and “terminal drop” refer to the phenomenon of increased cognitive decline in proximity to death. Given that these terms are not necessarily synonymous, we examined the important theoretical distinction between the two alternative trajectories or shapes of changes they imply. Methods. We used 12-year (5-wave) data from the Victoria Longitudinal Study to directly test whether pre-death cognitive decrements follow a terminal decline (generally gradual) or a terminal drop (more abrupt) shape. Pre-death trajectories of cognitive decline for n = 265 decedents (Mage = 72.67 years, SD = 6.44) were examined separately for 5 key cognitive constructs (verbal speed, working memory, episodic memory, semantic memory, and crystallized ability). Results. Several classes of linear mixed models evaluated whether cognitive decline increased per additional year closer to death. Findings indicated that the shape of pre-death cognitive change was predominantly characterized by decline that is steeper as compared with typical aging-related change, but still best described as slow and steady decline, especially as compared with precipitous drop. Discussion. The present findings suggest that terminal decline and terminal drop trajectories may not be mutually exclusive but could rather reflect distinct developmental trajectories within the same individual. PMID:21300703

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

Moving Forward: Age Effects on the Cerebellum Underlie Cognitive and Motor Declines

PubMed Central

Bernard, Jessica A.; Seidler, Rachael D.

2014-01-01

Though the cortical contributions to age-related declines in motor and cognitive performance are well-known, the potential contributions of the cerebellum are less clear. The diverse functions of the cerebellum make it an important structure to investigate in aging. Here, we review the extant literature on this topic. To date, there is evidence to indicate that there are morphological age differences in the cerebellum that are linked to motor and cognitive behavior. Cerebellar morphology is often as good as -- or even better -- at predicting performance than the prefrontal cortex. We also touch on the few studies using functional neuroimaging and connectivity analyses that further implicate the cerebellum in age-related performance declines. Importantly, we provide a conceptual framework for the cerebellum influencing age differences in performance, centered on the notion of degraded internal models. The evidence indicating that cerebellar age differences associate with performance highlights the need for additional work in this domain to further elucidate the role of the cerebellum in age differences in movement control and cognitive function. PMID:24594194

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

PubMed

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

2017-02-01

Although social-communication difficulties and repetitive behaviors are hallmark features of autism spectrum disorder (ASD) and persist across the lifespan, very few studies have compared age-related differences in these behaviors between youth with ASD and same-age typically developing (TD) peers. We examined this issue using SRS-2 (Social Responsiveness Scale-Second Edition) measures of social-communicative functioning and repetitive behaviors in a stratified cross-sectional sample of 324 youth with ASD in the absence of intellectual disability, and 438 TD youth (aged 4-29 years). An age-by-group interaction emerged indicating that TD youth exhibited age-related improvements in social-communication scores while the ASD group demonstrated age-related declines in these scores. This suggests that adolescents/adults with ASD may fall increasingly behind their same-age peers in social-communicative skills.

Sex-related differences in the wheel-running activity of mice decline with increasing age.

PubMed

Bartling, Babett; Al-Robaiy, Samiya; Lehnich, Holger; Binder, Leonore; Hiebl, Bernhard; Simm, Andreas

2017-01-01

Laboratory mice of both sexes having free access to running wheels are commonly used to study mechanisms underlying the beneficial effects of physical exercise on health and aging in human. However, comparative wheel-running activity profiles of male and female mice for a long period of time in which increasing age plays an additional role are unknown. Therefore, we permanently recorded the wheel-running activity (i.e., total distance, median velocity, time of breaks) of female and male mice until 9months of age. Our records indicated higher wheel-running distances for females than males which were highest in 2-month-old mice. This was mainly reached by higher running velocities of the females and not by longer running times. However, the sex-related differences declined in parallel to the age-associated reduction in wheel-running activities. Female mice also showed more variances between the weekly running distances than males, which were recorded most often for females being 4-6months old but not older. Additional records of 24-month-old mice of both sexes indicated highly reduced wheel-running activities at old age. Surprisingly, this reduction at old age resulted mainly from lower running velocities and not from shorter running times. Old mice also differed in their course of night activity which peaked later compared to younger mice. In summary, we demonstrated the influence of sex on the age-dependent activity profile of mice which is somewhat contrasting to humans, and this has to be considered when transferring exercise-mediated mechanism from mouse to human. Copyright © 2016. Published by Elsevier Inc.

Entorhinal Tau Pathology, Episodic Memory Decline, and Neurodegeneration in Aging.

PubMed

Maass, Anne; Lockhart, Samuel N; Harrison, Theresa M; Bell, Rachel K; Mellinger, Taylor; Swinnerton, Kaitlin; Baker, Suzanne L; Rabinovici, Gil D; Jagust, William J

2018-01-17

The medial temporal lobe (MTL) is an early site of tau accumulation and MTL dysfunction may underlie episodic-memory decline in aging and dementia. Postmortem data indicate that tau pathology in the transentorhinal cortex is common by age 60, whereas spread to neocortical regions and worsening of cognition is associated with β-amyloid (Aβ). We used [ 18 F]AV-1451 and [ 11 C]PiB positron emission tomography, structural MRI, and neuropsychological assessment to investigate how in vivo tau accumulation in temporal lobe regions, Aβ, and MTL atrophy contribute to episodic memory in cognitively normal older adults ( n = 83; age, 77 ± 6 years; 58% female). Stepwise regressions identified tau in MTL regions known to be affected in old age as the best predictor of episodic-memory performance independent of Aβ status. There was no interactive effect of MTL tau with Aβ on memory. Higher MTL tau was related to higher age in the subjects without evidence of Aβ. Among temporal lobe subregions, episodic memory was most strongly related to tau-tracer uptake in the parahippocampal gyrus, particularly the posterior entorhinal cortex, which in our parcellation includes the transentorhinal cortex. In subjects with longitudinal MRI and cognitive data ( n = 57), entorhinal atrophy mirrored patterns of tau pathology and their relationship with memory decline. Our data are consistent with neuropathological studies and further suggest that entorhinal tau pathology underlies memory decline in old age even without Aβ. SIGNIFICANCE STATEMENT Tau tangles and β-amyloid (Aβ) plaques are key lesions in Alzheimer's disease (AD) but both pathologies also occur in cognitively normal older people. Neuropathological data indicate that tau tangles in the medial temporal lobe (MTL) underlie episodic-memory impairments in AD dementia. However, it remains unclear whether MTL tau pathology also accounts for memory impairments often seen in elderly people and how Aβ affects this relationship

Molecular profiling of aged neural progenitors identifies Dbx2 as a candidate regulator of age-associated neurogenic decline.

PubMed

Lupo, Giuseppe; Nisi, Paola S; Esteve, Pilar; Paul, Yu-Lee; Novo, Clara Lopes; Sidders, Ben; Khan, Muhammad A; Biagioni, Stefano; Liu, Hai-Kun; Bovolenta, Paola; Cacci, Emanuele; Rugg-Gunn, Peter J

2018-06-01

Adult neurogenesis declines with aging due to the depletion and functional impairment of neural stem/progenitor cells (NSPCs). An improved understanding of the underlying mechanisms that drive age-associated neurogenic deficiency could lead to the development of strategies to alleviate cognitive impairment and facilitate neuroregeneration. An essential step towards this aim is to investigate the molecular changes that occur in NSPC aging on a genomewide scale. In this study, we compare the transcriptional, histone methylation and DNA methylation signatures of NSPCs derived from the subventricular zone (SVZ) of young adult (3 months old) and aged (18 months old) mice. Surprisingly, the transcriptional and epigenomic profiles of SVZ-derived NSPCs are largely unchanged in aged cells. Despite the global similarities, we detect robust age-dependent changes at several hundred genes and regulatory elements, thereby identifying putative regulators of neurogenic decline. Within this list, the homeobox gene Dbx2 is upregulated in vitro and in vivo, and its promoter region has altered histone and DNA methylation levels, in aged NSPCs. Using functional in vitro assays, we show that elevated Dbx2 expression in young adult NSPCs promotes age-related phenotypes, including the reduced proliferation of NSPC cultures and the altered transcript levels of age-associated regulators of NSPC proliferation and differentiation. Depleting Dbx2 in aged NSPCs caused the reverse gene expression changes. Taken together, these results provide new insights into the molecular programmes that are affected during mouse NSPC aging, and uncover a new functional role for Dbx2 in promoting age-related neurogenic decline. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Early-life Infection is a Vulnerability Factor for Aging-Related Glial Alterations and Cognitive Decline

PubMed Central

Bilbo, Staci D.

2010-01-01

There is significant individual variability in cognitive decline during aging, suggesting the existence of “vulnerability factors” for eventual deficits. Neuroinflammation may be one such factor; increased glial reactivity is a common outcome of aging, which in turn is associated with numerous neurodegenerative conditions. Early-life infection leads to cognitive impairment in conjunction with an inflammatory challenge in young adulthood, which led us to explore whether it might also accelerate the cognitive decline associated with aging. Rats were treated on postnatal day 4 with PBS or E. coli, and then tested for learning & memory at 2 or 16 month of age, using 2 fear conditioning tasks (context pre-exposure and ambiguous cue), and a spatial water maze task. Neonatally-infected rats exhibited memory impairments in both the ambiguous cue fear-conditioning task and in the water maze, but only at 16 month. There were no differences in anxiety between groups. Neonatally-infected rats also exhibited greater aging-induced increases in glial markers (CD11b and MHC II on microglia, and GFAP on astrocytes), as well as selective changes in NMDA receptor subunit expression within the hippocampus, but not in amygdala or parietal cortex compared to controls. Taken together, these data suggest that early-life infection leads to less successful cognitive aging, which may be linked to changes in glial reactivity. PMID:20388544

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

PubMed

Bilbo, Staci D

2010-07-01

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

Context Memory Decline in Middle Aged Adults is Related to Changes in Prefrontal Cortex Function

PubMed Central

Kwon, Diana; Maillet, David; Pasvanis, Stamatoula; Ankudowich, Elizabeth; Grady, Cheryl L.; Rajah, M. Natasha

2016-01-01

The ability to encode and retrieve spatial and temporal contextual details of episodic memories (context memory) begins to decline at midlife. In the current study, event-related fMRI was used to investigate the neural correlates of context memory decline in healthy middle aged adults (MA) compared with young adults (YA). Participants were scanned while performing easy and hard versions of spatial and temporal context memory tasks. Scans were obtained at encoding and retrieval. Significant reductions in context memory retrieval accuracy were observed in MA, compared with YA. The fMRI results revealed that overall, both groups exhibited similar patterns of brain activity in parahippocampal cortex, ventral occipito-temporal regions and prefrontal cortex (PFC) during encoding. In contrast, at retrieval, there were group differences in ventral occipito-temporal and PFC activity, due to these regions being more activated in MA, compared with YA. Furthermore, only in YA, increased encoding activity in ventrolateral PFC, and increased retrieval activity in occipital cortex, predicted increased retrieval accuracy. In MA, increased retrieval activity in anterior PFC predicted increased retrieval accuracy. These results suggest that there are changes in PFC contributions to context memory at midlife. PMID:25882039

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

PubMed

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

2016-02-01

Low insulin-like growth factor-1 (IGF-1) signaling is associated with improved longevity, but is paradoxically linked with several age-related diseases in humans. Insulin-like growth factor-1 has proven to be particularly beneficial to the brain, where it confers protection against features of neuronal and cognitive decline. While aging is characterized by central insulin resistance in the face of hyperinsulinemia, the somatotropic axis markedly declines in older humans. Thus, we hypothesized that increasing IGF-1 in the brain may prove to be a novel therapeutic alternative to overcome central insulin resistance and restore whole-body insulin action in aging. Utilizing hyperinsulinemic-euglycemic clamps, we show that old insulin-resistant rats with age-related declines in IGF-1 level demonstrate markedly improved whole-body insulin action, when treated with central IGF-1, as compared to central vehicle or insulin (P < 0.05). Furthermore, central IGF-1, but not insulin, suppressed hepatic glucose production and increased glucose disposal rates in aging rats (P < 0.05). Taken together, IGF-1 action in the brain and periphery provides a 'balance' between its beneficial and detrimental actions. Therefore, we propose that strategies aimed at 'tipping the balance' of IGF-1 action centrally are the optimal approach to achieve healthy aging and longevity in humans. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

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. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Pattern of age-associated decline of static and dynamic balance in community-dwelling older women.

PubMed

Takeshima, Nobuo; Islam, Mohammod M; Rogers, Michael E; Koizumi, Daisuke; Tomiyama, Naoki; Narita, Makoto; Rogers, Nicole L

2014-07-01

Falling is the leading cause of injury-related deaths in older adults, and a loss of balance is often the precursor to a fall. However, little is known about the rate at which balance declines with age. The objective of the present study was to determine whether there is an age-associated decline in static (SB) and/or dynamic (DB) balance in community-dwelling older women. SB and DB were determined in 971 older women. Intraclass correlation coefficients (ICC) were used to determine test-retest reliability. Sway velocity was used to measure SB standing on a platform and foam with eyes open and closed. DB was characterized by limits of stability (LOS) that measured end-point excursion (EXE) and maximum excursion (MXE) of the body's center of pressure. ICC for EXE and MXE for the LOS test were excellent (EPE = 0.96, MXE = 0.96). ICC for SB tests, except for the eyes open firm surface condition (ICC = 0.10), showed a high level of reproducibility (ICC = 0.88 and 0.90). Relationships existed between age and SB (r = 0.31, P < 0.001), and between age and DB (r = -0.46--0.48, P < 0.001). The rate of decline for both DB and SB was approximately 1% per year. Age was significantly associated with all balance measures. DB got significantly lower with advancing age until 80 years, and then plateaued. SB did not decline with age until 80 years, and then decreased significantly thereafter. Although large individual variation was found with balance ability, an age-related decline was found with both dynamic and static balance for Japanese older women. © 2013 Japan Geriatrics Society.

Men's Preferences for Female Facial Femininity Decline With Age.

PubMed

Marcinkowska, Urszula M; Dixson, Barnaby J; Kozlov, Mikhail V; Prasai, Keshav; Rantala, Markus J

2017-01-01

Women tend to have a smaller chin, fuller lips, and rounder eyes than men, due in part to the effects of estrogen. These features associated with facial femininity have been found to be positively associated with fertility. Although young men in their 20s typically judge facial femininity as more attractive than facial masculinity, at all ages, men with higher sexual desire and testosterone levels tend to show a marked preference for feminine faces. In the current study, we extend this research using a large cross-national sample to test the hypothesis that facial femininity preferences will be stronger among younger men than among older men. We also tested whether these preferences are influenced by self-reported sexual openness, national health indices, and gross national income. We quantified attractiveness judgments (i.e., preferences) among 2,125 heterosexual men (aged 17-73 years) for female faces that were manipulated to appear more or less feminine using a computer graphics program. Facial femininity preferences decreased with age, being highest among men in their 30s and lowest among men in their 70s. This pattern was independent of men's sexual openness and cross-national variation in health and socioeconomic development. Our study shows that men's preferences for facial femininity are age dependent. At the proximate level, differences in preferences could reflect age-related declines in testosterone levels. These age-related declines in preferences could benefit older men, who are less able to invest in mating effort, and thus may opt out of competition with younger men for mates with potentially higher fertility. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

PubMed

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

2008-02-26

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. 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. 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 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.

Age-related differences in associative memory: Empirical evidence and theoretical perspectives.

PubMed

Naveh-Benjamin, Moshe; Mayr, Ulrich

2018-02-01

Systematic research and anecdotal evidence both indicate declines in episodic memory in older adults in good health without dementia-related disorders. Several hypotheses have been proposed to explain these age-related changes in episodic memory, some of which attribute such declines to a deterioration in associative memory. The current special issue of Psychology and Aging on Age-Related Differences in Associative Memory includes 16 articles by top researchers in the area of memory and aging. Their contributions provide a wealth of empirical work that addresses different aspects of aging and associative memory, including different mediators and predictors of age-related declines in binding and associative memory, cognitive, noncognitive, genetic, and neuro-related ones. The contributions also address the processing phases where these declines manifest themselves and look at ways to ameliorate these age-related declines. Furthermore, the contributions in this issue draw on different theoretical perspectives to explain age-related changes in associative memory and provide a wealth of varying methodologies to assess older and younger adults' performance. Finally, although most of the studies focus on normative/healthy aging, some of them contain insights that are potentially applicable to disorders and pathologies. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Context Memory Decline in Middle Aged Adults is Related to Changes in Prefrontal Cortex Function.

PubMed

Kwon, Diana; Maillet, David; Pasvanis, Stamatoula; Ankudowich, Elizabeth; Grady, Cheryl L; Rajah, M Natasha

2016-06-01

The ability to encode and retrieve spatial and temporal contextual details of episodic memories (context memory) begins to decline at midlife. In the current study, event-related fMRI was used to investigate the neural correlates of context memory decline in healthy middle aged adults (MA) compared with young adults (YA). Participants were scanned while performing easy and hard versions of spatial and temporal context memory tasks. Scans were obtained at encoding and retrieval. Significant reductions in context memory retrieval accuracy were observed in MA, compared with YA. The fMRI results revealed that overall, both groups exhibited similar patterns of brain activity in parahippocampal cortex, ventral occipito-temporal regions and prefrontal cortex (PFC) during encoding. In contrast, at retrieval, there were group differences in ventral occipito-temporal and PFC activity, due to these regions being more activated in MA, compared with YA. Furthermore, only in YA, increased encoding activity in ventrolateral PFC, and increased retrieval activity in occipital cortex, predicted increased retrieval accuracy. In MA, increased retrieval activity in anterior PFC predicted increased retrieval accuracy. These results suggest that there are changes in PFC contributions to context memory at midlife. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

Cognitive declines in healthy aging: evidence from multiple aspects of interference resolution.

PubMed

Pettigrew, Corinne; Martin, Randi C

2014-06-01

The present study tested the hypothesis that older adults show age-related deficits in interference resolution, also referred to as inhibitory control. Although oftentimes considered as a unitary aspect of executive function, various lines of work support the notion that interference resolution may be better understood as multiple constructs, including resistance to proactive interference (PI) and response-distractor inhibition (e.g., Friedman & Miyake, 2004). Using this dichotomy, the present study assessed whether older adults (relative to younger adults) show impaired performance across both, 1, or neither of these interference resolution constructs. To do so, we used multiple tasks to tap each construct and examined age effects at both the single task and latent variable levels. Older adults consistently demonstrated exaggerated interference effects across resistance to PI tasks. Although the results for the response-distractor inhibition tasks were less consistent at the individual task level analyses, age effects were evident on multiple tasks, as well as at the latent variable level. However, results of the latent variable modeling suggested declines in interference resolution are best explained by variance that is common to the 2 interference resolution constructs measured herein. Furthermore, the effect of age on interference resolution was found to be both distinct from declines in working memory, and independent of processing speed. These findings suggest multiple cognitive domains are independently sensitive to age, but that declines in the interference resolution constructs measured herein may originate from a common cause. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Increased Re-Entry into Cell Cycle Mitigates Age-Related Neurogenic Decline in the Murine Subventricular Zone

PubMed Central

Stoll, Elizabeth A.; Habibi, Behnum A.; Mikheev, Andrei M.; Lasiene, Jurate; Massey, Susan C.; Swanson, Kristin R.; Rostomily, Robert C.; Horner, Philip J.

2012-01-01

Although new neurons are produced in the subventricular zone (SVZ) of the adult mammalian brain, fewer functional neurons are produced with increasing age. The age-related decline in neurogenesis has been attributed to a decreased pool of neural progenitor cells (NPCs), an increased rate of cell death, and an inability to undergo neuronal differentiation and develop functional synapses. The time between mitotic events has also been hypothesized to increase with age, but this has not been directly investigated. Studying primary-cultured NPCs from the young adult and aged mouse forebrain, we observe that fewer aged cells are dividing at a given time; however, the mitotic cells in aged cultures divide more frequently than mitotic cells in young cultures during a 48-hour period of live-cell time-lapse imaging. Double-thymidine-analog labeling also demonstrates that fewer aged cells are dividing at a given time, but those that do divide are significantly more likely to re-enter the cell cycle within a day, both in vitro and in vivo. Meanwhile, we observed that cellular survival is impaired in aged cultures. Using our live-cell imaging data, we developed a mathematical model describing cell cycle kinetics to predict the growth curves of cells over time in vitro and the labeling index over time in vivo. Together, these data surprisingly suggest that progenitor cells remaining in the aged SVZ are highly proliferative. PMID:21948688

Polyphenol- and PUFA-rich walnuts protect against age-associated cognitive decline through epigenetic modulation

USDA-ARS?s Scientific Manuscript database

A demographic shift towards an aging population and the incidence of age-related brain disorders are on the rise worldwide. A rapid decline in brain health with aging is primarily caused by the brain’s exceptionally high demand for energy which drives high oxygen consumption, leading to a subsequent...

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

Declining lymphoid progenitor fitness promotes aging-associated leukemogenesis.

PubMed

Henry, Curtis J; Marusyk, Andriy; Zaberezhnyy, Vadym; Adane, Biniam; DeGregori, James

2010-12-14

Aging is associated with the functional decline of cells, tissues, and organs. At the same time, age is the single most important prognostic factor in the development of most human cancers, including chronic myelogenous and acute lymphoblastic leukemias initiated by Bcr-Abl oncogenic translocations. Prevailing paradigms attribute the association between aging and cancers to the accumulation of oncogenic mutations over time, because the accrual of oncogenic events is thought to be the rate-limiting step in initiation and progression of cancers. Conversely, aging-associated functional decline caused by both cell-autonomous and non-cell-autonomous mechanisms is likely to reduce the fitness of stem and progenitor cell populations. This reduction in fitness should be conducive for increased selection of oncogenic mutations that can at least partially alleviate fitness defects, thereby promoting the initiation of cancers. We tested this hypothesis using mouse hematopoietic models. Our studies indicate that the dramatic decline in the fitness of aged B-lymphopoiesis coincides with altered receptor-associated kinase signaling. We further show that Bcr-Abl provides a much greater competitive advantage to old B-lymphoid progenitors compared with young progenitors, coinciding with restored kinase signaling pathways, and that this enhanced competitive advantage translates into increased promotion of Bcr-Abl-driven leukemias. Moreover, impairing IL-7-mediated signaling is sufficient to promote selection for Bcr-Abl-expressing B progenitors. These studies support an unappreciated causative link between aging and cancer: increased selection of oncogenic mutations as a result of age-dependent alterations of the fitness landscape.

Income differentials in functional disability in old age: relative risks of onset, recovery, decline, attrition and mortality.

PubMed

Broese van Groenou, Marjolein I; Deeg, Dorly J H; Penninx, Brenda W J H

2003-04-01

Socioeconomic status (SES) differences in health decline in late life may be underestimated, because the relatively higher risks of attrition of lower-SES persons are seldom taken into account. This longitudinal study aimed at comparing income differences in the course of disability, non-mortality attrition and mortality in older adults. A sample population of 3107 older adults who participated in the 1992/1993 baseline of the Longitudinal Aging Study Amsterdam was examined regarding changes in functional disability in 1998/1999. SES was indicated by household income. Multinomial regression analyses revealed that, for men without disability at baseline, the relative rate for attrition was four times higher and the mortality rate was twice as high for low-income vs high-income persons. For non-disabled women, the relative risk for the onset of disability was nearly twice as high for low-income vs high-income persons. For both men and women, these risks decreased only slightly when behavioral and psychosocial risk factors were taken into account. Among persons with disability at baseline, the relative risks for attrition (for women) and mortality (for men) were twice as high for low-income persons, but no income differences were found with respect to recovery and decline. Adjustment for risk factors decreased the relative risks for attrition and mortality to a non-significant level. Income inequality in health in late life is to a large degree explained by the higher incidence of disability among lower-status women and by the higher attrition and mortality risks among lower-status men.

Expertise and age-related changes in components of intelligence.

PubMed

Masunaga, H; Horn, J

2001-06-01

In a sample of 263 male GO players at 48 levels of expertise and ranging from 18 to 78 years of age, it was found that factors of expertise deductive reasoning (EDR) and expertise working memory (EWM) were independent of factors of fluid reasoning (Gf) and short-term working memory (STWM) that, along with cognitive speed (Gs), have been found to characterize decline of intelligence in adulthood. The main effects of analyses of cross-sectional age differences indicated age-related decline in EDR and EWM as well as in Gf, STWM, and Gs. However, interaction and partialing analyses indicated that decline in EDR and EWM decreased to no decline with increase in level of expertise. The results thus suggest that with increase in factors known to raise the level of expertise--particularly, intensive, well-designed practice--there may be no age-related decline in the intelligence that is measured in the abilities of expertise.

Assessing age-related gray matter decline with voxel-based morphometry depends significantly on segmentation and normalization procedures

PubMed Central

Callaert, Dorothée V.; Ribbens, Annemie; Maes, Frederik; Swinnen, Stephan P.; Wenderoth, Nicole

2014-01-01

Healthy ageing coincides with a progressive decline of brain gray matter (GM) ultimately affecting the entire brain. For a long time, manual delineation-based volumetry within predefined regions of interest (ROI) has been the gold standard for assessing such degeneration. Voxel-Based Morphometry (VBM) offers an automated alternative approach that, however, relies critically on the segmentation and spatial normalization of a large collection of images from different subjects. This can be achieved via different algorithms, with SPM5/SPM8, DARTEL of SPM8 and FSL tools (FAST, FNIRT) being three of the most frequently used. We complemented these voxel based measurements with a ROI based approach, whereby the ROIs are defined by transforms of an atlas (containing different tissue probability maps as well as predefined anatomic labels) to the individual subject images in order to obtain volumetric information at the level of the whole brain or within separate ROIs. Comparing GM decline between 21 young subjects (mean age 23) and 18 elderly (mean age 66) revealed that volumetric measurements differed significantly between methods. The unified segmentation/normalization of SPM5/SPM8 revealed the largest age-related differences and DARTEL the smallest, with FSL being more similar to the DARTEL approach. Method specific differences were substantial after segmentation and most pronounced for the cortical structures in close vicinity to major sulci and fissures. Our findings suggest that algorithms that provide only limited degrees of freedom for local deformations (such as the unified segmentation and normalization of SPM5/SPM8) tend to overestimate between-group differences in VBM results when compared to methods providing more flexible warping. This difference seems to be most pronounced if the anatomy of one of the groups deviates from custom templates, a finding that is of particular importance when results are compared across studies using different VBM methods. PMID

Preliminary development of a new individualised questionnaire measuring quality of life in older men with age-related hormonal decline: the A-RHDQoL

PubMed Central

McMillan, Carolyn V; Bradley, Clare; Giannoulis, Manthos; Martin, Finbarr; Sönksen, Peter H

2003-01-01

Background There is increasing interest in hormone replacement therapy to improve health and quality of life (QoL) of older men with age-related decline in hormone levels. This paper reports the preliminary development and evaluation of the psychometric properties of a new individualised questionnaire, the A-RHDQoL, measuring perceived impact of age-related hormonal decline on QoL of older men. A-RHDQoL design was based on the HDQoL for people with growth hormone (GH) deficiency and the ADDQoL (for diabetes). Methods Internal consistency reliability and some aspects of validity of the A-RHDQoL were investigated in a cross-sectional survey of 128 older men (age range: 64 – 80 yrs), being screened for inclusion in a trial of GH and testosterone (T) replacement, and who completed the A-RHDQoL once. Respondents rated personally applicable life domains for importance and impact of their hormonal decline. A single overview item measured present QoL. Serum levels of Insulin-like Growth Factor-I and total T were measured. Results Of the 24 A-RHDQoL domains, 21 were rated as relevant and important for older men. All domains were perceived as negatively impacted by hormonal decline. The most negatively impacted domains were: memory (-4.54 ± 3.02), energy (-4.44 ± 2.49), sex life (-4.34 ± 3.08) and physical stamina (-4.29 ± 2.41), (maximum range -9 to +9). The shorter 21-domain A-RHDQoL had high internal consistency reliability (Cronbach's alpha coefficient = 0.935, N = 103) and applicable domains could be weighted and summed into an overall Average Weighted Impact score. The questionnaire was acceptable to the majority of respondents and content validity was good. The single overview item measuring present QoL correlated significantly with total T levels [r = 0.26, p <0.01, N = 114]. Conclusion The new 21-item A-RHDQoL is an individualised questionnaire measuring perceived impact of age-related hormonal decline on the QoL of older men. The internal consistency

Do glutathione levels decline in aging human brain?

PubMed

Tong, Junchao; Fitzmaurice, Paul S; Moszczynska, Anna; Mattina, Katie; Ang, Lee-Cyn; Boileau, Isabelle; Furukawa, Yoshiaki; Sailasuta, Napapon; Kish, Stephen J

2016-04-01

For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age-related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain. Copyright © 2016 Elsevier Inc. All rights reserved.

A prospectus for ethical analysis of ageing individuals' responsibility to prevent cognitive decline.

PubMed

Forlini, Cynthia; Hall, Wayne

2017-11-01

As the world's population ages, governments and non-governmental organizations in developed countries are promoting healthy cognitive ageing to reduce the rate of age-related cognitive decline and sustain economic productivity in an ageing workforce. Recommendations from the Productivity Commission (Australia), Dementia Australia, Government Office for Science (UK), Presidential Commission for the Study of Bioethical Issues (USA), Institute of Medicine (USA), among others, are encouraging older adults to engage in mental, physical, and social activities. These lifestyle recommendations for healthy cognitive ageing are timely and well supported by scientific evidence but they make implicit normative judgments about the responsibility of ageing individuals to prevent cognitive decline. Ethical tensions arise when this individual responsibility collides with social and personal realities of ageing populations. First, we contextualize the priority given to healthy cognitive ageing within the current brain-based medical and social discourses. Second, we explore the individual responsibility by examining the economic considerations, medical evidence and individual interests that relate to the priority given to healthy cognitive ageing. Third, we identify three key ethical challenges for policymakers seeking to implement lifestyle recommendations as an effective population-level approach to healthy cognitive ageing. The result is a prospectus for future in-depth analysis of ethical tensions that arise from current policy discussions of healthy cognitive ageing. © 2017 John Wiley & Sons Ltd.

The rate of change in declining steroid hormones: a new parameter of healthy aging in men?

PubMed

Walther, Andreas; Philipp, Michel; Lozza, Niclà; Ehlert, Ulrike

2016-09-20

Research on healthy aging in men has increasingly focused on age-related hormonal changes. Testosterone (T) decline is primarily investigated, while age-related changes in other sex steroids (dehydroepiandrosterone [DHEA], estradiol [E2], progesterone [P]) are mostly neglected. An integrated hormone parameter reflecting aging processes in men has yet to be identified. 271 self-reporting healthy men between 40 and 75 provided both psychometric data and saliva samples for hormone analysis. Correlation analysis between age and sex steroids revealed negative associations for the four sex steroids (T, DHEA, E2, and P). Principal component analysis including ten salivary analytes identified a principal component mainly unifying the variance of the four sex steroid hormones. Subsequent principal component analysis including the four sex steroids extracted the principal component of declining steroid hormones (DSH). Moderation analysis of the association between age and DSH revealed significant moderation effects for psychosocial factors such as depression, chronic stress and perceived general health. In conclusion, these results provide further evidence that sex steroids decline in aging men and that the integrated hormone parameter DSH and its rate of change can be used as biomarkers for healthy aging in men. Furthermore, the negative association of age and DSH is moderated by psychosocial factors.

The rate of change in declining steroid hormones: a new parameter of healthy aging in men?

PubMed Central

Walther, Andreas; Philipp, Michel; Lozza, Niclà; Ehlert, Ulrike

2016-01-01

Research on healthy aging in men has increasingly focused on age-related hormonal changes. Testosterone (T) decline is primarily investigated, while age-related changes in other sex steroids (dehydroepiandrosterone [DHEA], estradiol [E2], progesterone [P]) are mostly neglected. An integrated hormone parameter reflecting aging processes in men has yet to be identified. 271 self-reporting healthy men between 40 and 75 provided both psychometric data and saliva samples for hormone analysis. Correlation analysis between age and sex steroids revealed negative associations for the four sex steroids (T, DHEA, E2, and P). Principal component analysis including ten salivary analytes identified a principal component mainly unifying the variance of the four sex steroid hormones. Subsequent principal component analysis including the four sex steroids extracted the principal component of declining steroid hormones (DSH). Moderation analysis of the association between age and DSH revealed significant moderation effects for psychosocial factors such as depression, chronic stress and perceived general health. In conclusion, these results provide further evidence that sex steroids decline in aging men and that the integrated hormone parameter DSH and its rate of change can be used as biomarkers for healthy aging in men. Furthermore, the negative association of age and DSH is moderated by psychosocial factors. PMID:27589836

Age-Related Changes in Creative Thinking

ERIC Educational Resources Information Center

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

2008-01-01

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

Association of Family History of Exceptional Longevity With Decline in Physical Function in Aging.

PubMed

Ayers, Emmeline; Barzilai, Nir; Crandall, Jill P; Milman, Sofiya; Verghese, Joe

2017-11-09

Although many genetic and nongenetic factors interact to determine an individual's physical phenotype, there has been limited examination of the contribution of family history of exceptional parental longevity on decline in physical function in aging. The LonGenity study recruited a relatively genetically homogenous cohort of Ashkenazi Jewish adults age 65 and older, who were defined as either offspring of parents with exceptional longevity ([OPEL]: having at least one parent who lived to age 95 or older) or offspring of parents with usual survival ([OPUS]: neither parent survived to age 95). Decline in performance on objective measures of strength (grip strength), balance (unipedal stance), and mobility (gait speed) as well as a composite physical function measure, the Short physical performance battery (SPPB), were compared between the two groups over a median follow-up of 3.2 years, accounting for age, sex, education, and comorbidities. Of the 984 LonGenity participants (mean age 76, 55% women), 448 were OPEL and 536 were OPUS. Compared to OPUS, OPEL had slower decline on measures of unipedal stance (-0.03 log-units/year, p = .026), repeated chair rise (0.13 s/year, p = .020) and SPPB (-0.11 points/year, p = .002). OPEL women had slower decline on chair rise and SPPB scores compared to OPUS women, although OPEL men had slower decline on unipedal stance compared to OPUS men. Our findings provide evidence that variation in late-life decline in physical function is associated with familial longevity, and may vary for men and women. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Mediterranean Diet and Age-Related Cognitive Decline: A Randomized Clinical Trial.

PubMed

Valls-Pedret, Cinta; Sala-Vila, Aleix; Serra-Mir, Mercè; Corella, Dolores; de la Torre, Rafael; Martínez-González, Miguel Ángel; Martínez-Lapiscina, Elena H; Fitó, Montserrat; Pérez-Heras, Ana; Salas-Salvadó, Jordi; Estruch, Ramon; Ros, Emilio

2015-07-01

Oxidative stress and vascular impairment are believed to partly mediate age-related cognitive decline, a strong risk factor for development of dementia. Epidemiologic studies suggest that a Mediterranean diet, an antioxidant-rich cardioprotective dietary pattern, delays cognitive decline, but clinical trial evidence is lacking. To investigate whether a Mediterranean diet supplemented with antioxidant-rich foods influences cognitive function compared with a control diet. Parallel-group randomized clinical trial of 447 cognitively healthy volunteers from Barcelona, Spain (233 women [52.1%]; mean age, 66.9 years), at high cardiovascular risk were enrolled into the Prevención con Dieta Mediterránea nutrition intervention trial from October 1, 2003, through December 31, 2009. All patients underwent neuropsychological assessment at inclusion and were offered retesting at the end of the study. Participants were randomly assigned to a Mediterranean diet supplemented with extravirgin olive oil (1 L/wk), a Mediterranean diet supplemented with mixed nuts (30 g/d), or a control diet (advice to reduce dietary fat). Rates of cognitive change over time based on a neuropsychological test battery: Mini-Mental State Examination, Rey Auditory Verbal Learning Test (RAVLT), Animals Semantic Fluency, Digit Span subtest from the Wechsler Adult Intelligence Scale, Verbal Paired Associates from the Wechsler Memory Scale, and the Color Trail Test. We used mean z scores of change in each test to construct 3 cognitive composites: memory, frontal (attention and executive function), and global. Follow-up cognitive tests were available in 334 participants after intervention (median, 4.1 years). In multivariate analyses adjusted for confounders, participants allocated to a Mediterranean diet plus olive oil scored better on the RAVLT (P = .049) and Color Trail Test part 2 (P = .04) compared with controls; no between-group differences were observed for the other cognitive tests

A critical review of vitamin C for the prevention of age-related cognitive decline and Alzheimer's disease.

PubMed

Harrison, Fiona E

2012-01-01

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.

Supercomplexes of the mitochondrial electron transport chain decline in the aging rat heart.

PubMed

Gómez, Luis A; Monette, Jeffrey S; Chavez, Juan D; Maier, Claudia S; Hagen, Tory M

2009-10-01

Accumulation of mitochondrial electron transport chain (ETC) defects is a recognized hallmark of the age-associated decline in cardiac bioenergetics; however, the molecular events involved are only poorly understood. In the present work, we hypothesized that age-related ETC deterioration stemmed partly from disassociation of large solid-state macromolecular assemblies termed "supercomplexes". Mitochondrial proteins from young and old rat hearts were separated by blue native-PAGE, protein bands analyzed by LC-MALDI-MS/MS, and protein levels quantified by densitometry. Results showed that supercomplexes comprised of various stoichiometries of complexes I, III and IV were observed, and declined significantly (p<0.05, n=4) with age. Supercomplexes displaying the highest molecular masses were the most severely affected. Considering that certain diseases (e.g. Barth Syndrome) display similar supercomplex destabilization as our results for aging, the deterioration in ETC supercomplexes may be an important underlying factor for both impaired mitochondrial function and loss of cardiac bioenergetics with age.

Decline in offspring viability as a manifestation of aging in Drosophila melianogaster.

PubMed

Kern, S; Ackermann, M; Stearns, S C; Kawecki, T J

2001-09-01

The evolutionary explanation of senescence proposes that selection against alleles with deleterious effects manifested only late in life is weak because most individuals die earlier for extrinsic reasons. This argument also applies to alleles whose deleterious effects are nongenetically transmitted from mother to progeny, that is, that affect the performance of progeny produced at late ages rather than of the aging individuals themselves. We studied the effect of maternal age on offspring viability (egg hatching success and larva-to-adult survival) in two sets of Drosophila melanogaster lines (HAM/LAM and YOUNG/OLD), originating from two long-term selection experiments. In each set, some lines (HAM and YOUNG, respectively) have been selected for early reproduction, whereas later reproduction was favored in their counterparts (LAM and OLD). In the HAM and LAM lines, both egg hatching success and larval viability declined with mother's age and did so with accelerating rates. The hatching success declined significantly faster with maternal age in HAM than in LAM lines, according to one of two statistical approaches used. Egg hatching success also declined with maternal age in YOUNG and OLD lines, with no difference between the selection regimes. However, the relationship between mother's age and offspring larva-to-adult viability differed significantly between these two selection regimes: a decline of larval viability with maternal age occurred in YOUNG lines but not in OLD lines. This suggests that the rate with which offspring viability declines with mother's age responded to selection for early versus late reproduction. We suggest broadening the evolutionary concept of senescence to include intrinsically caused declines in offspring quality with maternal age.

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

Prevalence of ageing-associated cognitive decline in an elderly population.

PubMed

Hanninen, T; Koivisto, K; Reinikainen, K J; Helkala, E L; Soininen, H; Mykkänen, L; Laakso, M; Riekkinen, P J

1996-05-01

Different diagnostic definitions have been proposed for use in the characterization of mild cognitive disorders associated with ageing. Previously, we reported a high (38.4%) prevalence of age-associated memory impairment (AAMI) using the National Institute of Mental Health criteria in an elderly population. Recently, a work group of the International Psychogeriatric Association proposed criteria for 'ageing-associated cognitive decline' (AACD). The objective of this study was to evaluate the prevalence of AACD in an elderly population. We examined 403 randomly selected subjects (68-78 years of age) with tests of memory, cognitive processing, attention, verbal and visuoconstructive functions and with a structured questionnaire for health status and subjective complaints of cognitive decline. In all, 26.6% of the subjects (24.4% of women, 30. 1% or men) fulfilled the AACD criteria. The prevalence was slightly related to age and education. The rate was lowest in the oldest age of 75 - 78 years (20.5%) and highest in the age of 71 -74 years (30%). Subjects with less than 4 years of education had the lowest (14.3%) and subjects with more than 6 years of education had the highest rate (29.4%) for AACD. However, the differences between these subgroups were not statistically significant. These results suggest that the prevalence of AACD is lower than that of AAMI. As AAMI tends to identify a very heterogeneous subject group, the AACD diagnosis, which takes into account age and education specific norms in its inclusion criteria, might prove superior to AAMI in differentiating a meaningful subgroup from an elderly population both for research purposes and in clinical settings.

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

PubMed

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

2009-01-01

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

Molecular Inflammation: Underpinnings of Aging and Age-related Diseases

PubMed Central

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

2013-01-01

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

An Age-Associated Decline in Thymic Output Differs in Dog Breeds According to Their Longevity.

PubMed

Holder, Angela; Mella, Stephanie; Palmer, Donald B; Aspinall, Richard; Catchpole, Brian

2016-01-01

The age associated decline in immune function is preceded in mammals by a reduction in thymic output. Furthermore, there is increasing evidence of a link between immune competence and lifespan. One approach to determining thymic output is to quantify signal joint T cell receptor excision circles (sj-TRECs), a method which has been developed and used in several mammalian species. Life expectancy and the rate of aging vary in dogs depending upon their breed. In this study, we quantified sj-TRECs in blood samples from dogs of selected breeds to determine whether there was a relationship between longevity and thymic output. In Labrador retrievers, a breed with a median expected lifespan of 11 years, there was an age-associated decline in sj-TREC values, with the greatest decline occurring before 5 years of age, but with sj-TREC still detectable in some geriatric animals, over 13 years of age. In large short-lived breeds (Burnese mountain dogs, Great Danes and Dogue de Bordeaux), the decline in sj-TREC values began earlier in life, compared with small long-lived breeds (Jack Russell terriers and Yorkshire terriers), and the presence of animals with undetectable sj-TRECs occurred at a younger age in the short-lived breeds. The study findings suggest that age-associated changes in canine sj-TRECs are related to breed differences in longevity, and this research highlights the use of dogs as a potential model of immunosenescence.

Diffusion tensor imaging detects age related white matter change over a 2 year follow-up which is associated with working memory decline.

PubMed

Charlton, R A; Schiavone, F; Barrick, T R; Morris, R G; Markus, H S

2010-01-01

Diffusion tensor imaging (DTI) is a sensitive method for detecting white matter damage, and in cross sectional studies DTI measures correlate with age related cognitive decline. However, there are few data on whether DTI can detect age related changes over short time periods and whether such change correlates with cognitive function. In a community sample of 84 middle-aged and elderly adults, MRI and cognitive testing were performed at baseline and after 2 years. Changes in DTI white matter histograms, white matter hyperintensity (WMH) volume and brain volume were determined. Change over time in performance on tests of executive function, working memory and information processing speed were also assessed. Significant change in all MRI measures was detected. For cognition, change was detected for working memory and this correlated with change in DTI only. In a stepwise regression, with change in working memory as the dependent variable, a DTI histogram measure explained 10.8% of the variance in working memory. Change in WMH or brain volume did not contribute to the model. DTI is sensitive to age related change in white matter ultrastructure and appears useful for monitoring age related white matter change even over short time periods.

Does Sensory Function Decline Independently or Concomitantly with Age? Data from the Baltimore Longitudinal Study of Aging.

PubMed

Gadkaree, Shekhar K; Sun, Daniel Q; Li, Carol; Lin, Frank R; Ferrucci, Luigi; Simonsick, Eleanor M; Agrawal, Yuri

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).

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

Quantitative evaluation of age-related decline in control of preprogramed movement

PubMed Central

Lee, Jongho; Kodama, Mitsuhiko; Kakei, Shinji; Masakado, Yoshihisa

2017-01-01

In this paper, we examined the age-related changes in control of preprogramed movement, with emphasis on its accuracy. Forty-nine healthy subjects participated in this study, and were divided into three groups depending on their ages: the young group (20–39 years) (n = 16), the middle-age group (40–59 years) (n = 16), and the elderly group (60–79 years) (n = 17). We asked the subjects to perform step-tracking movements of the wrist joint with a manipulandum, and recorded the movements. We evaluated the accuracy of control of preprogramed movement in the three groups in terms of the primary submovement, which was identified as the first segment of the step-tracking movement based on the bell-shaped velocity profile, and calculated the distance between the end position of the primary submovement and the target (i.e. error). The error in the young group was found to be significantly smaller than that in the middle-age and elderly groups, i.e., the error was larger for the higher age groups. These results suggest that young subjects have better control of preprogramed movement than middle-age or elderly subjects. Finally, we examined the temporal property of the primary submovement and its age-related changes. The duration of the primary submovement tended to be longer for the aged groups, although significance was reached only for the elderly group. In particular, the ratio of the duration of the primary submovement to total movement time tended to be lower for the aged groups, suggesting that the proportion of additional movements that are required to compensate for the incomplete control in the preprogramed movement, which are under feedback control, was higher for the aged groups. Consequently, our results indicate that the distance between the end point of the primary submovement and the target center (i.e. error) in the step-tracking movement is a useful parameter to evaluate the age-related changes in control of preprogramed movement. PMID:29186168

Quantitative evaluation of age-related decline in control of preprogramed movement.

PubMed

Shimoda, Naoshi; Lee, Jongho; Kodama, Mitsuhiko; Kakei, Shinji; Masakado, Yoshihisa

2017-01-01

In this paper, we examined the age-related changes in control of preprogramed movement, with emphasis on its accuracy. Forty-nine healthy subjects participated in this study, and were divided into three groups depending on their ages: the young group (20-39 years) (n = 16), the middle-age group (40-59 years) (n = 16), and the elderly group (60-79 years) (n = 17). We asked the subjects to perform step-tracking movements of the wrist joint with a manipulandum, and recorded the movements. We evaluated the accuracy of control of preprogramed movement in the three groups in terms of the primary submovement, which was identified as the first segment of the step-tracking movement based on the bell-shaped velocity profile, and calculated the distance between the end position of the primary submovement and the target (i.e. error). The error in the young group was found to be significantly smaller than that in the middle-age and elderly groups, i.e., the error was larger for the higher age groups. These results suggest that young subjects have better control of preprogramed movement than middle-age or elderly subjects. Finally, we examined the temporal property of the primary submovement and its age-related changes. The duration of the primary submovement tended to be longer for the aged groups, although significance was reached only for the elderly group. In particular, the ratio of the duration of the primary submovement to total movement time tended to be lower for the aged groups, suggesting that the proportion of additional movements that are required to compensate for the incomplete control in the preprogramed movement, which are under feedback control, was higher for the aged groups. Consequently, our results indicate that the distance between the end point of the primary submovement and the target center (i.e. error) in the step-tracking movement is a useful parameter to evaluate the age-related changes in control of preprogramed movement.

Use it or lose it: engaged lifestyle as a buffer of cognitive decline in aging?

PubMed

Hultsch, D F; Hertzog, C; Small, B J; Dixon, R A

1999-06-01

Data from the Victoria Longitudinal Study were used to examine the hypothesis that maintaining intellectual engagement through participation in everyday activities buffers individuals against cognitive decline in later life. The sample consisted of 250 middle-aged and older adults tested 3 times over 6 years. Structural equation modeling techniques were used to examine the relationships among changes in lifestyle variables and an array of cognitive variables. There was a relationship between changes in intellectually related activities and changes in cognitive functioning. These results are consistent with the hypothesis that intellectually engaging activities serve to buffer individuals against decline. However, an alternative model suggested the findings were also consistent with the hypothesis that high-ability individuals lead intellectually active lives until cognitive decline in old age limits their activities.

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

PubMed

Fama, Rosemary; Sullivan, Edith V

2015-07-01

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

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.

An experimental test of the causes of forest growth decline with stand age.

Treesearch

Michael G. Ryan; Dan Binkley; James H. Fownes; Christian Giardina; Randy S. Senock

2004-01-01

The decline in aboveground wood production after canopy closure in even-aged forest stands is a common pattern in forests, but clear evidence for the mechanism causing the decline is lacking. The problem is fundamental to forest biology, commercial forestry (the decline sets the rotation age), and to carbon storage in forests. We tested three hypotheses...

Internet use, social engagement and health literacy decline during ageing in a longitudinal cohort of older English adults

PubMed Central

Kobayashi, Lindsay C; Wardle, Jane; von Wagner, Christian

2015-01-01

Background Health literacy skills tend to decline during ageing, which is often attributed to age-related cognitive decline. Whether health literacy skills may be influenced by technological and social factors during ageing is unknown. Methods We investigated whether internet use and social engagement protect against health literacy decline during ageing, independent of cognitive decline. We used prospective data from 4368 men and women aged ≥52 years in the English Longitudinal Study of Ageing from 2004 to 2011. Health literacy was measured at baseline (2004–2005) and at follow-up (2010–2011) using a reading comprehension test of a fictitious medicine label. The influences of consistent internet use and engagement in each of the civic, leisure and cultural activities on health literacy decline over the follow-up were estimated. Results After adjusting for cognitive decline and other covariates, consistent internet use (1379/4368; 32%) was protectively associated with health literacy decline (OR=0.77; 95% CI 0.60 to 0.99), as was consistent engagement in cultural activities (1715/4368; 39%; OR=0.73; 95% CI 0.56 to 0.93). As the number of activities engaged in increased, the likelihood of health literacy decline steadily decreased (ptrend<0.0001), with OR=0.51 (95% CI 0.33 to 0.79) for engaging in all four of the internet use and civic, leisure and cultural activities versus none. Conclusions Internet use and social engagement, particularly in cultural activities (eg, attending the cinema, art galleries, museums and the theatre), may help older adults to maintain health literacy during ageing. Support for older adults to maintain socially engaged lives and to access the internet should help promote the maintenance of functional literacy skills during ageing. PMID:25428933

Internet use, social engagement and health literacy decline during ageing in a longitudinal cohort of older English adults.

PubMed

Kobayashi, Lindsay C; Wardle, Jane; von Wagner, Christian

2015-03-01

Health literacy skills tend to decline during ageing, which is often attributed to age-related cognitive decline. Whether health literacy skills may be influenced by technological and social factors during ageing is unknown. We investigated whether internet use and social engagement protect against health literacy decline during ageing, independent of cognitive decline. We used prospective data from 4368 men and women aged ≥52 years in the English Longitudinal Study of Ageing from 2004 to 2011. Health literacy was measured at baseline (2004-2005) and at follow-up (2010-2011) using a reading comprehension test of a fictitious medicine label. The influences of consistent internet use and engagement in each of the civic, leisure and cultural activities on health literacy decline over the follow-up were estimated. After adjusting for cognitive decline and other covariates, consistent internet use (1379/4368; 32%) was protectively associated with health literacy decline (OR=0.77; 95% CI 0.60 to 0.99), as was consistent engagement in cultural activities (1715/4368; 39%; OR=0.73; 95% CI 0.56 to 0.93). As the number of activities engaged in increased, the likelihood of health literacy decline steadily decreased (ptrend<0.0001), with OR=0.51 (95% CI 0.33 to 0.79) for engaging in all four of the internet use and civic, leisure and cultural activities versus none. Internet use and social engagement, particularly in cultural activities (eg, attending the cinema, art galleries, museums and the theatre), may help older adults to maintain health literacy during ageing. Support for older adults to maintain socially engaged lives and to access the internet should help promote the maintenance of functional literacy skills during ageing. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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…

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.

Cognitive performance and age-related changes in the hippocampal proteome.

PubMed

Freeman, W M; VanGuilder, H D; Bennett, C; Sonntag, W E

2009-03-03

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 two-dimensional in-gel electrophoresis and 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 were used.

APOE E4 status predicts age-related cognitive decline in the ninth decade: longitudinal follow-up of the Lothian Birth Cohort 1921.

PubMed

Schiepers, O J G; Harris, S E; Gow, A J; Pattie, A; Brett, C E; Starr, J M; Deary, I J

2012-03-01

Carriers of the APOE E4 allele have an increased risk of developing Alzheimer's disease. However, it is less clear whether APOE E4 status may also be involved in non-pathological cognitive ageing. The present study investigated the associations between APOE genotypes and cognitive change over 8 years in older community-dwelling individuals. APOE genotype was determined in 501 participants of the Lothian Birth Cohort 1921, whose intelligence had been measured in childhood in the Scottish Mental Survey 1932. A polymorphic variant of TOMM40 (rs10524523) was included to differentiate between the effects of the APOE E3 and E4 allelic variants. Cognitive performance on the domains of verbal memory, abstract reasoning and verbal fluency was assessed at mean age 79 years (n=501), and again at mean ages of 83 (n=284) and 87 (n=187). Using linear mixed models adjusted for demographic variables, vascular risk factors and IQ at age 11 years, possession of the APOE E4 allele was associated with a higher relative rate of cognitive decline over the subsequent 8 years for verbal memory and abstract reasoning. Individuals with the long allelic variant of TOMM40, which is linked to APOE E4, showed similar results. Verbal fluency was not affected by APOE E4 status. APOE E2 status was not associated with change in cognitive performance over 8 years. In non-demented older individuals, possession of the APOE E4 allele predicted a higher rate of cognitive decline on tests of verbal memory and abstract reasoning between 79 and 87 years. Thus, possession of the APOE E4 allele may not only predispose to Alzheimer's disease, but also appears to be a risk factor for non-pathological decline in verbal memory and abstract reasoning in the ninth decade of life.

Age-related epigenetic drift and phenotypic plasticity loss: implications in prevention of age-related human diseases

PubMed Central

Li, Yuanyuan; Tollefsbol, Trygve O

2016-01-01

Aging is considered as one of the most important developmental processes in organisms and is closely associated with global deteriorations of epigenetic markers such as aberrant methylomic patterns. This altered epigenomic state, referred to ‘epigenetic drift’, reflects deficient maintenance of epigenetic marks and contributes to impaired cellular and molecular functions in aged cells. Epigenetic drift-induced abnormal changes during aging are scantily repaired by epigenetic modulators. This inflexibility in the aged epigenome may lead to an age-related decline in phenotypic plasticity at the cellular and molecular levels due to epigenetic drift. This perspective aims to provide novel concepts for understanding epigenetic effects on the aging process and to provide insights into epigenetic prevention and therapeutic strategies for age-related human disease. PMID:27882781

Differential effects of enriched environment at work on cognitive decline in old age.

PubMed

Then, Francisca S; Luck, Tobias; Luppa, Melanie; König, Hans-Helmut; Angermeyer, Matthias C; Riedel-Heller, Steffi G

2015-05-26

The aim of the present study was to investigate how different mentally demanding work conditions during the professional life-i.e., enriched environments at work-might influence the rate of cognitive decline in old age. Individuals (n = 1,054) of the Leipzig Longitudinal Study of the Aged, a representative population-based cohort study of individuals aged 75 years and older, underwent cognitive testing via the Mini-Mental State Examination (MMSE) in up to 6 measurement waves. Type and level of mentally demanding work conditions in the participants' former professional life were classified based on the O*NET job descriptor database. In multivariate mixed-model analyses (controlling for sociodemographic and health-related factors), a high level of mentally demanding work tasks stimulating verbal intelligence was significantly associated with a better cognitive functioning at baseline (on average 5 MMSE points higher) as well as a lower rate of cognitive decline (on average 2 MMSE points less) over the 8-year follow-up period compared with a low level. The rate of cognitive decline in old age was also significantly lower (on average 3 MMSE points less) in individuals who had a high level of mentally demanding work tasks stimulating executive functions than those who had a low level. The results suggest that a professional life enriched with work tasks stimulating verbal intelligence and executive functions may help to sustain a good cognitive functioning in old age (75+ years). The findings thus emphasize that today's challenging work conditions may also promote positive health effects. © 2015 American Academy of Neurology.

Age-Related Decline in the Variation of Dynamic Functional Connectivity: A Resting State Analysis.

PubMed

Chen, Yuanyuan; Wang, Weiwei; Zhao, Xin; Sha, Miao; Liu, Ya'nan; Zhang, Xiong; Ma, Jianguo; Ni, Hongyan; Ming, Dong

2017-01-01

Normal aging is typically characterized by abnormal resting-state functional connectivity (FC), including decreasing connectivity within networks and increasing connectivity between networks, under the assumption that the FC over the scan time was stationary. In fact, the resting-state FC has been shown in recent years to vary over time even within minutes, thus showing the great potential of intrinsic interactions and organization of the brain. In this article, we assumed that the dynamic FC consisted of an intrinsic dynamic balance in the resting brain and was altered with increasing age. Two groups of individuals ( N = 36, ages 20-25 for the young group; N = 32, ages 60-85 for the senior group) were recruited from the public data of the Nathan Kline Institute. Phase randomization was first used to examine the reliability of the dynamic FC. Next, the variation in the dynamic FC and the energy ratio of the dynamic FC fluctuations within a higher frequency band were calculated and further checked for differences between groups by non-parametric permutation tests. The results robustly showed modularization of the dynamic FC variation, which declined with aging; moreover, the FC variation of the inter-network connections, which mainly consisted of the frontal-parietal network-associated and occipital-associated connections, decreased. In addition, a higher energy ratio in the higher FC fluctuation frequency band was observed in the senior group, which indicated the frequency interactions in the FC fluctuations. These results highly supported the basis of abnormality and compensation in the aging brain and might provide new insights into both aging and relevant compensatory mechanisms.

Age-Related Decline in Primary CD8+ T Cell Responses Is Associated with the Development of Senescence in Virtual Memory CD8+ T Cells.

PubMed

Quinn, Kylie M; Fox, Annette; Harland, Kim L; Russ, Brendan E; Li, Jasmine; Nguyen, Thi H O; Loh, Liyen; Olshanksy, Moshe; Naeem, Haroon; Tsyganov, Kirill; Wiede, Florian; Webster, Rosela; Blyth, Chantelle; Sng, Xavier Y X; Tiganis, Tony; Powell, David; Doherty, Peter C; Turner, Stephen J; Kedzierska, Katherine; La Gruta, Nicole L

2018-06-19

Age-associated decreases in primary CD8 + T cell responses occur, in part, due to direct effects on naive CD8 + T cells to reduce intrinsic functionality, but the precise nature of this defect remains undefined. Aging also causes accumulation of antigen-naive but semi-differentiated "virtual memory" (T VM ) cells, but their contribution to age-related functional decline is unclear. Here, we show that T VM cells are poorly proliferative in aged mice and humans, despite being highly proliferative in young individuals, while conventional naive T cells (T N cells) retain proliferative capacity in both aged mice and humans. Adoptive transfer experiments in mice illustrated that naive CD8 T cells can acquire a proliferative defect imposed by the aged environment but age-related proliferative dysfunction could not be rescued by a young environment. Molecular analyses demonstrate that aged T VM cells exhibit a profile consistent with senescence, marking an observation of senescence in an antigenically naive T cell population. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Fish consumption, intake of fats and cognitive decline at middle and older age: the Doetinchem Cohort Study.

PubMed

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

2018-06-01

To get insight in the impact of fish and fat intake in the prevention of accelerated cognitive decline with ageing, we tested associations between fish and different fat intakes and 5-year change in cognitive functions. In 2612 men and women of the Doetinchem Cohort Study, aged 43-70 years at baseline, dietary intake (including fish consumption) and cognitive function were assessed at baseline and at 5-year follow-up. Average fish consumption (frequency) and intakes (as energy percentages) of total fat, saturated, mono unsaturated, and polyunsaturated fatty acids (PUFA), linoleic, docosahexaenoic, eicosapentaenoic, and a-linolenic acid (ALA), and cholesterol were averaged over baseline and follow-up. Intakes were studied in relation to 5-year change in global cognitive function, memory, information processing speed, and cognitive flexibility, using ANCOVA and multivariate linear regression analyses. No consistent association between (fatty) fish consumption and cognitive decline was observed. Higher cholesterol intake was associated with faster cognitive decline (p < 0.05). Higher n-3 PUFA (especially ALA) intake was associated with slower decline in global cognitive function and memory (p < 0.01). Intakes of other fatty acids were not associated with cognitive decline. Higher cholesterol intake was detrimental, while higher ALA intake was beneficial for maintaining cognitive function with ageing, already at middle age.

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

Knock-in reporter mice demonstrate that DNA repair by non-homologous end joining declines with age.

PubMed

Vaidya, Amita; Mao, Zhiyong; Tian, Xiao; Spencer, Brianna; Seluanov, Andrei; Gorbunova, Vera

2014-07-01

Accumulation of genome rearrangements is a characteristic of aged tissues. Since genome rearrangements result from faulty repair of DNA double strand breaks (DSBs), we hypothesized that DNA DSB repair becomes less efficient with age. The Non-Homologous End Joining (NHEJ) pathway repairs a majority of DSBs in vertebrates. To examine age-associated changes in NHEJ, we have generated an R26NHEJ mouse model in which a GFP-based NHEJ reporter cassette is knocked-in to the ROSA26 locus. In this model, NHEJ repair of DSBs generated by the site-specific endonuclease, I-SceI, reconstitutes a functional GFP gene. In this system NHEJ efficiency can be compared across tissues of the same mouse and in mice of different age. Using R26NHEJ mice, we found that NHEJ efficiency was higher in the skin, lung, and kidney fibroblasts, and lower in the heart fibroblasts and brain astrocytes. Furthermore, we observed that NHEJ efficiency declined with age. In the 24-month old animals compared to the 5-month old animals, NHEJ efficiency declined 1.8 to 3.8-fold, depending on the tissue, with the strongest decline observed in the skin fibroblasts. The sequence analysis of 300 independent NHEJ repair events showed that, regardless of age, mice utilize microhomology sequences at a significantly higher frequency than expected by chance. Furthermore, the frequency of microhomology-mediated end joining (MMEJ) events increased in the heart and lung fibroblasts of old mice, suggesting that NHEJ becomes more mutagenic with age. In summary, our study provides a versatile mouse model for the analysis of NHEJ in a wide range of tissues and demonstrates that DNA repair by NHEJ declines with age in mice, which could provide a mechanism for age-related genomic instability and increased cancer incidence with age.

Age-Related Decline in the Variation of Dynamic Functional Connectivity: A Resting State Analysis

PubMed Central

Chen, Yuanyuan; Wang, Weiwei; Zhao, Xin; Sha, Miao; Liu, Ya’nan; Zhang, Xiong; Ma, Jianguo; Ni, Hongyan; Ming, Dong

2017-01-01

Normal aging is typically characterized by abnormal resting-state functional connectivity (FC), including decreasing connectivity within networks and increasing connectivity between networks, under the assumption that the FC over the scan time was stationary. In fact, the resting-state FC has been shown in recent years to vary over time even within minutes, thus showing the great potential of intrinsic interactions and organization of the brain. In this article, we assumed that the dynamic FC consisted of an intrinsic dynamic balance in the resting brain and was altered with increasing age. Two groups of individuals (N = 36, ages 20–25 for the young group; N = 32, ages 60–85 for the senior group) were recruited from the public data of the Nathan Kline Institute. Phase randomization was first used to examine the reliability of the dynamic FC. Next, the variation in the dynamic FC and the energy ratio of the dynamic FC fluctuations within a higher frequency band were calculated and further checked for differences between groups by non-parametric permutation tests. The results robustly showed modularization of the dynamic FC variation, which declined with aging; moreover, the FC variation of the inter-network connections, which mainly consisted of the frontal-parietal network-associated and occipital-associated connections, decreased. In addition, a higher energy ratio in the higher FC fluctuation frequency band was observed in the senior group, which indicated the frequency interactions in the FC fluctuations. These results highly supported the basis of abnormality and compensation in the aging brain and might provide new insights into both aging and relevant compensatory mechanisms. PMID:28713261

Age-related practice effects across longitudinal neuropsychological assessments in older people with schizophrenia.

PubMed

Granholm, Eric; Link, Peter; Fish, Scott; Kraemer, Helena; Jeste, Dilip

2010-09-01

The relationship between aging and practice effects on longitudinal neuropsychological assessments was investigated in middle-aged and older people with schizophrenia and healthy controls. Older people with schizophrenia (n = 107; M age = 56.1) and age-comparable nonpsychiatric controls (n = 107; M age = 57.7) were scheduled to receive annual assessments on a comprehensive battery of neuropsychological tests for an average of 2.5 years (range 11 months to 4 years). Mixed-model analyses were used to separately examine the effects of practice and age on test performance. Number of prior assessments (practice) was associated with significant performance improvement across assessments, whereas older age was associated with significant decline in performance. The groups did not differ significantly in extent of age-related cognitive decline, but a three-way interaction among group, age, and practice was found, such that greater age-related decline in practice effects were found for older people with schizophrenia relative to nonpsychiatric participants. This study did not find any evidence of neurodegenerative age-related decline in neuropsychological abilities in middle-aged and older people with schizophrenia, but older age was associated with diminished ability to benefit from repeated exposure to cognitive tasks in people with schizophrenia. Cognitive impairment in schizophrenia may combine with cognitive decline associated with normal aging to reduce practice effects in older patients. These findings have important implications for the design of studies examining the longitudinal trajectory of cognitive functioning across the life span of people with schizophrenia, as well as clinical trials that attempt to demonstrate cognitive enhancement in these individuals. Copyright 2010 APA, all rights reserved.

Interplay between financial assets and social relations on decline in physical function and mortality among older people.

PubMed

Jørgensen, Terese Sara Høj; Lund, Rikke; Siersma, Volkert Dirk; Nilsson, Charlotte Juul

2018-06-01

It is well established that socioeconomic position (SEP) and social relations impact physical function and mortality in old age. Due to differential vulnerability, few social relations may lead to greater decline in physical function and mortality among older people with low compared to high SEP. The aim was to investigate whether older people with few social relations experience greater decline in physical function and mortality when also subject to low financial assets? The study population included 4060 older people aged 75 or 80 years at baseline in 1998-1999. Social relations at baseline and physical function at baseline and after 1.5, 3.0 and 4.5 years were obtained from questionnaires. Financial assets at baseline and mortality during 10 years of follow-up were obtained from registers. Analyses of the associations between financial assets combined with social relations and decline in physical function and mortality, respectively, were conducted. Among males, but not females, low financial assets and few social relations were associated with the greatest decline in physical function. Yet, interaction only reached significance between financial assets and visits. Among males and females, low financial assets and few social relations were associated with the highest mortality. Interactions only reached significance between financial assets and visits for females and social activity for males. In conclusion, few social relations implied greater decline in physical function among older males and higher mortality among older males and females with low financial assets; however, the study only supports the presence of differential vulnerability for visits and social activity.

Cohort Differences in Cognitive Aging and Terminal Decline in the Seattle Longitudinal Study

PubMed Central

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 differences in the rate of cognitive aging and if, at the very end of life, pervasive mortality-related processes overshadow and minimize cohort differences. We used data on 5 primary mental abilities from the Seattle Longitudinal Study (Schaie, 2005) to compare both age-related and mortality-related changes between earlier born cohorts (1886–1913) and later born cohorts (1914–1948). Our models covary for several individual and cohort differences in central indicators of life expectancy, education, health, and gender. Age-related growth models corroborate and extend earlier findings by documenting level differences at age 70 of up to 0.50 SD and less steep rates of cognitive aging on all abilities between 50 and 80 years of age favoring the later born cohort. In contrast, mortality-related models provide limited support for positive cohort differences. The later born cohort showed steeper mortality-related declines. We discuss possible reasons why often reported positive secular trends in age-related processes may not generalize to the vulnerable segment of the population that is close to death and suggest routes for further inquiry. PMID:21517155

An hypothesis: the dramatic decline in heart attacks in the United States is temporally related to the decline in duodenal ulcer disease and Helicobacter pylori infection.

PubMed

Hughes, William S

2014-06-01

Studies of autopsies of military members dying in three US wars indicate that the prevalence of atherosclerosis in successive cohorts of healthy young men and women has dramatically decreased over the past half century. The objective of this study was to compare the decline in the prevalence of atherosclerosis and myocardial infarction with previously published studies on the decline in the prevalence of duodenal ulcer. A plot of the prevalence of coronary atherosclerosis and the prevalence of myocardial infarction in three cohorts of young men and women born from 1930 to 1980 was constructed. The figure shows a marked decline in prevalence in atherosclerosis beginning in a military cohort born around 1930 and a similar marked decline in prevalence of myocardial infarction in the US population beginning in 1970. In published studies duodenal ulcer began to decline in prevalence in 1960. As duodenal ulcers began to occur at age 30 and myocardial infarctions began to occur at age 40 at the time of peak prevalence, the cohort born in 1930 was the first to experience a decline in prevalence of both duodenal ulcer and heart attacks. The study shows that the decline in heart attacks is temporally related to the decline in duodenal ulcer and by inference, Helicobacter pylori infection. © 2014 John Wiley & Sons Ltd.

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

PubMed

Phoenix, Cassandra; Smith, Brett

2011-09-01

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

AGED DOMINANT NEGATIVE p38α MAPK MICE ARE RESISTANT TO AGE-DEPENDENT DECLINE IN ADULT-NEUROGENESIS AND CONTEXT DISCRIMINATION FEAR CONDITIONING

PubMed Central

Cortez, IbDanelo; Bulavin, Dmitry V.; Wu, Ping; McGrath, Erica L; Cunningham, Kathryn A; Wakamiya, Maki; Papaconstantinou, John; Dineley, Kelly T

2018-01-01

A major aspect of mammalian aging is the decline in functional competence of many self-renewing cell types, including adult-born neuronal precursors. Since age-related senescence of self-renewal occurs simultaneously with chronic up-regulation of the p38MAPKalpha (p38α) signaling pathway, we used the dominant negative mouse model for attenuated p38α activity (DN-p38αAF/+ ) in which Thr180 and Tyr182 are mutated (T→A/Y→F) to prevent phosphorylation activation (DN-p38αAF/+) and kinase activity. As a result, aged DN-p38αAF/+ mice are resistant to age-dependent decline in proliferation and regeneration of several peripheral tissue progenitors when compared to wild-type littermates. Aging is the major risk factor for non-inherited forms of Alzheimer’s disease (AD); environmental and genetic risk factors that accelerate the senescence phenotype are thought to contribute to an individual’s relative risk. In the present study, we evaluated aged DN-p38αAF/+ and wildtype littermates in a series of behavioral paradigms to test if p38α mutant mice exhibit altered baseline abnormalities in neurological reflexes, locomotion, anxiety-like behavior, and age-dependent cognitive decline. While aged DN-p38αAF/+ and wildtype littermates appear equal in all tested baseline neurological and behavioral parameters, DN-p38αAF/+ exhibit superior context discrimination fear conditioning. Context discrimination is a cognitive task that is supported by proliferation and differentiation of adult-born neurons in the dentate gyrus of the hippocampus. Consistent with enhanced context discrimination in aged DN-p38αAF/+, we discovered enhanced production of adult-born neurons in the dentate gyrus of DN-p38αAF/+ mice compared to wildtype littermates. Our findings support the notion that p38α inhibition has therapeutic utility in aging diseases that affect cognition, such as AD. PMID:27765672

Aged dominant negative p38α MAPK mice are resistant to age-dependent decline in adult-neurogenesis and context discrimination fear conditioning.

PubMed

Cortez, IbDanelo; Bulavin, Dmitry V; Wu, Ping; McGrath, Erica L; Cunningham, Kathryn A; Wakamiya, Maki; Papaconstantinou, John; Dineley, Kelly T

2017-03-30

A major aspect of mammalian aging is the decline in functional competence of many self-renewing cell types, including adult-born neuronal precursors. Since age-related senescence of self-renewal occurs simultaneously with chronic up-regulation of the p38MAPKalpha (p38α) signaling pathway, we used the dominant negative mouse model for attenuated p38α activity (DN-p38α AF/+ ) in which Thr180 and Tyr182 are mutated (T→A/Y→F) to prevent phosphorylation activation (DN-p38α AF/+ ) and kinase activity. As a result, aged DN-p38α AF/+ mice are resistant to age-dependent decline in proliferation and regeneration of several peripheral tissue progenitors when compared to wild-type littermates. Aging is the major risk factor for non-inherited forms of Alzheimer's disease (AD); environmental and genetic risk factors that accelerate the senescence phenotype are thought to contribute to an individual's relative risk. In the present study, we evaluated aged DN-p38α AF/+ and wildtype littermates in a series of behavioral paradigms to test if p38α mutant mice exhibit altered baseline abnormalities in neurological reflexes, locomotion, anxiety-like behavior, and age-dependent cognitive decline. While aged DN-p38α AF/+ and wildtype littermates appear equal in all tested baseline neurological and behavioral parameters, DN-p38α AF/+ exhibit superior context discrimination fear conditioning. Context discrimination is a cognitive task that is supported by proliferation and differentiation of adult-born neurons in the dentate gyrus of the hippocampus. Consistent with enhanced context discrimination in aged DN-p38α AF/+ , we discovered enhanced production of adult-born neurons in the dentate gyrus of DN-p38α AF/+ mice compared to wildtype littermates. Our findings support the notion that p38α inhibition has therapeutic utility in aging diseases that affect cognition, such as AD. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Education does not slow cognitive decline with aging: 12-year evidence from the victoria longitudinal study.

PubMed

Zahodne, Laura B; Glymour, M Maria; Sparks, Catharine; Bontempo, Daniel; Dixon, Roger A; MacDonald, Stuart W S; Manly, Jennifer J

2011-11-01

Although the relationship between education and cognitive status is well-known, evidence regarding whether education moderates the trajectory of cognitive change in late life is conflicting. Early studies suggested that higher levels of education attenuate cognitive decline. More recent studies using improved longitudinal methods have not found that education moderates decline. Fewer studies have explored whether education exerts different effects on longitudinal changes within different cognitive domains. In the present study, we analyzed data from 1014 participants in the Victoria Longitudinal Study to examine the effects of education on composite scores reflecting verbal processing speed, working memory, verbal fluency, and verbal episodic memory. Using linear growth models adjusted for age at enrollment (range, 54-95 years) and gender, we found that years of education (range, 6-20 years) was strongly related to cognitive level in all domains, particularly verbal fluency. However, education was not related to rates of change over time for any cognitive domain. Results were similar in individuals older or younger than 70 at baseline, and when education was dichotomized to reflect high or low attainment. In this large longitudinal cohort, education was related to cognitive performance but unrelated to cognitive decline, supporting the hypothesis of passive cognitive reserve with aging.

Dietary enrichment with medium chain triglycerides (AC-1203) elevates polyunsaturated fatty acids in the parietal cortex of aged dogs: implications for treating age-related cognitive decline.

PubMed

Taha, Ameer Y; Henderson, Samuel T; Burnham, W M

2009-09-01

Dogs demonstrate an age-related cognitive decline, which may be related to a decrease in the concentration of omega-3 polyunsaturated fatty acids (n-3 PUFA) in the brain. Medium chain triglycerides (MCT) increase fatty acid oxidation, and it has been suggested that this may raise brain n-3 PUFA levels by increasing mobilization of n-3 PUFA from adipose tissue to the brain. The goal of the present study was to determine whether dietary MCT would raise n-3 PUFA concentrations in the brains of aged dogs. Eight Beagle dogs were randomized to a control diet (n = 4) or an MCT (AC-1203) enriched diet (n = 4) for 2 months. The animals were then euthanized and the parietal cortex was removed for phospholipid, cholesterol and fatty acid determinations by gas-chromatography. Dietary enrichment with MCT (AC-1203) resulted in a significant increase in brain phospholipid and total lipid concentrations (P < 0.05). In particular, n-3 PUFA within the phospholipid, unesterified fatty acid, and total lipid fractions were elevated in AC-1203 treated subjects as compared to controls (P < 0.05). Brain cholesterol concentrations did not differ significantly between the groups (P > 0.05). These results indicate that dietary enrichment with MCT, raises n-3 PUFA concentrations in the parietal cortex of aged dogs.

Senescent Cells: A Novel Therapeutic Target for Aging and Age-Related Diseases

PubMed Central

Naylor, RM; Baker, DJ; van Deursen, JM

2014-01-01

Aging is the main risk factor for most chronic diseases, disabilities, and declining health. It has been proposed that senescent cells—damaged cells that have lost the ability to divide—drive the deterioration that underlies aging and age-related diseases. However, definitive evidence for this relationship has been lacking. The use of a progeroid mouse model (which expresses low amounts of the mitotic checkpoint protein BubR1) has been instrumental in demonstrating that p16Ink4a-positive senescent cells drive age-related pathologies and that selective elimination of these cells can prevent or delay age-related deterioration. These studies identify senescent cells as potential therapeutic targets in the treatment of aging and age-related diseases. Here, we describe how senescent cells develop, the experimental evidence that causally implicates senescent cells in age-related dysfunction, the chronic diseases and disorders that are characterized by the accumulation of senescent cells at sites of pathology, and the therapeutic approaches that could specifically target senescent cells. PMID:23212104

Decline in semicircular canal and otolith function with age

PubMed Central

Agrawal, Yuri; Zuniga, M. Geraldine; Davalos-Bichara, Marcela; Schubert, Michael C.; Walston, Jeremy D.; Hughes, Jennifer; Carey, John P.

2012-01-01

Objective To characterize the physiologic nature of the vestibular dysfunction that occurs with the normative aging process. Study design Cross-sectional study. Setting Tertiary care academic medical center. Patients Fifty individuals age 70 and above. Interventions Head thrust dynamic visual acuity testing (htDVA) and cervical and ocular vestibular-evoked myogenic potential (VEMP) testing. Main Outcome Measures Semicircular canal function measured by htDVA in each of the three semicircular canal planes, and saccular and utricular function measured by cVEMP and oVEMP testing, respectively. Results We observed significant declines in semicircular canal function in each of the canal planes as well as otolith function associated with aging. We found that individuals with impaired horizontal and superior semicircular canal function were likely to also have concomitant deficits in utricular but not saccular function. Overall, we noted that the prevalence of semicircular canal dysfunction was highest followed by saccular then utricular impairment, although we did observe individuals with isolated otolith deficits. Conclusions These data suggest an overall decline in semicircular canal as well as otolith function associated with aging, although the magnitude of impairment was greater for the semicircular canals than the otoliths in this elderly population. A better understanding of the specific vestibular deficits that occur with aging can inform the development of rational screening, vestibular rehabilitation and fall risk reduction strategies in older individuals. PMID:22699991

Verbal Memory Declines More Rapidly with Age in HIV Infected versus Uninfected Adults

PubMed Central

Seider, Talia R.; Luo, Xi; Gongvatana, Assawin; Devlin, Kathryn N.; de la Monte, Suzanne M.; Chasman, Jesse D.; Yan, Peisi; Tashima, Karen T.; Navia, Bradford; Cohen, Ronald A.

2015-01-01

Objectives In the current era of effective antiretroviral treatment, the number of older adults living with HIV is rapidly increasing. This study investigated the combined influence of age and HIV infection on longitudinal changes in verbal and visuospatial learning and memory. Methods In this longitudinal, case-control design, 54 HIV seropositive and 30 seronegative individuals aged 40–74 received neurocognitive assessments at baseline visits and again one year later. Assessment included tests of verbal and visuospatial learning and memory. Linear regression was used to predict baseline performance and longitudinal change on each test using HIV serostatus, age, and their interaction as predictors. MANOVA was used to assess the effects of these predictors on overall baseline performance and overall longitudinal change. Results The interaction of HIV and age significantly predicted longitudinal change in verbal memory performance, as did HIV status, indicating that although the seropositive group declined more than the seronegative group overall, the rate of decline depended on age such that greater age was associated with a greater decline in this group. The regression models for visuospatial learning and memory were significant at baseline, but did not predict change over time. HIV status significantly predicted overall baseline performance and overall longitudinal change. Conclusions This is the first longitudinal study focused on the effects of age and HIV on memory. Findings suggest that age and HIV interact to produce larger declines in verbal memory over time. Further research is needed to gain a greater understanding of the effects of HIV on the aging brain. PMID:24645772

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.

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

PubMed

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

2016-01-01

To investigate the association between sleep-related characteristics and cognitive change over 3 years of follow up in an aged population. 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. 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. 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. © 2016 Associated Professional Sleep Societies, LLC.

Peptidylarginine deiminase 4 promotes age-related organ fibrosis

PubMed Central

Erpenbeck, Luise; Savchenko, Alexander; Hayashi, Hideki; Cherpokova, Deya; Gallant, Maureen; Mauler, Maximilian; Cifuni, Stephen M.

2017-01-01

Aging promotes inflammation, a process contributing to fibrosis and decline in organ function. The release of neutrophil extracellular traps (NETs [NETosis]), orchestrated by peptidylarginine deiminase 4 (PAD4), damages organs in acute inflammatory models. We determined that NETosis is more prevalent in aged mice and investigated the role of PAD4/NETs in age-related organ fibrosis. Reduction in fibrosis was seen in the hearts and lungs of aged PAD4−/− mice compared with wild-type (WT) mice. An increase in left ventricular interstitial collagen deposition and a decline in systolic and diastolic function were present only in WT mice, and not in PAD4−/− mice. In an experimental model of cardiac fibrosis, cardiac pressure overload induced NETosis and significant platelet recruitment in WT but not PAD4−/− myocardium. DNase 1 was given to assess the effects of extracellular chromatin. PAD4 deficiency or DNase 1 similarly protected hearts from fibrosis. We propose a role for NETs in cardiac fibrosis and conclude that PAD4 regulates age-related organ fibrosis and dysfunction. PMID:28031479

Probability of treatment following acute decline in lung function in children with cystic fibrosis is related to baseline pulmonary function.

PubMed

Morgan, Wayne J; Wagener, Jeffrey S; Yegin, Ashley; Pasta, David J; Millar, Stefanie J; Konstan, Michael W

2013-10-01

To determine whether the association between high forced expiratory volume in 1 second (FEV1) and increased rate of decline in FEV1 in children with cystic fibrosis could be due to less frequent intervention after acute declines (sudden decline events) in FEV1. Patients with cystic fibrosis aged 6-17 years enrolled in the Epidemiologic Study of Cystic Fibrosis were assessed for a sudden decline event, defined as a 10% relative decline in FEV1% predicted from an average of 3 consecutive stable baseline spirometries. The likelihood of therapeutic intervention within 14 days before and 56 days after this event was then related to their baseline FEV1% predicted age-specific decile using a logistic regression adjusting for age group (6-12 years, 13-17 years) and presence of Pseudomonas aeruginosa on respiratory culture. A total of 10 888 patients had at least 1 sudden decline event in FEV1. Patients in the highest FEV1 decile were significantly less likely than those in the lowest decile to receive intravenous antibiotics (OR, 0.14; 95% CI, 0.11-0.18; P < .001) or be hospitalized (OR, 0.18; 95% CI, 0.14-0.23; P < .001) following decline. Children and adolescents with high baseline lung function are less likely to receive a therapeutic intervention following an acute decline in FEV1, which may explain their greater rate of FEV1 decline. Copyright © 2013 Mosby, Inc. All rights reserved.

Caloric restriction impedes age-related decline of mitochondrial function and neuronal activity

PubMed Central

Lin, Ai-Ling; Coman, Daniel; Jiang, Lihong; Rothman, Douglas L; Hyder, Fahmeed

2014-01-01

Caloric restriction (CR) prolongs lifespan and retards many detrimental effects of aging, but its effect on brain mitochondrial function and neuronal activity—especially in healthy aging—remains unexplored. Here we measured rates of neuronal glucose oxidation and glutamate–glutamine neurotransmitter cycling in young control, old control (i.e., healthy aging), and old CR rats using in vivo nuclear magnetic resonance spectroscopy. We found that, compared with the young control, neuronal energy production and neurotransmission rates were significantly reduced in healthy aging, but were preserved in old CR rats. The results suggest that CR mitigated the age-related deceleration of brain physiology. PMID:24984898

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

PubMed

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

2014-12-30

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

Mathematical modelling of decline in follicle pool during female reproductive ageing.

PubMed

Thilagam, Alagu

2016-03-01

The factors which govern the subtle links between follicle loss and mammalian female reproductive ageing remain unclear despite extensive studies undertaken to understand the critical physiological and biochemical mechanisms that underly the accelerated decline in follicle numbers in women older than 37 years. It is not certain whether there is a sole control by the ovary or whether other factors which affect ageing also intersect with the ovarian effect. There is convincing experimental evidence for an interplay of several processes that seem to influence the follicle loss-female reproductive ageing links, with specific hormones (follicle-stimulating hormone, anti-Müllerian hormone, dehydroepiandrosterone) noted to play important roles in follicular dynamics and ovarian ageing. In this work, we examine the subtle links between the rate of follicular decline with ageing and the role of hormones via a series of non-autonomous equations. Simulation results based on the time evolution of the number of ovarian follicles and biochemical changes in the ovarian environment influenced by hormone levels is compared with empirical data based on follicle loss-reproductive ageing correlation studies. © Crown copyright 2015.

Declines in arrestin and rhodopsin in the macula with progression of age-related macular degeneration.

PubMed

Ethen, Cheryl M; Feng, Xiao; Olsen, Timothy W; Ferrington, Deborah A

2005-03-01

Biochemical analysis of age-related macular degeneration (AMD) at distinct stages of the disease will help further understanding of the molecular events associated with disease progression. This study was conducted to determine the ability of a new grading system for eye bank eyes, the Minnesota Grading System (MGS), to discern distinct stages of AMD so that retinal region-specific changes in rod photoreceptor protein expression from donors could be determined. Donor eyes were assigned to a specific level of AMD by using the MGS. Expression of the rod photoreceptor proteins rhodopsin and arrestin was evaluated by Western immunoblot analysis in the macular and peripheral regions of the neurosensory retina from donors at different stages of AMD. A significant linear decline in both arrestin and rhodopsin content correlated with progressive MGS levels in the macula. In contrast, the peripheral region showed no significant correlation between MGS level and the content of either protein. The statistically significant relationship between decreasing macular rod photoreceptor proteins and progressive MGS levels of AMD demonstrates the utility of the clinically based MGS to correspond with specific protein changes found at known, progressive stages of degeneration. Future biochemical analysis of clinically characterized donor eyes will further understanding of the pathobiochemistry of AMD.

DNA-PK Promotes the Mitochondrial, Metabolic, and Physical Decline that Occurs During Aging.

PubMed

Park, Sung-Jun; Gavrilova, Oksana; Brown, Alexandra L; Soto, Jamie E; Bremner, Shannon; Kim, Jeonghan; Xu, Xihui; Yang, Shutong; Um, Jee-Hyun; Koch, Lauren G; Britton, Steven L; Lieber, Richard L; Philp, Andrew; Baar, Keith; Kohama, Steven G; Abel, E Dale; Kim, Myung K; Chung, Jay H

2017-05-02

Hallmarks of aging that negatively impact health include weight gain and reduced physical fitness, which can increase insulin resistance and risk for many diseases, including type 2 diabetes. The underlying mechanism(s) for these phenomena is poorly understood. Here we report that aging increases DNA breaks and activates DNA-dependent protein kinase (DNA-PK) in skeletal muscle, which suppresses mitochondrial function, energy metabolism, and physical fitness. DNA-PK phosphorylates threonines 5 and 7 of HSP90α, decreasing its chaperone function for clients such as AMP-activated protein kinase (AMPK), which is critical for mitochondrial biogenesis and energy metabolism. Decreasing DNA-PK activity increases AMPK activity and prevents weight gain, decline of mitochondrial function, and decline of physical fitness in middle-aged mice and protects against type 2 diabetes. In conclusion, DNA-PK is one of the drivers of the metabolic and fitness decline during aging, and therefore DNA-PK inhibitors may have therapeutic potential in obesity and low exercise capacity. Published by Elsevier Inc.

Left Ventricular Hypertrophy and Cognitive Decline in Old Age.

PubMed

Mahinrad, Simin; Vriend, Annelotte E; Jukema, J Wouter; van Heemst, Diana; Sattar, Naveed; Blauw, Gerard Jan; Macfarlane, Peter W; Clark, Elaine N; de Craen, Anton J M; Sabayan, Behnam

2017-01-01

Patients with advanced heart failure run a greater risk of dementia. Whether early cardiac structural changes also associate with cognitive decline is yet to be determined. We tested whether left ventricular hypertrophy (LVH) derived from electrocardiogram associates with cognitive decline in older subjects at risk of cardiovascular disease. We included 4,233 participants (mean age 75.2 years, 47.8% male) from PROSPER (PROspective Study of Pravastatin in the Elderly at Risk). LVH was assessed from baseline electrocardiograms by measuring the Sokolow-Lyon index. Higher levels of Sokolow-Lyon index indicate higher degrees of LVH. Cognitive domains involving selective attention, processing speed, and immediate and delayed memory were measured at baseline and repeated during a mean follow-up of 3.2 years. At baseline, LVH was not associated with worse cognitive function. During follow-up, participants with higher levels of LVH had a steeper decline in cognitive function including in selective attention (p = 0.009), processing speed (p = 0.010), immediate memory (p < 0.001), and delayed memory (p = 0.002). These associations were independent of cardiovascular risk factors, co-morbidities, and medications. LVH assessed by electrocardiogram associates with steeper decline in cognitive function of older subjects independent of cardiovascular risk factors and co-morbidities. This study provides further evidence on the link between subclinical cardiac structural changes and cognitive decline in older subjects.

Some economic consequences of an ageing and declining population in Denmark.

PubMed

Leeson, G W

1983-01-01

Figures for 1981 indicate that Denmark has a fertility level of 1.45 which has been below replacement level since 1968. In that same time period, natural increase has decreased from over 27,000 in 1968 to only 1354 in 1980 and a negative natural increase in 1981 with deaths outnumbering births by 3001. Even during the depression in the 1930's, net population increase was between 6-9/1000 with a fertility level which hovered around replacement level. At that time, the number of females in the childbearing ages was enough to provide population growth, whereas the number is much less today. Population increase is only 0.3/1000. The national population projections for Denmark for 1981-2010 assume an increase in the fertility level from 1.45-1.70 by 1991 after which it remains constant. The number of 20-39 year olds increased steadily until 1945 after which there was a decline as the cohorts from periods with low fertility levels entered this age group, but this was again followed by a steady increase to the present day. The number of females aged 0-39 years is expected to decrease in all age groups to the year 2000. Those aged 40-59 increased in numbers from 1920 to the mid 1960s, since then they have decreased in number, but an increase is forcast for the remainder of the century. The number of elderly females also increased steadily from 1930-80, from about 200,000 to over 550,000; this is expected to continue until 1990 when a short-term decline will set in. Regarding the economic and social consequences of these trends, it is shown that the present decline in fertility has its origins in a period of low unemployment and its negative growth while there was still relatively low unemployment and economic growth. In 1973 the unemployed rate was 0.9% of the work force and this rose to 9.2% in 1981. The Danish population has aged from one with 1/4 million people aged 60 and over at the turn of the century to about 1 million of that age today. Also, the aged themselves

Age-related slowing of digit symbol substitution revisited: what do longitudinal age changes reflect?

PubMed

MacDonald, Stuart W S; Hultsch, David F; Strauss, Esther; Dixon, Roger A

2003-05-01

A previous investigation reported that cross-sectional age differences in Digit Symbol Substitution (DSS) test performance reflect declines in perceptual processing speed. Support for the tenability of the processing speed hypothesis requires examining whether longitudinal age-related change in DSS performance is largely mediated by changes in speed. The present study used data from the Victoria Longitudinal Study to examine patterns and predictors of longitudinal change in DSS for 512 older adults (M(age) = 68.37 years, SD = 7.43). On the basis of multilevel modeling, baseline DSS performance was poorer for older participants and men, with longitudinal declines more pronounced with increasing age and decreasing speed. In contrast to the present cross-sectional findings, statistical control of change trajectories in perceptual speed using the same data did not substantially attenuate age changes. These discrepancies suggest different sources of variance may underlie cross-sectional age differences and longitudinal age changes for DSS.

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. (c) 2015 APA, all rights reserved).

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

The use of films to simulate age-related declines in yellow vision.

PubMed

Yoshida, C A; Sakuraba, S

1996-06-01

One of characteristics of normal age-related vision losses depends on yellow-intensity in the lens of the eye. (1) We investigated discrimination between seven intensities of yellow in 303 elderly people aged from late 60s to early 90s. The results demonstrated that the failures of vision increase with age, and the losses depend on yellow intensity. (2) We got a yellow index (YI) from different Y-intensity color charts used in (I) above, covering 12 kinds of marketable yellow films, and selected two kinds of films which match (YI) original color charts, corresponding to 53% or 89% of Y intensity. (3) Finally, we judged that all of these colors' xy-chromaticities with or without the two films, were exactly on the unique-yellow line in the diagram, which means a pure yellow, not mixed. (4) Then, these two films could simulate each of the mid-level or high-level Y intensity, respectively, in age-related vision. (5) We analyzed changes of all kinds of colors (220) in xy-chromaticity diagrams and obtained mean changing distances from every original chromatogram compared to the others. These data would be useful for architects or designers to design cities or buildings for use by the elderly.

Aging Exacerbates Obesity-induced Cerebromicrovascular Rarefaction, Neurovascular Uncoupling, and Cognitive Decline in Mice

PubMed Central

Tucsek, Zsuzsanna; Toth, Peter; Tarantini, Stefano; Sosnowska, Danuta; Gautam, Tripti; Warrington, Junie P.; Giles, Cory B.; Wren, Jonathan D.; Koller, Akos; Ballabh, Praveen; Sonntag, William E.; Csiszar, Anna

2014-01-01

Epidemiological studies show that obesity has deleterious effects on the brain and cognitive function in the elderly population. However, the specific mechanisms through which aging and obesity interact to promote cognitive decline remain unclear. To test the hypothesis that aging exacerbates obesity-induced cerebromicrovascular impairment, we compared young (7 months) and aged (24 months) high-fat diet–fed obese C57BL/6 mice. We found that aging exacerbates the obesity-induced decline in microvascular density both in the hippocampus and in the cortex. The extent of hippocampal microvascular rarefaction and the extent of impairment of hippocampal-dependent cognitive function positively correlate. Aging exacerbates obesity-induced loss of pericyte coverage on cerebral microvessels and alters hippocampal angiogenic gene expression signature, which likely contributes to microvascular rarefaction. Aging also exacerbates obesity-induced oxidative stress and induction of NADPH oxidase and impairs cerebral blood flow responses to whisker stimulation. Collectively, obesity exerts deleterious cerebrovascular effects in aged mice, promoting cerebromicrovascular rarefaction and neurovascular uncoupling. The morphological and functional impairment of the cerebral microvasculature in association with increased blood–brain barrier disruption and neuroinflammation (Tucsek Z, Toth P, Sosnowsk D, et al. Obesity in aging exacerbates blood–brain barrier disruption, neuroinflammation and oxidative stress in the mouse hippocampus: effects on expression of genes involved in beta-amyloid generation and Alzheimer’s disease. J Gerontol Biol Med Sci. 2013. In press, PMID: 24269929) likely contribute to obesity-induced cognitive decline in aging. PMID:24895269

Developmental decline in height growth in Douglas-fir.

Treesearch

Barbara J. Bond; Nicole M. Czarnomski; Clifton Cooper; Michael E. Day; Michael S. Greenwood

2007-01-01

The characteristic decline in height growth that occurs over a tree's lifespan is often called "age-related decline." But is the reduction in height growth in aging trees a function of age or of size? We grafted shoot tips across different ages and sizes of Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) trees to determine whether...

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. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Demographic and clinical characteristics related to cognitive decline in Alzheimer disease in China: A multicenter survey from 2011 to 2014.

PubMed

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

2016-06-01

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.

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

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.

Fertility Decline, Gender Composition of Families, and Expectations of Old Age Support.

PubMed

Allendorf, Keera

2015-08-01

Recent fertility declines in non-Western countries may have the potential to transform gender systems. One pathway for such transformations is the creation of substantial proportions of families with children of only one gender. Such families, particularly those with only daughters, may facilitate greater symmetry between sons and daughters. This article explores whether such shifts may influence gendered expectations of old age support. In keeping with patriarchal family systems, old age support is customarily provided by sons, but not daughters, in India. Using data from the 2005 Indian Human Development Survey, I find that women with sons overwhelmingly expect old age support from a son. By contrast, women with only daughters largely expect support from a daughter or a source besides a child. These findings suggest that fertility decline may place demographic pressure on gendered patterns of old age support and the gender system more broadly.

Fertility Decline, Gender Composition of Families, and Expectations of Old Age Support

PubMed Central

Allendorf, Keera

2017-01-01

Recent fertility declines in non-Western countries may have the potential to transform gender systems. One pathway for such transformations is the creation of substantial proportions of families with children of only one gender. Such families, particularly those with only daughters, may facilitate greater symmetry between sons and daughters. This article explores whether such shifts may influence gendered expectations of old age support. In keeping with patriarchal family systems, old age support is customarily provided by sons, but not daughters, in India. Using data from the 2005 Indian Human Development Survey, I find that women with sons overwhelmingly expect old age support from a son. By contrast, women with only daughters largely expect support from a daughter or a source besides a child. These findings suggest that fertility decline may place demographic pressure on gendered patterns of old age support and the gender system more broadly. PMID:28344373

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

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.

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

PubMed

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

2007-12-01

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

Idiom understanding in adulthood: examining age-related differences.

PubMed

Hung, Pei-Fang; Nippold, Marilyn A

2014-03-01

Idioms are figurative expressions such as hold your horses, kick the bucket, and lend me a hand, which commonly occur in everyday spoken and written language. Hence, the understanding of these expressions is essential for daily communication. In this study, we examined idiom understanding in healthy adults in their 20s, 40s, 60s and 80s (n=30 per group) to determine if performance would show an age-related decline. Participants judged their own familiarity with a set of 20 idioms, explained the meaning of each, described a situation in which the idiom could be used, and selected the appropriate interpretation from a set of choices. There was no evidence of an age-related decline on any tasks. Rather, the 60s group reported greater familiarity and offered better explanations than did the 20s group. Moreover, greater familiarity with idioms was associated with better understanding in adults.

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

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.

Age-related white matter integrity differences in oldest-old without dementia.

PubMed

Bennett, Ilana J; Greenia, Dana E; Maillard, Pauline; Sajjadi, S Ahmad; DeCarli, Charles; Corrada, Maria M; Kawas, Claudia H

2017-08-01

Aging is known to have deleterious effects on cerebral white matter, yet little is known about these white matter alterations in advanced age. In this study, 94 oldest-old adults without dementia (90-103 years) underwent diffusion tensor imaging to assess relationships between chronological age and multiple measures of integrity in 18 white matter regions across the brain. Results revealed significant age-related declines in integrity in regions previously identified as being sensitive to aging in younger-old adults (corpus callosum, fornix, cingulum, external capsule). For the corpus callosum, the effect of age on genu fractional anisotropy was significantly weaker than the relationship between age and splenium fractional anisotropy. Importantly, age-related declines in white matter integrity did not differ in cognitively normal and cognitively impaired not demented oldest-old, suggesting that they were not solely driven by cognitive dysfunction or preclinical dementia in this advanced age group. Instead, white matter in these regions appears to remain vulnerable to normal aging processes through the 10th decade of life. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Joint dysfunction and functional decline in middle age myostatin null mice.

PubMed

Guo, Wen; Miller, Andrew D; Pencina, Karol; Wong, Siu; Lee, Amanda; Yee, Michael; Toraldo, Gianluca; Jasuja, Ravi; Bhasin, Shalender

2016-02-01

Since its discovery as a potent inhibitor for muscle development, myostatin has been actively pursued as a drug target for age- and disease-related muscle loss. However, potential adverse effects of long-term myostatin deficiency have not been thoroughly investigated. We report herein that male myostatin null mice (mstn(-/-)), in spite of their greater muscle mass compared to wild-type (wt) mice, displayed more significant functional decline from young (3-6months) to middle age (12-15months) than age-matched wt mice, measured as gripping strength and treadmill endurance. Mstn(-/-) mice displayed markedly restricted ankle mobility and degenerative changes of the ankle joints, including disorganization of bone, tendon and peri-articular connective tissue, as well as synovial thickening with inflammatory cell infiltration. Messenger RNA expression of several pro-osteogenic genes was higher in the Achilles tendon-bone insertion in mstn(-/-) mice than wt mice, even at the neonatal age. At middle age, higher plasma concentrations of growth factors characteristic of excessive bone remodeling were found in mstn(-/-) mice than wt controls. These data collectively indicate that myostatin may play an important role in maintaining ankle and wrist joint health, possibly through negative regulation of the pro-osteogenic WNT/BMP pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Negative Perceptions of Aging and Decline in Walking Speed: A Self-Fulfilling Prophecy

PubMed Central

Robertson, Deirdre A.; Savva, George M.; King-Kallimanis, Bellinda L.; Kenny, Rose Anne

2015-01-01

Introduction Walking speed is a meaningful marker of physical function in the aging population. While it is a primarily physical measure, experimental studies have shown that merely priming older adults with negative stereotypes about aging results in immediate declines in objective walking speed. What is not clear is whether this is a temporary experimental effect or whether negative aging stereotypes have detrimental effects on long term objective health. We sought to explore the association between baseline negative perceptions of aging in the general population and objective walking speed 2 years later. Method 4,803 participations were assessed over 2 waves of The Irish Longitudinal Study on Ageing (TILDA), a prospective, population representative study of adults aged 50+ in the Republic of Ireland. Wave 1 measures – which included the Aging Perceptions Questionnaire, walking speed and all covariates - were taken between 2009 and 2011. Wave 2 measures – which included a second measurement of walking speed and covariates - were collected 2 years later between March and December 2012. Walking speed was measured as the number of seconds to complete the Timed Up-And-Go (TUG) task. Participations with a history of stroke, Parkinson’s disease or an MMSE < 18 were excluded. Results After full adjustment for all covariates (age, gender, level of education, disability, chronic conditions, medications, global cognition and baseline TUG) negative perceptions of aging at baseline were associated with slower TUG speed 2 years later (B=.03, 95% CI = .01 to 05, p< .05). Conclusions Walking speed has previously been considered to be a consequence of physical decline but these results highlight the direct role of psychological state in predicting an objective aging outcome. Negative perceptions about aging are a potentially modifiable risk factor of some elements of physical decline in aging. PMID:25923334

Vitamin K Status Is not Associated with Cognitive Decline in Middle Aged Adults.

PubMed

van den Heuvel, E G H M; van Schoor, N M; Vermeer, C; Zwijsen, R M L; den Heijer, M; Comijs, H C

2015-11-01

The aim of this study was to examine the association between dephospho-uncarboxylated matrix Gla protein (dp-ucMGP), an indicator of vitamin K status, and cognitive decline, and the modifying role of 25(OH)D. Longitudinal study with six years follow-up. Community based. 599 participants of the Longitudinal Aging Study Amsterdam (aged 55-65 years). Information processing speed and a composite Z-score by combining three domains of cognition reflecting general cognitive functioning. Generalized estimating equations (GEE) showed no significant associations between dp-ucMGP and decline in general cognitive functioning. Vitamin D modified the association between dp-ucMGP and speed of information processing (p<0.05). In the group with a 25(OH)D concentration > 50 nmol/l, the highest tertile of dp-ucMGP (>406 pmol/l), which corresponds to lower vitamin K levels, was associated with 1.5 higher score on information processing speed (p=0.023) as compared to the lowest tertile of dp-ucMGP. In contrast to our hypothesis, a suboptimal vitamin K was not associated with cognitive decline in middle-aged adults.

Hypertension, cerebrovascular impairment, and cognitive decline in aged AβPP/PS1 mice.

PubMed

Wiesmann, Maximilian; Zerbi, Valerio; Jansen, Diane; Lütjohann, Dieter; Veltien, Andor; Heerschap, Arend; Kiliaan, Amanda J

2017-01-01

Cardiovascular risk factors, especially hypertension, are also major risk factors for Alzheimer's disease (AD). To elucidate the underlying vascular origin of neurodegenerative processes in AD, we investigated the relation between systolic blood pressure (SBP) cerebral blood flow (CBF) and vasoreactivity with brain structure and function in a 16-18 months old double transgenic AβPP swe /PS1 dE9 (AβPP/PS1) mouse model for AD. These aging AβPP/PS1 mice showed an increased SBP linked to a declined regional CBF. Furthermore, using advanced MRI techniques, decline of functional and structural connectivity was revealed in the AD-like mice coupled to impaired cognition, increased locomotor activity, and anxiety-related behavior. Post mortem analyses demonstrated also increased neuroinflammation, and both decreased synaptogenesis and neurogenesis in the AβPP/PS1 mice. Additionally, deviant levels of fatty acids and sterols were present in the brain tissue of the AβPP/PS1 mice indicating maladapted brain fatty acid metabolism. Our findings suggest a link between increased SBP, decreased cerebral hemodynamics and connectivity in an AD mouse model during aging, leading to behavioral and cognitive impairments. As these results mirror the complex clinical symptomatology in the prodromal phase of AD, we suggest that this AD-like murine model could be used to investigate prevention and treatment strategies for early AD patients. Moreover, this study helps to develop more efficient therapies and diagnostics for this very early stage of AD.

Initial brain aging: heterogeneity of mitochondrial size is associated with decline in complex I-linked respiration in cortex and hippocampus.

PubMed

Thomsen, Kirsten; Yokota, Takashi; Hasan-Olive, Md Mahdi; Sherazi, Niloofar; Fakouri, Nima Borhan; Desler, Claus; Regnell, Christine Elisabeth; Larsen, Steen; Rasmussen, Lene Juel; Dela, Flemming; Bergersen, Linda Hildegard; Lauritzen, Martin

2018-01-01

Brain aging is accompanied by declining mitochondrial respiration. We hypothesized that mitochondrial morphology and dynamics would reflect this decline. Using hippocampus and frontal cortex of a segmental progeroid mouse model lacking Cockayne syndrome protein B (CSB m/m ) and C57Bl/6 (WT) controls and comparing young (2-5 months) to middle-aged mice (13-14 months), we found that complex I-linked state 3 respiration (CI) was reduced at middle age in CSB m/m hippocampus, but not in CSB m/m cortex or WT brain. In hippocampus of both genotypes, mitochondrial size heterogeneity increased with age. Notably, an inverse correlation between heterogeneity and CI was found in both genotypes, indicating that heterogeneity reflects mitochondrial dysfunction. The ratio between fission and fusion gene expression reflected age-related alterations in mitochondrial morphology but not heterogeneity. Mitochondrial DNA content was lower, and hypoxia-induced factor 1α mRNA was greater at both ages in CSB m/m compared to WT brain. Our findings show that decreased CI and increased mitochondrial size heterogeneity are highly associated and point to declining mitochondrial quality control as an initial event in brain aging. Copyright © 2017 Elsevier Inc. All rights reserved.

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…

An overall decline both in recollection and familiarity in healthy aging.

PubMed

Pitarque, Alfonso; Sales, Alicia; Meléndez, Juan C; Mayordomo, Teresa; Satorres, Encar

2015-01-01

In the area of recognition memory, the experimental data have been inconsistent about whether or not familiarity declines in healthy aging. A recent meta-analysis concluded that familiarity is impaired when estimated with the remember-know procedure, but not with the process-dissociation procedure. We present an associative recognition experiment with remember-know judgments that allow us to estimate both recollection and familiarity using both procedures in the same task and with the same participants (a sample of healthy older people and another sample of young people). Moreover, we performed a within-subjects manipulation of the type of materials (pairs of words or pairs of pictures), and the repetition or not of the pairs during the study phase. The results show that familiarity, estimated using both estimation procedures, declines significantly with age, although the effect size obtained with the process-dissociation procedure is significantly smaller than the one obtained with the remember-know procedure. Our results show that aging is associated with significant decreases both in recollection and, to a lesser extent, familiarity.

Premature hippocampus-dependent memory decline in middle-aged females of a genetic rat model of depression.

PubMed

Lim, Patrick H; Wert, Stephanie L; Tunc-Ozcan, Elif; Marr, Robert; Ferreira, Adriana; Redei, Eva E

2018-02-25

Aging and major depressive disorder are risk factors for dementia, including Alzheimer's Disease (AD), but the mechanism(s) linking depression and dementia are not known. Both AD and depression show greater prevalence in women. We began to investigate this connection using females of the genetic model of depression, the inbred Wistar Kyoto More Immobile (WMI) rat. These rats consistently display depression-like behavior compared to the genetically close control, the Wistar Kyoto Less Immobile (WLI) strain. Hippocampus-dependent contextual fear memory did not differ between young WLI and WMI females, but, by middle-age, female WMIs showed memory deficits compared to same age WLIs. This deficit, measured as duration of freezing in the fear provoking-context was not related to activity differences between the strains prior to fear conditioning. Hippocampal expression of AD-related genes, such as amyloid precursor protein, amyloid beta 42, beta secretase, synucleins, total and dephosphorylated tau, and synaptophysin, did not differ between WLIs and WMIs in either age group. However, hippocampal transcript levels of catalase (Cat) and hippocampal and frontal cortex expression of insulin-like growth factor 2 (Igf2) and Igf2 receptor (Igf2r) paralleled fear memory differences between middle-aged WLIs and WMIs. This data suggests that chronic depression-like behavior that is present in this genetic model is a risk factor for early spatial memory decline in females. The molecular mechanisms of this early memory decline likely involve the interaction of aging processes with the genetic components responsible for the depression-like behavior in this model. Copyright © 2018 Elsevier B.V. All rights reserved.

Age Related Changes in Metabolite Concentrations in the Normal Spinal Cord

PubMed Central

Abdel-Aziz, Khaled; Solanky, Bhavana S.; Yiannakas, Marios C.; Altmann, Daniel R.; Wheeler-Kingshott, Claudia A. M.; Thompson, Alan J.; Ciccarelli, Olga

2014-01-01

Magnetic resonance spectroscopy (MRS) studies have previously described metabolite changes associated with aging of the healthy brain and provided insights into normal brain aging that can assist us in differentiating age-related changes from those associated with neurological disease. The present study investigates whether age-related changes in metabolite concentrations occur in the healthy cervical spinal cord. 25 healthy volunteers, aged 23–65 years, underwent conventional imaging and single-voxel MRS of the upper cervical cord using an optimised point resolved spectroscopy sequence on a 3T Achieva system. Metabolite concentrations normalised to unsuppressed water were quantified using LCModel and associations between age and spinal cord metabolite concentrations were examined using multiple regressions. A linear decline in total N-Acetyl-aspartate concentration (0.049 mmol/L lower per additional year of age, p = 0.010) and Glutamate-Glutamine concentration (0.054 mmol/L lower per additional year of age, p = 0.002) was seen within our sample age range, starting in the early twenties. The findings suggest that neuroaxonal loss and/or metabolic neuronal dysfunction, and decline in glutamate-glutamine neurotransmitter pool progress with aging. PMID:25310093

Disconnected Aging: Cerebral White Matter Integrity and Age-Related Differences in Cognition

PubMed Central

Bennett, Ilana J.; Madden, David J.

2013-01-01

Cognition arises as a result of coordinated processing among distributed brain regions and disruptions to communication within these neural networks can result in cognitive dysfunction. Cortical disconnection may thus contribute to the declines in some aspects of cognitive functioning observed in healthy aging. Diffusion tensor imaging (DTI) is ideally suited for the study of cortical disconnection as it provides indices of structural integrity within interconnected neural networks. The current review summarizes results of previous DTI aging research with the aim of identifying consistent patterns of age-related differences in white matter integrity, and of relationships between measures of white matter integrity and behavioral performance as a function of adult age. We outline a number of future directions that will broaden our current understanding of these brain-behavior relationships in aging. Specifically, future research should aim to (1) investigate multiple models of age-brain-behavior relationships; (2) determine the tract-specificity versus global effect of aging on white matter integrity; (3) assess the relative contribution of normal variation in white matter integrity versus white matter lesions to age-related differences in cognition; (4) improve the definition of specific aspects of cognitive functioning related to age-related differences in white matter integrity using information processing tasks; and (5) combine multiple imaging modalities (e.g., resting-state and task-related functional magnetic resonance imaging; fMRI) with DTI to clarify the role of cerebral white matter integrity in cognitive aging. PMID:24280637

A molecular network of the aging human brain provides insights into the pathology and cognitive decline of Alzheimer's disease.

PubMed

Mostafavi, Sara; Gaiteri, Chris; Sullivan, Sarah E; White, Charles C; Tasaki, Shinya; Xu, Jishu; Taga, Mariko; Klein, Hans-Ulrich; Patrick, Ellis; Komashko, Vitalina; McCabe, Cristin; Smith, Robert; Bradshaw, Elizabeth M; Root, David E; Regev, Aviv; Yu, Lei; Chibnik, Lori B; Schneider, Julie A; Young-Pearse, Tracy L; Bennett, David A; De Jager, Philip L

2018-06-01

There is a need for new therapeutic targets with which to prevent Alzheimer's disease (AD), a major contributor to aging-related cognitive decline. Here we report the construction and validation of a molecular network of the aging human frontal cortex. Using RNA sequence data from 478 individuals, we first build a molecular network using modules of coexpressed genes and then relate these modules to AD and its neuropathologic and cognitive endophenotypes. We confirm these associations in two independent AD datasets. We also illustrate the use of the network in prioritizing amyloid- and cognition-associated genes for in vitro validation in human neurons and astrocytes. These analyses based on unique cohorts enable us to resolve the role of distinct cortical modules that have a direct effect on the accumulation of AD pathology from those that have a direct effect on cognitive decline, exemplifying a network approach to complex diseases.

AIDS-related dementia: a case report of rapid cognitive decline.

PubMed

Morgan, M K; Clark, M E; Hartman, W L

1988-11-01

Little is known psychometrically about the pattern of cognitive decline associated with acquired immunodeficiency syndrome (AIDS)-related dementia. Pre- and posttest results are presented to illustrate a case example of rapid cognitive decline. Increased psychometric assessment is recommended with additional examination of inconsistent results, which may be dismissed mistakenly as related to psychiatric symptoms. Implications for clinical practice and the role of the psychologist are discussed.

Rising Energetic Cost of Walking Predicts Gait Speed Decline With Aging.

PubMed

Schrack, Jennifer A; Zipunnikov, Vadim; Simonsick, Eleanor M; Studenski, Stephanie; Ferrucci, Luigi

2016-07-01

Slow gait is a robust biomarker of health and a predictor of functional decline and death in older adults, yet factors contributing to the decline in gait speed with aging are not well understood. Previous research suggests that the energetic cost of walking at preferred speed is inversely associated with gait speed, but whether individuals with a rising energetic cost of walking experience a steeper rate of gait speed decline has not been investigated. In participants of the Baltimore Longitudinal Study of Aging, the energetic cost of overground walking at preferred speed (mL/kg/m) was assessed between 2007 and 2014 using a portable indirect calorimeter. The longitudinal association between the energetic cost of walking and usual gait speed over 6 meters (m/s) was assessed with multivariate linear regression models, and the risk of slow gait (<1.0 m/s) was analyzed using Cox proportional hazards models. The study population consisted of 457 participants aged 40 and older who contributed 1,121 person-visits to the analysis. In fully adjusted models, increases in the energetic cost of walking predicted the rate of gait speed decline in those older than 65 years (β = -0.008 m/s, p < .001). Moreover, those with a higher energetic cost of walking (>0.17mL/kg/m) had a 57% greater risk of developing slow gait compared with a normal energetic cost of walking (≤0.17mL/kg/m; adjusted hazard ratio = 1.57, 95% confidence interval: 1.01-2.46). These findings suggest that strategies to maintain walking efficiency hold significant implications for maintaining mobility in late life. Efforts to curb threats to walking efficiency should focus on therapies to treat gait and balance impairments, and reduce clinical disease burden. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Age-Dependent Decline of Endogenous Pain Control: Exploring the Effect of Expectation and Depression

PubMed Central

Grashorn, Wiebke; Sprenger, Christian; Forkmann, Katarina; Wrobel, Nathalie; Bingel, Ulrike

2013-01-01

Although chronic pain affects all age ranges, it is particularly common in the elderly. One potential explanation for the high prevalence of chronic pain in the older population is impaired functioning of the descending pain inhibitory system which can be studied in humans using conditioned pain modulation (CPM) paradigms. In this study we investigated (i) the influence of age on CPM and (ii) the role of expectations, depression and gender as potential modulating variables of an age-related change in CPM. 64 healthy volunteers of three different age groups (young = 20–40 years, middle-aged = 41–60 years, old = 61–80 years) were studied using a classical CPM paradigm that combined moderate heat pain stimuli to the right forearm as test stimuli (TS) and immersion of the contralateral foot into ice water as the conditioning stimulus (CS). The CPM response showed an age-dependent decline with strong CPM responses in young adults but no significant CPM responses in middle-aged and older adults. These age-related changes in CPM responses could not be explained by expectations of pain relief or depression. Furthermore, changes in CPM responses did not differ between men and women. Our results strongly support the notion of a genuine deterioration of descending pain inhibitory mechanisms with age. PMID:24086595

Age-Related Differences in Listening Effort During Degraded Speech Recognition.

PubMed

Ward, Kristina M; Shen, Jing; Souza, Pamela E; Grieco-Calub, Tina M

The purpose of the present study was to quantify age-related differences in executive control as it relates to dual-task performance, which is thought to represent listening effort, during degraded speech recognition. Twenty-five younger adults (YA; 18-24 years) and 21 older adults (OA; 56-82 years) completed a dual-task paradigm that consisted of a primary speech recognition task and a secondary visual monitoring task. Sentence material in the primary task was either unprocessed or spectrally degraded into 8, 6, or 4 spectral channels using noise-band vocoding. Performance on the visual monitoring task was assessed by the accuracy and reaction time of participants' responses. Performance on the primary and secondary task was quantified in isolation (i.e., single task) and during the dual-task paradigm. Participants also completed a standardized psychometric measure of executive control, including attention and inhibition. Statistical analyses were implemented to evaluate changes in listeners' performance on the primary and secondary tasks (1) per condition (unprocessed vs. vocoded conditions); (2) per task (single task vs. dual task); and (3) per group (YA vs. OA). Speech recognition declined with increasing spectral degradation for both YA and OA when they performed the task in isolation or concurrently with the visual monitoring task. OA were slower and less accurate than YA on the visual monitoring task when performed in isolation, which paralleled age-related differences in standardized scores of executive control. When compared with single-task performance, OA experienced greater declines in secondary-task accuracy, but not reaction time, than YA. Furthermore, results revealed that age-related differences in executive control significantly contributed to age-related differences on the visual monitoring task during the dual-task paradigm. OA experienced significantly greater declines in secondary-task accuracy during degraded speech recognition than YA. These

Age-related differences in listening effort during degraded speech recognition

PubMed Central

Ward, Kristina M.; Shen, Jing; Souza, Pamela E.; Grieco-Calub, Tina M.

2016-01-01

Objectives The purpose of the current study was to quantify age-related differences in executive control as it relates to dual-task performance, which is thought to represent listening effort, during degraded speech recognition. Design Twenty-five younger adults (18–24 years) and twenty-one older adults (56–82 years) completed a dual-task paradigm that consisted of a primary speech recognition task and a secondary visual monitoring task. Sentence material in the primary task was either unprocessed or spectrally degraded into 8, 6, or 4 spectral channels using noise-band vocoding. Performance on the visual monitoring task was assessed by the accuracy and reaction time of participants’ responses. Performance on the primary and secondary task was quantified in isolation (i.e., single task) and during the dual-task paradigm. Participants also completed a standardized psychometric measure of executive control, including attention and inhibition. Statistical analyses were implemented to evaluate changes in listeners’ performance on the primary and secondary tasks (1) per condition (unprocessed vs. vocoded conditions); (2) per task (baseline vs. dual task); and (3) per group (younger vs. older adults). Results Speech recognition declined with increasing spectral degradation for both younger and older adults when they performed the task in isolation or concurrently with the visual monitoring task. Older adults were slower and less accurate than younger adults on the visual monitoring task when performed in isolation, which paralleled age-related differences in standardized scores of executive control. When compared to single-task performance, older adults experienced greater declines in secondary-task accuracy, but not reaction time, than younger adults. Furthermore, results revealed that age-related differences in executive control significantly contributed to age-related differences on the visual monitoring task during the dual-task paradigm. Conclusions Older

Glutathione maintenance mitigates age-related susceptibility to redox cycling agents.

PubMed

Thomas, Nicholas O; Shay, Kate P; Kelley, Amanda R; Butler, Judy A; Hagen, Tory M

2016-12-01

Isolated hepatocytes from young (4-6mo) and old (24-26mo) F344 rats were exposed to increasing concentrations of menadione, a vitamin K derivative and redox cycling agent, to determine whether the age-related decline in Nrf2-mediated detoxification defenses resulted in heightened susceptibility to xenobiotic insult. An LC 50 for each age group was established, which showed that aging resulted in a nearly 2-fold increase in susceptibility to menadione (LC 50 for young: 405μM; LC 50 for old: 275μM). Examination of the known Nrf2-regulated pathways associated with menadione detoxification revealed, surprisingly, that NAD(P)H: quinone oxido-reductase 1 (NQO1) protein levels and activity were induced 9-fold and 4-fold with age, respectively (p=0.0019 and p=0.018; N=3), but glutathione peroxidase 4 (GPX4) declined by 70% (p=0.0043; N=3). These results indicate toxicity may stem from vulnerability to lipid peroxidation instead of inadequate reduction of menadione semi-quinone. Lipid peroxidation was 2-fold higher, and GSH declined by a 3-fold greater margin in old versus young rat cells given 300µM menadione (p<0.05 and p≤0.01 respectively; N=3). We therefore provided 400µMN-acetyl-cysteine (NAC) to hepatocytes from old rats before menadione exposure to alleviate limits in cysteine substrate availability for GSH synthesis during challenge. NAC pretreatment resulted in a >2-fold reduction in cell death, suggesting that the age-related increase in menadione susceptibility likely stems from attenuated GSH-dependent defenses. This data identifies cellular targets for intervention in order to limit age-related toxicological insults to menadione and potentially other redox cycling compounds. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

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. Copyright © 2015 Elsevier Inc. All rights reserved.

Differential declines in syphilis-related mortality in the United States, 2000-2014.

PubMed

Barragan, Noel C; Moschetti, Kristin; Smith, Lisa V; Sorvillo, Frank; Kuo, Tony

2017-04-01

After reaching an all time low in 2000, the rate of syphilis in the United States has been steadily increasing. Parallel benchmarking of the disease's mortality burden has not been undertaken. Using ICD-10 classification, all syphilis-related deaths in the national Multiple Cause of Death dataset were examined for the period 2000-2014. Descriptive statistics and age-adjusted mortality rates were generated. Poisson regression was performed to analyze trends over time. A matched case-control analysis was conducted to assess the associations between syphilis-related deaths and comorbid conditions listed in the death records. A total of 1,829 deaths were attributed to syphilis; 32% (n = 593) identified syphilis as the underlying cause of death. Most decedents were men (60%) and either black (48%) or white (39%). Decedents aged ≥85 years had the highest average mortality rate (0.47 per 100,000 population; 95% confidence interval [CI], 0.42-0.52). For the sampled period, the average annual decline in mortality was -2.90% (95% CI, -3.93% to -1.87%). However, the average annual percent change varied across subgroups of interest. Declines in U.S. syphilis mortality suggest early detection and improved treatment access likely helped attenuate disease progression; however, increases in the disease rate since 2000 may be offsetting the impact of these advancements. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

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.

Aβ-related memory decline in APOE ε4 noncarriers: Implications for Alzheimer disease.

PubMed

Lim, Yen Ying; Laws, Simon M; Villemagne, Victor L; Pietrzak, Robert H; Porter, Tenielle; Ames, David; Fowler, Christopher; Rainey-Smith, Stephanie; Snyder, Peter J; Martins, Ralph N; Salvado, Olivier; Bourgeat, Pierrick; Rowe, Christopher C; Masters, Colin L; Maruff, Paul

2016-04-26

As the absence of Aβ-related memory decline in APOE ε4 noncarriers may be due to the relative brevity of previous studies, we aimed to characterize Aβ-related cognitive decline over 72 months in APOE ε4 carriers and noncarriers who were cognitively normal (CN). CN older adults (n = 423) underwent Aβ imaging and APOE genotyping. Participants completed comprehensive neuropsychological testing at baseline 18-, 36-, 54-, and 72-month assessments. Relative to Aβ- CN ε4 noncarriers, both Aβ+ CN ε4 carriers and noncarriers showed significantly increased decline in measures of memory, language, and executive function as well as higher rates of progression to a clinical classification of mild cognitive impairment. Memory decline was greater in Aβ+ CN ε4 carriers than in Aβ+ CN ε4 noncarriers. No cognitive decline was evident in Aβ- CN ε4 carriers. In CN older adults, Aβ+ is associated with memory decline in ε4 noncarriers; however, the rate of this decline is much slower than that observed in ε4 carriers. These data indicate that the processes by which ε4 carriage increases the rate of Aβ-related cognitive decline occur in the preclinical stage of Alzheimer disease. © 2016 American Academy of Neurology.

BioAge: Toward A Multi-Determined, Mechanistic Account of Cognitive Aging

PubMed Central

DeCarlo, Correne A.; Tuokko, Holly A.; Williams, Dorothy; Dixon, Roger A.; MacDonald, Stuart W.S.

2014-01-01

The search for reliable early indicators of age-related cognitive decline represents a critical avenue for progress in aging research. Chronological age is a commonly used developmental index; however, it offers little insight into the mechanisms underlying cognitive decline. In contrast, biological age (BioAge), reflecting the vitality of essential biological systems, represents a promising operationalization of developmental time. Current BioAge models have successfully predicted age-related cognitive deficits. Research on aging-related cognitive function indicates that the interaction of multiple risk and protective factors across the human lifespan confers individual risk for late-life cognitive decline, implicating a multi-causal explanation. In this review, we explore current BioAge models, describe three broad yet pathologically relevant biological processes linked to cognitive decline, and propose a novel operationalization of BioAge accounting for both moderating and causal mechanisms of cognitive decline and dementia. We argue that a multivariate and mechanistic BioAge approach will lead to a greater understanding of disease pathology as well as more accurate prediction and early identification of late-life cognitive decline. PMID:25278166

Distinct age-related differences in temporal discounting and risk taking in adolescents and young adults.

PubMed

de Water, Erik; Cillessen, Antonius H N; Scheres, Anouk

2014-01-01

Age-related differences in temporal discounting (TD) and risk taking, and their association, were examined in adolescents and young adults (n = 337) aged 12-27 years. Since monetary rewards are typically used in TD and risk-taking tasks, the association between monetary reward valuation and age and decision making in these tasks was explored as well. TD declined linearly with age, with a particularly sharp decline from 15 to 16 years. In contrast, risk taking was not correlated with age and TD. Reward valuation was not associated with TD and risk taking, and age-related differences in TD remained significant after controlling for reward valuation. Together, these findings suggest that risk taking and TD are two separate constructs with distinct age-related differences in adolescence and young adulthood. © 2014 The Authors. Child Development © 2014 Society for Research in Child Development, Inc.

Do apolipoprotein E genotype and educational attainment predict the rate of cognitive decline in normal aging? A 12-year follow-up of the Maastricht Aging Study.

PubMed

Van Gerven, Pascal W M; Van Boxtel, Martin P J; Ausems, Eleonora E B; Bekers, Otto; Jolles, Jelle

2012-07-01

We investigated suspected longitudinal interaction effects of apolipoprotein E (APOE) genotype and educational attainment on cognitive decline in normal aging. Our sample consisted of 571 healthy, nondemented adults aged between 49 and 82 years. Linear mixed-models analyses were performed with four measurement time points: baseline, 3-year, 6-year, and 12-year follow-up. Covariates included age at baseline, sex, and self-perceived physical and mental health. Dependent measures were global cognitive functioning (Mini-Mental State Examination; Folstein, Folstein, & McHugh, 1975), Stroop performance (Stroop Color-Word Test; Van der Elst, Van Boxtel, Van Breukelen, & Jolles, 2006a), set-shifting performance (Concept Shifting Test; Van der Elst, Van Boxtel, Van Breukelen, & Jolles, 2006b), cognitive speed (Letter-Digit Substitution Test; Van der Elst, Van Boxtel, Van Breukelen, & Jolles, 2006c), verbal learning (Verbal Learning Test: Sum of five trials; Van der Elst, Van Boxtel, Van Breukelen, & Jolles, 2005), and long-term memory (Verbal Learning Test: Delayed recall). We found only faint evidence that older, high-educated carriers of the APOE-ε4 allele (irrespective of zygosity) show a more pronounced decline than younger, low-educated carriers and noncarriers (irrespective of educational attainment). Moreover, this outcome was confined to concept-shifting performance and was especially observable between 6- and 12-year follow-ups. No protective effects of higher education were found on any of the six cognitive measures. We conclude that the combination of APOE-ε4 allele and high educational attainment may be a risk factor for accelerated cognitive decline in older age, as has been reported before, but only to a very limited extent. Moreover, we conclude that, within the cognitive reserve framework, education does not have significant protective power against age-related cognitive decline.

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…

Age-related normative values for handgrip strength and grip strength’s usefulness as a predictor of mortality and both cognitive and physical decline in older adults in northwest Russia

PubMed Central

Turusheva, A.; Frolova, E.; Degryse, J-M.

2017-01-01

Objectives: This paper sought to provide normative values for grip strength among older adults across different age groups in northwest Russia and to investigate their predictive value for adverse events. Methods: A population-based prospective cohort study of 611 community-dwelling individuals 65+. Grip strength was measured using the standard protocol applied in the Groningen Elderly Tests. The cut-off thresholds for grip strength were defined separately for men and women of different ages using a weighted polynomial regression. A Cox regression analysis, the c-statistic, a risk reclassification analysis, and bootstrapping techniques were used to analyze the data. The outcomes were the 5-year mortality rate, the loss of autonomy and mental decline. Results: We determined the age-related reference intervals of grip strength for older adults. The 5th and 10th percentiles of grip strength were associated with a higher risk for malnutrition, low autonomy, physical and mental functioning and 5-year mortality. The 5th percentile of grip strength was associated with a decline in autonomy. Conclusions: This study presents age- and sex-specific reference values for grip strength in the 65+ Russian population derived from a prospective cohort study. The norms can be used in clinical practice to identify patients at increased risk for adverse outcomes. PMID:28250246

Disconnected aging: cerebral white matter integrity and age-related differences in cognition.

PubMed

Bennett, I J; Madden, D J

2014-09-12

Cognition arises as a result of coordinated processing among distributed brain regions and disruptions to communication within these neural networks can result in cognitive dysfunction. Cortical disconnection may thus contribute to the declines in some aspects of cognitive functioning observed in healthy aging. Diffusion tensor imaging (DTI) is ideally suited for the study of cortical disconnection as it provides indices of structural integrity within interconnected neural networks. The current review summarizes results of previous DTI aging research with the aim of identifying consistent patterns of age-related differences in white matter integrity, and of relationships between measures of white matter integrity and behavioral performance as a function of adult age. We outline a number of future directions that will broaden our current understanding of these brain-behavior relationships in aging. Specifically, future research should aim to (1) investigate multiple models of age-brain-behavior relationships; (2) determine the tract-specificity versus global effect of aging on white matter integrity; (3) assess the relative contribution of normal variation in white matter integrity versus white matter lesions to age-related differences in cognition; (4) improve the definition of specific aspects of cognitive functioning related to age-related differences in white matter integrity using information processing tasks; and (5) combine multiple imaging modalities (e.g., resting-state and task-related functional magnetic resonance imaging; fMRI) with DTI to clarify the role of cerebral white matter integrity in cognitive aging. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Aging enhances serum cytokine response but not task-induced grip strength declines in a rat model of work-related musculoskeletal disorders

PubMed Central

2011-01-01

Background We previously reported early tissue injury, increased serum and tissue inflammatory cytokines and decreased grip in young rats performing a moderate demand repetitive task. The tissue cytokine response was transient, the serum response and decreased grip were still evident by 8 weeks. Thus, here, we examined their levels at 12 weeks in young rats. Since aging is known to enhance serum cytokine levels, we also examined aged rats. Methods Aged and young rats, 14 mo and 2.5 mo of age at onset, respectfully, were trained 15 min/day for 4 weeks, and then performed a high repetition, low force (HRLF) reaching and grasping task for 2 hours/day, for 12 weeks. Serum was assayed for 6 cytokines: IL-1alpha, IL-6, IFN-gamma, TNF-alpha, MIP2, IL-10. Grip strength was assayed, since we have previously shown an inverse correlation between grip strength and serum inflammatory cytokines. Results were compared to naïve (grip), and normal, food-restricted and trained-only controls. Results Serum cytokines were higher overall in aged than young rats, with increases in IL-1alpha, IFN-gamma and IL-6 in aged Trained and 12-week HRLF rats, compared to young Trained and HRLF rats (p < 0.05 and p < 0.001, respectively, each). IL-6 was also increased in aged 12-week HRLF versus aged normal controls (p < 0.05). Serum IFN-gamma and MIP2 levels were also increased in young 6-week HRLF rats, but no cytokines were above baseline levels in young 12-week HRLF rats. Grip strength declined in both young and aged 12-week HRLF rats, compared to naïve and normal controls (p < 0.05 each), but these declines correlated only with IL-6 levels in aged rats (r = -0.39). Conclusion Aging enhanced a serum cytokine response in general, a response that was even greater with repetitive task performance. Grip strength was adversely affected by task performance in both age groups, but was apparently influenced by factors other than serum cytokine levels in young rats. PMID:21447183

Age-related differences in idea generation and selection for propositional language.

PubMed

Madden, Daniel L; Sale, Martin V; Robinson, Gail A

2018-05-21

Conceptual preparation mechanisms such as novel idea generation and selection from amongst competing alternatives are critical for language production and may contribute to age-related language deficits. This study investigated whether older adults show diminished idea generation and selection abilities, compared to younger adults. Twenty younger (18-35 years) and 20 older (60-80 years) adults completed two novel experimental tasks, an idea generation task and a selection task. Older participants were slower than younger participants overall on both tasks. Importantly, this difference was more pronounced for task conditions with greater demands on generation and selection. Older adults were also significantly reduced on a semantic, but not phonemic, word fluency task. Overall, the older group showed evidence of age-related decline specific to idea generation and selection ability. This has implications for the message formulation stage of propositional language decline in normal aging.

Sleep duration and age-related changes in brain structure and cognitive performance.

PubMed

Lo, June C; Loh, Kep Kee; Zheng, Hui; Sim, Sam K Y; Chee, Michael W L

2014-07-01

To investigate the contribution of sleep duration and quality to age-related changes in brain structure and cognitive performance in relatively healthy older adults. Community-based longitudinal brain and cognitive aging study using a convenience sample. Participants were studied in a research laboratory. Relatively healthy adults aged 55 y and older at study commencement. N/A. Participants underwent magnetic resonance imaging and neuropsychological assessment every 2 y. Subjective assessments of sleep duration and quality and blood samples were obtained. Each hour of reduced sleep duration at baseline augmented the annual expansion rate of the ventricles by 0.59% (P = 0.007) and the annual decline rate in global cognitive performance by 0.67% (P = 0.050) in the subsequent 2 y after controlling for the effects of age, sex, education, and body mass index. In contrast, global sleep quality at baseline did not modulate either brain or cognitive aging. High-sensitivity C-reactive protein, a marker of systemic inflammation, showed no correlation with baseline sleep duration, brain structure, or cognitive performance. In healthy older adults, short sleep duration is associated with greater age-related brain atrophy and cognitive decline. These associations are not associated with elevated inflammatory responses among short sleepers. Lo JC, Loh KK, Zheng H, Sim SK, Chee MW. Sleep duration and age-related changes in brain structure and cognitive performance.

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. Copyright © 2016 Elsevier B.V. All rights reserved.

Molecular inflammation as an underlying mechanism of the aging process and age-related diseases.

PubMed

Chung, H Y; Lee, E K; Choi, Y J; Kim, J M; Kim, D H; Zou, Y; Kim, C H; Lee, J; Kim, H S; Kim, N D; Jung, J H; Yu, B P

2011-07-01

Aging is a biological process characterized by time-dependent functional declines that are influenced by changes in redox status and by oxidative stress-induced inflammatory reactions. An organism's pro-inflammatory status may underlie the aging process and age-related diseases. In this review, we explore the molecular basis of low-grade, unresolved, subclinical inflammation as a major risk factor for exacerbating the aging process and age-related diseases. We focus on the redox-sensitive transcription factors, NF-κB and FOXO, which play essential roles in the expression of pro-inflammatory mediators and anti-oxidant enzymes, respectively. Major players in molecular inflammation are discussed with respect to the age-related up-regulation of pro-inflammatory cytokines and adhesion molecules, cyclo-oxygenase-2, lipoxygenase, and inducible nitric oxide synthase. The molecular inflammation hypothesis proposed by our laboratory is briefly described to give further molecular insights into the intricate interplay among redox balance, pro-inflammatory gene activation, and chronic age-related inflammatory diseases. The final section discusses calorie restriction as an aging-retarding intervention that also exhibits extraordinarily effective anti-inflammatory activity by modulating GSH redox, NF-κB, SIRT1, PPARs, and FOXOs.

Age-Related Normogram for Ovarian Antral Follicle Count in Women with Polycystic Ovary Syndrome and Comparison with Age Matched Controls Using Magnetic Resonance Imaging.

PubMed

Aiyappan, Senthil Kumar; Karpagam, Bulabai; Vadanika, V; Chidambaram, Prem Kumar; Vinayagam, S; Saravanan, K C

2016-01-01

Antral Follicle count (AFC) is a reliable marker for ovarian reserve. Previous studies have used transvaginal ultrasound for estimation of AFC, however we used magnetic resonance imaging (MRI) for estimation of AFC and for creating an age-related normogram in patients with polycystic ovary syndrome (PCOS) and compared it with normal patients. The aim of this study is to create an age related normogram for AFC in women with PCOS and to compare that with women without polycystic ovarian syndrome using MRI. A total of 1500 women were examined, out of which 400 fitted the criteria for PCOS. They all underwent MRI study and similar age matched women without PCOS also underwent MRI examination. Normogram for AFC were obtained using LMS software and a percentile chart was obtained. Normogram for AFC in PCOS women showed decline in number of AFC as the age progresses and the decline was linear. The normogram for AFC was compared with equal number of patients without PCOS and they also showed decline in AFC as the age progresses, however the decline was exponential and faster. Age related normogram for AFC is widely used and considered as best clinical predictor for ovarian response in assisted reproductive technology. Knowledge of ovarian reserve is important in PCOS and non-PCOS females as PCOS patients are at risk for ovarian hyperstimulation syndrome during gonadotrophin theraphy. MRI is an equally effective and in some times better alternative to transvaginal ultrasound as it has got its own advantages.

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.

Age-related change in handgrip strength in men and women: is muscle quality a contributing factor?

PubMed

Abe, Takashi; Thiebaud, Robert S; Loenneke, Jeremy P

2016-02-01

Age-related changes in muscle quality and muscle mass in the forearm, which relate to decline in handgrip strength (HGS), have not been reported. The purpose of this study was to investigate the relationships between age-related declines in HGS and loss of muscle thickness and/or muscle quality in the forearm of 613 adults (306 men and 307 women) aged 20-89. Anterior forearm muscle thickness (MT-ulna) and HGS were measured using an ultrasound and a hand dynamometer, respectively, in the dominant hand. Muscle quality (fMQ) was defined as a ratio of HGS to MT-ulna. HGS was similar among younger (ages 20-29, 30-39, and 40-49) groups and was progressively lower with increasing age in both sexes. MT-ulna was similar between ages 20-29 and 60-69 in men and between ages 20-29 and 70-79 in women. In men, MT-ulna was lower in ages 70-79 and 80-89 compared with other age groups. In women, MT-ulna was lower in ages 80-89 compared with ages 20-29 and 40-49. In both men and women, fMQ was identical among younger (ages 20-29, 30-39, and 40-49) groups. After that fMQ was progressively lower with age in both men and women. The results indicated that age-related decline in HGS is associated with fMQ, but it appears to be accelerated after the seventh decade due to muscle loss.

BioAge: toward a multi-determined, mechanistic account of cognitive aging.

PubMed

DeCarlo, Correne A; Tuokko, Holly A; Williams, Dorothy; Dixon, Roger A; MacDonald, Stuart W S

2014-11-01

The search for reliable early indicators of age-related cognitive decline represents a critical avenue for progress in aging research. Chronological age is a commonly used developmental index; however, it offers little insight into the mechanisms underlying cognitive decline. In contrast, biological age (BioAge), reflecting the vitality of essential biological systems, represents a promising operationalization of developmental time. Current BioAge models have successfully predicted age-related cognitive deficits. Research on aging-related cognitive function indicates that the interaction of multiple risk and protective factors across the human lifespan confers individual risk for late-life cognitive decline, implicating a multi-causal explanation. In this review, we explore current BioAge models, describe three broad yet pathologically relevant biological processes linked to cognitive decline, and propose a novel operationalization of BioAge accounting for both moderating and causal mechanisms of cognitive decline and dementia. We argue that a multivariate and mechanistic BioAge approach will lead to a greater understanding of disease pathology as well as more accurate prediction and early identification of late-life cognitive decline. Copyright © 2014 Elsevier B.V. All rights reserved.

Cognitive training and Bacopa monnieri: Evidence for a combined intervention to alleviate age associated cognitive decline.

PubMed

McPhee, Grace M; Downey, Luke A; Noble, Anthony; Stough, Con

2016-10-01

As the elderly population grows the impact of age associated cognitive decline as well as neurodegenerative diseases such as Alzheimer's disease and dementia will increase. Ageing is associated with consistent impairments in cognitive processes (e.g., processing speed, memory, executive function and learning) important for work, well-being, life satisfaction and overall participation in society. Recently, there has been increased effort to conduct research examining methods to improve cognitive function in older citizens. Cognitive training has been shown to improve performance in some cognitive domains; including memory, processing speed, executive function and attention in older adults. These cognitive changes are thought to be related to improvements in brain connectivity and neural circuitry. Bacopa monnieri has also been shown to improve specific domains of cognition, sensitive to age associated cognitive decline (particularly processing speed and memory). These Bacopa monnieri dependent improvements may be due to the increase in specific neuro-molecular mechanisms implicated in the enhancement of neural connections in the brain (i.e. synaptogenesis). In particular, a number of animal studies have shown Bacopa monnieri consumption upregulates calcium dependent kinases in the synapse and post-synaptic cell, crucial for strengthening and growing connections between neurons. These effects have been shown to occur in areas important for cognitive processes, such as the hippocampus. As Bacopa monnieri has shown neuro-molecular mechanisms that encourage synaptogenesis, while cognitive training enhances brain connectivity, Bacopa monnieri supplementation could theoretically enhance and strengthen synaptic changes acquired through cognitive training. Therefore, the current paper hypothesises that the combination of these two interventions could improve cognitive outcomes, over and above the effects of administrating these interventions independently, as an effective

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.

Relationship of race and poverty to lower extremity function and decline: findings from the Women's Health and Aging Study.

PubMed

Thorpe, Roland James; Kasper, Judith D; Szanton, Sarah L; Frick, Kevin D; Fried, Linda P; Simonsick, Eleanor M

2008-02-01

Race- and poverty-related disparities in physical function are well documented, though little is known about effects of race and poverty on functional decline and the progression of disability. We examined cross-sectional and longitudinal relationships between race, poverty and lower extremity function using data from moderately to severely disabled women in the U.S. Women's Health and Aging Study. Severity of lower extremity functional limitation was determined from scaled responses of reported difficulty walking (1/4) mile, walking across a room, climbing stairs, and stooping, crouching or kneeling. Usual walking speed assessed over 4m was our objective measure of function. Of the 996 women who described themselves as black or white, 284 (29%) were black and 367 (37%) were living at or below 100% of the federal poverty level. Independent of demographic and health-related factors, among white women, the poor exhibited consistently worse lower extremity function than the non-poor; this association, however, was not observed in black women. Among the non-poor, black women had slower walking speeds, and reported more limitation in lower extremity function than their non-poor white counterparts, even after adjusting for demographic variables and health-related characteristics. After 3 years, accounting for baseline function, demographic and health-related factors, race and poverty status were unrelated to functional decline. Thus, while race and poverty status were associated with functional deficits in old age, they do not appear to impact the rate of functional decline or progression of disability over 3 years.

An Examination of Age-Based Stereotype Threat About Cognitive Decline.

PubMed

Barber, Sarah J

2017-01-01

"Stereotype threat" is often thought of as a singular construct, with moderators and mechanisms that are stable across groups and domains. However, this is not always true. To illustrate this, the current review focuses on the stereotype threat that older adults face about their cognitive abilities. Drawing upon the multithreat framework, I first provide evidence that this is a self-concept threat and not a group-reputation threat. Because this differs from the forms of stereotype threat experienced by other groups (e.g., the threat that minority students face about their intellectual abilities), the moderators of stereotype threat observed in other groups (i.e., group identification) do not always generalize to age-based stereotype threat about cognitive decline. Looking beyond the forms of stereotype threat elicited, this review also provides evidence that the mechanisms underlying stereotype-threat effects may vary across the adult life span. Because of age-related improvements in emotion-regulation abilities, stereotype threat does not seem to reduce older adults' executive-control resources. Overall, this review highlights the need to approach the concept of stereotype threat with more granularity, allowing researchers to design more effective stereotype-threat interventions. It will also shed light on why certain stereotype threat effects "fail to replicate" across domains or groups.

Learning to remember: cognitive training-induced attenuation of age-related memory decline depends on sex and cognitive demand, and can transfer to untrained cognitive domains.

PubMed

Talboom, Joshua S; West, Stephen G; Engler-Chiurazzi, Elizabeth B; Enders, Craig K; Crain, Ian; Bimonte-Nelson, Heather A

2014-12-01

Aging is associated with progressive changes in learning and memory. A potential approach to attenuate age-related cognitive decline is cognitive training. In this study, adult male and female rats were given either repeated exposure to a T-maze, or no exposure to any maze, and then tested on a final battery of cognitive tasks. Two groups of each sex were tested from 6 to 18 months old on the same T-maze; Group one received a version testing spatial reference memory, and Group two received only the procedural testing components with minimal cognitive demand. Groups three and four of each sex had no maze exposure until the final battery, and were comprised of aged or young rats, respectively. The final maze battery included the practiced T-maze plus two novel tasks, one with a similar, and one with a different, memory type to the practice task. Group five of each sex was not maze tested, serving as an aged control for the effects of maze testing on neurotrophin protein levels in cognitive brain regions. Results showed that adult intermittent cognitive training enhanced performance on the practice task when aged in both sexes, that cognitive training benefits transferred to novel tasks only in females, and that cognitive demand was necessary for these effects, since rats receiving only the procedural testing components showed no improvement on the final maze battery. Further, for both sexes, rats that showed faster learning when young demonstrated better memory when aged. Age-related increases in neurotrophin concentrations in several brain regions were revealed, which were related to performance on the training task only in females. This longitudinal study supports the tenet that cognitive training can help one remember later in life, with broader enhancements and associations with neurotrophins in females. Published by Elsevier Inc.

Learning to remember: Cognitive training-induced attenuation of age-related memory decline depends on sex and cognitive demand, and can transfer to untrained cognitive domains

PubMed Central

Talboom, Joshua S.; West, Stephen G.; Engler-Chiurazzi, Elizabeth B.; Enders, Craig K.; Crain, Ian; Bimonte-Nelson, Heather A.

2014-01-01

Aging is associated with progressive changes in learning and memory. A potential approach to attenuate age-related cognitive decline is cognitive training. In this study, adult male and female rats were given either repeated exposure to a T-maze, or no exposure to any maze, and then tested on a final battery of cognitive tasks. Two groups of each sex were tested from 6-18 months old on the same T-maze; one group received a version testing spatial reference memory, and the other group received only the procedural testing components with minimal cognitive demand. Groups three and four of each sex had no maze exposure until the final battery, and were comprised of aged or young rats. The final maze battery included the practiced T-maze plus two novel tasks, one with a similar, and one with a different, memory type to the practice task. The fifth group of each sex was not maze tested, serving as an aged control for the effects of maze testing on neurotrophin protein levels in cognitive brain regions. Results showed that adult intermittent cognitive training enhanced performance on the practice task when aged in both sexes, that cognitive training benefits transferred to novel tasks only in females, and that cognitive demand was necessary for these effects since rats receiving only the procedural testing components showed no improvement on the final maze battery. Further, for both sexes, rats that showed faster learning when young demonstrated better memory when aged. Age-related increases in neurotrophin concentrations in several brain regions were revealed, which was related to performance on the training task only in females. This longitudinal study supports the tenet that cognitive training can help one remember later in life, with broader enhancements and associations with neurotrophins in females. PMID:25104561

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

PubMed

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

2014-04-01

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

Sleep Duration and Age-Related Changes in Brain Structure and Cognitive Performance

PubMed Central

Lo, June C.; Loh, Kep Kee; Zheng, Hui; Sim, Sam K.Y.; Chee, Michael W.L.

2014-01-01

Study Objectives: To investigate the contribution of sleep duration and quality to age-related changes in brain structure and cognitive performance in relatively healthy older adults. Design: Community-based longitudinal brain and cognitive aging study using a convenience sample. Setting: Participants were studied in a research laboratory. Participants: Relatively healthy adults aged 55 y and older at study commencement. Interventions: N/A. Measurements and Results: Participants underwent magnetic resonance imaging and neuropsychological assessment every 2 y. Subjective assessments of sleep duration and quality and blood samples were obtained. Each hour of reduced sleep duration at baseline augmented the annual expansion rate of the ventricles by 0.59% (P = 0.007) and the annual decline rate in global cognitive performance by 0.67% (P = 0.050) in the subsequent 2 y after controlling for the effects of age, sex, education, and body mass index. In contrast, global sleep quality at baseline did not modulate either brain or cognitive aging. High-sensitivity C-reactive protein, a marker of systemic inflammation, showed no correlation with baseline sleep duration, brain structure, or cognitive performance. Conclusions: In healthy older adults, short sleep duration is associated with greater age-related brain atrophy and cognitive decline. These associations are not associated with elevated inflammatory responses among short sleepers. Citation: Lo JC, Loh KK, Zheng H, Sim SK, Chee MW. Sleep duration and age-related changes in brain structure and cognitive performance. SLEEP 2014;37(7):1171-1178. PMID:25061245

Loss of Cdk5 function in the nucleus accumbens decreases wheel running and may mediate age-related declines in voluntary physical activity.

PubMed

Ruegsegger, Gregory N; Toedebusch, Ryan G; Childs, Thomas E; Grigsby, Kolter B; Booth, Frank W

2017-01-01

greater in 8- vs. 14-week-old rats. In depth analysis of these networks showed significant (∼20-30%; P < 0.05) decreases in cell adhesion molecule (Cadm)4 and p39 mRNAs, as well as their proteins from 8 to 14 weeks of age in running and sedentary rats. Furthermore, Cadm4, cyclin-dependent kinase 5 (Cdk5) and p39 mRNAs were significantly correlated with voluntary running distance. Analysis of dendritic spine density in the NAc showed that wheel access increased spine density (P < 0.001), whereas spine density was lower in 14- vs. 8-week-old sedentary rats (P = 0.03). Intriguingly, intra-NAc injection of the Cdk5 inhibitor roscovitine, dose-dependently decreased wheel running. Collectively, these experiments suggest that an age-dependent loss in synaptic function and Cdk5/p39 activity in the NAc may be partially responsible for age-related declines in voluntary running behaviour. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Fast but fleeting: adaptive motor learning processes associated with aging and cognitive decline.

PubMed

Trewartha, Kevin M; Garcia, Angeles; Wolpert, Daniel M; Flanagan, J Randall

2014-10-01

Motor learning has been shown to depend on multiple interacting learning processes. For example, learning to adapt when moving grasped objects with novel dynamics involves a fast process that adapts and decays quickly-and that has been linked to explicit memory-and a slower process that adapts and decays more gradually. Each process is characterized by a learning rate that controls how strongly motor memory is updated based on experienced errors and a retention factor determining the movement-to-movement decay in motor memory. Here we examined whether fast and slow motor learning processes involved in learning novel dynamics differ between younger and older adults. In addition, we investigated how age-related decline in explicit memory performance influences learning and retention parameters. Although the groups adapted equally well, they did so with markedly different underlying processes. Whereas the groups had similar fast processes, they had different slow processes. Specifically, the older adults exhibited decreased retention in their slow process compared with younger adults. Within the older group, who exhibited considerable variation in explicit memory performance, we found that poor explicit memory was associated with reduced retention in the fast process, as well as the slow process. These findings suggest that explicit memory resources are a determining factor in impairments in the both the fast and slow processes for motor learning but that aging effects on the slow process are independent of explicit memory declines. Copyright © 2014 the authors 0270-6474/14/3413411-11$15.00/0.

Body-mass dependence of age-related deterioration in human muscular function.

PubMed

Meltzer, D E

1996-04-01

Maximal anaerobic power of human muscles declines with increasing chronological age and is correlated with body mass. This study investigated whether the rate of deterioration in human muscular function among trained weight lifters is also correlated with body mass. Cross-sectional analysis of performance data of over 1,100 Masters competitors in Olympic-style weight lifting was carried out; eight body-weight classes and six age groups were represented. Two-lift total data (sum of snatch and clean and jerk lifts) were analyzed. Mean deterioration rates in the performance of athletes of widely diverse body masses were compared over the following age ranges: 42-57, 42-62, and 42-67 yr. No statistically significant correlation (P < 0.05) was found between rate of performance decline and body mass. The relationship between body mass and the magnitude of age-related variation of deterioration rate was also studied; no significant correlation was found. Previous studies have demonstrated that performance in Olympic-style weight lifting is correlated with maximal anaerobic muscular power. This leads us to suggest that the age-related deterioration rate of anaerobic power in trained subjects may not be correlated with the body mass of the individual.

The relationship of bilingualism to cognitive decline: The Australian Longitudinal Study of Ageing.

PubMed

Mukadam, Naaheed; Jichi, Fatima; Green, David; Livingston, Gill

2018-02-01

We wished to clarify the link between bilingualism and cognitive decline, and examine whether improved executive function due to bilingualism may be a factor in preventing cognitive decline. We used the Australian Longitudinal Study of Ageing which collected data on 2087 participants aged over 65 over 20 years. We compared baseline demographics, health, and social characteristics between bilingual and non-bilingual participants. We used linear mixed models analysis to explore the effect of bilingualism on MMSE score over time and linear regression to explore the effect of bilingualism on baseline MMSE scores, controlling for pre-specified potential confounders. Bilingual participants had lower baseline MMSE scores than the non-bilingual population (mean difference = -2.3 points; 95% confidence intervals = 1.56-2.90). This was fully explained by education and National Adult Reading Test scores (17.4; standard deviation [SD] =7.7 versus 28.1; SD = 8.2) which also partly explained baseline executive function test scores differences. Bilingual and non-bilingual participants did not differ in MMSE decline over time (-0.33 points, P = 0.31) nor on baseline tests of executive function (-0.26, P = 0.051). In this cohort, education rather than bilingualism was a predictor of MMSE score, and being bilingual did not protect from cognitive decline. We conclude that bilingualism is complex, and when it is not the result of greater educational attainment, it does not always protect from cognitive decline. Neuroprotective effects of bilingualism over time may be attributable to the precise patterns of language use but not to bilingualism per se. Copyright © 2017 John Wiley & Sons, Ltd.

Nutritional Considerations for Healthy Aging and Reduction in Age-Related Chronic Disease.

PubMed

Shlisky, Julie; Bloom, David E; Beaudreault, Amy R; Tucker, Katherine L; Keller, Heather H; Freund-Levi, Yvonne; Fielding, Roger A; Cheng, Feon W; Jensen, Gordon L; Wu, Dayong; Meydani, Simin N

2017-01-01

A projected doubling in the global population of people aged ≥60 y by the year 2050 has major health and economic implications, especially in developing regions. Burdens of unhealthy aging associated with chronic noncommunicable and other age-related diseases may be largely preventable with lifestyle modification, including diet. However, as adults age they become at risk of "nutritional frailty," which can compromise their ability to meet nutritional requirements at a time when specific nutrient needs may be high. This review highlights the role of nutrition science in promoting healthy aging and in improving the prognosis in cases of age-related diseases. It serves to identify key knowledge gaps and implementation challenges to support adequate nutrition for healthy aging, including applicability of metrics used in body-composition and diet adequacy for older adults and mechanisms to reduce nutritional frailty and to promote diet resilience. This review also discusses management recommendations for several leading chronic conditions common in aging populations, including cognitive decline and dementia, sarcopenia, and compromised immunity to infectious disease. The role of health systems in incorporating nutrition care routinely for those aged ≥60 y and living independently and current actions to address nutritional status before hospitalization and the development of disease are discussed. © 2017 American Society for Nutrition.

Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines

PubMed Central

Rea, Irene Maeve; Gibson, David S.; McGilligan, Victoria; McNerlan, Susan E.; Alexander, H. Denis; Ross, Owen A.

2018-01-01

Cytokine dysregulation is believed to play a key role in the remodeling of the immune system at older age, with evidence pointing to an inability to fine-control systemic inflammation, which seems to be a marker of unsuccessful aging. This reshaping of cytokine expression pattern, with a progressive tendency toward a pro-inflammatory phenotype has been called “inflamm-aging.” Despite research there is no clear understanding about the causes of “inflamm-aging” that underpin most major age-related diseases, including atherosclerosis, diabetes, Alzheimer’s disease, rheumatoid arthritis, cancer, and aging itself. While inflammation is part of the normal repair response for healing, and essential in keeping us safe from bacterial and viral infections and noxious environmental agents, not all inflammation is good. When inflammation becomes prolonged and persists, it can become damaging and destructive. Several common molecular pathways have been identified that are associated with both aging and low-grade inflammation. The age-related change in redox balance, the increase in age-related senescent cells, the senescence-associated secretory phenotype (SASP) and the decline in effective autophagy that can trigger the inflammasome, suggest that it may be possible to delay age-related diseases and aging itself by suppressing pro-inflammatory molecular mechanisms or improving the timely resolution of inflammation. Conversely there may be learning from molecular or genetic pathways from long-lived cohorts who exemplify good quality aging. Here, we will discuss some of the current ideas and highlight molecular pathways that appear to contribute to the immune imbalance and the cytokine dysregulation, which is associated with “inflammageing” or parainflammation. Evidence of these findings will be drawn from research in cardiovascular disease, cancer, neurological inflammation and rheumatoid arthritis. PMID:29686666

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…

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

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.

Age-related changes in event-cued visual and auditory prospective memory proper.

PubMed

Uttl, Bob

2006-06-01

We rely upon prospective memory proper (ProMP) to bring back to awareness previously formed plans and intentions at the right place and time, and to enable us to act upon those plans and intentions. To examine age-related changes in ProMP, younger and older participants made decisions about simple stimuli (ongoing task) and at the same time were required to respond to a ProM cue, either a picture (visually cued ProM test) or a sound (auditorily cued ProM test), embedded in a simultaneously presented series of similar stimuli (either pictures or sounds). The cue display size or loudness increased across trials until a response was made. The cue size and cue loudness at the time of response indexed ProMP. The main results showed that both visual and auditory ProMP declined with age, and that such declines were mediated by age declines in sensory functions (visual acuity and hearing level), processing resources, working memory, intelligence, and ongoing task resource allocation.

Putting age-related task activation into large-scale brain networks: A meta-analysis of 114 fMRI studies on healthy aging.

PubMed

Li, Hui-Jie; Hou, Xiao-Hui; Liu, Han-Hui; Yue, Chun-Lin; Lu, Guang-Ming; Zuo, Xi-Nian

2015-10-01

Normal aging is associated with cognitive decline and underlying brain dysfunction. Previous studies concentrated less on brain network changes at a systems level. Our goal was to examine these age-related changes of fMRI-derived activation with a common network parcellation of the human brain function, offering a systems-neuroscience perspective of healthy aging. We conducted a series of meta-analyses on a total of 114 studies that included 2035 older adults and 1845 young adults. Voxels showing significant age-related changes in activation were then overlaid onto seven commonly referenced neuronal networks. Older adults present moderate cognitive decline in behavioral performance during fMRI scanning, and hypo-activate the visual network and hyper-activate both the frontoparietal control and default mode networks. The degree of increased activation in frontoparietal network was associated with behavioral performance in older adults. Age-related changes in activation present different network patterns across cognitive domains. The systems neuroscience approach used here may be useful for elucidating the underlying network mechanisms of various brain plasticity processes during healthy aging. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Declining performance of master athletes: silhouettes of the trajectory of healthy human ageing?

PubMed

Lazarus, Norman R; Harridge, Stephen D R

2017-05-01

Analysis of world record performances by master athletes suggests an essentially linear decline with age until around the eighth decade after which performance decline accelerates. Because these records are obtained from highly trained individuals they can be viewed as being reflective of the diminution of integrative physiological prowess that occurs solely as a result of ageing, unaffected by the confounding effects of inactivity. It can also be argued that these performance profiles mirror and provide an insight into the trajectory of the physiology of the human ageing process. Here we propose a set point theory that hypothesises that a given threshold of physical activity is needed to age optimally and to maximise the 'healthspan'. Exercising at levels below the set point will result in ageing being contaminated by the unpredictable and pathological effects of inactivity. Exercise above this threshold stimulates adaptations towards maximising athletic performance, but is unlikely to have further beneficial effects on health. Thus the decades-long, controlled diminution in athletic performance, should not be seen as a disease process. The ageing process is separate from, and independent of, exercise-mediated processes that maintain or adapt physiological function. Whether an understanding of these mechanisms will also help uncover mechanisms underpinning the ageing process itself is open to question. However, any model which does not take into account the effects of activity will not adequately describe the inherent ageing process. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Raspberry supplementation alleviates age-related motor dysfunction in select populations

USDA-ARS?s Scientific Manuscript database

Age-related declines in balance, muscle strength and coordination often lead to a higher incidence of falling. Among older adults, falls are the leading cause of distress, pain, injury, loss of confidence, and ultimately, loss of independence and death. Previous studies in our laboratory have demons...

[Effects of fertilizing regime and planting age on soil calcium decline in Luochuan apple orchards].

PubMed

Li, Peng; Li, Chun Yue; Wang, Yi Quan; Jiao, Cai Qiang

2017-05-18

This study was conducted to assess the effects of fertilizing regime and orchard planting age on soil calcium contents and stocks in the apple orchards on the Loess Plateau. The apple orchards in Luochuan County, one of the best regions for apple plantation in the world, were selec-ted in this study. The contents of calcium carbonate,water-soluble calcium and exchangeable cal-cium at 0-100 cm soil layer under different fertilizing regimes and various planting ages were mea-sured, their stocks were calculated and their variation features were analyzed. The results showed that soil in the apple orchards in the study region was characterized by the decline in calcium contents. The decline was more serious in apple orchards with long-term application of chemical fertili-zer than in those with combined application of chemical fertilizer and farmyard manure. The average contents of calcium carbonate, water-soluble calcium and exchangeable calcium at 0-100 cm soil layer in apple orchards with long-term application of chemical fertilizer decreased by 38.8%, 25.4% and 5.6% respectively than those in the apple orchards with long-term application of both chemical fertilizer and farmyard manure. The stocks of calcium carbonate, water-soluble calcium and exchangeable calcium decreased by 36.4%, 26.0% and 4.3%, respectively. The decline of soil cal-cium was aggravated with the increase of orchard planting age. The contents of calcium carbonate, water-soluble calcium and exchangeable calcium at 0-100 cm soil layer in orchards of more than 25 years of planting age decreased by 48.8%, 69.4% and 39.5% respectively, compared with orchards of less than 10 years of planting age, and the stocks decreased by 40.8%, 64.1% and 33.0%, respectively. These results indicated that either long-term application of chemical fertilizer or long-term plantation of apple trees obviously depleted soil calcium carbonate, water-soluble calcium and exchangeable calcium. Therefore, it was recommended that

Feature-selective attention in healthy old age: a selective decline in selective attention?

PubMed

Quigley, Cliodhna; Müller, Matthias M

2014-02-12

Deficient selection against irrelevant information has been proposed to underlie age-related cognitive decline. We recently reported evidence for maintained early sensory selection when older and younger adults used spatial selective attention to perform a challenging task. Here we explored age-related differences when spatial selection is not possible and feature-selective attention must be deployed. We additionally compared the integrity of feedforward processing by exploiting the well established phenomenon of suppression of visual cortical responses attributable to interstimulus competition. Electroencephalogram was measured while older and younger human adults responded to brief occurrences of coherent motion in an attended stimulus composed of randomly moving, orientation-defined, flickering bars. Attention was directed to horizontal or vertical bars by a pretrial cue, after which two orthogonally oriented, overlapping stimuli or a single stimulus were presented. Horizontal and vertical bars flickered at different frequencies and thereby elicited separable steady-state visual-evoked potentials, which were used to examine the effect of feature-based selection and the competitive influence of a second stimulus on ongoing visual processing. Age differences were found in feature-selective attentional modulation of visual responses: older adults did not show consistent modulation of magnitude or phase. In contrast, the suppressive effect of a second stimulus was robust and comparable in magnitude across age groups, suggesting that bottom-up processing of the current stimuli is essentially unchanged in healthy old age. Thus, it seems that visual processing per se is unchanged, but top-down attentional control is compromised in older adults when space cannot be used to guide selection.

Age-related changes in rostral basal forebrain cholinergic and GABAergic projection neurons: Relationship with spatial impairment

PubMed Central

Bañuelos, C.; LaSarge, C. L.; McQuail, J. A.; Hartman, J. J.; Gilbert, R. J.; Ormerod, B. K.; Bizon, J. L.

2013-01-01

Both cholinergic and GABAergic projections from the rostral basal forebrain have been implicated in hippocampal function and mnemonic abilities. While dysfunction of cholinergic neurons has been heavily implicated in age-related memory decline, significantly less is known regarding how age-related changes in co-distributed GABAergic projection neurons contribute to a decline in hippocampal-dependent spatial learning. In the current study, confocal stereology was used to quantify cholinergic (choline acetyltransferase (ChAT) immunopositive) neurons, GABAergic projection (glutamic decarboxylase 67 (GAD67) immunopositive) neurons, and total (NeuN immunopositive) neurons in the rostral basal forebrain of young and aged rats that were first characterized on a spatial learning task. ChAT immunopositive neurons were significantly but modestly reduced in aged rats. Although ChAT immunopositive neuron number was strongly correlated with spatial learning abilities among young rats, the reduction of ChAT immunopositive neurons was not associated with impaired spatial learning in aged rats. In contrast, the number of GAD67 immunopositive neurons was robustly and selectively elevated in aged rats that exhibited impaired spatial learning. Interestingly, the total number of rostral basal forebrain neurons was comparable in young and aged rats, regardless of their cognitive status. These data demonstrate differential effects of age on phenotypically distinct rostral basal forebrain projection neurons, and implicate dysregulated cholinergic and GABAergic septohippocampal circuitry in age-related mnemonic decline. PMID:22817834

An age-related deficit in spatial-feature reference memory in homing pigeons (Columba livia).

PubMed

Coppola, Vincent J; Flaim, Mary E; Carney, Samantha N; Bingman, Verner P

2015-03-01

Age-related memory decline in mammals has been well documented. By contrast, very little is known about memory decline in birds as they age. In the current study we trained younger and older homing pigeons on a reference memory task in which a goal location could be encoded by spatial and feature cues. Consistent with a previous working memory study, the results revealed impaired acquisition of combined spatial-feature reference memory in older compared to younger pigeons. Following memory acquisition, we used cue-conflict probe trials to provide an initial assessment of possible age-related differences in cue preference. Both younger and older pigeons displayed a similarly modest preference for feature over spatial cues. Copyright © 2014 Elsevier B.V. All rights reserved.

microRNA in Cardiovascular Aging and Age-Related Cardiovascular Diseases

PubMed Central

de Lucia, Claudio; Komici, Klara; Borghetti, Giulia; Femminella, Grazia Daniela; Bencivenga, Leonardo; Cannavo, Alessandro; Corbi, Graziamaria; Ferrara, Nicola; Houser, Steven R.; Koch, Walter J.; Rengo, Giuseppe

2017-01-01

Over the last decades, life expectancy has significantly increased although several chronic diseases persist in the population, with aging as the leading risk factor. Despite improvements in diagnosis and treatment, many elderlies suffer from cardiovascular problems that are much more frequent in an older, more fragile organism. In the long term, age-related cardiovascular diseases (CVDs) contribute to the decline of quality of life and ability to perform normal activities of daily living. microRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression at the posttranscriptional level in both physiological and pathological conditions. In this review, we will focus on the role of miRNAs in aging and age-related CVDs as heart failure, hypertension, atherosclerosis, atrial fibrillation, and diabetes mellitus. miRNAs are key regulators of complex biological mechanisms, representing an exciting potential therapeutic target in CVDs. Moreover, one major challenge in geriatric medicine is to find reliable biomarkers for diagnosis, prognosis, and prediction of the response to specific drugs. miRNAs represent a very promising tool due to their stability in the circulation and unique signature in CVDs. However, further studies are needed to investigate their translational potential in the real clinical practice. PMID:28660188

Age-related effects on perceptual and semantic encoding in memory.

PubMed

Kuo, M C C; Liu, K P Y; Ting, K H; Chan, C C H

2014-03-07

This study examined the age-related subsequent memory effect (SME) in perceptual and semantic encoding using event-related potentials (ERPs). Seventeen younger adults and 17 older adults studied a series of Chinese characters either perceptually (by inspecting orthographic components) or semantically (by determining whether the depicted object makes sounds). The two tasks had similar levels of difficulty. The participants made studied or unstudied judgments during the recognition phase. Younger adults performed better in both conditions, with significant SMEs detected in the time windows of P2, N3, P550, and late positive component (LPC). In the older group, SMEs were observed in the P2 and N3 latencies in both conditions but were only detected in the P550 in the semantic condition. Between-group analyses showed larger frontal and central SMEs in the younger sample in the LPC latency regardless of encoding type. Aging effect appears to be stronger on influencing perceptual than semantic encoding processes. The effects seem to be associated with a decline in updating and maintaining representations during perceptual encoding. The age-related decline in the encoding function may be due in part to changes in frontal lobe function. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Longitudinal association between hippocampus atrophy and episodic-memory decline.

PubMed

Gorbach, Tetiana; Pudas, Sara; Lundquist, Anders; Orädd, Greger; Josefsson, Maria; Salami, Alireza; de Luna, Xavier; Nyberg, Lars

2017-03-01

There is marked variability in both onset and rate of episodic-memory decline in aging. Structural magnetic resonance imaging studies have revealed that the extent of age-related brain changes varies markedly across individuals. Past studies of whether regional atrophy accounts for episodic-memory decline in aging have yielded inconclusive findings. Here we related 15-year changes in episodic memory to 4-year changes in cortical and subcortical gray matter volume and in white-matter connectivity and lesions. In addition, changes in word fluency, fluid IQ (Block Design), and processing speed were estimated and related to structural brain changes. Significant negative change over time was observed for all cognitive and brain measures. A robust brain-cognition change-change association was observed for episodic-memory decline and atrophy in the hippocampus. This association was significant for older (65-80 years) but not middle-aged (55-60 years) participants and not sensitive to the assumption of ignorable attrition. Thus, these longitudinal findings highlight medial-temporal lobe system integrity as particularly crucial for maintaining episodic-memory functioning in older age. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Aging and Visual Attention

PubMed Central

Madden, David J.

2007-01-01

Older adults are often slower and less accurate than are younger adults in performing visual-search tasks, suggesting an age-related decline in attentional functioning. Age-related decline in attention, however, is not entirely pervasive. Visual search that is based on the observer’s expectations (i.e., top-down attention) is relatively preserved as a function of adult age. Neuroimaging research suggests that age-related decline occurs in the structure and function of brain regions mediating the visual sensory input, whereas activation of regions in the frontal and parietal lobes is often greater for older adults than for younger adults. This increased activation may represent an age-related increase in the role of top-down attention during visual tasks. To obtain a more complete account of age-related decline and preservation of visual attention, current research is beginning to explore the relation of neuroimaging measures of brain structure and function to behavioral measures of visual attention. PMID:18080001

Workers who decline employment-related health insurance.

PubMed

Bernard, Didem M; Selden, Thomas M

2006-05-01

Families of workers who decline coverage represent a substantial share of the uninsured and publicly-insured population in the United States. We examined health status, access to health care, utilization, and expenditures among families that declined health insurance coverage offered by employers using data from the Medical Expenditure Panel Survey for 2001 and 2002. We found differences in insurance status for adults and children among families with offers. We found that among low-income families with offers, children are less likely to have private insurance compared with adults. However, the majority of children who decline private insurance end up with public coverage, whereas most of adults who decline offers remain uninsured. Decliners are more likely to report poor health, yet they are also less likely to have high cost medical conditions. Families declining coverage have weaker preferences for insurance than families that take up. Although access to care is lower among the decliners who remain uninsured, decliners with public insurance have similar access to care as those with private insurance. Families turning down coverage are more likely to face high expenditure burdens as a percentage of income and more likely to have financial barriers to care. Families who decline coverage rely heavily on the safety net. Public sources and uncompensated care account for 72% of total expenditures among adults who decline coverage. Our results suggest that policy initiatives aimed at increasing take up among workers need to take into account the incentives workers face given the availability of care through public sources and uncompensated care.

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

PubMed

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

2017-01-01

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

A greater decline in female facial attractiveness during middle age reflects women's loss of reproductive value.

PubMed

Maestripieri, Dario; Klimczuk, Amanda C E; Traficonte, Daniel M; Wilson, M Claire

2014-01-01

Facial attractiveness represents an important component of an individual's overall attractiveness as a potential mating partner. Perceptions of facial attractiveness are expected to vary with age-related changes in health, reproductive value, and power. In this study, we investigated perceptions of facial attractiveness, power, and personality in two groups of women of pre- and post-menopausal ages (35-50 years and 51-65 years, respectively) and two corresponding groups of men. We tested three hypotheses: (1) that perceived facial attractiveness would be lower for older than for younger men and women; (2) that the age-related reduction in facial attractiveness would be greater for women than for men; and (3) that for men, there would be a larger increase in perceived power at older ages. Eighty facial stimuli were rated by 60 (30 male, 30 female) middle-aged women and men using online surveys. Our three main hypotheses were supported by the data. Consistent with sex differences in mating strategies, the greater age-related decline in female facial attractiveness was driven by male respondents, while the greater age-related increase in male perceived power was driven by female respondents. In addition, we found evidence that some personality ratings were correlated with perceived attractiveness and power ratings. The results of this study are consistent with evolutionary theory and with previous research showing that faces can provide important information about characteristics that men and women value in a potential mating partner such as their health, reproductive value, and power or possession of resources.

HbA1c, diabetes and cognitive decline: the English Longitudinal Study of Ageing.

PubMed

Zheng, Fanfan; Yan, Li; Yang, Zhenchun; Zhong, Baoliang; Xie, Wuxiang

2018-04-01

The aim of the study was to evaluate longitudinal associations between HbA 1c levels, diabetes status and subsequent cognitive decline over a 10 year follow-up period. Data from wave 2 (2004-2005) to wave 7 (2014-2015) of the English Longitudinal Study of Ageing (ELSA) were analysed. Cognitive function was assessed at baseline (wave 2) and reassessed every 2 years at waves 3-7. Linear mixed models were used to evaluate longitudinal associations. The study comprised 5189 participants (55.1% women, mean age 65.6 ± 9.4 years) with baseline HbA 1c levels ranging from 15.9 to 126.3 mmol/mol (3.6-13.7%). The mean follow-up duration was 8.1 ± 2.8 years and the mean number of cognitive assessments was 4.9 ± 1.5. A 1 mmol/mol increment in HbA 1c was significantly associated with an increased rate of decline in global cognitive z scores (-0.0009 SD/year, 95% CI -0.0014, -0.0003), memory z scores (-0.0005 SD/year, 95% CI -0.0009, -0.0001) and executive function z scores (-0.0008 SD/year, 95% CI -0.0013, -0.0004) after adjustment for baseline age, sex, total cholesterol, HDL-cholesterol, triacylglycerol, high-sensitivity C-reactive protein, BMI, education, marital status, depressive symptoms, current smoking, alcohol consumption, hypertension, CHD, stroke, chronic lung disease and cancer. Compared with participants with normoglycaemia, the multivariable-adjusted rate of global cognitive decline associated with prediabetes and diabetes was increased by -0.012 SD/year (95% CI -0.022, -0.002) and -0.031 SD/year (95% CI -0.046, -0.015), respectively (p for trend <0.001). Similarly, memory, executive function and orientation z scores showed an increased rate of cognitive decline with diabetes. Significant longitudinal associations between HbA 1c levels, diabetes status and long-term cognitive decline were observed in this study. Future studies are required to determine the effects of maintaining optimal glucose control on the rate of cognitive decline in people

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

Cognitive decline, mortality, and organophosphorus exposure in aging Mexican Americans.

PubMed

Paul, Kimberly C; Ling, Chenxiao; Lee, Anne; To, Tu My; Cockburn, Myles; Haan, Mary; Ritz, Beate

2018-01-01

Cognitive impairment is a major health concern among older Mexican Americans, associated with significant morbidity and mortality, and may be influenced by environmental exposures. To investigate whether agricultural based ambient organophosphorus (OP) exposure influences 1) the rate of cognitive decline and mortality and 2) whether these associations are mediated through metabolic or inflammatory biomarkers. In a subset of older Mexican Americans from the Sacramento Area Latino Study on Aging (n = 430), who completed modified mini-mental state exams (3MSE) up to 7 times (1998-2007), we examined the relationship between estimated ambient OP exposures and cognitive decline (linear repeated measures model) and time to dementia or being cognitively impaired but not demented (CIND) and time to mortality (cox proportional hazards model). We then explored metabolic and inflammatory biomarkers as potential mediators of these relationships (additive hazards mediation). OP exposures at residential addresses were estimated with a geographic information system (GIS) based exposure assessment tool. Participants with high OP exposure in the five years prior to baseline experienced faster cognitive decline (β = 0.038, p = 0.02) and higher mortality over follow-up (HR = 1.91, 95% CI = 1.12, 3.26). The direct effect of OP exposure was estimated at 241 (95% CI = 27-455) additional deaths per 100,000 person-years, and the proportion mediated through the metabolic hormone adiponectin was estimated to be 4% 1.5-19.2). No other biomarkers were associated with OP exposure. Our study provides support for the involvement of OP pesticides in cognitive decline and mortality among older Mexican Americans, possibly through biologic pathways involving adiponectin. Copyright © 2017 Elsevier Inc. All rights reserved.

Central obesity, leptin and cognitive decline: the Sacramento Area Latino Study on Aging.

PubMed

Zeki Al Hazzouri, Adina; Haan, Mary N; Whitmer, Rachel A; Yaffe, Kristine; Neuhaus, John

2012-01-01

Central obesity is a risk factor for cognitive decline. Leptin is secreted by adipose tissue and has been associated with better cognitive function. Aging Mexican Americans have higher levels of obesity than non-Hispanic Whites, but no investigations examined the relationship between leptin and cognitive decline among them or the role of central obesity in this association. We analyzed 1,480 dementia-free older Mexican Americans who were followed over 10 years. Cognitive function was assessed every 12-15 months with the Modified Mini Mental State Exam (3MSE) and the Spanish and English Verbal Learning Test (SEVLT). For females with a small waist circumference (≤35 inches), an interquartile range difference in leptin was associated with 35% less 3MSE errors and 22% less decline in the SEVLT score over 10 years. For males with a small waist circumference (≤40 inches), an interquartile range difference in leptin was associated with 44% less 3MSE errors and 30% less decline in the SEVLT score over 10 years. There was no association between leptin and cognitive decline among females or males with a large waist circumference. Leptin interacts with central obesity in shaping cognitive decline. Our findings provide valuable information about the effects of metabolic risk factors on cognitive function. Copyright © 2012 S. Karger AG, Basel.

High-sensitivity C-reactive protein and cognitive decline: the English Longitudinal Study of Ageing.

PubMed

Zheng, Fanfan; Xie, Wuxiang

2018-06-01

High-sensitivity C-reactive protein (hs-CRP) has been suggested to be involved in the process of cognitive decline. However, the results from previous studies exploring the relationship between hs-CRP concentration and cognitive decline are inconsistent. We employed data from wave 2 (2004-2005) to wave 7 (2014-2015) of the English Longitudinal Study of Ageing. Cognitive function was assessed at baseline (wave 2) and reassessed biennially at waves 3-7. A total of 5257 participants (54.9% women, mean age 65.4 ± 9.4 years) with baseline hs-CRP levels ranged from 0.2 to 210.0 mg/L (median: 2.0 mg/L, interquartile range: 0.9-4.1 mg/L) were studied. The mean follow-up duration was 8.1 ± 2.8 years, and the mean number of cognitive assessment was 4.9 ± 1.5. Linear mixed models show that a one-unit increment in natural log-transformed hs-CRP was associated with faster declines in global cognitive scores [-0.048 points/year, 95% confidence interval (CI) -0.072 to -0.023], memory scores (-0.022 points/year, 95% CI -0.031 to -0.013), and executive function scores (-0.025 points/year, 95% CI -0.043 to -0.006), after multivariable adjustment. Compared with the lowest quartile of hs-CRP, the multivariable-adjusted rate of global cognitive decline associated with the second, third, and highest quartile was faster by -0.043 points/year (95% CI -0.116 to 0.029), -0.090 points/year (95% CI -0.166 to -0.015), -0.145 (95% CI -0.221 to -0.069), respectively (p for trend <0.001). Similarly, memory and executive function also declined faster with increasing quartiles of hs-CRP. A significant association between hs-CRP concentration and long-term cognitive decline was observed in this study. Hs-CRP might serve as a biomarker for cognitive decline.

Physical activity and motor decline in older persons.

PubMed

Buchman, A S; Boyle, P A; Wilson, R S; Bienias, Julia L; Bennett, D A

2007-03-01

We tested the hypothesis that physical activity modifies the course of age-related motor decline. More than 850 older participants of the Rush Memory and Aging Project underwent baseline assessment of physical activity and annual motor testing for up to 8 years. Nine strength measures and nine motor performance measures were summarized into composite measures of motor function. In generalized estimating equation models, global motor function declined during follow-up (estimate, -0.072; SE, 0.008; P < 0.001). Each additional hour of physical activity at baseline was associated with about a 5% decrease in the rate of global motor function decline (estimate, 0.004; SE, 0.001; P = 0.007). Secondary analyses suggested that the association of physical activity with motor decline was mostly due to the effect of physical activity on the rate of motor performance decline. Thus, higher levels of physical activity are associated with a slower rate of motor decline in older persons.

Age-associated and deslorelin-induced declines in serum anti-Müllerian hormone concentrations in female cheetahs, Acinonyx jubatus.

PubMed

Place, Ned J; Crosier, Adrienne E; Comizzoli, Pierre; Nagashima, Jennifer B; Haefele, Holly; Schmidt-Küntzel, Anne; Marker, Laurie L

2017-09-01

Anti-Müllerian hormone (AMH) is widely used in human medicine to non-invasively estimate the size of the ovarian follicle reserve and to predict the ovarian response to gonadotropin stimulation in the context of assisted reproductive technologies (e.g., IVF). These applications of AMH testing have recently expanded to non-human mammals, with production animals, such as cows, goats and sheep being the primary focus of AMH research. However, few investigations have involved exotic species, and in particular carnivores. In this study, we measured AMH concentrations (0.078-3.078ng/mL) in archived serum samples that had been collected from 36 adult female cheetahs across their reproductive lifespan (2-15years of age). Similar to other mammals, AMH concentration in cheetahs declined with age, and its variability among females of the same age was considerable. The rates at which AMH declined over time in individual cheetahs were also highly variable. Five cheetahs had been contracepted with the long-acting GnRH agonist deslorelin for 6-18months prior to sample collection, and their AMH concentrations were relatively low compared to untreated females. In this first study of AMH in an exotic carnivore, the findings demonstrate that the age-associated decline in AMH is highly variable and that deslorelin appears to suppress AMH concentration in serum. Owing to the increased use of assisted reproductive technologies in ex situ populations of threatened and endangered species, such as cheetahs, the present study's findings will need to be taken into consideration if AMH is to be used successfully to optimize breeding management decisions in exotic species. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2015-01-01

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

Nutritional Considerations for Healthy Aging and Reduction in Age-Related Chronic Disease12

PubMed Central

Shlisky, Julie; Bloom, David E; Beaudreault, Amy R; Tucker, Katherine L; Keller, Heather H; Freund-Levi, Yvonne; Fielding, Roger A; Cheng, Feon W; Jensen, Gordon L; Wu, Dayong; Meydani, Simin N

2017-01-01

A projected doubling in the global population of people aged ≥60 y by the year 2050 has major health and economic implications, especially in developing regions. Burdens of unhealthy aging associated with chronic noncommunicable and other age-related diseases may be largely preventable with lifestyle modification, including diet. However, as adults age they become at risk of “nutritional frailty,” which can compromise their ability to meet nutritional requirements at a time when specific nutrient needs may be high. This review highlights the role of nutrition science in promoting healthy aging and in improving the prognosis in cases of age-related diseases. It serves to identify key knowledge gaps and implementation challenges to support adequate nutrition for healthy aging, including applicability of metrics used in body-composition and diet adequacy for older adults and mechanisms to reduce nutritional frailty and to promote diet resilience. This review also discusses management recommendations for several leading chronic conditions common in aging populations, including cognitive decline and dementia, sarcopenia, and compromised immunity to infectious disease. The role of health systems in incorporating nutrition care routinely for those aged ≥60 y and living independently and current actions to address nutritional status before hospitalization and the development of disease are discussed. PMID:28096124

Age-related differences in the neural bases of phonological and semantic processes

PubMed Central

Diaz, Michele T.; Johnson, Micah A.; Burke, Deborah M.; Madden, David J.

2014-01-01

Changes in language functions during normal aging are greater for phonological compared to semantic processes. To investigate the behavioral and neural basis for these age-related differences, we used functional magnetic resonance imaging (fMRI) to examine younger and older adults who made semantic and phonological decisions about pictures. The behavioral performance of older adults was less accurate and less efficient than younger adults’ in the phonological task, but did not differ in the semantic task. In the fMRI analyses, the semantic task activated left-hemisphere language regions, while the phonological task activated bilateral cingulate and ventral precuneus. Age-related effects were widespread throughout the brain, and most often expressed as greater activation for older adults. Activation was greater for younger compared to older adults in ventral brain regions involved in visual and object processing. Although there was not a significant Age x Condition interaction in the whole-brain fMRI results, correlations examining the relationship between behavior and fMRI activation were stronger for younger compared to older adults. Our results suggest that the relationship between behavior and neural activation declines with age and this may underlie some of the observed declines in performance. PMID:24893737

Lifelong Bilingualism Contributes to Cognitive Reserve against White Matter Integrity Declines in Aging

PubMed Central

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

2013-01-01

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. PMID:24103400

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

PubMed

Koppik, Mareike; Fricke, Claudia

2017-12-01

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

Comprehensive Analysis of Large Sets of Age-Related Physiological Indicators Reveals Rapid Aging around the Age of 55 Years.

PubMed

Lixie, Erin; Edgeworth, Jameson; Shamir, Lior

2015-01-01

While many studies show a correlation between chronological age and physiological indicators, the nature of this correlation is not fully understood. To perform a comprehensive analysis of the correlation between chronological age and age-related physiological indicators. Physiological aging scores were deduced using principal component analysis from a large dataset of 1,227 variables measured in a cohort of 4,796 human subjects, and the correlation between the physiological aging scores and chronological age was assessed. Physiological age does not progress linearly or exponentially with chronological age: a more rapid physiological change is observed around the age of 55 years, followed by a mild decline until around the age of 70 years. These findings provide evidence that the progression of physiological age is not linear with that of chronological age, and that periods of mild change in physiological age are separated by periods of more rapid aging. © 2015 S. Karger AG, Basel.

Systemic Mesenchymal Stromal Cell Transplantation Prevents Functional Bone Loss in a Mouse Model of Age-Related Osteoporosis.

PubMed

Kiernan, Jeffrey; Hu, Sally; Grynpas, Marc D; Davies, John E; Stanford, William L

2016-05-01

Age-related osteoporosis is driven by defects in the tissue-resident mesenchymal stromal cells (MSCs), a heterogeneous population of musculoskeletal progenitors that includes skeletal stem cells. MSC decline leads to reduced bone formation, causing loss of bone volume and the breakdown of bony microarchitecture crucial to trabecular strength. Furthermore, the low-turnover state precipitated by MSC loss leads to low-quality bone that is unable to perform remodeling-mediated maintenance--replacing old damaged bone with new healthy tissue. Using minimally expanded exogenous MSCs injected systemically into a mouse model of human age-related osteoporosis, we show long-term engraftment and markedly increased bone formation. This led to improved bone quality and turnover and, importantly, sustained microarchitectural competence. These data establish proof of concept that MSC transplantation may be used to prevent or treat human age-related osteoporosis. This study shows that a single dose of minimally expanded mesenchymal stromal cells (MSCs) injected systemically into a mouse model of human age-related osteoporosis display long-term engraftment and prevent the decline in bone formation, bone quality, and microarchitectural competence. This work adds to a growing body of evidence suggesting that the decline of MSCs associated with age-related osteoporosis is a major transformative event in the progression of the disease. Furthermore, it establishes proof of concept that MSC transplantation may be a viable therapeutic strategy to treat or prevent human age-related osteoporosis. ©AlphaMed Press.

Systemic Mesenchymal Stromal Cell Transplantation Prevents Functional Bone Loss in a Mouse Model of Age-Related Osteoporosis

PubMed Central

Kiernan, Jeffrey; Hu, Sally; Grynpas, Marc D.

2016-01-01

Age-related osteoporosis is driven by defects in the tissue-resident mesenchymal stromal cells (MSCs), a heterogeneous population of musculoskeletal progenitors that includes skeletal stem cells. MSC decline leads to reduced bone formation, causing loss of bone volume and the breakdown of bony microarchitecture crucial to trabecular strength. Furthermore, the low-turnover state precipitated by MSC loss leads to low-quality bone that is unable to perform remodeling-mediated maintenance—replacing old damaged bone with new healthy tissue. Using minimally expanded exogenous MSCs injected systemically into a mouse model of human age-related osteoporosis, we show long-term engraftment and markedly increased bone formation. This led to improved bone quality and turnover and, importantly, sustained microarchitectural competence. These data establish proof of concept that MSC transplantation may be used to prevent or treat human age-related osteoporosis. Significance This study shows that a single dose of minimally expanded mesenchymal stromal cells (MSCs) injected systemically into a mouse model of human age-related osteoporosis display long-term engraftment and prevent the decline in bone formation, bone quality, and microarchitectural competence. This work adds to a growing body of evidence suggesting that the decline of MSCs associated with age-related osteoporosis is a major transformative event in the progression of the disease. Furthermore, it establishes proof of concept that MSC transplantation may be a viable therapeutic strategy to treat or prevent human age-related osteoporosis. PMID:26987353

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. © 2016 Wiley Periodicals, Inc.

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

PubMed

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

2010-05-01

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. 2010 Elsevier Ltd. All rights reserved.

Age-Related Phasic Patterns of Mitochondrial Maintenance in Adult Caenorhabditis elegans Neurons

PubMed Central

Morsci, Natalia S.; Hall, David H.

2016-01-01

Aging is associated with cognitive decline and increasing risk of neurodegeneration. Perturbation of mitochondrial function, dynamics, and trafficking are implicated in the pathogenesis of several age-associated neurodegenerative diseases. Despite this fundamental importance, the critical understanding of how organismal aging affects lifetime neuronal mitochondrial maintenance remains unknown, particularly in a physiologically relevant context. To address this issue, we performed a comprehensive in vivo analysis of age-associated changes in mitochondrial morphology, density, trafficking, and stress resistance in individual Caenorhabditis elegans neurons throughout adult life. Adult neurons display three distinct stages of increase, maintenance, and decrease in mitochondrial size and density during adulthood. Mitochondrial trafficking in the distal neuronal processes declines progressively with age starting from early adulthood. In contrast, long-lived daf-2 mutants exhibit delayed age-associated changes in mitochondrial morphology, constant mitochondrial density, and maintained trafficking rates during adulthood. Reduced mitochondrial load at late adulthood correlates with decreased mitochondrial resistance to oxidative stress. Revealing aging-associated changes in neuronal mitochondria in vivo is an essential precedent that will allow future elucidation of the mechanistic causes of mitochondrial aging. Thus, our study establishes the critical foundation for the future analysis of cellular pathways and genetic and pharmacological factors regulating mitochondrial maintenance in aging- and disease-relevant conditions. SIGNIFICANCE STATEMENT Using Caenorhabditis elegans as a model, we address long-standing questions: How does aging affect neuronal mitochondrial morphology, density, trafficking, and oxidative stress resistance? Are these age-related changes amenable to genetic manipulations that slow down the aging process? Our study illustrates that mitochondrial

Age-Related Changes to the Neural Correlates of Social Evaluation

PubMed Central

Cassidy, Brittany S.; Shih, Joanne Y.; Gutchess, Angela H.

2012-01-01

Recent work suggests the existence of a specialized neural system underlying social processing that may be relatively spared with age, unlike pervasive aging-related decline occurring in many cognitive domains. We investigated how neural mechanisms underlying social evaluation are engaged with age, and how age-related changes to socioemotional goals affect recruitment of regions within this network. In a functional MRI study, fifteen young and fifteen older adults formed behavior-based impressions of individuals. They also responded to a prompt that was interpersonally meaningful, social but interpersonally irrelevant, or non-social. Both age groups engaged regions implicated in mentalizing and impression formation when making social relative to non-social evaluations, including dorsal and ventral medial prefrontal cortices, precuneus, and temporoparietal junction. Older adults had increased activation over young in right temporal pole when making social relative to non-social evaluations, suggesting reliance on past experiences when evaluating others. Young had greater activation than old in posterior cingulate gyrus when making interpersonally irrelevant, compared to interpersonally meaningful, evaluations, potentially reflecting enhanced valuation of this information. The findings demonstrate the age-related preservation of the neural correlates underlying social evaluation, and suggest that functioning in these regions might be mediated by age-related changes in socioemotional goals. PMID:22439896

Distinct aspects of frontal lobe structure mediate age-related differences in fluid intelligence and multitasking

PubMed Central

Kievit, Rogier A.; Davis, Simon W.; Mitchell, Daniel J.; Taylor, Jason R.; Duncan, John; Tyler, Lorraine K.; Brayne, Carol; Bullmore, Ed; Calder, Andrew; Cusack, Rhodri; Dalgleish, Tim; Matthews, Fiona; Marslen-Wilson, William; Rowe, James; Shafto, Meredith; Campbell, Karen; Cheung, Teresa; Geerligs, Linda; McCarrey, Anna; Tsvetanov, Kamen; Williams, Nitin; Bates, Lauren; Emery, Tina; Erzinçlioglu, Sharon; Gadie, Andrew; Gerbase, Sofia; Georgieva, Stanimira; Hanley, Claire; Parkin, Beth; Troy, David; Allen, Jodie; Amery, Gillian; Amunts, Liana; Barcroft, Anne; Castle, Amanda; Dias, Cheryl; Dowrick, Jonathan; Fair, Melissa; Fisher, Hayley; Goulding, Anna; Grewal, Adarsh; Hale, Geoff; Hilton, Andrew; Johnson, Frances; Johnston, Patricia; Kavanagh-Williamson, Thea; Kwasniewska, Magdalena; McMinn, Alison; Norman, Kim; Penrose, Jessica; Roby, Fiona; Rowland, Diane; Sargeant, John; Squire, Maggie; Stevens, Beth; Stoddart, Aldabra; Stone, Cheryl; Thompson, Tracy; Yazlik, Ozlem; Barnes, Dan; Dixon, Marie; Hillman, Jaya; Mitchell, Joanne; Villis, Laura; Henson, Richard N.A.

2014-01-01

Ageing is characterized by declines on a variety of cognitive measures. These declines are often attributed to a general, unitary underlying cause, such as a reduction in executive function owing to atrophy of the prefrontal cortex. However, age-related changes are likely multifactorial, and the relationship between neural changes and cognitive measures is not well-understood. Here we address this in a large (N=567), population-based sample drawn from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) data. We relate fluid intelligence and multitasking to multiple brain measures, including grey matter in various prefrontal regions and white matter integrity connecting those regions. We show that multitasking and fluid intelligence are separable cognitive abilities, with differential sensitivities to age, which are mediated by distinct neural subsystems that show different prediction in older versus younger individuals. These results suggest that prefrontal ageing is a manifold process demanding multifaceted models of neurocognitive ageing. PMID:25519467

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

PubMed Central

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

2015-01-01

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

Age-related effects in the neocortical organization of chimpanzees: gray and white matter volume, cortical thickness, and gyrification.

PubMed

Autrey, Michelle M; Reamer, Lisa A; Mareno, Mary Catherine; Sherwood, Chet C; Herndon, James G; Preuss, Todd; Schapiro, Steve J; Hopkins, William D

2014-11-01

Among primates, humans exhibit the most profound degree of age-related brain volumetric decline in particular regions, such as the hippocampus and the frontal lobe. Recent studies have shown that our closest living relatives, the chimpanzees, experience little to no volumetric decline in gray and white matter over the adult lifespan. However, these previous studies were limited with a small sample of chimpanzees of the most advanced ages. In the present study, we sought to further test for potential age-related decline in cortical organization in chimpanzees by expanding the sample size of aged chimpanzees. We used the BrainVisa software to measure total brain volume, gray and white matter volumes, gray matter thickness, and gyrification index in a cross-sectional sample of 219 captive chimpanzees (8-53 years old), with 38 subjects being 40 or more years of age. Mean depth and cortical fold opening of 11 major sulci of the chimpanzee brains were also measured. We found that chimpanzees showed increased gyrification with age and a cubic relationship between age and white matter volume. For the association between age and sulcus depth and width, the results were mostly non-significant with the exception of one negative correlation between age and the fronto-orbital sulcus. In short, results showed that chimpanzees exhibit few age-related changes in global cortical organization, sulcus folding and sulcus width. These findings support previous studies and the theory that the age-related changes in the human brain is due to an extended lifespan. Copyright © 2014 Elsevier Inc. All rights reserved.

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

PubMed

Kröger, Hannes; Fritzell, Johan; Hoffmann, Rasmus

2016-01-01

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. 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. 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. 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.

Neighborhood socioeconomic context and cognitive decline among older Mexican Americans: results from the Sacramento Area Latino Study on Aging.

PubMed

Zeki Al Hazzouri, Adina; Haan, Mary N; Osypuk, Theresa; Abdou, Cleopatra; Hinton, Ladson; Aiello, Allison E

2011-08-15

In 1 previous study, it was shown that neighborhood socioeconomic disadvantage is associated with cognitive decline among Latinos. No studies have explored whether and to what extent individual-level socioeconomic factors account for the relation between neighborhood disadvantage and cognitive decline. The purpose of the present study was to assess the influence of neighborhood socioeconomic position (SEP) on cognitive decline and examine how individual-level SEP factors (educational level, annual income, and occupation) influenced neighborhood associations over the course of 10 years. Participants (n = 1,789) were community-dwelling older Mexican Americans from the Sacramento Area Latino Study on Aging. Neighborhood SEP was derived by linking the participant's individual data to the 2000 decennial census. The authors assessed cognitive function with the Modified Mini-Mental State Examination. Analyses used 3-level hierarchical linear mixed models of time within individuals within neighborhoods. After adjustment for individual-level sociodemographic characteristics, higher neighborhood SEP was significantly associated with cognitive function (β = -0.033; P < 0.05) and rates of decline (β = -0.0009; P < 0.10). After adjustment for individual educational level, neighborhood SEP remained associated with baseline cognition but not with rates of decline. Differences in individual educational levels explained most of the intra- and interneighborhood variance. These results suggest that the effect of neighborhood SEP on cognitive decline among Latinos is primarily accounted for by education.

High Resolution Topography of Age-Related Changes in Non-Rapid Eye Movement Sleep Electroencephalography

PubMed Central

Sprecher, Kate E.; Riedner, Brady A.; Smith, Richard F.; Tononi, Giulio; Davidson, Richard J.; Benca, Ruth M.

2016-01-01

Sleeping brain activity reflects brain anatomy and physiology. The aim of this study was to use high density (256 channel) electroencephalography (EEG) during sleep to characterize topographic changes in sleep EEG power across normal aging, with high spatial resolution. Sleep was evaluated in 92 healthy adults aged 18–65 years old using full polysomnography and high density EEG. After artifact removal, spectral power density was calculated for standard frequency bands for all channels, averaged across the NREM periods of the first 3 sleep cycles. To quantify topographic changes with age, maps were generated of the Pearson’s coefficient of the correlation between power and age at each electrode. Significant correlations were determined by statistical non-parametric mapping. Absolute slow wave power declined significantly with increasing age across the entire scalp, whereas declines in theta and sigma power were significant only in frontal regions. Power in fast spindle frequencies declined significantly with increasing age frontally, whereas absolute power of slow spindle frequencies showed no significant change with age. When EEG power was normalized across the scalp, a left centro-parietal region showed significantly less age-related decline in power than the rest of the scalp. This partial preservation was particularly significant in the slow wave and sigma bands. The effect of age on sleep EEG varies substantially by region and frequency band. This non-uniformity should inform the design of future investigations of aging and sleep. This study provides normative data on the effect of age on sleep EEG topography, and provides a basis from which to explore the mechanisms of normal aging as well as neurodegenerative disorders for which age is a risk factor. PMID:26901503

Declining Statewide Trends in Motor Vehicle Crashes and Injury-Related Hospital Admissions

PubMed Central

Dischinger, Patricia C.; Ryb, Gabriel E.; Kufera, Joseph A.; Ho, Shiu M.

2013-01-01

Numbers of crashes, rates of police-reported injury severity, and hospital admission rates were calculated for the ten year period between 2001 and 2010 in Maryland. Comparisons were made for two 5-year periods of 2001–2005 and 2006–2010. Crash characteristics remained similar for the two five-year periods, but there was a significant increase in occupant age. Declines in police-reported injury severity were noted for each of four age groups: 16–29, 30–54, 55–64, and 65+, with smaller declines among older occupants. In addition, there were significant declines in hospital admissions, comparing the two time periods. Although reductions in crashes may be attributable to various roadway, behavioral, and other safety improvement efforts, reductions in hospital admission rates most likely reflect major improvements in crashworthiness implemented during the past decade. For those admitted to hospitals, significant increases in injury severity were noted between the first and second time periods. There was an association between age and ISS, a measure of total bodily injury, with the highest ISS scores noted for the youngest and oldest groups (16–29 and 55+, respectively). In addition, there was a significant increase in the mean age over time, from 39 in 2001 to 43 in 2010, p<.001. In general, the incidence and severity of injuries increased for all body regions. There was also a significant increase in hospital mortality, although length of hospital stay remained the same. Given these trends, increased efforts need to focus on both injury prevention and treatment for the increasing population of older, sometimes frail, vehicle occupants. PMID:24406962

A greater decline in female facial attractiveness during middle age reflects women’s loss of reproductive value

PubMed Central

Maestripieri, Dario; Klimczuk, Amanda C. E.; Traficonte, Daniel M.; Wilson, M. Claire

2014-01-01

Facial attractiveness represents an important component of an individual’s overall attractiveness as a potential mating partner. Perceptions of facial attractiveness are expected to vary with age-related changes in health, reproductive value, and power. In this study, we investigated perceptions of facial attractiveness, power, and personality in two groups of women of pre- and post-menopausal ages (35–50 years and 51–65 years, respectively) and two corresponding groups of men. We tested three hypotheses: (1) that perceived facial attractiveness would be lower for older than for younger men and women; (2) that the age-related reduction in facial attractiveness would be greater for women than for men; and (3) that for men, there would be a larger increase in perceived power at older ages. Eighty facial stimuli were rated by 60 (30 male, 30 female) middle-aged women and men using online surveys. Our three main hypotheses were supported by the data. Consistent with sex differences in mating strategies, the greater age-related decline in female facial attractiveness was driven by male respondents, while the greater age-related increase in male perceived power was driven by female respondents. In addition, we found evidence that some personality ratings were correlated with perceived attractiveness and power ratings. The results of this study are consistent with evolutionary theory and with previous research showing that faces can provide important information about characteristics that men and women value in a potential mating partner such as their health, reproductive value, and power or possession of resources. PMID:24592253

Multiple prethymic defects underlie age-related loss of T progenitor competence

PubMed Central

Zediak, Valerie P.; Maillard, Ivan

2007-01-01

Aging in mice and humans is characterized by declining T-lymphocyte production in the thymus, yet it is unclear whether aging impacts the T-lineage potential of hematopoietic progenitors. Although alterations in the lymphoid progenitor content of aged mouse bone marrow (BM) have been described, irradiation-reconstitution experiments have failed to reveal defects in T-lineage potential of BM hematopoietic progenitors or purified hematopoietic stem cells (HSCs) from aged mice. Here, we assessed T-progenitor potential in unmanipulated recipient mice without conditioning irradiation. T-progenitor potential was reduced in aged BM compared with young BM, and this reduction was apparent at the earliest stages of intrathymic differentiation. Further, enriched populations of aged HSCs or multipotent progenitors (MPPs) gave rise to fewer T-lineage cells than their young counterparts. Whereas the T-precursor frequency within the MPP pool was unchanged, there was a 4-fold decline in T-precursor frequency within the HSC pool. In addition, among the T-competent HSC clones, there were fewer highly proliferative clones in the aged HSC pool than in the young HSC pool. These results identify T-compromised aged HSCs and define the nature and cellular sites of prethymic, age-related defects in T-lineage differentiation potential. PMID:17456721

Menopause Is Associated with Accelerated Lung Function Decline.

PubMed

Triebner, Kai; Matulonga, Bobette; Johannessen, Ane; Suske, Sandra; Benediktsdóttir, Bryndís; Demoly, Pascal; Dharmage, Shyamali C; Franklin, Karl A; Garcia-Aymerich, Judith; Gullón Blanco, José Antonio; Heinrich, Joachim; Holm, Mathias; Jarvis, Debbie; Jõgi, Rain; Lindberg, Eva; Moratalla Rovira, Jesús Martínez; Muniozguren Agirre, Nerea; Pin, Isabelle; Probst-Hensch, Nicole; Puggini, Luca; Raherison, Chantal; Sánchez-Ramos, José Luis; Schlünssen, Vivi; Sunyer, Jordi; Svanes, Cecilie; Hustad, Steinar; Leynaert, Bénédicte; Gómez Real, Francisco

2017-04-15

Menopause is associated with changes in sex hormones, which affect immunity, inflammation, and osteoporosis and may impair lung function. Lung function decline has not previously been investigated in relation to menopause. To study whether lung function decline, assessed by FVC and FEV 1 , is accelerated in women who undergo menopause. The population-based longitudinal European Community Respiratory Health Survey provided serum samples, spirometry, and questionnaire data about respiratory and reproductive health from three study waves (n = 1,438). We measured follicle-stimulating hormone and luteinizing hormone and added information on menstrual patterns to determine menopausal status using latent class analysis. Associations with lung function decline were investigated using linear mixed effects models, adjusting for age, height, weight, pack-years, current smoking, age at completed full-time education, spirometer, and including study center as random effect. Menopausal status was associated with accelerated lung function decline. The adjusted mean FVC decline was increased by -10.2 ml/yr (95% confidence interval [CI], -13.1 to -7.2) in transitional women and -12.5 ml/yr (95% CI, -16.2 to -8.9) in post-menopausal women, compared with women menstruating regularly. The adjusted mean FEV 1 decline increased by -3.8 ml/yr (95% CI, -6.3 to -2.9) in transitional women and -5.2 ml/yr (95% CI, -8.3 to -2.0) in post-menopausal women. Lung function declined more rapidly among transitional and post-menopausal women, in particular for FVC, beyond the expected age change. Clinicians should be aware that respiratory health often deteriorates during reproductive aging.

Age- and size-related changes in physiological characteristics and chemical composition of Acer pseudoplatanus and Fraxinus excelsior trees.

PubMed

Abdul-Hamid, Hazandy; Mencuccini, Maurizio

2009-01-01

Forest growth is an important factor both economically and ecologically, and it follows a predictable trend with age. Generally, growth accelerates as canopies develop in young forests and declines substantially soon after maximum leaf area is attained. The causes of this decline are multiple and may be linked to age- or size-related processes, or both. Our objective was to determine the relative effects of tree age and tree size on the physiological attributes of two broadleaf species. As age and size are normally coupled during growth, an approach based on grafting techniques to separate the effects of size from those of age was adopted. Genetically identical grafted seedlings were produced from scions taken from trees of four age classes, ranging from 4 to 162 years. We found that leaf-level net photosynthetic rate per unit of leaf mass and some other leaf structural and biochemical characteristics had decreased substantially with increasing size of the donor trees in the field, whereas other gas exchange parameters expressed on a leaf area basis did not. In contrast, these parameters remained almost constant in grafted seedlings, i.e., scions taken from donor trees with different meristematic ages show no age-related trend after they were grafted onto young rootstocks. In general, the results suggested that size-related limitations triggered the declines in photosynthate production and tree growth, whereas less evidence was found to support a role of meristematic age.

Age decline in the activity of the Ca2+-sensitive K+ channel of human red blood cells.

PubMed

Tiffert, Teresa; Daw, Nuala; Etzion, Zipora; Bookchin, Robert M; Lew, Virgilio L

2007-05-01

The Ca(2+)-sensitive K(+) channel of human red blood cells (RBCs) (Gardos channel, hIK1, hSK4) was implicated in the progressive densification of RBCs during normal senescence and in the mechanism of sickle cell dehydration. Saturating RBC Ca(2+) loads were shown before to induce rapid and homogeneous dehydration, suggesting that Gardos channel capacity was uniform among the RBCs, regardless of age. Using glycated hemoglobin as a reliable RBC age marker, we investigated the age-activity relation of Gardos channels by measuring the mean age of RBC subpopulations exceeding a set high density boundary during dehydration. When K(+) permeabilization was induced with valinomycin, the oldest and densest cells, which started nearest to the set density boundary, crossed it first, reflecting conservation of the normal age-density distribution pattern during dehydration. However, when Ca(2+) loads were used to induce maximal K(+) fluxes via Gardos channels in all RBCs (F(max)), the youngest RBCs passed the boundary first, ahead of the older RBCs, indicating that Gardos channel F(max) was highest in those young RBCs, and that the previously observed appearance of uniform dehydration concealed a substantial degree of age scrambling during the dehydration process. Further analysis of the Gardos channel age-activity relation revealed a monotonic decline in F(max) with cell age, with a broad quasi-Gaussian F(max) distribution among the RBCs.

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

PubMed

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

2016-04-01

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

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

Female age and sperm competition: last-male precedence declines as female age increases.

PubMed

Mack, Paul D; Priest, Nicholas K; Promislow, Daniel E L

2003-01-22

Until very recently, most studies of sperm competition have focused on variation in male competitive ability. However, we now know that a number of reproductive traits, including oviposition rate, use of stored sperm and receptivity to mating, vary with female condition. Because females can play an active part in the movement of sperm within their reproductive tract, sperm competition may be influenced by female condition. Existing studies of sperm competition in fruitflies ignore the effects of female condition, using females that are 3-4 days old and in their reproductive prime. But condition will decline as a female senesces. Here, we examine the effect of female age on the outcome of sperm competition in three strains of the fruitfly, Drosophila melanogaster. Previous studies have shown that female age influences preference for mates and male ejaculation strategies. In this study, we find that when males are mated to females that are older than 17 days, last-male sperm precedence decreases significantly. These results could lead to a greater understanding of the physiological mechanisms that regulate the outcome of sperm competition.

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

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…

Functional decline at the aging neuromuscular junction is associated with altered laminin-α4 expression.

PubMed

Lee, Kah Meng; Chand, Kirat K; Hammond, Luke A; Lavidis, Nickolas A; Noakes, Peter G

2017-03-14

Laminin-α4 is involved in the alignment of active zones to postjunctional folds at the neuromuscular junction (NMJ). Prior study has implicated laminin-α4 in NMJ maintenance, with altered NMJ morphology observed in adult laminin-α4 deficient mice ( lama 4 -/- ). The present study further investigated the role of laminin-α4 in NMJ maintenance by functional characterization of transmission properties, morphological investigation of synaptic proteins including synaptic laminin-α4, and neuromotor behavioral testing. Results showed maintained perturbed transmission properties at lama 4 -/- NMJs from adult (3 months) through to aged (18-22 months). Hind-limb grip force demonstrated similar trends as transmission properties, with maintained weaker grip force across age groups in lama 4 -/- . Interestingly, both transmission properties and hind-limb grip force in aged wild-types resembled those observed in adult lama 4 -/- . Most significantly, altered expression of laminin-α4 was noted at the wild-type NMJs prior to the observed decline in transmission properties, suggesting that altered laminin-α4 expression precedes the decline of neurotransmission in aging wild-types. These findings significantly support the role of laminin-α4 in maintenance of the NMJ during aging.

Accelerated aging-related transcriptome changes in the female prefrontal cortex

PubMed Central

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

2012-01-01

Human female life expectancy is higher than that of males. Intriguingly, it has been reported that women display faster rates of age-related cognitive decline and a higher prevalence of Alzheimer’s disease (AD). To assess the molecular bases of these contradictory trends, we analyzed differences in expression changes with age between adult males and females, in four brain regions. In the superior frontal gyrus (SFG), a part of the prefrontal cortex, we observed manifest differences between the two sexes in the timing of age-related changes, that is, sexual heterochrony. Intriguingly, age-related expression changes predominantly occurred earlier, or at a faster pace, in females compared to men. These changes included decreased energy production and neural function and up-regulation of the immune response, all major features of brain aging. Furthermore, we found that accelerated expression changes in the female SFG correlated with expression changes observed in AD, as well as stress effects in the frontal cortex. Accelerated aging-related changes in the female SFG transcriptome may provide a link between a higher stress exposure or sensitivity in women and the higher prevalence of AD. PMID:22783978

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

PubMed

Intlekofer, Karlie A; Cotman, Carl W

2013-09-01

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

The effects of minimum legal drinking age 21 laws on alcohol-related driving in the United States.

PubMed

McCartt, Anne T; Hellinga, Laurie A; Kirley, Bevan B

2010-04-01

To examine trends in alcohol consumption and alcohol-related crashes among people younger than 21 in the United States and to review evidence on the effects of minimum legal drinking age (MLDA) laws. Trends in alcohol-related crashes and alcohol consumption among young people were examined, and studies on the effects of lowering and raising the drinking age were reviewed. MLDA laws underwent many changes during the 20th century in the United States. Since July 1988, the MLDA has been 21 in all 50 states and the District of Columbia. Surveys tracking alcohol consumption among high school students and young adults found that drinking declined since the late 1970 s, and most of the decline occurred by the early 1990 s. These were the years when states were establishing, or reinstating, a MLDA-21. Among fatally injured drivers ages 16-20, the percentage with positive BACs declined from 61% in 1982 to 31% in 1995, a bigger decline than for older age groups; declines occurred among the ages directly affected by raising MLDAs (ages 18-20) and among young teenagers not directly affected (ages 16-17). Almost all studies designed specifically to gauge the effects of drinking age changes show MLDAs of 21 reduce drinking, problematic drinking, drinking and driving, and alcohol-related crashes among young people. Yet many underage people still drink, many drink and drive, and alcohol remains an important risk factor in serious crashes of young drivers, especially as they progress through the teenage years. Stepped-up enforcement of MLDA and drinking and driving laws can reduce underage drinking. Recent efforts to lower MLDAs to 18 and issue licenses to drink upon completion of alcohol education have gained local and national media attention. There is no evidence that alcohol education can even partially replace the effect of MLDA-21. The cause and effect relationship between MLDAs of 21 and reductions in highway crashes is clear. Initiatives to lower the drinking age to 18

An Event Related Potentials Study of the Effects of Age, Load and Maintenance Duration on Working Memory Recognition.

PubMed

Pinal, Diego; Zurrón, Montserrat; Díaz, Fernando

2015-01-01

Age-related decline in cognitive capacities has been attributed to a generalized slowing of processing speed and a reduction in working memory (WM) capacity. Nevertheless, it is unclear how age affects visuospatial WM recognition and its underlying brain electrical activity. Whether age modulates the effects of memory load or information maintenance duration, which determine the limits of WM, remains also elusive. In this exploratory study, performance in a delayed match to sample task declined with age, particularly in conditions with high memory load. Event related potentials analysis revealed longer N2 and P300 latencies in old than in young adults during WM recognition, which may reflect slowing of stimulus evaluation and classification processes, respectively. Although there were no differences between groups in N2 or P300 amplitudes, the latter was more homogeneously distributed in old than in young adults, which may indicate an age-related increased reliance in frontal vs parietal resources during WM recognition. This was further supported by an age-related reduced posterior cingulate activation and increased superior frontal gyrus activation revealed through standardized low resolution electromagnetic tomography. Memory load and maintenance duration effects on brain activity were similar in both age groups. These behavioral and electrophysiological results add evidence in support of age-related decline in WM recognition theories, with a slowing of processing speed that may be limited to stimulus evaluation and categorization processes--with no effects on perceptual processes--and a posterior to anterior shift in the recruitment of neural resources.

An Event Related Potentials Study of the Effects of Age, Load and Maintenance Duration on Working Memory Recognition

PubMed Central

Pinal, Diego; Zurrón, Montserrat; Díaz, Fernando

2015-01-01

Age-related decline in cognitive capacities has been attributed to a generalized slowing of processing speed and a reduction in working memory (WM) capacity. Nevertheless, it is unclear how age affects visuospatial WM recognition and its underlying brain electrical activity. Whether age modulates the effects of memory load or information maintenance duration, which determine the limits of WM, remains also elusive. In this exploratory study, performance in a delayed match to sample task declined with age, particularly in conditions with high memory load. Event related potentials analysis revealed longer N2 and P300 latencies in old than in young adults during WM recognition, which may reflect slowing of stimulus evaluation and classification processes, respectively. Although there were no differences between groups in N2 or P300 amplitudes, the latter was more homogeneously distributed in old than in young adults, which may indicate an age-related increased reliance in frontal vs parietal resources during WM recognition. This was further supported by an age-related reduced posterior cingulate activation and increased superior frontal gyrus activation revealed through standardized low resolution electromagnetic tomography. Memory load and maintenance duration effects on brain activity were similar in both age groups. These behavioral and electrophysiological results add evidence in support of age-related decline in WM recognition theories, with a slowing of processing speed that may be limited to stimulus evaluation and categorization processes -with no effects on perceptual processes- and a posterior to anterior shift in the recruitment of neural resources. PMID:26569113

[Predictors of verbal memory decline following temporal lobe surgery].

PubMed

de Vanssay-Maigne, A; Boutin, M; Baudoin-Chial, S

2008-05-01

Verbal memory decline can occur after temporal lobe surgery, especially when the left dominant hemisphere is involved. This potential functional risk must be evaluated before surgery. Among all factors that have been identified by several studies, the side of surgery (left dominant) and high baseline memory performance have been found to be predictive of verbal memory decline. Other factors such as etiology, sex, age at surgery, age at seizure onset, and duration may influence memory decline, but the results are not clear. Our purpose was to identify, in our population of patients and among all risk factors, those that may be predictive of verbal memory decline. Logistic regression was used to examine the effect of each factor on the postoperative verbal memory index (WMS-R) in 101 patients who underwent a right (n=49) or left (n=52) anterior temporal lobe resection. In the group as a whole, 22 % of the patients demonstrated verbal memory decline of more than one standard deviation. The verbal memory decline was significantly related to surgery on the left side and a high level of verbal memory performance. These factors were significant predictors of decline. The other factors (etiology, sex, age at surgery, age at seizure onset, and duration) were not found to be predictive of this decline. Our analysis demonstrates that the patients who are most at risk of undergoing verbal memory deterioration are those who undergo left-sided temporal resection and have good memory scores preoperatively. The contradictions found in the literature about the other factors could be explained by the diversity of the tests and criteria used to assess memory decline.

Declines in marathon performance: Sex differences in elite and recreational athletes.

PubMed

Zavorsky, Gerald S; Tomko, Kelly A; Smoliga, James M

2017-01-01

The first aim of this study was to determine the age group at which marathon performance declines in top male and female runners and to compare that to the runners of average ability. Another aim of this of this study was to examine the age-related yearly decline in marathon performance between age group winners and the average marathon finisher. Data from the New York (NYC), Boston, and Chicago marathons from 2001-2016 were analyzed. Age, sex, and location were used in multiple linear regression models to determine the rate of decline in marathon times. Winners of each age group were assessed in 5-year increments from 16 through 74 years old (n = 47 per age group). The fastest times were between 25-34 years old, with overall champion males at 28.3 years old, and overall champion females at 30.8 years old (p = 0.004). At 35 years of age up to 74 years of age, female age group winners had a faster yearly decline in marathon finishing times compared to male age group winners, irrespective of marathon location [women = (min:sec) 2:33 per year, n = 336; men = 2:06 per year, n = 373, p < 0.01]. The median times between each age group only slowed beginning at 50 years old, thereafter the decline was similar between both men and women (women = 2:36, n = 140; men = 2:57, n = 150, p = 0.11). The median times were fastest at Boston and similar between Chicago and NYC. In conclusion, the rate of decline at 35 years old up to 74 years old is roughly linear (adjusted r2 = 0.88, p < 0.001) with female age group winners demonstrating 27 s per year greater decline per year compared to male age group winners.

Declines in marathon performance: Sex differences in elite and recreational athletes

PubMed Central

Tomko, Kelly A.; Smoliga, James M.

2017-01-01

The first aim of this study was to determine the age group at which marathon performance declines in top male and female runners and to compare that to the runners of average ability. Another aim of this of this study was to examine the age-related yearly decline in marathon performance between age group winners and the average marathon finisher. Data from the New York (NYC), Boston, and Chicago marathons from 2001–2016 were analyzed. Age, sex, and location were used in multiple linear regression models to determine the rate of decline in marathon times. Winners of each age group were assessed in 5-year increments from 16 through 74 years old (n = 47 per age group). The fastest times were between 25–34 years old, with overall champion males at 28.3 years old, and overall champion females at 30.8 years old (p = 0.004). At 35 years of age up to 74 years of age, female age group winners had a faster yearly decline in marathon finishing times compared to male age group winners, irrespective of marathon location [women = (min:sec) 2:33 per year, n = 336; men = 2:06 per year, n = 373, p < 0.01]. The median times between each age group only slowed beginning at 50 years old, thereafter the decline was similar between both men and women (women = 2:36, n = 140; men = 2:57, n = 150, p = 0.11). The median times were fastest at Boston and similar between Chicago and NYC. In conclusion, the rate of decline at 35 years old up to 74 years old is roughly linear (adjusted r2 = 0.88, p < 0.001) with female age group winners demonstrating 27 s per year greater decline per year compared to male age group winners. PMID:28187185

FDG metabolism associated with tau-amyloid interaction predicts memory decline

PubMed Central

Hanseeuw, Bernard J.; Betensky, Rebecca A.; Schultz, Aaron P.; Papp, Kate V.; Mormino, Elizabeth C.; Sepulcre, Jorge; Bark, John S.; Cosio, Danielle M.; LaPoint, Molly; Chhatwal, Jasmeer P.; Rentz, Dorene M.; Sperling, Reisa A.; Johnson, Keith

2017-01-01

Objective To evaluate in normal older adults and preclinical Alzheimer’s disease (AD) the impact of amyloid and regional tauopathy on cerebral glucose metabolism and subsequent memory decline. Methods We acquired positron emission tomography using F18 Flortaucipir (tau), C11 Pittsburgh Compound B (amyloid) and F18 Fluorodeoxyglucose in 90 clinically normal elderly of the Harvard Aging Brain Study. Results Posterior cingulate metabolism decreased when both amyloid and neocortical tau were high and predicted subsequent memory decline in a larger sample of normal elderly. In contrast, frontal hypometabolism related to the common age-related entorhinal tauopathy, but this dysfunction was independent of amyloid, and did not predict significant memory decline. Neocortical tauopathy was positively associated with metabolism in individuals with sub-threshold amyloid, suggesting that glucose metabolism increases before decreasing in the course of preclinical AD. Interpretation Our study identified a synergistic effect of amyloid and tau deposits and demonstrated for the first time in normal elderly its link to AD-like hypometabolism and to AD-like memory decline. The amyloid effect was seen with tau in neocortex, but not with tau in entorhinal cortex, which is the common site of age-related tauopathy. Entorhinal tau was associated with frontal hypometabolism, but this dysfunction was not associated with memory loss. PMID:28253546

Age-Related Mitochondrial DNA Depletion and the Impact on Pancreatic Beta Cell Function

PubMed Central

Nile, Donna L.; Brown, Audrey E.; Kumaheri, Meutia A.; Blair, Helen R.; Heggie, Alison; Miwa, Satomi; Cree, Lynsey M.; Payne, Brendan; Chinnery, Patrick F.; Brown, Louise; Gunn, David A.; Walker, Mark

2014-01-01

Type 2 diabetes is characterised by an age-related decline in insulin secretion. We previously identified a 50% age-related decline in mitochondrial DNA (mtDNA) copy number in isolated human islets. The purpose of this study was to mimic this degree of mtDNA depletion in MIN6 cells to determine whether there is a direct impact on insulin secretion. Transcriptional silencing of mitochondrial transcription factor A, TFAM, decreased mtDNA levels by 40% in MIN6 cells. This level of mtDNA depletion significantly decreased mtDNA gene transcription and translation, resulting in reduced mitochondrial respiratory capacity and ATP production. Glucose-stimulated insulin secretion was impaired following partial mtDNA depletion, but was normalised following treatment with glibenclamide. This confirms that the deficit in the insulin secretory pathway precedes K+ channel closure, indicating that the impact of mtDNA depletion is at the level of mitochondrial respiration. In conclusion, partial mtDNA depletion to a degree comparable to that seen in aged human islets impaired mitochondrial function and directly decreased insulin secretion. Using our model of partial mtDNA depletion following targeted gene silencing of TFAM, we have managed to mimic the degree of mtDNA depletion observed in aged human islets, and have shown how this correlates with impaired insulin secretion. We therefore predict that the age-related mtDNA depletion in human islets is not simply a biomarker of the aging process, but will contribute to the age-related risk of type 2 diabetes. PMID:25532126

Age-related mitochondrial DNA depletion and the impact on pancreatic Beta cell function.

PubMed

Nile, Donna L; Brown, Audrey E; Kumaheri, Meutia A; Blair, Helen R; Heggie, Alison; Miwa, Satomi; Cree, Lynsey M; Payne, Brendan; Chinnery, Patrick F; Brown, Louise; Gunn, David A; Walker, Mark

2014-01-01

Type 2 diabetes is characterised by an age-related decline in insulin secretion. We previously identified a 50% age-related decline in mitochondrial DNA (mtDNA) copy number in isolated human islets. The purpose of this study was to mimic this degree of mtDNA depletion in MIN6 cells to determine whether there is a direct impact on insulin secretion. Transcriptional silencing of mitochondrial transcription factor A, TFAM, decreased mtDNA levels by 40% in MIN6 cells. This level of mtDNA depletion significantly decreased mtDNA gene transcription and translation, resulting in reduced mitochondrial respiratory capacity and ATP production. Glucose-stimulated insulin secretion was impaired following partial mtDNA depletion, but was normalised following treatment with glibenclamide. This confirms that the deficit in the insulin secretory pathway precedes K+ channel closure, indicating that the impact of mtDNA depletion is at the level of mitochondrial respiration. In conclusion, partial mtDNA depletion to a degree comparable to that seen in aged human islets impaired mitochondrial function and directly decreased insulin secretion. Using our model of partial mtDNA depletion following targeted gene silencing of TFAM, we have managed to mimic the degree of mtDNA depletion observed in aged human islets, and have shown how this correlates with impaired insulin secretion. We therefore predict that the age-related mtDNA depletion in human islets is not simply a biomarker of the aging process, but will contribute to the age-related risk of type 2 diabetes.

Complexity and Synchronicity of Resting State BOLD FMRI in Normal Aging and Cognitive Decline

PubMed Central

Liu, Collin Y; Krishnan, Anitha P; Yan, Lirong; Smith, Robert X; Kilroy, Emily; Alger, Jeffery R; Ringman, John M; Wang, Danny JJ

2012-01-01

Purpose To explore the use of approximate entropy (ApEn) as an index of the complexity and the synchronicity of resting state BOLD fMRI in normal aging and cognitive decline associated with familial Alzheimer’s disease (fAD). Materials and Methods Resting state BOLD fMRI data were acquired at 3T from 2 independent cohorts of subjects consisting of healthy young (age 23±2 years, n=8) and aged volunteers (age 66±3 years, n=8), as well as 22 fAD associated subjects (14 mutation carriers, age 41.2±15.8 years; and 8 non-mutation carrying family members, age 28.8±5.9 years). Mean ApEn values were compared between the two age groups, and correlated with cognitive performance in the fAD group. Cross-ApEn (C-ApEn) was further calculated to assess the asynchrony between precuneus and the rest of the brain. Results Complexity of brain activity measured by mean ApEn in gray and white matter decreased with normal aging. In the fAD group, cognitive impairment was associated with decreased mean ApEn in gray matter as well as decreased regional ApEn in right precuneus, right lateral parietal regions, left precentral gyrus, and right paracentral gyrus. A pattern of asynchrony between BOLD fMRI series emerged from C-ApEn analysis, with significant regional anti-correlation with cross-correlation coefficient of functional connectivity analysis. Conclusion ApEn and C-ApEn may be useful for assessing the complexity and synchronicity of brain activity in normal aging and cognitive decline associated with neurodegenerative diseases PMID:23225622