scholarly journals INTEREST GROUP SESSION—EPIDEMIOLOGY OF AGING: BIOSOCIAL RESEARCH ON BRAIN AGING AND BIOLOGICAL AGING

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S348-S348
Author(s):  
Daniel W Belsky
Keyword(s):  
Life Course ◽  
Cognitive Aging ◽  
Brain Aging ◽  
Functional Decline ◽  
Biological Aging ◽  
Social Psychological ◽  
Aging Research ◽  
System Integrity ◽  
Organ Systems ◽  
The Brain

Abstract Our aging global population presents a new set of challenges for public health. Individual-disease focused models are becoming outmoded as geriatricians recognize multimorbidity and frailty as the central challenges in preserving health for older adults. Evidence from research into the biology of aging suggests that a set of common cellular-level processes underpin decline in system integrity that induces vulnerability to disease across multiple organ systems, including the brain. In parallel, research in life-course gerontology indicates that the roots of aging-related decline in system integrity extend from early life and encompass histories of social, psychological, and biochemical exposures. The research presented in this symposium aims to integrate these emerging paradigms in aging research by mapping connections among measures of aging in the brain and body and social, psychological, and nutrition exposures. Our symposium focuses on (1) links between social-psychological determinants of health and biological aging in the brain and body; and (2) social and behavioral protective factors that may buffer emerging biological risk in aging. The overarching goal of this symposium is to introduce an approach to gerontology that integrates geroscience with life-course social and psychiatric epidemiology to advance understanding of cognitive aging and functional decline, and ultimately identify novel interventions to extend healthy lifespan.

scholarly journals Quantification of biological aging in young adults

2015 ◽  
Vol 112 (30) ◽  
pp. E4104-E4110 ◽  
Author(s):  
Daniel W. Belsky ◽  
Avshalom Caspi ◽  
Renate Houts ◽  
Harvey J. Cohen ◽  
David L. Corcoran ◽  
...  
Keyword(s):  
Young Adults ◽  
Brain Aging ◽  
Multiple Organ ◽  
Biological Aging ◽  
Research Translation ◽  
Human Aging ◽  
Aging Research ◽  
Cross Sectional ◽  
Age Related ◽  
Organ Systems

Antiaging therapies show promise in model organism research. Translation to humans is needed to address the challenges of an aging global population. Interventions to slow human aging will need to be applied to still-young individuals. However, most human aging research examines older adults, many with chronic disease. As a result, little is known about aging in young humans. We studied aging in 954 young humans, the Dunedin Study birth cohort, tracking multiple biomarkers across three time points spanning their third and fourth decades of life. We developed and validated two methods by which aging can be measured in young adults, one cross-sectional and one longitudinal. Our longitudinal measure allows quantification of the pace of coordinated physiological deterioration across multiple organ systems (e.g., pulmonary, periodontal, cardiovascular, renal, hepatic, and immune function). We applied these methods to assess biological aging in young humans who had not yet developed age-related diseases. Young individuals of the same chronological age varied in their “biological aging” (declining integrity of multiple organ systems). Already, before midlife, individuals who were aging more rapidly were less physically able, showed cognitive decline and brain aging, self-reported worse health, and looked older. Measured biological aging in young adults can be used to identify causes of aging and evaluate rejuvenation therapies.

scholarly journals Multiscale Brain Aging in the Context of Neurodegeneration and Alzheimer's Disease

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 372-372
Author(s):  
Kyra Thrush ◽  
Yaroslav Markov
Keyword(s):  
Brain Aging ◽  
Functional Decline ◽  
Organ System ◽  
Normal Brain ◽  
Molecular Processes ◽  
Aging Research ◽  
Physical Trauma ◽  
New Approaches ◽  
Approaches To Study ◽  
The Brain

Abstract The brain, with a diverse array of specialized cells, regional substructures, and a relatively isolated microenvironment, represents a uniquely challenging organ system for aging research. The brain can experience physical trauma, interact with the periphery, and is responsible for cognitive and behavioral modifications that can feed back into the molecular processes of aging both within and external to the brain. Advances to our understanding and ability to intervene in the complexity that personifies brain aging and associated neurodegeneration will require integrated, multiscale approaches operating in tandem. Therefore, we have organized this symposium to highlight promising new approaches to study brain aging through the lens of multiple biological levels of organization. We will provide insight not only into normal brain aging, but will also suggest key spurious processes that may drive neurodegeneration and functional decline.

scholarly journals Association Between Elevated suPAR, a New Biomarker of Inflammation, and Accelerated Aging

2020 ◽  
Author(s):  
Line Jee Hartmann Rasmussen ◽  
Avshalom Caspi ◽  
Antony Ambler ◽  
Andrea Danese ◽  
Maxwell Elliott ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Functional Decline ◽  
Accelerated Aging ◽  
Multiple Organ ◽  
Biological Aging ◽  
Blood Levels ◽  
Urokinase Plasminogen Activator Receptor ◽  
Reactive Protein ◽  
Age Related ◽  
Organ Systems

Abstract Background To understand and measure the association between chronic inflammation, aging, and age-related diseases, broadly applicable standard biomarkers of systemic chronic inflammation are needed. We tested whether elevated blood levels of the emerging chronic inflammation marker soluble urokinase plasminogen activator receptor (suPAR) were associated with accelerated aging, lower functional capacity, and cognitive decline. Methods We used data from the Dunedin Study, a population-representative 1972–1973 New Zealand birth cohort (n = 1037) that has observed participants to age 45 years. Plasma suPAR levels were analyzed at ages 38 and 45 years. We performed regression analyses adjusted for sex, smoking, C-reactive protein, and current health conditions. Results Of 997 still-living participants, 875 (88%) had plasma suPAR measured at age 45. Elevated suPAR was associated with accelerated pace of biological aging across multiple organ systems, older facial appearance, and with structural signs of older brain age. Moreover, participants with higher suPAR levels had greater decline in physical function and cognitive function from childhood to adulthood compared to those with lower suPAR levels. Finally, improvements in health habits between ages 38 and 45 (smoking cessation or increased physical activity) were associated with less steep increases in suPAR levels over those years. Conclusions Our findings provide initial support for the utility of suPAR in studying the role of chronic inflammation in accelerated aging and functional decline.

scholarly journals GAIT SPEED AND CHILDHOOD-TO-MIDLIFE BRAIN HEALTH: RETHINKING GAIT

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S870-S870
Author(s):  
Line Rasmussen ◽  
Avshalom Caspi ◽  
Terrie Moffitt ◽  
Harvey J Cohen ◽  
Miriam C Morey ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Gait Speed ◽  
Functional Decline ◽  
Multiple Organ ◽  
Biological Aging ◽  
Brain Health ◽  
Organ Systems ◽  
Physical Functions ◽  
Physical Limitations ◽  
Midlife Adults

Abstract Background: Gait speed is a well-known predictor of functional decline and mortality in older adults, but little is known about the origins of gait speed earlier in life. We tested the hypothesis that slow gait reflects accelerated biological aging already at midlife, as well as poor neurocognitive functioning in childhood and childhood-to-midlife cognitive decline. Methods: Prospective study of the population-representative Dunedin Study birth cohort (n=1,037), followed to age 45 (until April 2019). We measured age-45 gait speed in 904 (90.7%) participants and tested associations with key life course factors. Results: The mean (SD) gait speeds (m/s) were: usual: 1.30 (0.17); dual task: 1.16 (0.23); and maximum: 1.99 (0.29). Among midlife adults, those with more physical limitations (β -0.27; P<.001), poorer physical functions (β 0.24–0.36; all P<.001), accelerated biological aging across multiple organ systems (β -0.33), older facial appearance (β -0.25), smaller brain volume (β 0.15), more cortical thinning (β 0.09), smaller cortical surface area (β 0.13), and more white matter hyperintensities (β -0.09) had slower gait speed, all P<.05. Participants with lower IQ in childhood (β 0.34) and midlife (β 0.38) and who exhibited childhood-to-midlife cognitive decline (β 0.10) had slower gait speed at midlife, all P<.01. Adults with poorer neurocognitive function as early as age 3 had slower gait in midlife (β 0.26; P<.001). Conclusion: Adults’ gait speed is more than an indicator of geriatric functional status, it is also an index of midlife aging and lifelong brain health.

scholarly journals Quantification of the pace of biological aging in humans through a blood test: The DunedinPoAm DNA methylation algorithm

2020 ◽  
Author(s):  
DW Belsky ◽  
A Caspi ◽  
L Arseneault ◽  
A Baccarelli ◽  
D Corcoran ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Functional Decline ◽  
Longitudinal Change ◽  
Biological Aging ◽  
Early Life Adversity ◽  
Progressive Decline ◽  
System Integrity ◽  
Aging Study ◽  
Point Measure

ABSTRACTBiological aging is the gradual, progressive decline in system integrity that occurs with advancing chronological age, causing morbidity and disability. Measurements of the pace of aging are needed to serve as surrogate endpoints in trials of therapies designed to prevent disease by slowing biological aging. We report a blood DNA-methylation measure that is sensitive to variation in the pace of biological aging among individuals born the same year. We first modeled longitudinal change in 18 biomarkers tracking organ-system integrity across 12 years of follow-up in the Dunedin birth cohort. Rates of change in each biomarker were composited to form a measure of aging-related decline, termed Pace of Aging. Elastic-net regression was used to develop a DNA-methylation predictor of Pace of Aging, called DunedinPoAm for Dunedin (P)ace (o)f (A)ging (m)ethylation. Validation analyses showed DunedinPoAm was associated with functional decline in the Dunedin Study and more advanced biological age in the Understanding Society Study, predicted chronic disease and mortality in the Normative Aging Study, was accelerated by early-life adversity in the E-risk Study, and DunedinPoAm prediction was disrupted by caloric restriction in the CALERIE trial. DunedinPoAm generally outperformed epigenetic clocks. Findings provide proof-of-principle for DunedinPoAm as a single-time-point measure of a person’s pace of biological aging.

scholarly journals Perceived Physical Fatigability: A Prognostic Marker of Biological, Organ System, and Brain Aging

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 207-207
Author(s):  
Nancy W Glynn ◽  
Eleanor Simonsick ◽  
Basil Eldadah
Keyword(s):  
Perceived Exertion ◽  
Cardiovascular Health ◽  
Brain Aging ◽  
Organ System ◽  
Rating Of Perceived Exertion ◽  
Prognostic Indicators ◽  
Biological Aging ◽  
Organ Systems ◽  
New Directions ◽  
Physical Task

Abstract Characterizing perceived physical fatigability enables researchers to quantify an individual’s susceptibility to experiencing fatigue in the context of a standardized physical task. This approach eliminates self-pacing, and is a less-biased, more sensitive means to measure the degree to which fatigue may limit activity. Our previous work with two validated measures of perceived fatigability, the Pittsburgh Fatigability Scale (PFS) and Borg Rating of Perceived Exertion (RPE) at the end of a standardized 5-minute treadmill walk, are prognostic indicators of phenotypic aging. This symposium will present new directions related to greater fatigability as a marker of biological aging, organ system health and functioning, as well as brain pathology and structure. Specifically, Mr. Katz will explore the relationship between leukocyte telomere length, a marker of biological aging, with PFS fatigability in participants from the Long Life Family Study. The other four papers use data from the Baltimore Longitudinal Study of Aging (BLSA) and RPE fatigability (RPE). Drs. Simonsick and Karikkineth investigate fatigability as an early marker of aging and disease related impacts on key organ systems, specifically diminished renal function as reflected in estimated Glomerular Filtration Rate and cardiovascular health evaluated as vascular stiffness. Ms. Liu and Dr. Schrack will share whether there are associations of perceived fatigability with brain health, specifically Alzheimer’s disease-related pathology (PiB) and changes in brain structure. Lastly, our Discussant, Dr. Eldadah, will critically review the presentations in the context of new directions in fatigability research.

scholarly journals CDKN2A Gene Expression as a Potential Aging Biomarker in Dogs

2021 ◽  
Vol 8 ◽  
Author(s):  
Sára Sándor ◽  
Kitti Tátrai ◽  
Kálmán Czeibert ◽  
Balázs Egyed ◽  
Enikő Kubinyi
Keyword(s):  
Gene Expression ◽  
Kinase Inhibitor ◽  
Brain Aging ◽  
Model Organisms ◽  
Aging Research ◽  
Temporal Muscle ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Age Related ◽  
The Brain

Describing evolutionary conserved physiological or molecular patterns, which can reliably mark the age of both model organisms and humans or predict the onset of age-related pathologies has become a priority in aging research. The age-related gene-expression changes of the Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) gene have been well-documented in humans and rodents. However, data is lacking from other relevant species, including dogs. Therefore, we quantified the CDKN2A mRNA abundance in dogs of different ages, in four tissue types: the frontal cortex of the brain, temporal muscle, skin, and blood. We found a significant, positive correlation between CDKN2A relative expression values and age in the brain, muscle, and blood; however, no correlation was detected in the skin. The strongest correlation was detected in the brain tissue (CDKN2A/GAPDH: r = 0.757, p < 0.001), similarly to human findings, while the muscle and blood showed weaker, but significant correlation. Our results suggest that CDKN2A might be a potential blood-borne biomarker of aging in dogs, although the validation and optimization will require further, more focused research. Our current results also clearly demonstrate that the role of CDKN2A in aging is conserved in dogs, regarding both tissue specificity and a pivotal role of CDKN2A in brain aging.

scholarly journals Quantification of the pace of biological aging in humans through a blood test: the DunedinPACE DNA methylation algorithm

2021 ◽  
Author(s):  
Daniel W Belsky ◽  
Avshalom Caspi ◽  
David L Corcoran ◽  
Karen Sugden ◽  
Richie Poulton ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Blood Test ◽  
Functional Decline ◽  
Childhood Adversity ◽  
Original Method ◽  
Effect Sizes ◽  
Biological Aging ◽  
Retest Reliability ◽  
System Integrity ◽  
Test Retest Reliability

Measures to quantify changes in the pace of biological aging in response to intervention are needed to evaluate geroprotective interventions for humans. Here, we report an advance on our original method (Belsky et al. 2020). We used data from the Dunedin Study 1972-3 birth cohort tracking within-individual decline in 19 organ-system integrity indicators across four timepoints spanning two decades to model Pace of Aging. We distilled two-decade Pace of Aging into a single-time-point DNA-methylation blood-test using elastic-net regression and DNA-methylation data restricted to exclude probes with low test-retest reliability. The resulting measure, DunedinPACE, showed high test-retest reliability, was associated with functional decline, morbidity, and mortality, and indicated accelerated Pace of Aging in young adults with childhood adversity across five datasets. DunedinPACE effect-sizes were similar to GrimAge-clock effect-sizes and larger than those for other benchmark DNA-methylation-clocks. DunedinPACE is a novel blood biomarker of the pace of aging for gerontology and geroscience

scholarly journals The Shifting Architecture of Cognition and Brain Function in Older Adulthood

2019 ◽  
Vol 14 (4) ◽  
pp. 523-542 ◽  
Author(s):  
R. Nathan Spreng ◽  
Gary R. Turner
Keyword(s):  
Real World ◽  
Cognitive Aging ◽  
Network Architecture ◽  
Semantic Processing ◽  
Brain Aging ◽  
Cognitive Architecture ◽  
Later Life ◽  
Integrative Model ◽  
Older Adulthood ◽  
The Brain

Cognitive aging is often described in the context of loss or decline. Emerging research suggests that the story is more complex, with older adults showing both losses and gains in cognitive ability. With increasing age, declines in controlled, or fluid, cognition occur in the context of gains in crystallized knowledge of oneself and the world. This inversion in cognitive capacities, from greater reliance on fluid abilities in young adulthood to increasingly crystallized or semanticized cognition in older adulthood, has profound implications for cognitive and real-world functioning in later life. The shift in cognitive architecture parallels changes in the functional network architecture of the brain. Observations of greater functional connectivity between lateral prefrontal brain regions, implicated in cognitive control, and the default network, implicated in memory and semantic processing, led us to propose the default-executive coupling hypothesis of aging. In this review we provide evidence that these changes in the functional architecture of the brain serve as a neural mechanism underlying the shifting cognitive architecture from younger to older adulthood. We incorporate findings spanning cognitive aging and cognitive neuroscience to present an integrative model of cognitive and brain aging, describing its antecedents, determinants, and implications for real-world functioning.

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