scholarly journals Epigenetic clocks and obesity: towards the next frontier using integrative approaches and early life models

Author(s):  
Fasil Tekola-Ayele

Abstract Why people of the same age show differences in age-related functional decline, and whether biological aging can be slowed down through lifestyle changes and therapeutics is a subject of active research. Molecular tools that predict biological age based on DNA methylation markers, known as epigenetic clocks, are facilitating these efforts. In this issue, Kresovich et al. (Am J Epidemiol. 2020;XXX(XX):XXXX–XXXX) investigated a cohort of non-Hispanic white women, demonstrating positive relations between adiposity measures and the ticking rate of epigenetic clocks in blood. This commentary emphasizes that integrating molecular and genetic epidemiology approaches is crucial to dissect the complex relationship between obesity and epigenetic aging. The early life period is explored as a unique opportunity to gain novel insights into links between developmental processes and aging in later life. Lastly, the landscape of the next frontier in aging research is described in light of the imperative for transdisciplinary approaches to outline a shared vision and public health implementation dilemmas.

Author(s):  
Line Jee Hartmann Rasmussen ◽  
Avshalom Caspi ◽  
Antony Ambler ◽  
Andrea Danese ◽  
Maxwell Elliott ◽  
...  

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.


2016 ◽  
Vol 283 (1841) ◽  
pp. 20161760 ◽  
Author(s):  
Mathieu Douhard ◽  
Leif Egil Loe ◽  
Audun Stien ◽  
Christophe Bonenfant ◽  
R. Justin Irvine ◽  
...  

The internal predictive adaptive response (internal PAR) hypothesis predicts that individuals born in poor conditions should start to reproduce earlier if they are likely to have reduced performance in later life. However, whether this is the case remains unexplored in wild populations. Here, we use longitudinal data from a long-term study of Svalbard reindeer to examine age-related changes in adult female life-history responses to environmental conditions experienced in utero as indexed by rain-on-snow (ROS utero ). We show that females experiencing high ROS utero had reduced reproductive success only from 7 years of age, independent of early reproduction. These individuals were able to maintain the same annual reproductive success between 2 and 6 years as phenotypically superior conspecifics that experienced low ROS utero . Young females born after high ROS utero engage in reproductive events at lower body mass (about 2.5 kg less) than those born after low ROS utero . The mean fitness of females that experienced poor environmental conditions in early life was comparable with that of females exposed to good environmental conditions in early life. These results are consistent with the idea of internal PAR and suggest that the life-history responses to early-life conditions can buffer the delayed effects of weather on population dynamics.


2015 ◽  
Vol 7 (1) ◽  
pp. 1 ◽  
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya

BACKGROUND: An organism’s lifespan is inevitably accompanied by the aging process, which involves functional decline, a steady increase of a plethora of chronic diseases, and ultimately death. Thus, it has been an ongoing dream of mankind to improve healthspan and extend life.CONTENT: There are only a few proposed aging interventions: caloric restriction, exercise, and the use of low-molecular-weight compounds, including spermidine, metformin, resveratrol, and rapamycin. Resveratrol, a constituent of red wine, has long been suspected to have cardioprotective effects. Interest in this compound has been renewed in recent years, first from its identification as a chemopreventive agent for skin cancer, and subsequently from reports that it activates sirtuin deacetylases and extends the lifespans of lower organisms. Resveratrol have been shown to prevent and reduce the severity of age-related diseases such as atherosclerosis, stroke, myocardial infarct, diabetes, neurodegenerative diseases, osteoarthritis, tumors and metabolic syndrome, along with their ability to extend lifespan.SUMMARY: The purpose of aging research is the identification of interventions that may avoid or ameliorate the ravages of time. In other words, the quest is for healthy aging, where improved longevity is coupled to a corresponding healthspan extension. It is only by extending the healthy human lifespan that we will truly meet the premise of the Roman poet Cicero: “No one is so old as to think that he may not live a year.”KEYWORDS: aging, caloric restriction, mimetic, healthspan, sirtuin activator


2020 ◽  
Author(s):  
Emily N. W. Wheater ◽  
Susan D. Shenkin ◽  
Susana Muñoz Maniega ◽  
Maria Valdés Hernández ◽  
Joanna M. Wardlaw ◽  
...  

AbstractBirth weight, an indicator of fetal growth, is associated with cognitive outcomes in early life and risk of metabolic and cardiovascular disease across the life course. Cognitive ability in early life is predictive of cognitive ability in later life. Brain health in older age, defined by MRI features, is associated with cognitive performance. However, little is known about how variation in normal birth weight impacts on brain structure in later life. In a community dwelling cohort of participants in their early seventies we tested the hypothesis that birthweight is associated with the following MRI features: total brain (TB), grey matter (GM) and normal appearing white matter (NAWM) volumes; whiter matter hyperintensity (WMH) volume; a general factor of fractional anisotropy (gFA) and peak width skeletonised mean diffusivity (PSMD) across the white matter skeleton. We also investigated the associations of birthweight with cortical surface area, volume and thickness. Birthweight was positively associated with TB, GM and NAWM volumes in later life (β ≥ 0.194), and with regional cortical surface area but not gFA, PSMD, WMH volume, or cortical volume or thickness. These positive relationships appear to be explained by larger intracranial volume rather than by age-related tissue atrophy, and are independent of body height and weight in adulthood. This suggests that larger birthweight is linked to increased brain tissue reserve in older life, rather than a resilience to age-related changes in brain structure, such as tissue atrophy or WMH volume.Significance StatementCognitive brain ageing carries a high personal, societal and financial cost and understanding its developmental origins is important for identifying possible preventative strategies. In a sample of older participants from the Lothian Birth Cohort 1936 we were able to explore the neurobiological correlates of birth weight, which is indicative of the fetal experience. We find that higher birth weight is related to larger brain tissue volumes in later life, but does not modify the trajectory of age-related change. This suggests that early life growth confers preserved differentiation, rather than differential preservation with regards to brain reserve. That these effects are detectable into later life indicates that this variable may be valuable biomarker in the epidemiology of ageing.


Author(s):  
Li Chu ◽  
Yang Fang ◽  
Vivian Hiu-Ling Tsang ◽  
Helene H. Fung

Cognitive processing of social and nonsocial information changes with age. These processes range from the ones that serve “mere” cognitive functions, such as recall strategies and reasoning, to those that serve functions that pertain to self-regulation and relating to others. However, aging and the development of social cognition unfold in different cultural contexts, which may assume distinct social norms and values. Thus, the resulting age-related differences in cognitive and social cognitive processes may differ across cultures. On the one hand, biological aging could render age-related differences in social cognition universal; on the other hand, culture may play a role in shaping some age-related differences. Indeed, many aspects of cognition and social cognition showed different age and culture interactions, and this makes the study of these phenomena more complex. Future aging research on social cognition should take cultural influences into consideration.


2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S348-S348
Author(s):  
Daniel W Belsky

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.


2020 ◽  
pp. 1-11 ◽  
Author(s):  
S. Guyonnet ◽  
Y. Rolland ◽  
C. Takeda ◽  
P.-J. Ousset ◽  
I. Ader ◽  
...  

Background: The Geroscience field focuses on the core biological mechanisms of aging, which are involved in the onset of age-related diseases, as well as declines in intrinsic capacity (IC) (body functions) leading to dependency. A better understanding on how to measure the true age of an individual or biological aging is an essential step that may lead to the definition of putative markers capable of predicting healthy aging. Objectives: The main objective of the INStitute for Prevention healthy agIng and medicine Rejuvenative (INSPIRE) Platform initiative is to build a program for Geroscience and healthy aging research going from animal models to humans and the health care system. The specific aim of the INSPIRE human translational cohort (INSPIRE-T cohort) is to gather clinical, digital and imaging data, and perform relevant and extensive biobanking to allow basic and translational research on humans. Methods: The INSPIRE-T cohort consists in a population study comprising 1000 individuals in Toulouse and surrounding areas (France) of different ages (20 years or over - no upper limit for age) and functional capacity levels (from robustness to frailty, and even dependency) with follow-up over 10 years. Diversified data are collected annually in research facilities or at home according to standardized procedures. Between two annual visits, IC domains are monitored every 4-month by using the ICOPE Monitor app developed in collaboration with WHO. Once IC decline is confirmed, participants will have a clinical assessment and blood sampling to investigate markers of aging at the time IC declines are detected. Biospecimens include blood, urine, saliva, and dental plaque that are collected from all subjects at baseline and then, annually. Nasopharyngeal swabs and cutaneous surface samples are collected in a large subgroup of subjects every two years. Feces, hair bulb and skin biopsy are collected optionally at the baseline visit and will be performed again during the longitudinal follow up. Expected Results: Recruitment started on October 2019 and is expected to last for two years. Bio-resources collected and explored in the INSPIRE-T cohort will be available for academic and industry partners aiming to identify robust (set of) markers of aging, age-related diseases and IC evolution that could be pharmacologically or non-pharmacologically targetable. The INSPIRE-T will also aim to develop an integrative approach to explore the use of innovative technologies and a new, function and person-centered health care pathway that will promote a healthy aging.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 967-967
Author(s):  
Adam Turnbull ◽  
Giulia Poerio ◽  
Feng Lin ◽  
Jonathan Smallwood

Abstract Understanding how age-related changes in cognition manifest in the real world is an important goal for aging research. One means of capturing these changes involves “experience sampling” participant’s self-reported thoughts as they go about their daily lives. Previous research using this method has shown age-related changes in ongoing thought: e.g., older adults have fewer thoughts unrelated to the here-and-now. However, it is currently unclear how these changes reflect cognitive aging or lifestyle changes. 78 younger adults and 35 older adults rated their thought contents along 20 dimensions and the difficulty of their current activity in their daily lives. They also performed cognitive tasks in the laboratory. In a set of exploratory analyses using Principal Component Analysis (PCA), we found that older adults spent more time thinking positive, wanted thoughts, particularly in demanding contexts, suggesting they may use different strategies to regulate their emotions. In line with previous research, older adults spent less time mind wandering about their future selves. Past-related thought related to episodic memory differently in older and younger adults. Additionally, PCA analyses performed separately in older and younger adults showed high similarity to an analysis performed on the combined sample, suggesting a similar structure to ongoing daily life thought in older and younger adults. These findings inform the use of experience sampling to understand cognitive aging, highlighting the need to consider content along multiple dimensions as well as the context in which thoughts are reported when analyzing aging ongoing thought.


2015 ◽  
Vol 112 (30) ◽  
pp. E4104-E4110 ◽  
Author(s):  
Daniel W. Belsky ◽  
Avshalom Caspi ◽  
Renate Houts ◽  
Harvey J. Cohen ◽  
David L. Corcoran ◽  
...  

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.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 831-831
Author(s):  
Jamie Justice ◽  
Stephen Kritchevsky ◽  
George Kuchel ◽  
James Kirkland

Abstract Aging is the leading risk factor for many chronic diseases. Through traditional approaches to drug development and treatment focus on treating one disease at a time, the geroscience hypothesis posits that by targeting fundamental aging processes one could alleviate multiple age-related diseases. Now several geroscience-guided interventions are at the point of entering human clinical trials. To accelerate testing of this important hypothesis, an interdisciplinary Translational Geroscience Network (TGN; R33 AG061456) has recently been established. The TGN is a new national resource of aging research centers committed to working together toward complementary, small-scale, proof-of-concept “use case” clinical studies. One such pilot will be highlighted: a translational trial of senolytics, or drugs targeting the biological aging process cellular senescence in patients with idiopathic pulmonary fibrosis. The promise of geroscience provides another reason “why age matters”: by studying the basic biology of aging, we may open novel therapeutic opportunities for challenging age-related diseases.


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