scholarly journals Social mobility and biological aging among older adults in the United States

2021 ◽  
Author(s):  
Gloria Huei-Jong Graf ◽  
Yalu Zhang ◽  
Benjamin W Domingue ◽  
Kathleen Mullan Harris ◽  
Meeraj Kothari ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Social Mobility ◽  
Healthy Aging ◽  
Upward Mobility ◽  
Blood Chemistry ◽  
The United States ◽  
Effect Sizes ◽  
Biological Aging ◽  
Educational Mobility ◽  
System Integrity

Lower socioeconomic status is associated with faster biological aging, the gradual and progressive decline in system integrity that accumulates with advancing age. Efforts to promote upward social mobility may therefore extend healthy lifespan. However, recent studies suggest that upward mobility may also have biological costs related to the stresses of crossing social boundaries. We analyzed blood-chemistry and DNA methylation (DNAm) data from n=9286 participants in the 2016 Health and Retirement Study (HRS) Venous Blood Study to test associations of life-course social mobility with biological aging. We quantified social mobility from childhood to later-life using data on childhood family characteristics, educational attainment, and wealth accumulation. We quantified biological aging using three DNA methylation "clocks" and three blood-chemistry algorithms. We observed substantial social mobility among study participants. Those who achieved upward mobility exhibited less-advanced and slower biological aging. Associations of upward mobility with less-advanced and slower aging were consistent for blood-chemistry and DNAm measures of biological aging and were similar for men and women and for Black and White Americans (Pearson-r effect-sizes ~0.2 for blood-chemistry measures and the DNAm GrimAge clock and DunedinPoAm pace-of-aging measures; effect-sizes were smaller for the DNAm PhenoAge clock). Analysis restricted to educational mobility revealed differential effects by racial identity, suggesting that mediating links between educational mobility and healthy aging may be disrupted by structural racism. In contrast, mobility producing accumulation of wealth appeared to benefit White and Black Americans equally, suggesting economic intervention to reduce wealth inequality may have potential to heal disparities in healthy 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 DunedinPACE, a DNA methylation biomarker of the pace of aging

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Daniel W Belsky ◽  
Avshalom Caspi ◽  
David L Corcoran ◽  
Karen Sugden ◽  
Richie Poulton ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Blood Test ◽  
Childhood Adversity ◽  
Effect Sizes ◽  
Biological Aging ◽  
Retest Reliability ◽  
Blood Biomarker ◽  
System Integrity ◽  
Test Retest Reliability ◽  
Single Time Point

Background: Measures to quantify changes in the pace of biological aging in response to intervention are needed to evaluate geroprotective interventions for humans. Previously we showed that quantification of the pace of biological aging from a DNA-methylation blood test was possible (Belsky et al. 2020). Here we report a next-generation DNA-methylation biomarker of Pace of Aging, DunedinPACE (for Pace of Aging Calculated from the Epigenome).Methods: We used data from the Dunedin Study 1972-3 birth cohort tracking within-individual decline in 19 indicators of organ-system integrity across four time points spanning two decades to model Pace of Aging. We distilled this two-decade Pace of Aging into a single-time-point DNA-methylation blood-test using elastic-net regression and a DNA-methylation dataset restricted to exclude probes with low test-retest reliability. We evaluated the resulting measure, named DunedinPACE, in five additional datasets.Results: DunedinPACE showed high test-retest reliability, was associated with morbidity, disability, and mortality, and indicated faster aging in young adults with childhood adversity. DunedinPACE effect-sizes were similar to GrimAge Clock effect-sizes. In analysis of incident morbidity, disability, and mortality, DunedinPACE and added incremental prediction beyond GrimAge.Conclusions: DunedinPACE is a novel blood biomarker of the pace of aging for gerontology and geroscience.Funding: This research was supported by US-National Institute on Aging grants AG032282, AG061378, AG066887, and UK Medical Research Council grant MR/P005918/1.

scholarly journals Testing DNA-methylation and blood-chemistry measures of biological aging in models of Black-White disparities in healthspan characteristics

2021 ◽  
Author(s):  
GH Graf ◽  
CL Crowe ◽  
M Kothari ◽  
D Kwon ◽  
JJ Manly ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Health Disparities ◽  
Daily Living ◽  
Blood Chemistry ◽  
The United States ◽  
Biological Aging ◽  
White Americans ◽  
Proof Of Concept ◽  
Black And White ◽  
Retirement Study

ABSTRACTBiological aging is a proposed mechanism through which social determinants drive health disparities. We conducted proof-of-concept testing of eight DNA-methylation and blood-chemistry quantifications of biological aging as mediators of disparities in healthspan between Black and White participants in the United States Health and Retirement Study (HRS; n=8231). We quantified biological aging from four DNA-methylation “clocks” (Horvath, Hannum, PhenoAge, and GrimAge), a DNA-methylation Pace of Aging (DunedinPoAm), and three blood-chemistry measures (PhenoAge, Klemera-Doubal method Biological Age, and homeostatic dysregulation). We quantified Black-White disparities in healthspan from tests of physical-performance, self-reported limitations to activities of daily living (ADLs), and physician-diagnosed chronic diseases. DNA-methylation and blood-chemistry quantifications of biological aging were moderately correlated (Pearson-r range 0.1-0.4). GrimAge, DunedinPoAm and all three blood-chemistry measures were associated with healthspan characteristics (10-25% increase in risk per SD of biological aging) and showed evidence of more advanced/faster biological aging in Black compared with White participants (Cohen’s d=.3-.5). In mediation analysis, these measures accounted for 19-48% of Black-White differences in healthspan-related characteristics. Evidence that Black Americans are both biologically older and aging more rapidly than White Americans of the same chronological age suggests that differences in aging may represent a novel pathway to understand and eliminate health disparities.

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.

Individual DNA Methylation Profile is Correlated with Age and can be Targeted to Modulate Healthy Aging and Longevity

2019 ◽  
Vol 25 (39) ◽  
pp. 4139-4149 ◽  
Author(s):  
Francesco Guarasci ◽  
Patrizia D'Aquila ◽  
Alberto Montesanto ◽  
Andrea Corsonello ◽  
Dina Bellizzi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mitochondrial Dna ◽  
Aging Process ◽  
Healthy Aging ◽  
Nuclear Dna ◽  
Epigenetic Modification ◽  
Biological Aging ◽  
Biomarkers Of Aging ◽  
Age Related

: Patterns of DNA methylation, the best characterized epigenetic modification, are modulated by aging. In humans, different studies at both site-specific and genome-wide levels have reported that modifications of DNA methylation are associated with the chronological aging process but also with the quality of aging (or biological aging), providing new perspectives for establishing powerful biomarkers of aging. : In this article, the role of DNA methylation in aging and longevity has been reviewed by analysing literature data about DNA methylation variations occurring during the lifetime in response to environmental factors and genetic background, and their association with the aging process and, in particular, with the quality of aging. Special attention has been devoted to the relationship between nuclear DNA methylation patterns, mitochondrial DNA epigenetic modifications, and longevity. Mitochondrial DNA has recently been reported to modulate global DNA methylation levels of the nuclear genome during the lifetime, and, in spite of the previous belief, it has been found to be the target of methylation modifications. : Analysis of DNA methylation profiles across lifetime shows that a remodeling of the methylome occurs with age and/or with age-related decline. Thus, it can be an excellent biomarker of aging and of the individual decline and frailty status. The knowledge about the mechanisms underlying these modifications is crucial since it might allow the opportunity for targeted treatment to modulate the rate of aging and longevity.

scholarly journals A toolkit for quantification of biological age from blood-chemistry and organ-function-test data: BioAge

2021 ◽  
Author(s):  
Dayoon Kwon ◽  
Daniel W Belsky
Keyword(s):  
Dna Methylation ◽  
Controlled Trial ◽  
Blood Chemistry ◽  
R Package ◽  
Biological Age ◽  
Superior Performance ◽  
Biological Aging ◽  
Measurement Tools ◽  
Population Science ◽  
Surrogate Measures

Methods to quantify biological aging are emerging as new measurement tools for epidemiology and population science and have been proposed as surrogate measures for healthy lifespan extension in geroscience clinical trials. Publicly available software packages to compute biological aging measurements from DNA methylation data have accelerated dissemination of these measures and generated rapid gains in knowledge about how different measures perform in a range of datasets. Biological age measures derived from blood chemistry data were introduced at the same time as the DNA methylation measures and, in multiple studies, demonstrate superior performance to these measures in prediction of healthy lifespan. However, their dissemination has been slow by comparison, resulting in a significant gap in knowledge. We developed a software package to help address this knowledge gap. The BioAge R package, available for download at GitHub (http://github.com/dayoonkwon/BioAge), implements three published methods to quantify biological aging based on analysis of chronological age and mortality risk: Klemera-Doubal Biological Age, PhenoAge, and homeostatic dysregulation. The package allows users to parametrize measurement algorithms using custom sets of biomarkers, to compare the resulting measurements to published versions of the Klemera-Doubal method and PhenoAge algorithms, and to score the measurements in new datasets. We applied BioAge to safety lab data from the CALERIETM randomized controlled trial, the first-ever human trial of long-term calorie restriction in healthy, non-obese adults, to test effects of intervention on biological aging. Results contribute evidence that CALERIE intervention slowed biological aging. BioAge is a toolkit to facilitate measurement of biological age for geroscience.

scholarly journals Socioeconomic position, social mobility, and health selection effects on allostatic load in the United States

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0254414
Author(s):  
Alexi Gugushvili ◽  
Grzegorz Bulczak ◽  
Olga Zelinska ◽  
Jonathan Koltai
Keyword(s):  
United States ◽  
Social Mobility ◽  
Socioeconomic Position ◽  
Allostatic Load ◽  
Upward Mobility ◽  
Disease Onset ◽  
Well Being ◽  
The United States ◽  
Adult Health ◽  
Health Selection

The contemporaneous association between higher socioeconomic position and better health is well established. Life course research has also demonstrated a lasting effect of childhood socioeconomic conditions on adult health and well-being. Yet, little is known about the separate health effects of intergenerational mobility—moving into a different socioeconomic position than one’s parents—among early adults in the United States. Most studies on the health implications of mobility rely on cross-sectional datasets, which makes it impossible to differentiate between health selection and social causation effects. In addition, understanding the effects of social mobility on health at a relatively young age has been hampered by the paucity of health measures that reliably predict disease onset. Analysing 4,713 respondents aged 25 to 32 from the National Longitudinal Study of Adolescent Health’s Waves I and IV, we use diagonal reference models to separately identify the effects of socioeconomic origin and destination, as well as social mobility on allostatic load among individuals in the United States. Using a combined measure of educational and occupational attainment, and accounting for individuals’ initial health, we demonstrate that in addition to health gradient among the socially immobile, individuals’ socioeconomic origin and destination are equally important for multi-system physiological dysregulation. Short-range upward mobility also has a positive and significant association with health. After mitigating health selection concerns in our observational data, this effect is observed only among those reporting poor health before experiencing social mobility. Our findings move towards the reconciliation of two theoretical perspectives, confirming the positive effect of upward mobility as predicted by the “rags to riches” perspective, while not contradicting potential costs associated with more extensive upward mobility experiences as predicted by the dissociative thesis.

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

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Daniel W Belsky ◽  
Avshalom Caspi ◽  
Louise Arseneault ◽  
Andrea Baccarelli ◽  
David L Corcoran ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Biological Aging ◽  
Surrogate Endpoints ◽  
Progressive Decline ◽  
Rates Of Change ◽  
System Integrity ◽  
Point Measure ◽  
Single Time Point ◽  
Time Point

Biological 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 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 pace of biological aging among individuals born the same year. We first modeled change-over-time in 18 biomarkers tracking organ-system integrity across 12 years of follow-up in n = 954 members of the Dunedin Study born in 1972–1973. Rates of change in each biomarker over ages 26–38 years 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 analysis in cohort studies and the CALERIE trial provide proof-of-principle for DunedinPoAm as a single-time-point measure of a person’s pace of biological aging.

scholarly journals Education and Intergenerational Social Mobility in Europe and the United States

2020 ◽  
Keyword(s):  
United States ◽  
World War Ii ◽  
Social Mobility ◽  
Upward Mobility ◽  
Social Background ◽  
The United States ◽  
Downward Mobility ◽  
Men And Women ◽  
Class Mobility ◽  
The Social

This book is about the role of education in shaping rates and patterns of intergenerational social mobility among men and women during the twentieth century. It examines intergenerational class mobility in the United States and seven European countries during this period. Class mobility compares the social class position of men and women with the class of the family they were born into. Mobility trends have been similar in all these countries, with increasing upward mobility among people born up to about 1950 and increasing downward mobility for those born later. The major driver of upward mobility was the massive changes in the occupational structure that took place in the thirty years after the end of World War II. Education was also important in promoting greater openness, not only through the growth of higher education, but also because, in many cases, the relationship between social background and educational attainment weakened.

scholarly journals Association of Facial Aging with DNA Methylation and Epigenetic Age Predictions

2018 ◽  
Author(s):  
Riccardo E Marioni ◽  
Daniel W Belsky ◽  
Ian J Deary ◽  
Wolfgang Wagner
Keyword(s):  
Dna Methylation ◽  
Healthy Aging ◽  
Later Life ◽  
Biological Age ◽  
Chronological Age ◽  
Biological Aging ◽  
Facial Aging ◽  
Epigenetic Age ◽  
All Cause Mortality ◽  
Facial Images

AbstractEvaluation of biological age, as opposed to chronological age, is of high relevance for interventions to increase healthy aging. Highly reproducible age-associated DNA methylation (DNAm) changes can be integrated into algorithms for epigenetic age predictions. These predictors have mostly been trained to correlate with chronological age, but they are also indicative for biological aging. For example accelerated epigenetic age of blood is associated with higher risk of all-cause mortality in later life. The perceived age of facial images (face-age) is also associated with all-cause mortality and other aging-associated traits. In this study, we therefore tested the hypothesis that an epigenetic predictor for biological age might be trained on face-age as surrogate for biological age, rather than on chronological age. Our data demonstrate that facial aging and DNAm changes in blood provide two independent measures for biological aging.

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