The Sociodemographic and Lifestyle Correlates of Epigenetic Aging in a Nationally Representative U.S. Study of Younger Adults

Abstract Importance Epigenetic clocks represent molecular evidence of disease risk and aging processes and have been used to identify how social and lifestyle characteristics are associated with accelerated biological aging. However, most of this research is based on older adult samples who already have measurable chronic disease. Objective To investigate whether and how sociodemographic and lifestyle characteristics are related to biological aging in a younger adult sample across a wide array of epigenetic clock(definition) measures. Design Nationally representative prospective cohort study. Setting United States (U.S.). Participants Data come from the National Longitudinal Study of Adolescent to Adult Health, a national cohort of adolescents in grades 7-12 in U.S. in 1994 followed for 25 years over five interview waves. Our analytic sample includes participants followed-up through Wave V in 2016-18 who provided blood samples for DNA methylation (DNAm) testing (n=4237) at Wave V. Exposure Sociodemographic (sex, race/ethnicity, immigrant status, socioeconomic status, geographic location) and lifestyle (obesity status, exercise, tobacco, and alcohol use) characteristics. Main Outcome Biological aging assessed from blood DNAm using 16 epigenetic clocks when the cohort was aged 33-44 in Wave V. Results While there is considerable variation in the mean and distribution of epigenetic clock estimates and in the correlations among the clocks, we found sociodemographic and lifestyle factors are more often associated with biological aging in clocks trained to predict current or dynamic phenotypes (e.g., PhenoAge, GrimAge and DunedinPACE) as opposed to clocks trained to predict chronological age alone (e.g., Horvath). Consistent and strong associations of faster biological aging were found for those with lower levels of education and income, and those with severe obesity, no weekly exercise, and tobacco use. Conclusions and Relevance Our study found important social and lifestyle factors associated with biological aging in a nationally representative cohort of younger-aged adults. These findings indicate that molecular processes underlying disease risk can be identified in adults entering midlife before disease is manifest and represent useful targets for interventions to reduce social inequalities in heathy aging and longevity. Key Points Question Are epigenetic clocks, measures of biological aging developed mainly on older-adult samples, meaningful for younger adults and associated with sociodemographic and lifestyle characteristics in expected patterns found in prior aging research? Findings Sociodemographic and lifestyle factors were associated with biological aging in clocks trained to predict morbidity and mortality showing accelerated aging among those with lower levels of education and income, and those with severe obesity, no weekly exercise, and tobacco use. Meaning Age-related molecular processes can be identified in younger-aged adults before disease manifests and represent potential interventions to reduce social inequalities in heathy aging and longevity.