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 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.

Familial Loss of a Loved One and Biological Aging

“…From 2018 to 2024, we conducted epigenome-wide profiling and construction of clocks, using whole-blood DNA for 4700 participants at wave 5 using the Infinium MethylationEPIC BeadChip JAMA Network Open | Genetics and Genomics array (Illumina, Inc), as previously described. 18 After standard quality control, we calculated 4 biological clocks, including GrimAge, PhenoAge, and Horvath, to assess epigenetic age acceleration, [19][20][21][22] and the DunedinPACE to assess pace of biological aging. 23,24 For analysis, Horvath, GrimAge, and PhenoAge were first residualized on chronological age and residuals were z-transformed to allow comparability across measures.…”