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 research is based on samples of older adults who already have measurable chronic disease. OBJECTIVE: To investigate whether and how sociodemographic and lifestyle characteristics are associated with biological aging in a younger adult sample across a wide array of epigenetic clock measures. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted using data from the National Longitudinal Study of Adolescent to Adult Health, a US representative cohort of adolescents in grades 7 to 12 in 1994 followed up for 25 years to 2018 over 5 interview waves. Participants who provided blood samples at wave V (2016-2018) were analyzed, with samples tested for DNA methylation (DNAm) in 2021 to 2024. Data were analyzed from February 2023 to May 2024. EXPOSURE: Sociodemographic (sex, race and ethnicity, immigrant status, socioeconomic status, and geographic location) and lifestyle (obesity status by body mass index [BMI] in categories of reference range or underweight [<25], overweight [25 to <30], obesity [30 to <40], and severe obesity [≥40]; exercise level; tobacco use; and alcohol use) characteristics were assessed. MAIN OUTCOME AND MEASURE: Biological aging assessed from banked blood DNAm using 16 epigenetic clocks. RESULTS: Data were analyzed from 4237 participants (mean [SD] age, 38.4 [2.0] years; percentage [SE], 51.3% [0.01] female and 48.7% [0.01] male; percentage [SE], 2.7% [<0.01] Asian or Pacific Islander, 16.7% [0.02] Black, 8.7% [0.01] Hispanic, and 71.0% [0.03] White). Sociodemographic and lifestyle factors were more often associated with biological aging in clocks trained to estimate morbidity and mortality (eg, PhenoAge, GrimAge, and DunedinPACE) than clocks trained to estimate chronological age (eg, Horvath). For example, the β for an annual income less than $25 000 vs $100 000 or more was 1.99 years (95% CI, 0.45 to 3.52 years) for PhenoAgeAA, 1.70 years (95% CI, 0.68 to 2.72 years) for GrimAgeAA, 0.33 SD (95% CI, 0.17 to 0.48 SD) for DunedinPACE, and -0.17 years (95% CI, -1.08 to 0.74 years) for Horvath1AA. Lower education, lower income, higher obesity levels, no exercise, and tobacco use were associated with faster biological aging across several clocks; associations with GrimAge were particularly robust (no college vs college or higher: β = 2.63 years; 95% CI, 1.67-3.58 years; lower vs higher annual income: <$25 000 vs ≥$100 000: β = 1.70 years; 95% CI, 0.68-2.72 years; severe obesity vs no obesity: β = 1.57 years; 95% CI, 0.51-2.63 years; no weekly exercise vs ≥5 bouts/week: β = 1.33 years; 95% CI, 0.67-1.99 years; current vs no smoking: β = 7.16 years; 95% CI, 6.25-8.07 years). CONCLUSIONS AND RELEVANCE: This study found that important social and lifestyle factors were associated with biological aging in a nationally representative cohort of younger adults. These findings suggest that molecular processes underlying disease risk may be identified in adults entering midlife before disease is manifest and inform interventions aimed at reducing social inequalities in heathy aging and longevity.