Association between epigenetic age acceleration and depressive symptoms in a prospective cohort study of urban-dwelling adults

Abstract

ObjectiveThis study tests associations of DNA methylation-based (DNAm) measures of epigenetic age acceleration (EAA) with cross-sectional and longitudinal depressive symptoms in an urban sample of middle-aged adults. MethodsWhite and African–American adult participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span study for whom DNA samples were analyzed (baseline age: 30–65 years) we included. We estimated three DNAm based EAA measures: (1) universal epigenetic age acceleration (AgeAccel); (2) intrinsic epigenetic age acceleration (IEAA); and (3) extrinsic epigenetic age acceleration (EEAA). Depressive symptoms were assessed using the 20-item Center for Epidemiological Studies-Depression scale total and sub-domain scores at baseline (2004–2009) and follow-up visits (2009–2013). Linear mixed-effects regression models were conducted, adjusting potentially confounding covariates, selection bias and multiple testing (N = 329 participants, ∼52% men, k = 1.9 observations/participant, mean follow-up time∼4.7 years). ResultsNone of the epigenetic age acceleration measures were associated with total depressive symptom scores at baseline or over time. IEAA – a measure of cellular epigenetic age acceleration irrespective of white blood cell composition – was cross-sectionally associated with decrement in “positive affect” in the total population (γ011± SE = −0.090 ± 0.030, P = 0.003, Cohen's D: −0.16) and among Whites (γ011 ± SE = −0.135 ± 0.048, P = 0.005, Cohen's D: −0.23), after correction for multiple testing. Baseline “positive affect” was similarly associated with AgeAccel. LimitationsLimitations included small sample size, weak-moderate effects and measurement error. ConclusionsIEAA and AgeAccel, two measures of EAA using Horvath algorithm, were linked to a reduced “positive affect”, overall and among Whites. Future studies are needed to replicate our findings and test bi-directional relationships.