Chronological age is an imperfect estimate of molecular aging. Epigenetic age, derived from DNA methylation data, provides a more nuanced representation of aging-related biological processes. We examine the bidirectional relationship between epigenetic age and brain health events (stroke, dementia, late-life depression) using data from 4,018 participants. Participants with a prior brain health event are 4% epigenetically older (β = 0.04, SE = 0.01), indicating these conditions are associated with accelerated aging beyond that captured by chronological age. Additionally, a one standard deviation increase in epigenetic age is associated with 70% higher odds of experiencing a brain health event in the next four years (OR = 1.70, 95% CI = 1.16–2.50), suggesting epigenetic age acceleration is not just a consequence but also a predictor of poor brain health. Mendelian Randomization analyses replicate these findings, supporting their causal nature. Our results support using epigenetic age as a biomarker to evaluate interventions aimed at preventing and promoting recovery after brain health events.
Depression, but not anxiety, is associated with epigenetic age accelerations among Asian older adults
Aging is a complex biological process, and biological aging can be quantified by epigenetic clocks. Depression and anxiety are highly prevalent among older adults and are established risk factors for adverse health outcomes. However, their relationships with epigenetic age acceleration (EAA) remain unclear, particularly in Asian populations. Using data from the Diet and Healthy Aging cohort, the present study examined the associations between depressive and anxiety symptoms and EAA within community-dwelling older adults (aged ≥ 60 years, n = 672). Depressive symptoms were assessed using the Geriatric Depression Scale (GDS), and anxiety symptoms were measured using the Geriatric Anxiety Inventory (GAI). Linear mixed-effects models were fitted to all available observations to account for within-person clustering, with additional within-person change analysis conducted among participants with repeated DNA methylation profiles (n = 116). These were followed by rigorous sensitivity analyses to inspect robustness. We found that depressive symptoms, but not anxiety, were robustly associated with higher EAA, primarily indexed by PCPhenoEAA. In fully adjusted models, each standard deviation (SD) increase in depressive symptoms corresponded to a 0.087 SD increase in PCPhenoEAA (β = 0.087, 95% CI [0.023, 0.151], p = 0.008). Participants screening positive for depression (GDS ≥ 5) exhibited, on average, 0.244 SD higher PCPhenoEAA compared with those without depression (β = 0.244, 95% CI [0.027, 0.461], p = 0.030). Despite relatively stable EAA across the follow-up period, within-person change in depressive symptoms was associated with a concomitant increase in PCPhenoEAA. Our findings highlight depression as an important and potentially modifiable factor in delaying biological aging among older Asian adults, highlighting the need for timely screening and interventions to promote healthy aging.