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.