Psychological adversities and epigenetic ageing in midlife and older age: A systematic review and meta-analysis

Background Epigenetic modification is a hallmark of aging that encloses physiological information relevant to health and longevity and has been used to construct epigenetic clocks that estimate epigenetic age acceleration (EAA) to monitor population health across the life span. Psychological adversities (PA) are recognized contributors to poor health; however, their potential role in EAA remains insufficiently understood in older adults. Objective This study systematically reviews and meta-analyzes the association between PA and EAA from midlife onward. Methods Eligible literatures were indexed in five databases up to July 2025. Study quality was assessed using an adapted Newcastle-Ottawa scale. Meta-analyses were performed using random-effects models, followed by post hoc and sensitivity analyses to assess robustness. Results Twenty-two studies were included, of which fifteen were classified as high quality. Irrespective of the type of psychological adversity, positive associations were consistently observed for second-generation epigenetic clocks (PhenoAge and GrimAge). Meta-analyses revealed that greater loneliness (β = 0.07, 95 % CI [0.06, 0.08], I 2 = 0 %, p = 0.002), depression (β = 0.08, 95 % CI [0.04, 0.13], I 2 = 55.2 %, p = 0.003), and stress (β = 0.10, 95 % CI [0.03, 0.16], I2 = 68.4 %, p = 0.009) were each associated with higher EAA. Conclusions Psychosocial stress, depression, and loneliness are each associated with accelerated aging from midlife onward. Notable gaps include the lack of studies examining anxiety and underrepresentation of non-Western population. Whether alleviating psychological adversities translates into decelerated aging trajectories requests future intervention studies.