Cumulative stress and epigenetic aging: Examining the role of psychological moderators

Cellular epigenetic aging has become an important marker of healthy or unhealthy aging. The current study examined whether lifelong cumulative stressors across multiple domains were linked with epigenetic age acceleration (EAA; i.e., epigenetic age greater than chronological age) and whether psychological factors moderated this association. Dimensions of psychological well-being were hypothesized as protective factors, while neuroticism was posited as a vulnerability factor.

Data from the Midlife in the United States (MIDUS) Genomics Project (N = 1,006) were used, which include deoxyribonucleic acid methylation data from a subset of participants in MIDUS Core Wave 2 and MIDUS Refresher Wave 1. Epigenetic aging values were calculated using the deoxyribonucleic acid methylation profiles at cytosine-phosphate-guanine sites. Cumulative stressors and psychological factors were assessed using the survey data at MIDUS Core Wave 2 and MIDUS Refresher Wave 1.

The results revealed that cumulative stressors were not directly associated with EAA but were contingent on the levels of psychological well-being and neuroticism. Specifically, higher levels of cumulative stressors were significantly linked to EAA, measured by GrimAge2, among those who had lower levels of psychological well-being (β = -.23 to -.36, SE = .12 to .13, p = .04 to < .01) or higher neuroticism (β = .26, SE = .12, p = .03). Conversely, EAA in individuals who had higher levels of psychological well-being or lower neuroticism was not impacted by the levels of cumulative stressors.

The findings underscore the importance of considering individual psychological assets and vulnerabilities in the pathways linking cumulative stressors to epigenetic aging. (PsycInfo Database Record (c) 2025 APA, all rights reserved).