Abstract
Our society is experiencing more stress than ever before, leading to both negative psychiatric and physical outcomes. Chronic stress is linked to negative long-term health consequences, raising the possibility that stress is related to accelerated aging. In this study, we examine whether resilience factors affect stress-associated biological age acceleration. Recently developed “epigenetic clocks” such as GrimAge have shown utility in predicting biological age and mortality. Here, we assessed the impact of cumulative stress, stress physiology, and resilience on accelerated aging in a community sample (N = 444). Cumulative stress was associated with accelerated GrimAge (P = 0.0388) and stress-related physiologic measures of adrenal sensitivity (Cortisol/ACTH ratio) and insulin resistance (HOMA). After controlling for demographic and behavioral factors, HOMA correlated with accelerated GrimAge (P = 0.0186). Remarkably, psychological resilience factors of emotion regulation and self-control moderated these relationships. Emotion regulation moderated the association between stress and aging (P = 8.82e−4) such that with worse emotion regulation, there was greater stress-related age acceleration, while stronger emotion regulation prevented any significant effect of stress on GrimAge. Self-control moderated the relationship between stress and insulin resistance (P = 0.00732), with high self-control blunting this relationship. In the final model, in those with poor emotion regulation, cumulative stress continued to predict additional GrimAge Acceleration even while accounting for demographic, physiologic, and behavioral covariates. These results demonstrate that cumulative stress is associated with epigenetic aging in a healthy population, and these associations are modified by biobehavioral resilience factors.
Highlights
Cumulative stress can have adverse psychiatric and physical effects, increasing risk for cardiometabolic diseases, mood disorders, post-traumatic stress disorder and addiction [1,2,3,4,5,6,7,8,9,10,11]
We focus on GrimAge acceleration (GAA), which is defined as the residuals of a linear correlation of GrimAge to chronologic age
In this study, we report novel findings that cumulative stress is associated with accelerated epigenetic aging in a healthy, youngto-middle-aged community sample, even after adjusting for sex, race, BMI, smoking, alcohol use, income, marital status, and education
Summary
Cumulative stress can have adverse psychiatric and physical effects, increasing risk for cardiometabolic diseases, mood disorders, post-traumatic stress disorder and addiction [1,2,3,4,5,6,7,8,9,10,11]. We hypothesized that cumulative stress will be positively associated with GrimAge Acceleration (GAA), that stress effects on GrimAge will be related to changes in the hypothalamic-pituitary-adrenal axis (HPA) and insulin sensitivity, and that strong emotion regulation as measured by the Difficulties in Emotion Regulation Scale (DERS, [65]) and high self-control as measured by the Self Control Scale-Brief (SCS-B, [66]) will moderate the relationships between stress, physiology, and accelerated aging Assessment of the individual variables’ attributable GrimAge acceleration as well as confidence intervals were calculated using the Emmeans package using unadjusted pairwise comparisons
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