Hormetic association between perceived stress and human epigenetic aging based on resilience capacity

Chronic stress is associated with deleterious health outcomes and mortality risk. A potential mechanism by which stress affects healthspan and lifespan is acceleration of cellular aging. Biologic age prediction models, termed epigenetic clocks, have been developed to estimate biologic age differences among people with the same chronologic age. This study evaluates the simultaneous impact of perceived chronic stress and resilience on Grim Age acceleration. The perceived stress score (PSS) and Connor-Davidson Resilience Scale (CD-RISC) were used to measure chronic stress and resilience, respectively. DNA was extracted from whole blood and analyzed using the MethylationEPIC BeadChip. GrimAge estimates were calculated using the methylation age calculator. Forty-seven business executives were categorized by levels of high or low stress and resilience scores. Compared to participants with low stress and high resilience, those with low stress and low resilience demonstrated the strongest association with Grim Age acceleration (p = 0.044), after controlling for age and estimated cellular proportions. Interestingly, among participants with low resilience, those with high perceived stress had a weaker association with Grim Age acceleration than participants with low perceived stress. However, among participants with high resilience, low perceived stress had a weaker association with Grim Age acceleration than high perceived stress. Our findings suggest that the impact of perceived stress on epigenetic age acceleration may differ based on resilience capacity, with a potential paradoxical beneficial effect among those with low resilience.