Reduced Epigenetic Age in Older Adults With High Sense of Purpose in Life.

Abstract

Psychosocial risk factors have been linked with accelerated epigenetic aging, but little is known about whether psychosocial resilience factors (eg, Sense of Purpose in Life) might reduce epigenetic age acceleration. In this study, we tested if older adults who experience high levels of Purpose might show reduced epigenetic age acceleration. We evaluated the relationship between Purpose and epigenetic age acceleration as measured by 13 DNA methylation (DNAm) "epigenetic clocks" assessed in 1 572 older adults from the Health and Retirement Study (mean age 70 years). We quantified the total association between Purpose and DNAm age acceleration as well as the extent to which that total association might be attributable to demographic factors, chronic disease, other psychosocial variables (eg, positive affect), and health-related behaviors (heavy drinking, smoking, physical activity, and body mass index [BMI]). Purpose in Life was associated with reduced epigenetic age acceleration across 4 "second-generation" DNAm clocks optimized for predicting health and longevity (false discovery rate [FDR] q < 0.0001: PhenoAge, GrimAge, Zhang epigenetic mortality index; FDR q < 0.05: DunedinPoAm). These associations were independent of demographic and psychosocial factors, but substantially attenuated after adjusting for health-related behaviors (drinking, smoking, physical activity, and BMI). Purpose showed no significant association with 9 "first-generation" DNAm epigenetic clocks trained on chronological age. Older adults with greater Purpose in Life show "younger" DNAm epigenetic age acceleration. These results may be due in part to associated differences in health-related behaviors. Results suggest new opportunities to reduce biological age acceleration by enhancing Purpose and its behavioral sequelae in late adulthood.