Epigenetic entropy, social disparity, and health and lifespan in the Women's Health Initiative

ABSTRACTThe pace of aging varies between individuals and is marked by changes in DNA methylation (DNAm) including an increase in randomness or entropy. Here, we computed epigenetic scores of aging and entropy using DNAm datasets from the Womens Health Initiative (WHI). We investigated how different epigenetic aging metrics relate to demographic and health variables, and mortality risk. Income and education, two proxies of socioeconomics (SE), had consistent associations with epigenetic aging and entropy. Notably, stochastic increases in DNAm at sites targeted by the polycomb proteins were significantly related to both aging and SE. While higher income was associated with reduced age-related DNAm changes in White women, the protective effect of income was diminished in Black and Hispanic women, and on average, Black and Hispanic women had relatively more aged epigenomes. Faster pace of aging, as estimated by the DunedinPACE, predicted higher mortality risk, while the maintenance of methylation at enhancer regions was associated with improved survival. Our findings demonstrate close ties between social and economic factors and aspects of epigenetic aging, suggesting potential biological mechanisms through which societal disparities may contribute to differences in health outcomes and lifespan across demographic groups.