The role of epigenetic aging in education and racial/ethnic mortality disparities among older US Women

Background: Higher mortality experienced by socially disadvantaged groups and/or racial/ethnic minorities is hypothesized to be, at least in part, due to an acceleration of the aging process. Using a new epigenetic aging measure, Levine DNAmAge, this study aimed to investigate whether epigenetic aging accounts for mortality disparities by race/ethnicity and education in a sample of U.S. postmenopausal women. Methods: 1834 participants from an ancillary study (BA23) in the Women's Health Initiative, a national study that recruited postmenopausal women (50-79 years) were included. Over the 22 years of follow-up, 551 women died, and 31,946 person-years were observed. Levine DNAmAge (unit in years) was calculated based on an equation that we previously developed in an independent sample, which incorporates methylation levels at 513 CpG sites. Results: As previously reported, non-Hispanic blacks and Hispanics were epigenetically older than non-Hispanic whites of the same chronological age. Similarly, those with less education had older epigenetic ages than expected in the full sample, as well as among non-Hispanic whites and Hispanics, but not among non-Hispanic blacks. Non-Hispanic blacks and those with low education exhibited the greatest risk of mortality. However, this association was partially attenuated when accounting for differences in DNAmAge. Furthermore, formal mediation analysis suggested that DNAmAge partially mediated the mortality increase among non-Hispanic blacks, compared to non-Hispanic whites (proportion mediated, 15.8%, P = 0.002), as well as the mortality increase for those with less than high school education, compared to college educated (proportion mediated, 11.6%, P < 2E-16). Conclusions: Among a group of postmenopausal women, non-Hispanic blacks and those with less education exhibit higher epigenetic aging, which partially accounts for their shorter life expectancies.