Cumulative neighborhood disadvantage and racial and geographic disparities in epigenetic aging.

Living in a socioeconomically disadvantaged neighborhood is associated with worse health. However, the biological pathways underpinning this association remain unclear. Using 1388 adults from Researching Epigenetics, Weathering and Residential Disadvantage (REWARD), an ancillary study to the Survey of the Health of Wisconsin (SHOW), we examined the contribution of cumulative neighborhood disadvantage across the life course to racial and geographic disparities in epigenetic markers of biological aging. Results showed that urban Black adults experienced faster epigenetic aging than urban, suburban, and rural White adults across three epigenetic aging clocks. Approximately 37 % (GrimAge), 70 % (DunedinPACE), and 100 % (PhenoAge) of the White-urban Black disparities in epigenetic age acceleration were explained by differential exposure to cumulative neighborhood disadvantage over the life course. Interactions testing differential susceptibility to neighborhood disadvantage by race were not significant. In summary, differential exposure to cumulative neighborhood disadvantage over the life course, rather than differential biological response to these exposures, shapes racial and geographic disparities in epigenetic aging.