Epigenetic aging & embodying injustice: US My Body My Story and Multi-Ethnic Atherosclerosis Study

ImportanceEpigenetic accelerated aging is associated with exposure to social and economic adversity and may increase risk of premature morbidity and mortality. However, no studies have included measures of structural racism and few have compared estimates within or across the 1st and 2nd generation of epigenetic clocks (the latter additionally trained on phenotypic data). ObjectiveTo determine if accelerated epigenetic aging is associated with exposures to diverse measures of racialized, economic, and environmental injustice measured at different levels and time periods. DesignCross-sectional My Body My Story Study (MBMS; US, 2008-2010) and Exam 5 Multi-Ethnic Atherosclerosis Study (MESA; US, 2010-2012). MBMS DNA extraction: 2021; linkage of structural measures to MBMS and MESA: 2022. SettingMBMS recruited a random sample of US-born Black non-Hispanic (BNH) and white non-Hispanic (WNH) participants from 4 community health centers in Boston, MA. The MESA Exam 5 epigenetic component included 975 randomly selected US-born BNH, WNH, and Hispanic participants from four field sites: Baltimore, MD; Forsyth County, NC; New York City, NY; St. Paul, MN. ParticipantsUS-born persons (MBMS: 224 BNH, 69 WNH; MESA: 229 BNH, 555 WNH, 191 Hispanic). Main outcome and measures10 epigenetic clocks (six 1st generation; four 2nd generation), computed using DNA methylation data (DNAm) from blood spots (MBMS; N = 293) and purified monocytes (MESA; N = 975). ResultsAmong Black non-Hispanic MBMS participants, epigenetic age acceleration was associated with being born in a Jim Crow state by 0.14 standard deviations (95% confidence interval [CI] 0.00, 0.27) and with birth state conservatism (0.06, 95% CI 0.00, 0.05), pooling across all clocks, as was low parental education for both Black non-Hispanic and white non-Hispanic MBMS participants (respectively: 0.24, 95% CI 0.08, 0.39, and 0.27, 95% CI 0.03, 0.51. Adult impoverishment was positively associated with the pooled 2nd generation clocks among the MESA participants (Black non-Hispanic: 0.06, 95% CI 0.01, 0.12; white non-Hispanic: 0.05, 95% CI 0.01, 0.08; Hispanic: 0.07, 95% CI 0.01, 0.14). Conclusions and RelevanceEpigenetic accelerated aging may be one of the biological mechanisms linking exposure to racialized and economic injustice to well-documented inequities in premature morbidity and mortality. KEY POINTSQuestion: Is accelerated epigenetic aging associated with exposure to racialized, economic, and environmental injustice? Findings: In the US cross-sectional My Body My Story (MBMS; n = 263) and Multi-Ethnic Atherosclerosis Study (MESA, Exam 5; n = 1264)), epigenetic accelerated aging was associated with Jim Crow birth state for MBMS Black non-Hispanic participants (by 0.14 standard deviations, 95% confidence interval 0.00, 0.27) and similarly with low parental education (MBMS: Black and white non-Hispanic participants) and adult impoverishment (MESA: Black and white non-Hispanic and Hispanic participants). Meaning: Epigenetic accelerated aging may be a biological pathway for embodying racialized and economic injustice.