Novel age-associated DNA methylation changes and epigenetic age acceleration in middle-aged African Americans and whites

Abstract

Background: African Americans (AAs) experience premature chronic health outcomes and longevity disparities consistent with an accelerated aging phenotype. DNA methylation (DNAm) levels at specific CpG positions are hallmarks of aging evidenced by the presence of age-associated differentially methylated CpG positions (aDMPs) that are the basis for the epigenetic clock for measuring biological age acceleration. Since DNAm has not been widely studied among non-European populations, we examined the association between DNAm and chronological age in AAs and whites, and the association between race, poverty, sex, and epigenetic age acceleration. Results: We measured genome-wide DNA methylation (866,836 CpGs) using the Illumina MethylationEPIC BeadChip in blood DNA extracted from 487 middle-aged AA (N = 244) and white (N = 243), men (N = 248), and women (N = 239). The mean (sd) age was 48.4 (8.8) in AA and 49.0 (8.7) in whites (p = 0.48). We identified 4930 significantly associated aDMPs in AAs and 469 in whites. Of these, 75.6% and 53.1% were novel, largely driven by the increased number of measured CpGs in the EPIC array, in AA and whites, respectively. AAs had more age-associated DNAm changes than whites in genes implicated in age-related diseases and cellular pathways involved in growth and development. We assessed three epigenetic age acceleration measures (universal, intrinsic, and extrinsic). AAs had a significantly slower extrinsic aging compared to whites. Furthermore, compared to AA women, both AA and white men had faster aging in the universal age acceleration measure (+ 2.04 and + 1.24 years, respectively, p < 0.05). Conclusions: AAs have more wide-spread methylation changes than whites. Race and sex interact to underlie biological age acceleration suggesting altered DNA methylation patterns may be important in age-associated health disparities.