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

Salman M Tajuddin,Brian H Chen,Michele K Evans,Mike A Nalls,Nicole Noren Hooten,Dena G Hernandez,Nicolle A Mode,Andrew B Singleton,Ngozi Ejiogu,Alan B Zonderman,Kumaraswamy Naidu Chitrala

doi:10.1186/s13148-019-0722-1

Salman M Tajuddin, Brian H Chen + Show 9 more

Open Access

https://doi.org/10.1186/s13148-019-0722-1

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Abstract

BackgroundAfrican 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.ResultsWe 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).ConclusionsAAs 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.

Highlights

African Americans (AAs) experience premature chronic health outcomes and longevity disparities consistent with an accelerated aging phenotype
We found that chronological age was associated with widespread DNA methylation changes in various CpG positions and that AAs compared to whites had more associated differentially methylated CpG positions (aDMPs)
In summary, we found that age differences are associated with DNA methylation (DNAm) changes at several genes enriched for predicted functional genomic regulatory regions and that AAs compared to whites have more aDMPs, majority of which are novel CpG sites

Summary

Introduction

African Americans (AAs) experience premature chronic health outcomes and longevity disparities consistent with an accelerated aging phenotype. Tajuddin et al Clinical Epigenetics (2019) 11:119 found that AAs age significantly faster than whites and that biological aging was associated with all-cause mortality rates [3]. The causes of health disparities and its premature aging phenotype are multifactorial and include but are not limited to socioeconomic status, psychosocial stress, genetics, poor access to health care, education, and toxic environmental exposures. It has never been fully explained how social determinants of health result in the premature aging phenotype, poor health outcomes, and reduced overall survival. There is evidence from targeted methylation studies that DNA methylation changes are associated with socioeconomic status and age-related diseases [6, 7]

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