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.

中文翻译：

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中年非裔美国人和白人中与年龄相关的新型DNA甲基化变化和表观遗传年龄加速。

背景技术非洲裔美国人（AAs）经历过早的慢性健康结果和寿命差异，与加速的衰老表型一致。在特定CpG位置的DNA甲基化（DNAm）水平是衰老的标志，其存在是与年龄相关的差异甲基化CpG位置（aDMP）的存在，它们是测量生物年龄加速的表观遗传时钟的基础。由于尚未在非欧洲人口中对DNAm进行广泛研究，因此我们研究了DNAm与AA和白人的年龄之间的关联以及种族，贫困，性别和表观遗传的年龄加速之间的关联。结果我们使用Illumina甲基化EPIC BeadChip在从487名中年AA（N = 244）和白人（N = 243），男性（N = 248）提取的血液DNA中测量了全基因组DNA甲基化（866,836 CpGs）。和女性（N = 239）。AA的平均（sd）年龄为48.4（8.8），白人为49.0（8.7）（p = 0.48）。我们在AA中鉴定出4930个显着相关的aDMP，在白人中鉴定出469个。其中75.6％和53.1％是新颖的，主要是由EPIC阵列（分别为AA和白色）中测得的CpG数量增加所驱动。与年龄相关的疾病和涉及生长发育的细胞途径有关的基因中，AA的年龄相关的DNAm变化要比白人多。我们评估了三种表观遗传加速年龄的方法（通用，内在和外在）。与白人相比，AA的外在衰老要慢得多。此外，与AA女性相比，AA和白人男性在普遍年龄加速指标中的衰老速度更快（分别为+2.04和+1.24年，p <0.05）。结论AA比白人具有更广泛的甲基化变化。种族和性别相互作用是生物学年龄加速的基础，这表明改变的DNA甲基化模式可能在与年龄相关的健康差异中很重要。