Accelerated DNA methylation age and medication use among African Americans.
Accelerated DNA methylation age and medication use among African Americans.
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DOI：
10.18632/aging.203115
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发表时间：
2021-06-03
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影响因子：
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通讯作者：
Smith JA
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作者：
Kho M;Wang YZ;Chaar D;Zhao W;Ratliff SM;Mosley TH;Peyser PA;Kardia SLR;Smith JA
DNA甲基化年龄加速，表观遗传年龄和实际年龄之间的差异，与死亡率和慢性疾病，包括糖尿病，高血压和高脂血症有关。在这项研究中，我们调查了15种药物类别中常用于治疗这些疾病的药物是否与四种表观遗传年龄加速指标相关：年龄加速度（HorvathAA），Hannum年龄加速度（HannumAA）、PhenoAge加速度和GrimAge加速度（GrimAA），使用横截面（1期，N= 1，100）和纵向（1期和2期，N=266）数据，来自动脉病遗传流行病学网络（GENOA）研究中的非裔美国人。在横断面分析中，调整包括高血压在内的协变量后，钙通道阻滞剂的使用与HannumAA降低1.27年相关（p=0.001）。纵向分析显示，与从未使用抗高血压药物的患者相比，在第1阶段后开始使用抗高血压药物的患者GrimAA下降了0.97年（p=0.007）。此外，与从未使用NSAID镇痛剂的患者相比，在第1阶段后开始使用NSAID镇痛剂的患者的HorvathAA增加了2.61年（p=0.0005）。我们的研究表明，三种常用药物与非裔美国人的DNA年龄加速有关，并揭示了药物在细胞水平上对衰老的潜在表观遗传效应。
DNA methylation age acceleration, the discrepancy between epigenetic age and chronological age, is associated with mortality and chronic diseases, including diabetes, hypertension, and hyperlipidemia. In this study, we investigate whether medications commonly used to treat these diseases in 15 drug categories are associated with four epigenetic age acceleration measures: HorvathAge acceleration (HorvathAA), HannumAge acceleration (HannumAA), PhenoAge acceleration, and GrimAge acceleration (GrimAA) using cross-sectional (Phase 1, N=1,100) and longitudinal (Phases 1 and 2, N=266) data from African Americans in the Genetic Epidemiology Network of Arteriopathy (GENOA) study. In cross-sectional analyses, the use of calcium channel blockers was associated with 1.27 years lower HannumAA after adjusting for covariates including hypertension (p=0.001). Longitudinal analyses showed that, compared to those who never used antihypertensives, those who started to take antihypertensives after Phase 1 had a 0.97-year decrease in GrimAA (p=0.007). In addition, compared to those who never used NSAID analgesics, those who started to take them after Phase 1 had a 2.61-year increase in HorvathAA (p=0.0005). Our study demonstrates that three commonly used medications are associated with DNAm age acceleration in African Americans and sheds light on the potential epigenetic effects of pharmaceuticals on aging at the cellular level.