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非裔美国人的加速 DNA 甲基化年龄与药物使用。

Accelerated DNA methylation age and medication use among African Americans.

机构信息

Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.

Memory Impairment and Neurodegenerative Dementia (MIND) Center, University of Mississippi Medical Center, Jackson, MS 39216, USA.

出版信息

Aging (Albany NY). 2021 Jun 3;13(11):14604-14629. doi: 10.18632/aging.203115.

Abstract

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.

摘要

DNA 甲基化年龄加速,即表观年龄与实际年龄之间的差异,与死亡率和慢性疾病有关,包括糖尿病、高血压和高血脂。在这项研究中,我们调查了在 15 个药物类别中常用的治疗这些疾病的药物是否与四种表观年龄加速测量值有关:HorvathAge 加速(HorvathAA)、HannumAge 加速(HannumAA)、PhenoAge 加速和 GrimAge 加速(GrimAA),使用来自遗传流行病学网络动脉粥样硬化(GENOA)研究的非裔美国人的横断面(第 1 阶段,N=1100)和纵向(第 1 阶段和第 2 阶段,N=266)数据。在横断面分析中,在调整包括高血压在内的协变量后,使用钙通道阻滞剂与 HannumAA 降低 1.27 年相关(p=0.001)。纵向分析显示,与从未使用过抗高血压药物的人相比,在第 1 阶段后开始使用抗高血压药物的人,GrimAA 减少了 0.97 年(p=0.007)。此外,与从未使用过非甾体抗炎药(NSAID)镇痛剂的人相比,在第 1 阶段后开始使用 NSAID 镇痛剂的人,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 DNAm 年龄加速有关,并揭示了药物对细胞水平衰老的潜在表观遗传学影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afff/8221348/8c883c8fdb91/aging-13-203115-g001.jpg

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