Yannatos Isabel, Stites Shana D, Boen Courtney, Xie Sharon X, Brown Rebecca T, McMillan Corey T
Department of Neurology, University of Pennsylvania, Philadelphia, USA.
Department of Psychiatry, Perelman School of Medicine, Philadelphia, USA.
medRxiv. 2023 Oct 2:2023.09.29.23296351. doi: 10.1101/2023.09.29.23296351.
Epigenetic age, a biological aging marker measured by DNA methylation, is a potential mechanism by which social factors drive disparities in age-related health. Epigenetic age gap is the residual between epigenetic age measures and chronological age. Previous studies showed associations between epigenetic age gap and age-related outcomes including cognitive capacity and performance on some functional measures, but whether epigenetic age gap contributes to disparities in these outcomes is unknown. We use data from the Health and Retirement Study to examine the role of epigenetic age gap in racial disparities in cognitive and functional outcomes and consider the role of socioeconomic status (SES). Epigenetic age measures are GrimAge or Dunedin Pace of Aging methylation (DPoAm). Cognitive outcomes are cross-sectional score and two-year change in Telephone Interview for Cognitive Status (TICS). Functional outcomes are prevalence and incidence of limitations performing Instrumental Activities of Daily Living (IADLs). We find, relative to White participants, Black participants have lower scores and greater decline in TICS, higher prevalence and incidence rates of IADL limitations, and higher epigenetic age gap. Age- and gender-adjusted analyses reveal that higher GrimAge and DPoAm gap are both associated with worse cognitive and functional outcomes and mediate 6-11% of racial disparities in cognitive outcomes and 19-39% of disparities in functional outcomes. Adjusting for SES attenuates most DPoAm associations and most mediation effects. These results support that epigenetic age gap contributes to racial disparities in cognition and functioning and may be an important mechanism linking social factors to disparities in health outcomes.
表观遗传年龄是一种通过DNA甲基化测量的生物衰老标志物,是社会因素导致与年龄相关健康差异的潜在机制。表观遗传年龄差距是表观遗传年龄测量值与实际年龄之间的残差。先前的研究表明,表观遗传年龄差距与包括认知能力和一些功能测量表现在内的与年龄相关的结果之间存在关联,但表观遗传年龄差距是否导致这些结果的差异尚不清楚。我们使用来自健康与退休研究的数据,来检验表观遗传年龄差距在认知和功能结果的种族差异中的作用,并考虑社会经济地位(SES)的作用。表观遗传年龄测量指标为GrimAge或达尼丁衰老速度甲基化(DPoAm)。认知结果是认知状态电话访谈(TICS)的横断面得分和两年变化。功能结果是日常生活工具性活动(IADL)受限的患病率和发病率。我们发现,相对于白人参与者,黑人参与者TICS得分更低、下降幅度更大,IADL受限的患病率和发病率更高,表观遗传年龄差距也更大。年龄和性别调整分析显示,较高的GrimAge和DPoAm差距均与较差的认知和功能结果相关,并介导了认知结果中6%-11%的种族差异以及功能结果中19%-39%的差异。对SES进行调整会减弱大多数DPoAm关联和大多数中介效应。这些结果支持表观遗传年龄差距导致认知和功能方面的种族差异,并且可能是将社会因素与健康结果差异联系起来的重要机制。