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社会经济梯度在表观遗传时钟中的体现:来自动脉粥样硬化多民族研究和健康退休研究的证据。

The Socioeconomic Gradient in Epigenetic Ageing Clocks: Evidence from the Multi-Ethnic Study of Atherosclerosis and the Health and Retirement Study.

机构信息

Robert M. La Follette School of Public Affairs, University of Wisconsin-Madison, USA.

Department of Epidemiology, School of Public Health, University of Michigan, USA.

出版信息

Epigenetics. 2022 Jun;17(6):589-611. doi: 10.1080/15592294.2021.1939479. Epub 2021 Jul 6.

Abstract

Epigenetic clocks have been widely used to predict disease risk in multiple tissues or cells. Their success as a measure of biological ageing has prompted research on the connection between epigenetic pathways of ageing and the socioeconomic gradient in health and mortality. However, studies examining social correlates of epigenetic ageing have yielded inconsistent results. We conducted a comprehensive, comparative analysis of associations between various dimensions of socioeconomic status (SES) (education, income, wealth, occupation, neighbourhood environment, and childhood SES) and eight epigenetic clocks in two well-powered US ageing studies: The Multi-Ethnic Study of Atherosclerosis (MESA) (n = 1,211) and the Health and Retirement Study (HRS) (n = 4,018). In both studies, we found robust associations between SES measures in adulthood and the GrimAge and DunedinPoAm clocks (Bonferroni-corrected -value < 0.01). In the HRS, significant associations with the Levine and Yang clocks were also evident. These associations were only partially mediated by smoking, alcohol consumption, and obesity, which suggests that differences in health behaviours alone cannot explain the SES gradient in epigenetic ageing in older adults. Further analyses revealed concurrent associations between polygenic risk for accelerated intrinsic epigenetic ageing, SES, and the Levine clock, indicating that genetic risk and social disadvantage may contribute additively to faster biological aging.

摘要

表观遗传时钟已被广泛用于预测多种组织或细胞的疾病风险。它们作为衡量生物衰老的指标取得了成功,这促使人们研究衰老的表观遗传途径与健康和死亡率的社会经济梯度之间的联系。然而,研究社会相关性的表观遗传衰老的研究结果并不一致。我们在两项功能强大的美国衰老研究中(动脉粥样硬化多民族研究[MESA](n=1211)和健康与退休研究[HRS](n=4018))对社会经济地位(SES)的各个方面(教育、收入、财富、职业、邻里环境和儿童 SES)与八个表观遗传时钟之间的关联进行了全面、比较分析。在这两项研究中,我们发现成年期 SES 衡量指标与 GrimAge 和 DunedinPoAm 时钟之间存在强大的关联(Bonferroni 校正 - 值<0.01)。在 HRS 中,与 Levine 和 Yang 时钟也存在显著关联。这些关联仅部分通过吸烟、饮酒和肥胖来介导,这表明仅健康行为的差异并不能解释老年人表观遗传衰老的 SES 梯度。进一步的分析显示,加速内在表观遗传衰老的多基因风险、SES 和 Levine 时钟之间存在同时关联,表明遗传风险和社会劣势可能会加速生物衰老。

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