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

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 p-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.

表观遗传时钟（epigenetic clocks）已被广泛用于预测多种组织或细胞的疾病风险。其作为生物衰老衡量指标的成功，推动了衰老表观遗传通路与健康及死亡的社会经济梯度之间关联的相关研究。然而，现有探讨表观遗传衰老社会相关性的研究结果并不一致。本研究依托两项具有充足统计效力的美国衰老研究队列——多民族动脉粥样硬化研究（Multi-Ethnic Study of Atherosclerosis, MESA，n=1211）与健康与退休研究（Health and Retirement Study, HRS，n=4018），开展了一项全面的比较分析，旨在探究社会经济地位（socioeconomic status, SES）的多个维度（教育、收入、财富、职业、邻里环境以及童年期SES）与8种表观遗传时钟之间的关联。在两项队列中，我们均发现成年期SES指标与GrimAge时钟及DunedinPoAm时钟之间存在稳健关联（邦费罗尼校正后P值<0.01）。在HRS队列中，与Levine时钟及Yang时钟的显著关联亦得到验证。这些关联仅部分由吸烟、饮酒与肥胖所介导，这表明仅靠健康行为差异无法解释老年人群表观遗传衰老中的SES梯度。进一步分析显示，加速的内在表观遗传衰老多基因风险、SES与Levine时钟之间存在共现关联，提示遗传风险与社会劣势可能以相加的方式促进更快的生物衰老。