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 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.

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。它们作为生物衰老的衡量标准的成功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，研究表观遗传衰老的社会相关性的研究产生了不一致的结果。我们在两项强有力的美国老龄化研究中对社会经济地位 (SES) 的各个维度（教育、收入、财富、职业、邻里环境和童年 SES）与八个表观遗传时钟之间的关联进行了全面的比较分析：动脉粥样硬化的种族研究 (MESA) (n = 1,211) 和健康与退休研究 (HRS) (n = 4,018)。在这两项研究中，p值 < 0.01)。在 HRS 中，与 Levine 和 Yang 时钟的显着关联也很明显。这些关联仅部分由吸烟、饮酒和肥胖介导，这表明仅健康行为的差异无法解释老年人表观遗传衰老的 SES 梯度。进一步的分析揭示了加速内在表观遗传衰老的多基因风险、SES 和莱文时钟之间的同时关联，表明遗传风险和社会劣势可能对加速生物衰老产生额外贡献。