Bell Sophie A, Beam Christopher R, Zandi Ebrahim, Kam Alyssa, Andrews Emily, Becker Jonathan, Finkel Deborah, Davis Deborah W, Turkheimer Eric
Department of Psychology, University of Virginia, Charlottesville, VA 22904, USA.
Department of Psychology, University of Southern California, Los Angeles, CA 90089, USA.
Aging (Albany NY). 2025 Jul 23;17(7):1702-1720. doi: 10.18632/aging.206284.
DNA methylation age (DNAmAge) surpasses chronological age in its ability to predict age-related morbidities and mortality. This study analyzed data from 287 middle-aged twins in the Louisville Twin Study (mean age 51.9 years ± 7.03) to investigate the effect of DNAmAge acceleration on change in IQ (ΔIQ) between childhood and midlife, while testing childhood socioeconomic status (SES) as a moderator of the relationship. DNAmAge was estimated with five commonly used algorithms, or epigenetic clocks (Horvath, Horvath Skin and Blood, GrimAge, and PhenoAge). A factor analysis of these measures produced a two-factor structure which we identified as first generation and second generation measures. Results of genetically informed, quasi-causal regression models indicated that accelerated second generation DNAmAge predicted more negative ΔIQ from childhood to midlife, after accounting for genetic and environmental confounds shared by twins. The relationship between DNAmAge and ΔIQ was moderated by childhood SES, with a stronger effect observed among twins from low SES backgrounds. Second generation DNAmAge measures trained to estimate phenotypic biological age show promise in their predictive value for cognitive decline in midlife. Our genetically informed twin design suggested that epigenetic aging may represent a pathway through which early-life socioeconomic disadvantage impacts midlife cognitive health.
DNA甲基化年龄（DNAmAge）在预测与年龄相关的发病率和死亡率方面，其能力超过了实际年龄。本研究分析了路易斯维尔双生子研究中287名中年双生子的数据（平均年龄51.9岁±7.03），以调查DNAmAge加速对儿童期至中年期智商变化（ΔIQ）的影响，同时将儿童期社会经济地位（SES）作为这种关系的调节因素进行检验。使用五种常用算法或表观遗传时钟（霍瓦斯、霍瓦斯皮肤和血液、GrimAge和PhenoAge）来估计DNAmAge。对这些测量值进行因素分析产生了一个双因素结构，我们将其确定为第一代和第二代测量值。遗传信息准因果回归模型的结果表明，在考虑了双生子共享的遗传和环境混杂因素后，加速的第二代DNAmAge预测从儿童期到中年期的ΔIQ更负。DNAmAge与ΔIQ之间的关系受到儿童期SES的调节，在低SES背景的双生子中观察到更强的影响。经过训练以估计表型生物学年龄的第二代DNAmAge测量值在预测中年认知衰退方面显示出有前景的预测价值。我们基于遗传信息的双生子设计表明，表观遗传衰老可能代表了一种早期社会经济劣势影响中年认知健康的途径。
