Rivier Cyprien A, Szejko Natalia, Renedo Daniela, Clocchiatti-Tuozzo Santiago, Huo Shufan, de Havenon Adam, Zhao Hongyu, Gill Thomas M, Sheth Kevin N, Falcone Guido J
Department of Neurology, Yale School of Medicine, New Haven, CT, US.
Yale Center for Brain and Mind Health, New Haven, CT, USA.
Nat Commun. 2025 Feb 1;16(1):1261. doi: 10.1038/s41467-024-54721-0.
Chronological age is an imperfect estimate of molecular aging. Epigenetic age, derived from DNA methylation data, provides a more nuanced representation of aging-related biological processes. We examine the bidirectional relationship between epigenetic age and brain health events (stroke, dementia, late-life depression) using data from 4,018 participants. Participants with a prior brain health event are 4% epigenetically older (β = 0.04, SE = 0.01), indicating these conditions are associated with accelerated aging beyond that captured by chronological age. Additionally, a one standard deviation increase in epigenetic age is associated with 70% higher odds of experiencing a brain health event in the next four years (OR = 1.70, 95% CI = 1.16-2.50), suggesting epigenetic age acceleration is not just a consequence but also a predictor of poor brain health. Mendelian Randomization analyses replicate these findings, supporting their causal nature. Our results support using epigenetic age as a biomarker to evaluate interventions aimed at preventing and promoting recovery after brain health events.
实足年龄是分子衰老的一个不完美的估计指标。从DNA甲基化数据得出的表观遗传年龄，能更细致地反映与衰老相关的生物学过程。我们使用来自4018名参与者的数据，研究了表观遗传年龄与脑健康事件（中风、痴呆、晚年抑郁症）之间的双向关系。有过脑健康事件的参与者表观遗传年龄要大4%（β = 0.04，标准误 = 0.01），这表明这些情况与超越实足年龄所反映的加速衰老有关。此外，表观遗传年龄每增加一个标准差，在未来四年发生脑健康事件的几率就会高出70%（比值比 = 1.70，95%置信区间 = 1.16 - 2.50），这表明表观遗传年龄加速不仅是脑健康状况不佳的结果，也是其预测指标。孟德尔随机化分析重复了这些发现，支持了它们的因果性质。我们的结果支持将表观遗传年龄用作生物标志物，以评估旨在预防脑健康事件及促进其恢复后康复的干预措施。
