Pan Yang, Huang Zhijie, Sun Xiao, De Anda-Duran Ileana, Zhang Ruiyuan, Chen Wei, Li Changwei, Capuano Ana W, Yaffe Kristine, Zhao Jinying, Bennett David A, Carmichael Owen T, Bazzano Lydia A, Kelly Tanika N
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, College of Medicine, University of Illinois Chicago, Chicago, IL, USA.
Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.
NPJ Aging. 2025 Aug 18;11(1):75. doi: 10.1038/s41514-025-00265-6.
The relationship between epigenetic age acceleration (EAA) and midlife cognitive function remains unclear, with limited causal evidence. We investigated this association in 1252 Black and White middle-aged adults from the Bogalusa Heart Study (BHS) and conducted a two-sample Mendelian randomization (MR) analysis using GWAS summary statistics for EAA (N = 34,710) and cognition (N ≤ 106,162). In BHS, higher Hannum age acceleration, PhenoAge acceleration, and GrimAge acceleration (GrimAA) were each associated with slower processing speed (p < 0.05). Additionally, GrimAA was linked to lower global cognition scores (p < 0.001), independent of covariates. MR analysis suggested a potential link, showing that genetically predicted GrimAA was nominally associated with slower processing speed (p = 0.05). These findings suggest that epigenetic aging, particularly GrimAA, is independently associated with lower cognitive function in midlife and may play an important role in cognitive impairment, especially in processing speed.
表观遗传年龄加速（EAA）与中年认知功能之间的关系仍不明确，因果证据有限。我们在来自博加卢萨心脏研究（BHS）的1252名黑人和白人中年成年人中调查了这种关联，并使用EAA（N = 34710）和认知（N≤106162）的全基因组关联研究（GWAS）汇总统计数据进行了两样本孟德尔随机化（MR）分析。在BHS中，较高的汉纳姆年龄加速、PhenoAge加速和GrimAge加速（GrimAA）均与较慢的处理速度相关（p < 0.05）。此外，GrimAA与较低的整体认知分数相关（p < 0.001），且独立于协变量。MR分析表明存在潜在联系，显示基因预测的GrimAA与较慢的处理速度名义上相关（p = 0.05）。这些发现表明，表观遗传衰老，尤其是GrimAA，与中年较低的认知功能独立相关，可能在认知障碍中起重要作用，特别是在处理速度方面。
