老年人衰弱指数与表观遗传衰老加速之间的关联：来自健康与退休研究的证据。

Association between frailty index and epigenetic aging acceleration in older adults: Evidence from the health and retirement study.

作者信息

Lin Xuhui, Hu Zhao, Tang Lu, Zhan Yiqiang

机构信息

Department of Social Medicine and Health Management, Xiangya School of Public Health, Central South University, China.

Department of Epidemiology, School of Public Health(Shen Zhen), Sun Yat-sen university, China.

出版信息

Exp Gerontol. 2025 Jun 15;205:112765. doi: 10.1016/j.exger.2025.112765. Epub 2025 Apr 24.

DOI:10.1016/j.exger.2025.112765

PMID:40286999

Abstract

BACKGOUND

This study aimed to examine the associations between the frailty index and four epigenetic aging acceleration (EAA) estimators in cross-sectional and longitudinal settings.

METHODS

The frailty index in the older adults was measured according to a cumulative health-deficit model. Four different epigenetic age measures (Hannum, PhenoAge, GrimAge, and DunedinPoAm38) were regressed against chronological age, and the resulting standardized residuals were indicative of EAA. The longitudinal relationship between EAA at baseline and changes in the frailty index during the 4-year follow-up were examined using a mixed linear model.

RESULTS

A single standard deviation (SD) increment in the frailty index was associated with a faster EAA, as indicated by the four clocks in Hannum (b = 0.057; P = 0.015), PhenoAge (b = 0.096; P < 0.001), GrimAge (b = 0.120; P < 0.001), and DunedinPoAm38 (b = 0.062; P = 0.002) in the fully adjusted model. A 1-SD increment in the GrimAge EAA was associated with a 0.003 frailty index increase (b = 0.003; P = 0.002). A 1-SD increment in DunedinPoAm38 EAA was associated with a 0.002 frailty index increase (b = 0.002; P = 0.009).

CONCLUSIONS

The frailty index was cross-sectionally associated with EAA, while only GrimAge and DunedinPoAm38 EAA predicted changes in the frailty index. More research is needed to understand the interplay between pathways.

摘要

背景

本研究旨在探讨在横断面和纵向研究中衰弱指数与四种表观遗传衰老加速（EAA）估计值之间的关联。

方法

根据累积健康缺陷模型测量老年人的衰弱指数。将四种不同的表观遗传年龄测量指标（汉纳姆法、表型年龄、格里姆年龄和达尼丁多组学衰老指标38）与实际年龄进行回归分析，所得标准化残差即为EAA。使用混合线性模型研究基线时的EAA与4年随访期间衰弱指数变化之间的纵向关系。

结果

在完全调整模型中，衰弱指数每增加一个标准差（SD），与更快的EAA相关，汉纳姆法（b = 0.057；P = 0.015）、表型年龄（b = 0.096；P < 0.001）、格里姆年龄（b = 0.120；P < 0.001）和达尼丁多组学衰老指标38（b = 0.062；P = 0.002）这四种时钟指标均显示如此。格里姆年龄EAA每增加1个标准差，与衰弱指数增加0.003相关（b = 0.003；P = 0.002）。达尼丁多组学衰老指标38 EAA每增加1个标准差，与衰弱指数增加0.002相关（b = 0.002；P = 0.009）。