2年间表观遗传测量的纵向变化:方法论上的含义
Rikuta Hamaya1, Sidong Li2, Brian H Chen3
1Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 900 Commonwealth Ave, Boston, MA, USA. rhamaya@bwh.harvard.edu.
GeroScience
|November 11, 2025
概括
在健康的老年人中,表观遗传钟在两年内显示出稳定性. 主要组件版本提供更高的测量稳定性,这表明它们可用于衰老研究和临床试验.
科学领域:
- 表观遗传学和衰老研究研究.
- 为老年学开发生物标志物
背景情况:
- 在临床试验中,表观遗传钟被提议作为替代终点.
- 在健康的老年人中,它们的短期行为需要进一步描述.
研究的目的:
- 评估老年人各种表观遗传钟的短期行为和稳定性.
- 评估表观遗传时钟在衰老干预中作为替代终点的适用性.
主要方法:
- 分析了基线,第一年和第二年899名参与者的DNA甲基化数据 (平均年龄70岁).
- 来自Horvath,Hannum,PhenoAge和GrimAge的钟表 (原始和主要组件版本) 和DunedinPACE.
- 使用线性混合效应模型和相关性分析计算表观遗传年龄加速和分析稳定性.
主要成果:
- 与原始时钟相比,主要组件 (PC) 时钟显示出更高的测量稳定性,较小的两年变化方差.
- 对于一些PC时钟来说,观察到表观遗传年龄加速的统计学上可检测的,但在数值上较小的年度增加.
- 基线表观遗传时钟值强烈预测了未来的测量 (PC时钟的R2 ≈ 0.71-0.88),表明了高度的可预测性.
结论:
- 目前的表观遗传测量,特别是PC时钟,在健康的老年人中,在2年内是稳定的和高度可预测的.
- 这些发现表明对短期变化的敏感性有限,支持它们在衰老试验中的使用.
- 经验标准偏差和相关性支持基于ANCOVA的方法,用于未来的试验分析和功率计算.
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