通过途径级表观遗传钟解读疾病特异性衰老机制:来自多队列验证的见解
Pan Li1, Jijun Zhu1, Shenghan Wang1
1Center for Intelligent Medicine, Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Fudan University, China.
EBioMedicine
|July 5, 2025
概括
一个新的表观遗传时钟PathwayAge使用途径级甲基化数据准确估计生物年龄. 这种生物知情模型增强了对衰老和疾病机制的理解,为精准医学提供了潜力.
科学领域:
- 表观遗传学和衰老研究研究.
- 计算生物学和生物信息学
- 基因组学和疾病协会研究研究.
背景情况:
- 衰老是一个复杂的过程,与慢性疾病有关.
- 现有的表观遗传钟经常使用孤立的CpG位点,限制了生物洞察力.
- "PathwayAge"的开发目的是提供一个生物可解释的老化模型.
研究的目的:
- 开发和验证PathwayAge,一种新的表观遗传时钟模型.
- 评估老化过程中途径水平甲基化变化的生物解释性.
- 调查表观遗传衰老加速与各种慢性疾病之间的关联.
主要方法:
- 利用全基因组DNA甲基化和来自多个队伍的10,000多名个体的转录组数据.
- 采用两阶段机器学习方法将CpG站点汇总到基因本体学 (GO) 或KEGG通路中,用于年龄预测.
- 计算了年龄加速残留值 (AgeAcc) 并测试了与九种疾病的相关性.
主要成果:
- 通过PathwayAge在不同队列中 (Rho高达0.979) 证明了高准确度的年龄预测.
- 该模型在年龄估计和疾病关联分析方面表现优于已有的表观遗传钟.
- 显著的年龄加速与九种疾病有关,通过 permutation 测试和交叉omics 验证确定了特定的途径.
结论:
- 路径年龄为表观遗传年龄估计提供了一个可解释的,基于生物学的框架.
- 该模型揭示了衰老途径和疾病发展之间的机制联系.
- 路径时代对生物标志物开发和推进精确衰老医学具有前景.
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