孤舟蓑笠翁 (2026-03-21 22:13):
paper 【doi】10.1038/s43587-026-01066-6;【发表年份】2026年;【期刊】Nature Aging;【标题】Longitudinal changes in epigenetic clocks predict survival in the InCHIANTI cohort。【内容总结】这篇论文的动机是探究表观遗传时钟的长期变化是否能比单次测量更好地预测生存,因为表观遗传时钟是基于DNA甲基化模式预测生物年龄的指标。研究对意大利InCHIANTI队列的699名成年人进行了长达24年的追踪,测量了他们2-3个时间点的DNA甲基化,并计算了七种不同的表观遗传时钟,包括第一代(如Hannum clock、Horvath clock)、第二代(如DNAmPhenoAge、DNAmGrimAge)和第三代(如DunedinPACE)时钟,分析了这些时钟的基线值和随时间变化的速率与死亡风险的关系。研究发现在调整了基线年龄等因素后,多种表观遗传时钟(如Hannum clock、DNAmPhenoAge)变化越快,死亡风险越高,且将基线值与变化速率结合使用的预测模型表现最佳。具体而言,在“仅基线”模型中,除Horvath时钟外,所有时钟都与死亡率显著相关,调整后的风险比在1.12到1.38之间;在“仅斜率”模型中,只有Hannum clock和DNAmPhenoAge的变化与死亡率显著相关;而在“基线+变化”的综合模型中,预测能力最强,其中结合了基线值和变化值的DNAmGrimAge v.2模型的C统计量最高,达到0.808。这表明,表观遗传时钟的动态变化能反映健康状况的演变,是预测死亡和评估抗衰老干预效果的敏感指标。
Longitudinal changes in epigenetic clocks predict survival in the InCHIANTI cohort
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Abstract:
Abstract Epigenetic clocks derived from DNA methylation patterns are among the most promising biomarkers of biological aging 1–7 , as they capture molecular signatures that predict morbidity and mortality beyond chronological age. Although cross-sectional assessments of epigenetic age have been linked consistently to health outcomes and lifespan, it remains unclear whether the rate of change in these clocks over time provides additional insight into aging trajectories. In this longitudinal study of 699 adults from the InCHIANTI cohort followed for up to 24 years, we evaluated whether temporal acceleration of several epigenetic clocks—including first-, second- and third-generation epigenetic clocks—was associated with mortality. We found that faster increases in several clocks were linked robustly to higher risk of death, independent of baseline epigenetic age and other confounders. These findings suggest that dynamic changes in epigenetic aging reflect evolving health status and may serve as sensitive indicators for interventions aimed at extending healthspan and longevity.
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