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短期PM_2.5 暴露和DNA甲基化改变昼夜节律基因:来自两项实验研究的证据

Yuting Wang¹, Huichu Li², Jing Huang¹

¹Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100871, China.

Environmental science & technology

|May 30, 2024

概括

短期暴露于细颗粒物 (PM2.5) 会改变昼夜基因中的DNA甲基化,影响衰老. 昼夜稳定中的这种表观遗传变化加速了生物衰老,特别是通过RORA基因.

科学领域:

环境表观遗传学环境表观遗传学
时间生物学时间生物学
衰老研究研究衰老研究

背景情况:

循环节律障碍与衰老有关,观察性研究表明与PM2.5暴露有关.
关联PM2.5暴露与昼夜节律障碍和衰老的机制,特别是DNA甲基化,尚不清楚.
对于PM2.5占主导地位的环境,实验数据有限.

研究的目的:

调查短期PM2.5暴露与昼夜基因中的DNA甲基化变化之间的关联.
在独立的队列中验证发现.
为了确定DNA甲基化是否介导PM2.5对表观遗传衰老的影响.

主要方法:

分析了32名年轻成年人 (FDU研究) 和26名暴露于PM2.5.5的个人 (PKU研究) 昼夜基因中的1188个CpG位点的DNA甲基化.
利用调解分析来评估DNA甲基化在PM2.5对表观遗传年龄的影响中的作用 (DNAmGrimAge,DunedinPoAm,死亡风险评分).
测量了像MDA和EGF这样的循环生物标志物.

主要成果:

确定了与个人PM2.5暴露相关的三个CpG位点 (CSNK2A2中的cg01248361,RORA中的cg17728065,PRKAG2中的cg22513396).
发现PM2.5对这些位点的急性影响是由循环生物标志物 (例如MDA,EGF) 中介的,高达30%左右.
证明这些位点调解PM2.5的衰老加速效应,其中cg17728065 (RORA) 显示出显著的调解效应 (7.54-12.52%).

结论:

短期的PM2.5暴露可以诱导昼夜基因中的DNA甲基化变化,反映出改变的昼夜平衡.
这些表观遗传变化有助于加速生物衰老.
罗拉基因的DNA甲基化是PM2.5诱导的衰老加速的关键媒介.

关键词:

通过DNA甲基化.对于PM2.5来说,这是一个很好的例子.生物衰老生物衰老昼夜节律昼夜节律表观遗传年龄表观遗传年龄

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