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肥胖与表观遗传衰老和端粒长度的因果关系:一个双向的门德尔随机化研究

Jixin Li¹, Wenru Wang¹, Zhenyu Yang²

¹Chinese Academy of Traditional Chinese Medicine, Xiyuan Hospital, Beijing, China.

Lipids in health and disease

|March 13, 2024

概括

肥胖导致加速表观遗传衰老,并缩短端粒长度. 这项研究使用了门德尔的随机化来证实这些联系,提供了对衰老缓解策略的见解.

科学领域:

遗传学和表观遗传学
衰老研究研究衰老研究
公共卫生公共卫生

背景情况:

观察性研究表明,肥胖,表观遗传年龄和端粒长度之间存在联系.
之前的研究已经产生了相互矛盾的结果.
因果关系仍然不清楚.

研究的目的:

调查肥胖和表观遗传年龄之间的因果关系.
探索肥胖和端粒长度之间的因果关系.
使用孟德尔随机化检查双向因果关系.

主要方法:

在欧洲祖先个体中进行全基因组关联研究.
双向门德尔随机化 (MR) 使用反变量加权,加权中位数,MR Egger和其他方法.
分析了三个肥胖指标 (BMI,WCadjBMI,WHRadjBMI) 和四个表观遗传年龄指标 (HannumAge,HorvathAge,GrimAge,PhenoAge).
对于多次测试应用的邦费罗尼校正.

主要成果:

在肥胖与加速的HannumAge,GrimAge,PhenoAge和端粒缩短之间发现了显著的因果关系.
WCadjBMI和PhenoAge加速显示出最强的因果关系 (OR:2.099).
反向MR分析表明表观遗传年龄测量和BMI之间存在显著的,尽管较小的因果关系.

结论:

肥胖导致加速表观遗传衰老,并缩短端粒长度.
研究结果支持过重和加速衰老标志物之间存在直接联系.
结果为开发减轻肥胖个体衰老的干预措施提供了基础.

关键词:

表观遗传年龄表观遗传年龄全基因组关联研究研究.门德尔的随机化肥胖问题肥胖问题泰洛米尔 (Telomere) 是一种电离体.

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