与衰老相关的LEF1的DNA甲基化调节炎症和神经退行性途径
Mengke Chen1,2, Lujie Zhou1, Yidan Gao3
1Department of Blood Transfusion, Huashan Hospital, Fudan University, Shanghai, China.
Frontiers in immunology
|September 8, 2025
概括
衰老在表观遗传上抑制了LEF1,它是免疫反应的关键调节者. 这种与年龄相关的LEF1沉默有助于炎症,并可能导致神经退行.
科学领域:
- 免疫学 免疫学 免疫学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 神经科学是一个神经科学.
背景情况:
- 衰老深刻地改变了免疫调节和表观遗传的景观.
- 与年龄相关的免疫和表观遗传变化的分子驱动因素仍然不清楚.
研究的目的:
- 确定与衰老相关的免疫失调的分子驱动因素.
- 研究表观遗传修饰在衰老中的作用.
- 确定LEF1对炎症和神经退行性通路的影响.
主要方法:
- 分析了来自年轻人和老年人的外周血液转录和甲基化数据.
- 利用染色体免疫沉测序 (ChIP-Seq) 和测量转化酶可访问染色体的测序 (ATAC-seq) 来探索调节机制.
- 通过细胞系淘汰实验进行功能验证,以评估炎症反应和反应性氧物种 (ROS) 水平.
主要成果:
- 老年人中LEF1表达显著下调,与促进体甲基化增加相关,表明表观遗传抑制.
- 综合的多omics分析将LEF1与免疫炎症和神经退行性途径联系起来.
- 在试验室中,LEF1的敲击加剧了炎症反应和ROS的产生,支持其在这些过程中的作用.
结论:
- 与年龄相关的LEF1表观遗传抑制有助于免疫炎症激活.
- 沉默LEF1可能在神经退行性疾病的发病过程中发挥作用.
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