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细胞衰老中的表观遗传调控。

Epigenetic regulation in cell senescence.

机构信息

State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, People's Republic of China.

出版信息

J Mol Med (Berl). 2017 Dec;95(12):1257-1268. doi: 10.1007/s00109-017-1581-x. Epub 2017 Sep 8.

Abstract

Cell senescence, which is an irreversible state of cell proliferative arrest, has emerged as a potentially important contributor to tissue dysfunction and organismal ageing. Cell senescence is triggered by a variety of senescence stressors, which affect gene expression and multiple signalling pathways that give rise to various senescence phenotypes. Epigenetic mechanisms, as critical regulators of chromosomal architecture and gene expression, have added an extra dimension to the molecular mechanisms of cell senescence. Cell senescence is accompanied by changes in DNA methylation, histone-associated epigenetic processes, chromatin remodelling and ncRNA expression. Those senescence-associated epigenetic alterations interact with the senescence regulatory programme networks and lead to various cell senescence phenotypes. This review provides a comprehensive overview of epigenetic changes and their effects on cell senescence. The differences in epigenetic alterations among different types of senescence are also discussed. Furthermore, we summarise the interactions among different epigenetic mechanisms during cell senescence and analyse the possibility of using epigenetic signatures as biomarkers and therapeutic targets for the treatment of senescence-associated diseases.

摘要

细胞衰老,即细胞增殖停滞的不可逆状态,已成为组织功能障碍和机体衰老的一个潜在重要因素。细胞衰老由多种衰老应激源触发,这些应激源影响基因表达和多种信号通路,从而产生各种衰老表型。表观遗传机制作为染色体结构和基因表达的关键调节剂,为细胞衰老的分子机制增添了一个额外的维度。细胞衰老伴随着 DNA 甲基化、组蛋白相关的表观遗传过程、染色质重塑和 ncRNA 表达的变化。这些与衰老相关的表观遗传改变与衰老调控程序网络相互作用,导致各种细胞衰老表型。本综述全面概述了表观遗传变化及其对细胞衰老的影响。还讨论了不同类型衰老之间表观遗传改变的差异。此外,我们总结了细胞衰老过程中不同表观遗传机制之间的相互作用,并分析了将表观遗传特征用作衰老相关疾病治疗的生物标志物和治疗靶点的可能性。

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