Epigenetic regulation in cell senescence

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.

Keywords: Chromatin remodelling complex; DNA methylation; Histone modification; Senescence; ncRNA.