Review Volume 10, Issue 11 pp 3590—3609
The senescent cell epigenome
- 1 National Institute on Aging, NIH, Laboratory of Genetics and Genomics, Functional Epigenomics Unit, Baltimore, MD 21224, USA
- 2 Epigenetics Institute and Department of Cell and Developmental Biology, University of Pennsylvania, Smilow Center for Translational Research, Philadelphia, PA 19104, USA
Received: August 26, 2018 Accepted: October 19, 2018 Published: November 3, 2018
https://doi.org/10.18632/aging.101617How to Cite
Abstract
A critical hallmark of aging is cellular senescence, a state of growth arrest and inflammatory cytokine release in cells, caused by a variety of stresses. Recent work has convincingly linked the accumulation of senescent cells in aged tissues to a decline in health and a limit of lifespan, primarily through "inflammaging". Importantly, interventions that clear senescent cells have achieved marked improvements in healthspan and lifespan in mice. A growing list of studies show that environmental stimuli can affect aging and longevity through conserved pathways which, in turn, modulate chromatin states. This review consolidates key findings of chromatin state changes in senescence including histone modifications, histone variants, DNA methylation and changes in three-dimensional genome organization. This information will facilitate the identification of mechanisms and discovery of potential epigenetic targets for therapeutic interventions in aging and age-related disease.