Chromatin modification and senescence

Abstract

Cells are the fundamental structure composing our bodies and hence cellular decline (called senescence) contributes to ageing. Endogenous and exogenous stresses may induce cellular senescence. Stressors are mainly macromolecule damage events, which include: shortening of chromosome telomeres; non-telomeric DNA damage; excessive mitogenic signals, which may cause DNA damage; and non-genotoxic stress, such as perturbations to chromatin organization. For many years the analysis of chromatin perturbation as a leading event in triggering senescence has been overlooked. Now, it is well recognized that chromatin DNA packaging is not immune to the ravages of time. All eukaryotes experience changes in chromatin organization and gene-expression patterns as they age. This can be due to perturbation in the function of chromatin modifiers. In this review we will discuss the role in the senescence process of the different types of chromatin modifiers, such as the ATP-dependent chromatin remodelling complexes, the enzymes that covalently modify histone tails and proteins involved in DNA methylation.