Mechanisms regulating chromatin structure and alterations associated with senescence

Abstract

The expected average human lifespan is constantly increasing. The negative effect of this phenomenon is more frequent incidences of age-related diseases. Experimental data have shown that cellular senescence is the cause of organismal aging. Cellular senescence is an irreversible cell cycle arrest while maintaining metabolic functions and can occur through the exhaustion of proliferative potential (replicative senescence - RS) or stress conditions (stress-induced premature senescence - SIPS). Both types of senescence cause a number of morphological changes, in particular, in the cell nucleus and gene expression. A gradual decrease of condensed heterochromatin in favor of relaxed euchromatin is observed. This is caused by the loss of histones, a disturbance of the balance between repressive and activating post-translational modifications of histones, the impairment in the activity of histone-decorating enzymes and proteins stabilizing the chromatin structure. This review detailed nuclear architecture and chromatin structure alterations during cellular senescence.