Epigenetics as a Protagonist in Cellular Senescence

Abstract

Cellular Senescence process has diverse and heterogeneous functions. Beneficial side of senescence is related to tissue homeostasis, as it plays an important role during embryonic development and tissue remodeling, where it favor’s tissue regenerative deceleration during states of inflammation or tumorigenesis. Potentially harmful side of senescence has to do with time. Prolonged times promote the uncontrolled accumulation of senescent cells, thus reducing tissue regenerative and functional potential. During life, multiple stress signals are induced in tissues that activate cellular senescence programs.  The molecular framework within which the cellular senescence process takes place includes a set of programs with sequentially induced effects such as deregulation of cyclin-dependent kinases (Cdks), upregulation of inhibitors of cyclin-dependent kinases (CdkIs), increase in metabolic activity, activation of DNA damage repair (DDR) pathways and induction of apoptotic process. Epigenetics as a regulator of genetic expression directs the activation or inhibition of genes that control all these programs. This review article describes in detail the epigenetic mechanisms responsible for acquisition of senescent phenotype in eukaryotic cells.