Cellular Senescence: What, Why, and How.

Cellular senescence is a process that results from a variety of stresses and leads to a state of irreversible growth arrest. Senescent cells accumulate during aging and have been implicated in promoting a variety of age-related diseases. Cellular senescence may play an important role in tumor suppression, wound healing, and protection against tissue fibrosis; however, accumulating evidence that senescent cells may have harmful effects in vivo and may contribute to tissue remodeling, organismal aging, and many age-related diseases also exists. Cellular senescence can be induced by various intrinsic and extrinsic factors. The pathways for the proteins p53/p21 and p16Ink4a/retinoblastoma protein are important for irreversible growth arrest and senescent cells. Senescent cells secrete numerous biologically active factors; the specific secretion phenotype by senescent cell contributes to physiological and pathological consequences in organisms. The purpose of this article is to review the molecular basis of cell-cycle arrest and the senescent-associated secretory phenotype within these cells contributing to pathological consequences.