Link Between Senescence and Cell Fate: Senescence-Associated Secretory Phenotype and Its Effects on Stem Cell Fate Transition

Rejuvenation Res. 2022 Aug;25(4):160-172. doi: 10.1089/rej.2022.0021. Epub 2022 Jul 28.

Abstract

Senescence is a form of durable cell cycle arrest elicited in response to a wide range of stimuli. Senescent cells remain metabolically active and secrete a variety of factors collectively termed senescence-associated secretory phenotype (SASP). SASP is highly pleiotropic and can impact numerous biological processes in which it has both beneficial and deleterious roles. The underlying mechanisms by which SASP exerts its pleiotropic influence remain largely unknown. SASP serves as an environmental factor, which regulates stem cell differentiation and alters its routine. The latter can potentially be accomplished through dedifferentiation, transdifferentiation, or reprogramming. Behavioral changes that cells undergo when exposed to SASP are involved in several senescence-associated physiological and pathological phenomena. These findings provide clues for identifying possible interventions to reduce the deleterious effects without interfering in the beneficial outcomes. In this study, we discuss the multifaceted effects of SASP and the changes occurring in cellular states upon exposure to SASP factors.

Keywords: SASP; dedifferentiation; differentiation; reprogramming; transdifferentiation.

MeSH terms

  • Cell Differentiation
  • Cellular Senescence* / genetics
  • Phenotype
  • Senescence-Associated Secretory Phenotype*
  • Stem Cells