Senescence and the SASP: many therapeutic avenues

Genes Dev. 2020 Dec 1;34(23-24):1565-1576. doi: 10.1101/gad.343129.120.

Abstract

Cellular senescence is a stress response that elicits a permanent cell cycle arrest and triggers profound phenotypic changes such as the production of a bioactive secretome, referred to as the senescence-associated secretory phenotype (SASP). Acute senescence induction protects against cancer and limits fibrosis, but lingering senescent cells drive age-related disorders. Thus, targeting senescent cells to delay aging and limit dysfunction, known as "senotherapy," is gaining momentum. While drugs that selectively kill senescent cells, termed "senolytics" are a major focus, SASP-centered approaches are emerging as alternatives to target senescence-associated diseases. Here, we summarize the regulation and functions of the SASP and highlight the therapeutic potential of SASP modulation as complimentary or an alternative to current senolytic approaches.

Keywords: SASP; aging; cancer; disease; inflammation; senescence; senolytics; senomorphics; therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / genetics
  • Aging / pathology*
  • Cellular Senescence / genetics*
  • Disease Susceptibility / therapy*
  • Drug Development
  • Drug Therapy*
  • Epigenesis, Genetic
  • Gene Expression Regulation
  • Humans
  • Pharmaceutical Preparations / chemistry
  • Secretory Pathway
  • Signal Transduction

Substances

  • Pharmaceutical Preparations