Senescence and the SASP: many therapeutic avenues

  1. Jesús Gil1,2
  1. 1MRC London Institute of Medical Sciences (LMS), London W12 0NN, United Kingdom;
  2. 2Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London W12 0NN, United Kingdom
  1. Corresponding author: jesus.gil{at}imperial.ac.uk

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

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