Senescence and tissue fibrosis: opportunities for therapeutic targeting

Trends Mol Med. 2024 Dec;30(12):1113-1125. doi: 10.1016/j.molmed.2024.05.012. Epub 2024 Jun 17.

Abstract

Cellular senescence is a key hallmark of aging. It has now emerged as a key mediator in normal tissue turnover and is associated with a variety of age-related diseases, including organ-specific fibrosis and systemic sclerosis (SSc). This review discusses the recent evidence of the role of senescence in tissue fibrosis, with an emphasis on SSc, a systemic autoimmune rheumatic disease. We discuss the physiological role of these cells, their role in fibrosis, and that targeting these cells specifically could be a new therapeutic avenue in fibrotic disease. We argue that targeting senescent cells, with senolytics or senomorphs, is a viable therapeutic target in fibrotic diseases which remain largely intractable.

Keywords: SASP; fibrosis; myofibroblasts; senescence; systemic sclerosis.

Publication types

  • Review

MeSH terms

  • Aging / pathology
  • Animals
  • Cellular Senescence* / drug effects
  • Fibrosis*
  • Humans
  • Molecular Targeted Therapy
  • Scleroderma, Systemic* / drug therapy
  • Scleroderma, Systemic* / metabolism
  • Scleroderma, Systemic* / pathology