Promises and challenges of senolytics in skin regeneration, pathology and ageing

Mech Ageing Dev. 2021 Dec:200:111588. doi: 10.1016/j.mad.2021.111588. Epub 2021 Oct 19.

Abstract

The research of the last two decades has defined a crucial role of cellular senescence in both the physiology and pathology of skin, and senescent cells have been detected in conditions including development, regeneration, aging, and disease. The pathophysiology of cellular senescence in skin is complex as the phenotype of senescence pertains to several different cell types including fibroblasts, keratinocytes and melanocytes, among others. Paradoxically, the transient presence of senescent cells is believed to be beneficial in the context of development and wound healing, while the chronic presence of senescent cells is detrimental in the context of aging, diseases, and chronic wounds, which afflict predominantly the elderly. Identifying strategies to prevent senescence induction or reduce senescent burden in the skin could broadly benefit the aging population. Senolytics, drugs known to specifically eliminate senescent cells while preserving non-senescent cells, are being intensively studied for use in the clinical setting. Here, we review recent research on skin senescence, on the methods for the detection of senescent cells and describe promises and challenges related to the application of senolytic drugs. This article is part of the Special Issue - Senolytics - Edited by Joao Passos and Diana Jurk.

Keywords: Aging; Inflammation; Molecular biology of aging; Senescence; Senolytics; Skin regeneration.

Publication types

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

MeSH terms

  • Aging* / pathology
  • Aging* / physiology
  • Drug Development / methods*
  • Humans
  • Regeneration / drug effects
  • Senotherapeutics / pharmacology*
  • Skin Aging* / drug effects
  • Skin Aging* / pathology
  • Skin Aging* / physiology

Substances

  • Senotherapeutics