Telomeres: beacons of autocrine and paracrine DNA damage during skin aging

Cell Cycle. 2020 Mar;19(5):532-540. doi: 10.1080/15384101.2020.1728016. Epub 2020 Feb 16.

Abstract

Cellular senescence is an irreversible cell cycle arrest, which can be triggered by a number of stressors, including telomere damage. Among many other phenotypic changes, senescence is accompanied by increased secretion of pro-inflammatory molecules, also known as the senescence-associated secretory phenotype (SASP). It is thought that accumulation of senescent cells contributes to age-associated tissue dysfunction partly by inducing senescence in neighboring cells through mechanisms involving SASP factors. Here, we will review evidence suggesting that telomeres can become dysfunctional irrespectively of shortening, and that this may be a mechanism-driving senescence in post-mitotic or slow dividing cells. Furthermore, we review recent evidence that supports that senescent melanocytes induce paracrine telomere damage during skin aging, which may be the mechanism responsible for propagation of senescent cells. We propose that telomeres are sensors of imbalances in the cellular milieu and act as beacons of stress, contributing to autocrine and paracrine senescence.

Keywords: Senescence; aging; mitochondria; telomeres.

Publication types

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

MeSH terms

  • Animals
  • Autocrine Communication*
  • Bystander Effect
  • Cellular Senescence* / genetics
  • DNA Damage* / genetics
  • Humans
  • Melanocytes / pathology*
  • Paracrine Communication*
  • Skin Aging / genetics
  • Skin Aging / pathology*
  • Stress, Physiological
  • Telomere / pathology*