The mitochondrial metabolic checkpoint in stem cell aging and rejuvenation

Mech Ageing Dev. 2020 Jun:188:111254. doi: 10.1016/j.mad.2020.111254. Epub 2020 Apr 25.

Abstract

Stem cell aging contributes to aging-associated tissue degeneration and dysfunction. Recent studies reveal a mitochondrial metabolic checkpoint that regulates stem cell quiescence and maintenance, and dysregulation of the checkpoint leads to functional deterioration of aged stem cells. Here, we present the evidence supporting the mitochondrial metabolic checkpoint regulating stem cell aging and demonstrating the feasibility to target this checkpoint to reverse stem cell aging. We discuss the mechanisms by which mitochondrial stress leads to stem cell deterioration. We speculate the therapeutic potential of targeting the mitochondrial metabolic checkpoint for rejuvenating aged stem cells and improving aging tissue functions.

Keywords: NLRP3; SIRT2; SIRT3; SIRT7; Stem cell aging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Cell Proliferation
  • Cellular Senescence*
  • Humans
  • Mice
  • Mitochondria / metabolism*
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Oxidative Stress
  • Phenotype
  • Protein Folding
  • Rejuvenation*
  • Sirtuin 2 / metabolism
  • Sirtuin 3 / metabolism
  • Sirtuins / metabolism
  • Stem Cells / cytology*

Substances

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • SIRT7 protein, human
  • SIRT2 protein, human
  • SIRT3 protein, human
  • Sirtuin 2
  • Sirtuin 3
  • Sirtuins