Autophagy Mediates the Mitotic Senescence Transition

Genes Dev. 2009 Apr 1;23(7):798-803. doi: 10.1101/gad.519709. Epub 2009 Mar 11.

Abstract

As a stress response, senescence is a dynamic process involving multiple effector mechanisms whose combination determines the phenotypic quality. Here we identify autophagy as a new effector mechanism of senescence. Autophagy is activated during senescence and its activation is correlated with negative feedback in the PI3K-mammalian target of rapamycin (mTOR) pathway. A subset of autophagy-related genes are up-regulated during senescence: Overexpression of one of those genes, ULK3, induces autophagy and senescence. Furthermore, inhibition of autophagy delays the senescence phenotype, including senescence-associated secretion. Our data suggest that autophagy, and its consequent protein turnover, mediate the acquisition of the senescence phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Autophagy / physiology*
  • Feedback, Physiological / physiology
  • Gene Expression Regulation
  • Humans
  • Immunohistochemistry
  • Microtubule-Associated Proteins / metabolism
  • Mitosis / physiology*
  • Neoplasms / physiopathology
  • Protein Kinases / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • TOR Serine-Threonine Kinases

Substances

  • Microtubule-Associated Proteins
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Protein-Serine-Threonine Kinases