Aberrant mTOR activation in senescence and aging: A mitochondrial stress response?

Exp Gerontol. 2015 Aug:68:66-70. doi: 10.1016/j.exger.2014.11.004. Epub 2014 Nov 6.

Abstract

Unexpected activation of mTOR signaling, measured by ribosomal S6 phosphorylation or ribosomal S6 kinase (p70S6K) activity, has been reported in aging-related settings. Evidence of elevated mTOR activity has been reported in the heart and muscle tissue in aged mice and humans, mouse models of progeria, and senescent human fibroblasts. We explore these reports and the possibility that activation of the mTOR/p70S6K kinase pathway may represent a ROS-mediated response to mitochondrial stress leading to the activation of senescence. This activation is a hallmark of both aged tissue and senescent human cells.

Keywords: Aging; Mitochondria; ROS; S6 kinase; Senescence; mTOR; p53; p70S6K.

Publication types

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

MeSH terms

  • Aging / physiology*
  • Animals
  • Autophagy / physiology
  • Cellular Senescence / physiology*
  • Humans
  • Longevity / physiology
  • Mechanistic Target of Rapamycin Complex 1
  • Mice
  • Mitochondria / metabolism
  • Multiprotein Complexes / metabolism*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / physiology
  • Stress, Physiological / physiology
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Multiprotein Complexes
  • Reactive Oxygen Species
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases