Akt-induced cellular senescence: implication for human disease

Cell Cycle. 2004 Apr;3(4):449-51. Epub 2004 Apr 1.

Abstract

Reduction-of-function mutations in components of the insulin/insulin-like growth factor-1/Akt pathway have been shown to extend the lifespan in organisms ranging from yeast to mice. It has also been reported that activation of Akt induces proliferation and survival of mammalian cells, thereby promoting tumorigenesis. We have recently shown that Akt activity increases with cellular senescence and that inhibition of Akt extends the lifespan of primary cultured human endothelial cells. Constitutive activation of Akt promotes senescence-like arrest of cell growth via a p53/p21-dependent pathway, leading to endothelial dysfunction. This novel role of Akt in regulating the cellular lifespan may contribute to various human diseases including atherosclerosis and diabetes mellitus.

MeSH terms

  • Animals
  • Arteriosclerosis / pathology
  • Cell Division
  • Cellular Senescence*
  • Diabetes Mellitus / pathology
  • Endothelium / metabolism
  • Humans
  • Mice
  • Models, Biological
  • Mutation
  • Protein-Serine-Threonine Kinases / metabolism
  • Protein-Serine-Threonine Kinases / physiology*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-akt

Substances

  • Proto-Oncogene Proteins
  • AKT1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt