Molecular signaling and genetic pathways of senescence: Its role in tumorigenesis and aging

J Cell Physiol. 2007 Mar;210(3):567-74. doi: 10.1002/jcp.20919.

Abstract

In response to progressive telomere shortening in successive cell divisions, normal somatic cells enter senescence, during which they cease to proliferate irreversibly and undergo dramatic changes in gene expression. Senescence can also be activated by various types of stressful stimuli, including aberrant oncogenic signaling, oxidative stress, and DNA damage. Because of the limited proliferative capacity imposed by senescence, as well as the ability of senescent cells to influence neighboring non-senescent cells, senescence has been proposed to play an important role in tumorigenesis and to contribute to aging. Considerable effort has been put into elucidating the molecular mechanisms of senescence, including the signals that trigger senescence, the molecular pathways by which cells enter senescence, and evidence that supports its role in tumorigenesis and aging.

Publication types

  • Review

MeSH terms

  • Aging / genetics*
  • Aging / physiology*
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / pathology*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / physiology
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / physiology
  • Humans
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / physiology
  • Signal Transduction / genetics*
  • Signal Transduction / physiology*
  • Telomere
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / physiology

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21
  • Retinoblastoma Protein
  • Tumor Suppressor Protein p53