Gadd45 proteins: relevance to aging, longevity and age-related pathologies

Ageing Res Rev. 2012 Jan;11(1):51-66. doi: 10.1016/j.arr.2011.09.003. Epub 2011 Oct 5.

Abstract

The Gadd45 proteins have been intensively studied, in view of their important role in key cellular processes. Indeed, the Gadd45 proteins stand at the crossroad of the cell fates by controlling the balance between cell (DNA) repair, eliminating (apoptosis) or preventing the expansion of potentially dangerous cells (cell cycle arrest, cellular senescence), and maintaining the stem cell pool. However, the biogerontological aspects have not thus far received sufficient attention. Here we analyzed the pathways and modes of action by which Gadd45 members are involved in aging, longevity and age-related diseases. Because of their pleiotropic action, a decreased inducibility of Gadd45 members may have far-reaching consequences including genome instability, accumulation of DNA damage, and disorders in cellular homeostasis - all of which may eventually contribute to the aging process and age-related disorders (promotion of tumorigenesis, immune disorders, insulin resistance and reduced responsiveness to stress). Most recently, the dGadd45 gene has been identified as a longevity regulator in Drosophila. Although further wide-scale research is warranted, it is becoming increasingly clear that Gadd45s are highly relevant to aging, age-related diseases (ARDs) and to the control of life span, suggesting them as potential therapeutic targets in ARDs and pro-longevity interventions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / genetics
  • Aging / pathology*
  • Aging / physiology
  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / physiology
  • Cell Death / genetics
  • Cellular Senescence / genetics
  • Cellular Senescence / physiology*
  • DNA Damage / genetics
  • Genomic Instability / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins / deficiency
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Longevity / genetics
  • Longevity / physiology*

Substances

  • Cell Cycle Proteins
  • GADD45 protein
  • Intracellular Signaling Peptides and Proteins