Apoptosis and aging: increased resistance to apoptosis enhances the aging process

Cell Mol Life Sci. 2011 Mar;68(6):1021-31. doi: 10.1007/s00018-010-0597-y. Epub 2010 Nov 30.

Abstract

Apoptosis is a vital component in the evolutionarily conserved host defense system. Apoptosis is the guardian of tissue integrity by removing unfit and injured cells without evoking inflammation. However, apoptosis seems to be a double-edged sword since during low-level chronic stress, such as in aging, increased resistance to apoptosis can lead to the survival of functionally deficient, post-mitotic cells with damaged housekeeping functions. Senescent cells are remarkably resistant to apoptosis, and several studies indicate that host defense mechanisms can enhance anti-apoptotic signaling, which subsequently induces a senescent, pro-inflammatory phenotype during the aging process. At the molecular level, age-related resistance to apoptosis involves (1) functional deficiency in p53 network, (2) increased activity in the NF-κB-IAP/JNK axis, and (3) changes in molecular chaperones, microRNAs, and epigenetic regulation. We will discuss the molecular basis of age-related resistance to apoptosis and emphasize that increased resistance could enhance the aging process.

Publication types

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

MeSH terms

  • Aging / physiology*
  • Animals
  • Apoptosis / physiology*
  • Cellular Senescence / physiology*
  • Epigenesis, Genetic*
  • Humans
  • MAP Kinase Kinase 4 / metabolism
  • Molecular Chaperones / metabolism
  • Morphogenesis / physiology*
  • NF-kappa B / metabolism
  • Neoplasms / physiopathology*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Molecular Chaperones
  • NF-kappa B
  • Tumor Suppressor Protein p53
  • MAP Kinase Kinase 4