Increased p53 activity does not accelerate telomere-driven ageing

EMBO Rep. 2006 May;7(5):546-52. doi: 10.1038/sj.embor.7400667. Epub 2006 Mar 31.

Abstract

There is a great interest in determining the impact of p53 on ageing and, for this, it is important to discriminate among the known causes of ageing. Telomere loss is a well-established source of age-associated damage, which by itself can recapitulate ageing in mouse models. Here, we have used a genetic approach to interrogate whether p53 contributes to the elimination of telomere-damaged cells and its impact on telomere-driven ageing. We have generated compound mice carrying three functional copies of the p53 gene (super-p53) in a telomerase-deficient background and we have measured the presence of chromosomal abnormalities and DNA damage in several tissues. We have found that the in vivo load of telomere-derived chromosomal damage is significantly decreased in super-p53/telomerase-null mice compared with normal-p53/telomerase-null mice. Interestingly, the presence of extra p53 activity neither accelerates nor delays telomere-driven ageing. From these observations, we conclude that p53 has an active role in eliminating telomere-damaged cells, and we exclude the possibility of an age-promoting effect of p53 on telomere-driven ageing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics*
  • Aging / metabolism
  • Animals
  • Gene Dosage / genetics
  • Kinetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Telomerase / deficiency
  • Telomerase / genetics
  • Telomere / enzymology
  • Telomere / genetics*
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / physiology
  • Up-Regulation / genetics

Substances

  • Tumor Suppressor Protein p53
  • Telomerase