Increased p53 activity does not accelerate telomere-driven ageing.

Authors: García-Cao I; García-Cao M; Tomás-Loba A; Martín-Caballero J; Flores JM; Klatt P; Blasco MA; Serrano M

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.

Keywords: Aging/*genetics/metabolism; Animals; Gene Dosage/genetics; Kinetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Telomerase/deficiency/genetics; Telomere/enzymology/*genetics; Tumor Suppressor Protein p53/*genetics/physiology; Up-Regulation/genetics
Journal: EMBO reports
Volume: 7
Issue: 5
Pages: 546-52
Date: April 4, 2006
PMID: 16582880
Select reference article to upload


García-Cao I, García-Cao M, Tomás-Loba A, Martín-Caballero J, Flores JM, Klatt P, Blasco MA, Serrano M (2006) Increased p53 activity does not accelerate telomere-driven ageing. EMBO reports 7: 546-52.

Update (Admin) | Auto-Update

Comment on This Data Unit