Authors: GarcÃa-Cao I; GarcÃa-Cao M; TomÃ¡s-Loba A; MartÃn-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
Date: April 4, 2006
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GarcÃa-Cao I, GarcÃa-Cao M, TomÃ¡s-Loba A, MartÃn-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.