Increased p53 activity does not accelerate telomere-driven ageing.

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.

journal_name

EMBO Rep

journal_title

EMBO reports

authors

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

doi

10.1038/sj.embor.7400667

keywords:

subject

Has Abstract

pub_date

2006-05-01 00:00:00

pages

546-52

issue

5

eissn

1469-221X

issn

1469-3178

pii

7400667

journal_volume

7

pub_type

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