Increased p53 activity does not accelerate telomere‐driven ageing

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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.