Increased p53 activity does not accelerate telomere-driven ageing.
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.
Tumor Suppression Group, Spanish National Cancer Center, Madrid.
Isabel
I
García-Cao
Marta
M
García-Cao
Antonia
A
Tomás-Loba
Juan
J
Martín-Caballero
Juana M
JM
Flores
Peter
P
Klatt
María A
MA
Blasco
Manuel
M
Serrano
D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D018628:Gene Dosage / Q000235:genetics; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019098:Telomerase / Q000172:deficiency / Q000235:genetics; D016615:Telomere / Q000201:enzymology / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics
D016159:Tumor Suppressor Protein p53; D019098:Telomerase