X-Message-Number: 27417
Date: Wed, 7 Dec 2005 20:59:31 -0800 (PST)
From: Doug Skrecky <>
Subject: p53 accelerates human aging

[This is not a big surprise, but it is still satisfying to see that humans
have a response to p53 that is similar to that of the much more short
lived rodent species. Note that humans and mice respond completely
differently to p66.]

Exp Gerontol. 2005 Jan-Feb;40(1-2):11-5.
Comment in:
Exp Gerontol. 2005 Jan-Feb;40(1-2):7-9.
Variation in the human TP53 gene affects old age survival and cancer mortality.
  Longevity may depend on a balance between tumor suppression and tissue
renewal mechanisms [Campisi, J., 2003. Cancer and ageing: rival
demons? Nat. Rev. Cancer 3 (5), 339-349]. Mice with constitutively
activated p53 are almost cancer free but their life span is reduced and
accompanied by early tissue atrophy [Tyner et al., 2002. p53 mutant mice
that display early ageing-associated phenotypes. Nature 415
(6867) 45-53]. Replacement of arginine (Arg) by proline (Pro) at position
72 of human p53 decreases its apoptotic potential [Dumont et al.,
2003. The codon 72 polymorphic variants of p53 have markedly different
apoptotic potential. Nat. Genet. 33 (3), 357-365] providing a tool to
test for a similar trade-off in humans. Using a formal meta-analysis of
the published literature we show that carriers of the TP53 codon 72
Pro/Pro genotype have an increased cancer risk compared to Arg/Arg
carriers (p<0.05). Next, in a prospective study of 1226 people aged 85
years and over we show that carriers of the Pro/Pro genotype have a 41%
increased survival (p = 0.032) despite a 2.54 fold increased (p =
0.007) proportional mortality from cancer. It is suggested that human p53
protect against cancer but at a cost of longevity.

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