The common germline Arg72Pro polymorphism of p53 and increased longevity in humans

Stig E. Bojesen & Børge G. Nordestgaard

Published online: 04 Feb 2008.

To cite this article: Stig E. Bojesen & Børge G. Nordestgaard (2008) The common germline Arg72Pro polymorphism of p53 and increased longevity in humans, Cell Cycle, 7:2, 158-163, DOI: 10.4161/cc.7.2.5249

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The common germline Arg72Pro polymorphism of p53 and increased longevity in humans

Stig E. Bojesen* and Børge G. Nordestgaard

Department of Clinical Biochemistry, Herlev Hospital, Herlev, Denmark; Copenhagen University Hospital, Herlev, Denmark

SNP, single nucleotide polymorphism

Key words: longevity, aging, mortality, p53, Arg72Pro, SNP, polymorphism, cancer risk

Ground allowing selection equilibrium to be established. These two assumptions, however, are not met when it comes to multifactorial diseases relevant to the aging population in modern affluent and fast-developing societies. Therefore, a priori it is quite possible that SNPs could be causative and thus associated with multifactorial diseases and even lifespan. The relative effect-size in most cases is probably small and in the order of 10-100% change of relative risk.

More than ten million single nucleotide polymorphisms (SNPs) have been identified in humans; however, the importance of most SNPs for health and disease is not understood. Most SNPs are indeed unimportant and because of often inadequately powered studies, many observations on SNP effects cannot be repeated by other researchers. SNPs are at best shown to influence protein function or level, rarely to influence the risk of disease, and almost never to influence total mortality, the ultimate endpoint.

A well-known functional SNP in the tumor suppressor TP53 gene leads to increased longevity: in the Danish general population (n=9219), homozygotes for the minor allele versus homozygotes for the major allele had an increase in median survival of 3 years. This is partly explained by increased survival after the development of cancer or other diseases, in accordance with the observation that Arg72Pro substitution in the p53 protein has an important influence on cell death via increased apoptosis. Thus, increased longevity may be due to a generally increased robustness after a diagnosis of any life-threatening disease. In contrast to widespread skepticism on the importance of SNPs in humans, this gain-of-function p53 SNP of importance for cell repair has a profound influence on longevity.