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Cellular and organismal ageing: Role of the p53 tumor suppressor protein in the induction of transient and terminal senescence

✍ Scribed by Gerald Schmid; Matthias P. Kramer; Margarita Maurer; Stefanie Wandl; Józefa Węsierska-Gądek

Publisher
John Wiley and Sons
Year
2007
Tongue
English
Weight
258 KB
Volume
101
Category
Article
ISSN
0730-2312

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✦ Synopsis

Abstract

In recent years, an impact of the p53 tumor suppressor protein in the processes of cellular and organismal ageing became evident. First hints were found in model organisms like Saccharomyces cerevisiae, Caenorhabditis elegans, and Drosophila melanogaster where a clear connection between ageing phenotypes and pathways that are regulated by p53, were found. Interestingly, pathways that are central to the ageing process are usually also involved in energy metabolism and are highly conserved throughout evolution. This also supports the long known empiric finding that caloric restriction has a positive impact on the life span of a wide variety of organisms. Within the last years, on the molecular level, an involvement of the insulin‐like growth factor and of the histone deacetylase SRIT1 could be shown. Insight on the impact of p53 on ageing at the organismal level came from mice expressing aberrant forms of the p53 protein. Obviously, the balance of the full length p53 protein and of the shorter p44/ΔNp53 isomer bear a strong impact on ageing. The shorter isoform regulates full length p53 and in cases where there is too much of the longer isoform, this leads to elevated apoptosis resulting in decreased tumor incidence but also in premature ageing due to exhaustion of the renewal potential. Therefore, modulating the expression of the truncated p53 isoform accordingly, might lead to increased health‐span and elevated life‐span. J. Cell. Biochem. 101: 1355–1369, 2007. © 2007 Wiley‐Liss, Inc.

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