Authors: Arum O; Johnson TE
Abstract: Hyperactivation of mammalian p53 has been shown to result in segmental progeria and decreased survivorship. Repression of the p53 homolog in Drosophila melanogaster has also been shown to increase survival. We show that RNA interference (RNAi) or genetic knockout of the Caenorhabditis elegans p53 ortholog, cep-1, leads to increased life span, which is dependent upon functional daf-16. Furthermore, one other DNA damage-responsive C. elegans mutant, hus-1(op241), exhibits a life-span increase. The cep-1(gk138) knockout mutant does not show increased resistance to heat, oxidative, or ultraviolet stress; nor to bacterial pathogenicity. cep-1 RNAi does not extend the life span of a sir-2.1(geIn3) overexpressing strain. cep-1 RNAi does not alter dauer formation propensity or nuclear-localization of DAF-16::GFP, even under heat stress; nor does it change nuclear-persistence and/or retention of DAF-16::GFP. This study clarifies the inverse relationship between cep-1 expression and C. elegans life span, and, by extrapolation, that between p53 expression and mammalian life span.
Keywords: Animals; Animals, Genetically Modified; Caenorhabditis elegans/*genetics/physiology; Caenorhabditis elegans Proteins/antagonists & inhibitors/*genetics/physiology; DNA Damage; *Genes, Helminth; Green Fluorescent Proteins/genetics; Longevity/*genetics/physiology; Mutation; RNA Interference; Recombinant Fusion Proteins/genetics; Transcription Factors/genetics/physiology; Tumor Suppressor Protein p53/antagonists & inhibitors/*genetics/physiology|
Journal: The journals of gerontology. Series A, Biological sciences and medical sciences Volume: 62 Issue: 9 Pages: 951-9 Date: Sept. 27, 2007 PMID: 17895432 |
Arum O, Johnson TE (2007) Reduced expression of the Caenorhabditis elegans p53 ortholog cep-1 results in increased longevity. The journals of gerontology. Series A, Biological sciences and medical sciences 62: 951-9.
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