Reduced expression of the Caenorhabditis elegans p53 ortholog cep-1 results in increased longevity.
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.
Arum
Oge
O
Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado,USA. oarum@siumed.edu
Johnson
Thomas E
TE
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D004249:DNA Damage; D051858:Forkhead Transcription Factors; D017238:Genes, Helminth; D049452:Green Fluorescent Proteins / Q000235:genetics; D008136:Longevity / Q000235:genetics* / Q000502:physiology; D009154:Mutation; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology
C438244:CEP-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C108831:daf-16 protein, C elegans; D049452:Green Fluorescent Proteins