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.