Adaptive responses to oxidative damage in three mutants of Caenorhabditis elegans (age-1, mev-1 and daf-16) that affect life span.

Oxidative damage shortens the life span of the nematode Caenorhabditis elegans (C. elegans), even in an age-1 mutant that is characterized by a long life and oxygen resistance. We found that daily short-term exposure (3 h) to hyperoxia further extended the life span of age-1, a phenomenon known as an adaptive response. age-1 also showed resistance to paraquat and heat. Acute hyperoxic treatment did not extend the life spans of wild type, daf-16 or mev-1. daf-16 mutant had a slightly shorter life span compared to wild type and was sensitive to heat and paraquat. The daf-16 phenotype resembles that of mev-1 showing a short life and oxygen sensitivity. We measured mRNA levels of superoxide dismutase genes (sod-1 through 4), catalase genes (clt-1 and ctl-2), known to encode anti-oxidant enzymes, and found they were elevated in age-1 young adults. On the other hand, in daf-16 and mev-1, the expression of sod-1, sod-2 and sod-3 genes was lower rather than in wild type. Conversely, ctl-1 and ctl-2 genes expression was significantly elevated in daf-16 and mev-1. This suggests that DAF-16, a forkhead/winged-helix transcription factor, whose expression is suppressed by AGE-1, phosphoinositide 3-kinase (PI3-kinase), regulates anti-oxidant genes as well as energy metabolism under atmospheric conditions. However, the level of gene expression of SOD and catalase was not elevated by short-term exposure to 90% oxygen in wild type, mev-1, daf-16 and even age-1. This suggests that SOD and catalase do not play a role in the adaptive response against oxidative stress under hyperoxia, at least under these experimental conditions.