Life span extensions associated with upregulation of gene expression of antioxidant enzymes in Caenorhabditis elegans; studies of mutation in the age-1, PI3 kinase homologue and short-term exposure to hyperoxia.

Abstract

Life span could be modified by genetic or environmental perturbations in Caenorhabditis elegans. Here we show that two extensions of life span are associated with oxidative stress resistance and upregulation of the gene expression of antioxidant enzymes. First, mutations in age-1 gene (PI3 kinase homologue)that confer life span extension, display oxidative stress resistance and increase in the gene expression of sod-3, one of two Mn-superoxide dismutases (SOD) and ctl-1, cytosolic catalase. In this study, these traits appear to be regulated by the following genetic pathway: daf-2 (insulin receptor family)-> daf-18 (PTEN homologue)-> age-1-> daf-16 (Fork head transcription factor family), similar to the genetic pathway for the life span extension. Second, we show that short-term exposure to hyperoxia extends life span slightly but significantly. This treatment increases oxidative stress resistance and the gene expression of three types of SOD isoforms. These results suggest that both of these two life span extensions are closely related with increase in the antioxidant defense function.