In nematodes an alternative third larval stage, often called the dauer stage, allows the animals to weather periods of low food availability (if free living) or to disperse (if parasitic). Genetic studies of mutations in the nematode Caenorhabditis elegans have indicated that mutations in several genes that control the entry into and exit from the dauer stage have a profound effect upon the life span of the animal. We have identified an unusual catalase gene, ctl-1, that is required in C. elegans for this life-span extension. ctl-1 mRNA is elevated in dauer larvae, and a ctl-1 mutation not only prevents the life-span extension of the dauer (daf) mutations, but also shortens life-span of wild-type animals, i.e., it is progeric. This catalase is unusual (in animal cells) because it is cytosolic (the C. elegans gene ctl-2 encodes the peroxisomal catalase). The ctl-1 cytosolic catalase may have evolved to allow prolonged periods of dormancy before reproductive maturity. The hypothesis driving the proposed research is that this catalase (along with superoxide dismutase) is an important determinant of dauer and adult life-span.
Specific aims designed to establish and extend this hypothesis are: 1) to analyze further the role of ctl-1 and ctl-2 in wild-type and life-span-altered mutants and under different environmental stresses (starvation and UV irradiation) by examining and altering their expression; and 2) to identify and characterize other genes that extend or shorten life-span using two novel genetic approaches.
