Characterization and genetics of induced stress resistance and life extension in Caenorhabditis elegans

The purpose of this thesis is to illuminate the positive relationship between increased stress resistance and life extension. To this end I have studied environmental and genetic influences on life span to learn how they might interact in the nematode Caenorhabditis elegans.; I characterized the increased stress resistance and the life extension displayed by C. elegans in response to sub-lethal stress pretreatments. I verified that increased stress resistance occurs in C. elegans in response to sub-lethal pretreatments with heat, hyperbaric oxygen or juglone (a reactive oxygen species), and that life extension occurs in C. elegans in response to sub lethal pretreatments with heat or oxygen.; I examined whether genes regulating entrance to the dauer formation pathway might also play roles in the adult hormetic responses of subsequent increased stress resistance and life extension. I found that function of one gene of this pathway, daf-18, is required for the full induction of increased stress (heat) resistance. I also found that three genes required for expression of dauer formation (daf-12, daf-16, and daf-18) are also required for the life extension seen in response to sub-lethal heat pretreatment. These three genes lie within that part of the dauer formation pathway which responds to insulin/IGF-like signaling. In contrast, I found that mutations in either of two other genes required for dauer formation (daf-3 and daf-5) do not block hormetic life extension. Both daf-3 and daf-5 lie on that arm of the dauer formation pathway which responds to TGFβ-like signaling rather than insulin/IGF-like signaling.; I confirmed and elaborated the role of the spe-10 gene in life extension and stress resistance. By making double mutants of this gene with age-1 (a representative gene of the dauer formation pathway) I demonstrated increases of life expectancy greater than would be expected from simple additive effects. I found that these double mutants are more resistant to heat and to UV irradiation than is either single mutant. (Abstract shortened by UMI.)...