GENES WITH MAJOR EFFECTS ON LIFE SPAN IN C ELEGANS

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DESCRIPTION (Adapted from the applicant's abstract): In the nematode Caenorhabditis elegans starvation or overcrowded conditions may activate a developmental switch so that the dauer larvae, a developmental arrested, non- feeding animal, is produced. Past investigations have identified both dauer- constitutive mutations, which cause animals to form dauer larvae in the presence of abundant food, and dauer-defective mutations, which prevent dauer formation under normal inducing conditions. Recently, temperature-sensitive dauer-constitutive alleles of the gene daf-2 have been shown to prolong adult lifespan (and be prevented by dauer-defective mutations in the gene daf-16). Additionally, mutations in daf-12 and daf-23 also affect this process. The goal of the present proposal is to understand how specific daf genes affect life span and to use these genes to understand the molecular and physiological processes that underlie life span determination. Emphasis will be placed on the analysis of the daf-2 and daf-12 genes. The complete sequences and patterns of expressions of both genes will be determined with particular emphasis in the latter experiments to ascertain whether specific cells are important for life-span determination. Downstream targets or genes interacting with or regulated by these genes will also be sought.