Principal Investigator Leonard Guarente
Co-investigator H Horvitz
C. elegans has four SIR2 homologs. Strains with a free duplication of the SIR2 ortholog, sir-2.1, show a significantly extended life span. Transgenic animals with elevated levels of sir-2.1 also live longer than wild type. A deletion of sir-2.1 has the opposite effect, life span is shortened. sir-2.1 appears to function in the insulin signaling pathway shown to regulate aging and dauer formation in C. elegans. This gene may also function in a second pathway to regulate life span. In another project, the possible role of cell death genes in limiting organismal life span is under study. In a third project, mutants that show premature aging have been identified and are being characterized.