GENES THAT REGULATE BOTH DEVELOPMENT AND LONGEVITY IN CAENORHABDITIS-ELEGANS

The nematode Caenorhabditis elegans responds to conditions of overcrow ding and limited food by arresting development as a dauer larva. Genet ic analysis of mutations that alter dauer larva formation (daf mutatio ns) is presented along with an updated genetic pathway for dauer vs. n ondauer development. Mutations in the daf-2 and daf-23 genes double ad ult life span, whereas mutations in four other dauer-constitutive gene s positioned in a separate branch of this pathway (daf-1, daf-4, daf-7 and daf-8) do not. The increased life spans are suppressed completely by a daf-16 mutation and partially in a daf-2; daf-18 double mutant. A genetic pathway for determination of adult life span is presented ba sed on the same strains and growth conditions used to characterize Daf phenotypes. Both dauer larva formation and adult life span are affect ed in daf-2; daf-12 double mutants in an allele-specific manner. Mutat ions in daf-12 do not extend adult life span, but certain combinations of daf-2 and daf-le mutant alleles nearly quadruple it. This synergis tic effect, which does not equivalently extend the fertile period, is the largest genetic extension of life span yet observed in a metazoan.