THE GENETICS OF CALORIC RESTRICTION IN CAENORHABDITIS-ELEGANS

Low caloric intake (caloric restriction) can lengthen the life span of a wide range of animals and possibly even of humans, To understand be tter how caloric restriction lengthens life span, we used genetic meth ods and criteria to investigate its mechanism of action in the nematod e Caenorhabditis elegans. Mutations in many genes (eat genes) result i n partial starvation of the worm by disrupting the function of the pha rynx, the feeding organ. We found that most eat mutations significantl y lengthen life span (by up to 50%). In C, elegans, mutations in a num ber of other genes that can extend life span have been found. Two gene tically distinct mechanisms of life span extension are known: a mechan ism involving genes that regulate dauer formation (age-1, daf-2, daf-I d, and daf-28) and a mechanism involving genes that affect the rate of development and behavior (clk-1, clk-2, clk-3, and gro-1), We find th at the long life of eat-2 mutants does not require the activity of DAF -16 and that eat-2; daf-2 double mutants live even longer than extreme ly long-lived daf-2 mutants, These findings demonstrate that food rest riction lengthens life span by a mechanism distinct from that of dauer -formation mutants, In contrast, we find that food restriction does no t further increase the life span of long-lived clk-1 mutants, suggesti ng that clk-1 and caloric restriction affect similar processes.