Caloric restriction, Ins/IGF-1 signalling and longevity in the nematode Caenorhabditis elegans

Several mechanisms of life span extension in C. elegans have been described, including caloric restriction, reduced Ins/IGF-1 signalling, Clk mutation and germ line ablation. Here, we describe the effects of caloric restriction on metabolism and life span in C. elegans and examine whether Ins/IGF-1 signalling is involved in the life extension observed in calorically restricted worms. We show that life span extension in restricted worms is not caused by a reduced metabolic rate, but is accompanied by enhanced stress resistance. We further show that caloric restriction and Ins/IGF-1 have additive effects on life span extension and on the stress defense enzyme activities, and that caloric restriction acts independently of daf-16. Thus, caloric restriction extends life span by mechanisms distinct from those affected by the Ins/IGF-1-like pathway.