Metabolic mechanisms of longevity: Caloric restriction in mammals and longevity mutations in Caenorhabditis elegans;...

Several recent studies in Caenorhabditis elegans have reported significant extension of the lifespan by probable loss of function mutations in various genes. When sequenced, many of these genes exhibited significant homology to genes in the mammalian insulin signaling cascade. For example, the daf-2 gene that has been shown to regulate lifespan in C elegans shares significant sequence homology with the insulin and IGF-1 receptor genes in mammals. Another longevity gene in the nematode, age-1, is homologous with the p110 subunit of phosphatidylinositol 3-kinase in mammals. This enzyme functions early in the mammalian insulin response cascade to influence many important cellular growth and metabolic processes. These findings and others have led to the suggestion that lifespan regulation in nematodes is controlled by a mechanism similar to that involved in lifespan extension by caloric restriction in mammals. Many intriguing similarities exist between these two model systems providing some support for this idea. However, at present there is insufficient data to conclude that similar genes or mechanisms regulate lifespan determination in nematodes and in mammals.