Genetic polymorphism in long-lived people: cues for the presence of an insulin/IGF-pathway-dependent network affecting human longevity.

Longevity in yeast, nematodes, fruit flies and mice is affected by mutations in the insulin/IGF-1 or homologous pathways. Studies on long-living people revealed some associations between genetic variants of the insulin/IGF-1 pathway and longevity. Here, we review such investigations, and we will report human longevity association studies regarding the variability of genes which modulate lifespan in model organisms by interacting with the insulin/IGF-1 pathway. These studies will be presented in three groups: (1) insulin/IGF-1 pathway transcriptional target, superoxide dismutase 2, heat shock protein, cytochrome p450 isoenzymes, glutathione transferases; (2) insulin/IGF-1 pathway accessory transduction proteins H-Ras, p66Shc; and (3) longevity pathways that converge on the insulin/IGF-1 pathway (Klotho, p53, Sirtuins, TGF-beta). The data reported support the notion that the insulin/IGF-1 pathway drives an evolutionarily conserved network that regulates lifespan and affects longevity across species.