The insulin/IGF-1 signaling in mammals and its relevance to human longevity.

Hormones, like insulin and insulin-like growth factor 1 (IGF-1), are thought to be deeply involved with longevity. Lower species have been the source for most of our current knowledge on the role of the insulin/IGF-1 signaling in modulating lifespan. This hormonal system may have originated from a very early common ancestor and is involved in many functions that are necessary for metabolism, growth, and fertility in animal models like flies, nematodes and mammalians. Disruption of the insulin/IGF-1 receptor in nematodes and flies increases lifespan significantly. With evolution, mammals developed two well characterized hormonal systems: insulin and growth hormone (GH)/IGF-1, with different metabolic and developmental functions. Abnormalities in the insulin signaling pathway generate age-related diseases and increased mortality, whereas the GH/IGF-1 axis could potentially modulate longevity in many species. In this review we briefly describe the lifespan regulatory role of the insulin/IGF-1 signaling of nematodes, flies and rodent models and compare it with the human equivalent.