Minireview: The Complexities of IGF/Insulin Signaling in Aging: Why Flies and Worms Are Not Humans.

A remarkable plasticity in life span has been uncovered in recent years, offering hope that the basic mechanisms of aging and interventions that delay aging may be identified in the coming decades. Life span extension has been achieved by genetic manipulation in multiple organisms including Sarcomyces cervisae, Caenorhabditis elegans, and Drosophila melanogaster, resulting in more than a doubling of life span in some cases. Typically, a reduction in function has been the most effective approach to extending life span, and a reduction in the insulin/IGF-1 signaling pathway appears to provide the most robust increase in life span. This highly conserved pathway integrates growth/survival signals with nutrient status. In mammals, it comprises part of the neuroendocrine axis, a critical regulator of growth and development. Reduced functionality of the neuroendocrine axis itself promotes life span extension in mammals; however, reduced activity of the IGF-1 signaling pathway specifically leads to less robust increases in life span. This review examines the differences in the insulin/IGF-1 axis between invertebrate and mammalian systems and discusses implications of these differences in terms of life span modulation.