Integrating metabolism and longevity through insulin and IGF1 signaling.

The insulin pathway coordinates growth, development, metabolic homoeostasis, fertility, and stress resistance, which influence life span. Compensatory hyperinsulinemia to overcome systemic insulin resistance circumvents the immediate consequences of hyperglycemia. Work on flies, nematodes, and mice indicate that excess insulin signaling damages cellular function and accelerates aging. Maintenance of the central nervous system (CNS) has particular importance for life span. Reduced insulin/IGF1 signaling in the CNS can dysregulate peripheral energy homeostasis and metabolism, promote obesity, and extend life span. Genetic manipulations of insulin/IGF1 signaling components are revealing neuronal circuits that might resolve the central regulation of systemic metabolism from organism longevity.