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Annu Rev Physiol. 2008;70:191-212.

Insulin-like signaling, nutrient homeostasis, and life span.

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  • 1Howard Hughes Medical Institute, Division of Endocrinology, Children's Hospital Boston, Harvard Medical School, Karp Family Research Laboratories, Boston, MA 02115, USA.


Insulin-like signaling is critical for nutrient homeostasis, growth and survival. However, work with lower metazoans-Caenorhabditis elegans and Drosophila-shows that reduced insulin-like signaling extends life span. In addition, reduced insulin signaling in higher animals-rodents and humans-causes glucose intolerance and hyperinsulinemia that progresses to diabetes and shortens the life span of affected individuals. Hyperinsulinemia usually develops to maintain glucose homeostasis and prevent the progression toward life-threatening type 2 diabetes; however, increased circulating insulin may have negative effects on the brain that promote age-related disease. We discuss the possibility that the brain is the site where reduced insulin-like signaling can consistently extend mammalian life span-just as reduced insulin-like signaling extends the life span of lower metazoans.

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