Abstract
Insulin/insulin-like growth factor-I (IGF-I) pathways are recognized as critical signaling pathways involved in the control of lifespans in lower organisms to mammals. Caloric restriction (CR) reduces plasma concentration of insulin, growth hormone (GH), and IGF-I. CR retards various age-dependent disorders such as nuerodegenerative diseases and extends lifespan in laboratory rodents. These beneficial effects of CR are partly mimicked in spontaneous or genetically engineered rodent models of reduced insulin and GH/IGF-I axis. Most of these long-living rodents show increased insulin sensitivity; however, recent study has revealed that some other rodents show normal or reduced insulin sensitivity. Thus, increased insulin sensitivity might be not prerequisite for lifespan extension in insulin/GH/IGF-I altered longevity rodent models. These results highlighted that, for lifespan extension, the intracellular signaling molecules of insulin/GH/IGF-I pathways might be more important than actual peripheral or systemic insulin action.
Highlights
Compared to animals allowed to access food freely, moderate restriction of food intake, but not malnutrition, reduces morbidity and mortality in laboratory animals [1]
1389-2029/07 $50.00+.00 genic (TG) rats, which have reduced plasma levels of insulin and insulin-like growth factor-I (IGF-I) [14,15]. These findings suggest that there might be different pathways in lifespan extension by growth hormone (GH)/IGF-I suppression and caloric restriction (CR); it is possible that they share some of the same regulatory molecules in the insulin/GH/IGF-I pathway
Reduction of function in in the Drosophila equivalents of daf-2 (InR) mutants and the null mutation of chico increased the mean lifespan in female flies. These findings suggest that insulin/IGF-I signaling is a highly conserved longevity signal from lower to higher organisms
Summary
Compared to animals allowed to access food freely, moderate restriction of food intake, but not malnutrition, reduces morbidity and mortality in laboratory animals [1]. We speculate the involvement of WD-repeat protein 6 (WDR6) as a candidate for the regulator of insulin/IGF-I signaling, which controls metabolism and longevity in the brain [22]. Fat specific insulin receptor knock out mice (FIRKO mice) show increased lifespan without reduction of the plasma IGF-I levels [38,39].
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