Does Reduced IGF-1R Signaling in Igf1r+/2 Mice Alter Aging?

Mutations in insulin/IGF-1 signaling pathway have been shown to lead to increased longevity in various invertebrate models. Therefore, the effect of the haplo- insufficiency of the IGF-1 receptor (Igf1r+/2) on longevity/aging was evaluated in C57Bl/6 mice using rigorous criteria where lifespan and end-of-life pathology were measured under optimal husbandry conditions using large sample sizes. Igf1r+/2 mice exhibited reductions in IGF-1 receptor levels and the activation of Akt by IGF-1, with no compensatory increases in serum IGF-1 or tissue IGF-1 mRNA levels, indicating that the Igf1r+/2 mice show reduced IGF-1 signaling. Aged male, but not female Igf1r+/2 mice were glucose intolerant, and both genders developed insulin resistance as they aged. Female, but not male Igf1r+/2mice survived longer than wild type mice after lethal paraquat and diquat exposure, and female Igf1r+/2 mice also exhibited less diquat-induced liver damage. However, no significant difference between the lifespans of the male Igf1r+/2 and wild type mice was observed; and the mean lifespan of th