Does reduced IGF-1R signaling in igf1r +/- mice alter aging?

Alex F. Bokov, Neha Garg, Yuji Ikeno, Sachin Thakur, Nicolas Musi, Ralph A. DeFronzo, Ning Zhang, Rebecca C. Erickson, Jon Gelfond, Gene B. Hubbard, Martin L. Adamo, Arlan Richardson

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Abstract

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 +/-) 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 +/- 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 +/- mice show reduced IGF-1 signaling. Aged male, but not female Igf1r +/- mice were glucose intolerant, and both genders developed insulin resistance as they aged. Female, but not male Igf1r +/- mice survived longer than wild type mice after lethal paraquat and diquat exposure, and female Igf1r +/- mice also exhibited less diquat-induced liver damage. However, no significant difference between the lifespans of the male Igf1r +/- and wild type mice was observed; and the mean lifespan of the Igf1r +/- females was increased only slightly (less than 5%) compared to wild type mice. A comprehensive pathological analysis showed no significant difference in end-of-life pathological lesions between the Igf1r +/- and wild type mice. These data show that the Igf1r +/- mouse is not a model of increased longevity and delayed aging as predicted by invertebrate models with mutations in the insulin/IGF-1 signaling pathway.

Original languageEnglish (US)
Article numbere26891
JournalPloS one
Volume6
Issue number11
DOIs
StatePublished - Nov 23 2011

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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