Title |
Does Reduced IGF-1R Signaling in Igf1r+/− Mice Alter Aging?
|
---|---|
Published in |
PLOS ONE, November 2011
|
DOI | 10.1371/journal.pone.0026891 |
Pubmed ID | |
Authors |
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 |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 3 | 4% |
United States | 1 | 1% |
Unknown | 76 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 23 | 29% |
Researcher | 10 | 13% |
Other | 7 | 9% |
Professor > Associate Professor | 6 | 8% |
Student > Doctoral Student | 5 | 6% |
Other | 16 | 20% |
Unknown | 13 | 16% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 23 | 29% |
Biochemistry, Genetics and Molecular Biology | 15 | 19% |
Medicine and Dentistry | 12 | 15% |
Neuroscience | 4 | 5% |
Immunology and Microbiology | 3 | 4% |
Other | 8 | 10% |
Unknown | 15 | 19% |