Does reduced IGF-1R signaling in Igf1r+/- 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(+/-)) on longevity/aging was evaluated in C57Bl/6 mice using rigorous criteria where lifespan and...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3223158?pdf=render |
| _version_ | 1811268925532405760 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Alex F Bokov |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T21:31:35Z |
| format | Article |
| id | doaj.art-cc091090517441c39e28556c68975de3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T21:31:35Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-cc091090517441c39e28556c68975de32022-12-22T03:16:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01611e2689110.1371/journal.pone.0026891Does reduced IGF-1R signaling in Igf1r+/- mice alter aging?Alex F BokovNeha GargYuji IkenoSachin ThakurNicolas MusiRalph A DeFronzoNing ZhangRebecca C EricksonJon GelfondGene B HubbardMartin L AdamoArlan RichardsonMutations 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.http://europepmc.org/articles/PMC3223158?pdf=render |
| spellingShingle | 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 Does reduced IGF-1R signaling in Igf1r+/- mice alter aging? PLoS ONE |
| title | Does reduced IGF-1R signaling in Igf1r+/- mice alter aging? |
| title_full | Does reduced IGF-1R signaling in Igf1r+/- mice alter aging? |
| title_fullStr | Does reduced IGF-1R signaling in Igf1r+/- mice alter aging? |
| title_full_unstemmed | Does reduced IGF-1R signaling in Igf1r+/- mice alter aging? |
| title_short | Does reduced IGF-1R signaling in Igf1r+/- mice alter aging? |
| title_sort | does reduced igf 1r signaling in igf1r mice alter aging |
| url | http://europepmc.org/articles/PMC3223158?pdf=render |
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