Does reduced IGF-1R signaling in Igf1r+/- mice alter aging?
Does reduced IGF-1R signaling in Igf1r+/- mice alter aging?
复制标题
IGF1R +/-小鼠中IGF-1R信号的降低会改变衰老吗？
DOI：
10.1371/journal.pone.0026891
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Richardson A
中科院分区：
文献类型：
--
作者：
Bokov AF;Garg N;Ikeno Y;Thakur S;Musi N;DeFronzo RA;Zhang N;Erickson RC;Gelfond J;Hubbard GB;Adamo ML;Richardson A
在各种无脊椎动物模型中，胰岛素/IGF-1信号通路的突变已被证明导致寿命延长。因此，我们用严格的标准评估了胰岛素样生长因子-1受体(IGF-1R+/−)单倍体缺陷对C57BL/6小鼠寿命/衰老的影响。IGF1R+/−小鼠表现出IGF1受体水平降低和Akt被IGF1激活，而血清IGF1或组织IGF1基因水平没有代偿性升高，表明IGF1+/−小鼠表现出IGF1信号转导减少。老年的雄性而不是雌性的Igf1r+/−小鼠是糖耐量异常的，并且随着年龄的增长，两性都会出现胰岛素抵抗。在致死的百草枯和敌草枯暴露后，雌性而不是雄性的Igf1r+/−小鼠比野生型小鼠存活的时间更长，雌性的Igf1r+/−小鼠也表现出较少的敌草净诱导的肝损伤。然而，雄性Igf1r+/−小鼠的寿命与野生型小鼠没有显著差异，雌性Igf1r+/−小鼠的平均寿命仅比野生型小鼠略有延长(不到5%)。综合病理分析表明，Igf1r+/−小鼠与野生型小鼠在生命末期的病理损害没有显著差异。这些数据表明，Igf1r+/−小鼠并不是胰岛素/胰岛素样生长因子-1信号通路突变的无脊椎动物模型所预测的延长寿命和延缓衰老的模型。
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.
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影响因子：
3.9
作者：
Bartke, Andrzej
通讯作者：
Bartke, Andrzej
DOI：
10.1098/rstb.2010.0276
发表时间：
2011-01-12
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
--
作者：
Kenyon C
通讯作者：
Kenyon C
影响因子：
4.8
作者：
Delahunty, K. M.;Shultz, K. L.;Rosen, C. J.
通讯作者：
Rosen, C. J.
DOI：
10.1073/pnas.111158898
发表时间：
2001-06-05
影响因子：
11.1
作者：
Flurkey, K;Papaconstantinou, J;Harrison, DE
通讯作者：
Harrison, DE
影响因子：
5.3
作者：
KLASS, MR
通讯作者：
KLASS, MR