Mice Producing Reduced Levels of Insulin-Like Growth Factor Type 1 Display an Increase in Maximum, but not Mean, Life Span
Mice Producing Reduced Levels of Insulin-Like Growth Factor Type 1 Display an Increase in Maximum, but not Mean, Life Span
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DOI：
10.1093/gerona/glt108
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发表时间：
2014-04-01
影响因子：
5.1
通讯作者：
Sell, Christian
中科院分区：
文献类型：
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作者：
Lorenzini, Antonello;Salmon, Adam B.;Sell, Christian
通过IGF 1型（IGF-1）受体的信号减少可延长多种无脊椎动物的寿命。对哺乳动物寿命的研究表明，降低IGF-1水平也可能延长寿命。然而，这些数据是相互矛盾的，并且由于哺乳动物神经内分泌系统的生理学而变得复杂。我们对Igf 1基因插入纯合子小鼠进行了寿命分析。这些小鼠产生降低水平的IGF-1，并显示与IGF-1显著降低一致的表型。在三个独立的位置进行寿命分析。虽然研究中心之间的寿命数据不同，但IGF-1缺陷小鼠的最大寿命显著延长，IGF-1缺陷小鼠的年龄特异性死亡率降低;然而，除一个研究中心外，平均寿命无差异，其中雌性IGF-1缺陷动物的平均寿命延长。在一组IGF-1缺陷小鼠中观察到早期生命死亡率。结果与IGF-1在寿命调节中的重要作用一致，但与已发表的低血压艾姆斯和斯内尔侏儒小鼠和生长激素受体缺失小鼠的寿命数据形成对比，表明单独降低IGF-1不足以增加小鼠的平均寿命和最大寿命。
Reduced signaling through the IGF type 1 (IGF-1) receptor increases life span in multiple invertebrate organisms. Studies on mammalian longevity suggest that reducing levels of IGF-1 may also increase life span. However, the data are conflicting and complicated by the physiology of the mammalian neuroendocrine system. We have performed life-span analysis on mice homozygous for an insertion in the Igf1 gene. These mice produce reduced levels of IGF-1 and display a phenotype consistent with a significant decrease in IGF-1. Life-span analysis was carried out at three independent locations. Although the life-span data varied between sites, the maximum life span of the IGF-1-deficient mice was significantly increased and age-specific mortality rates were reduced in the IGF-1-deficient mice; however, mean life span did not differ except at one site, where mean life span was increased in female IGF-1-deficient animals. Early life mortality was noted in one cohort of IGF-1-deficient mice. The results are consistent with a significant role for IGF-1 in the modulation of life span but contrast with the published life-span data for the hypopituitary Ames and Snell dwarf mice and growth hormone receptor null mice, indicating that a reduction in IGF-1 alone is insufficient to increase both mean and maximal life span in mice.