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首页> 外文期刊>The journals of gerontology.Series A. Biological sciences and medical sciences >A Dwarf Mouse Model With Decreased GH/IGF-1 Activity That Does Not Experience Life-Span Extension: Potential Impact of Increased Adiposity, Leptin, and Insulin With Advancing Age
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A Dwarf Mouse Model With Decreased GH/IGF-1 Activity That Does Not Experience Life-Span Extension: Potential Impact of Increased Adiposity, Leptin, and Insulin With Advancing Age

机译：GH / IGF-1活性降低且未经历寿命延长的矮人小鼠模型：随着年龄的增长，肥胖，瘦素和胰岛素增加的潜在影响

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Reduced growth hormone (GH) action is associated with extended longevity in many vertebrate species. GH receptor (GHR) null (GHR-'-) mice, which have a disruption in the GHR gene, are a well-studied example of mice that are insulin sensitive and long lived yet obese. However, unlike other mouse lines with reduced GH action, GH receptor antagonist (GHA) transgenic mice have reduced GH action yet exhibit a normal, not extended, life span. Understanding why GHA mice do not have extended life span though they share many physiological attributes with GHR"'" mice will help provide clues about how GH influences aging. For this study, we examined age- and sex-related changes in body composition, glucose homeostasis, circulating adipokines, and tissue weights in GHA mice and littermate controls. Compared with previous studies with GHR"'" mice, GHA mice had more significant increases in fat mass with advancing age. The increased obesity resulted in significant adipokine changes. Euglycemia was maintained in GHA mice; however, hyper-insulinemia developed in older male GHA mice. Overall, GHA mice experience a more substantial, generalized obesity accompanied by altered adipokine levels and glucose homeostasis than GHR'~ mice, which becomes more exaggerated with advancing age and which likely contributes to the lack of life-span extension in these mice.
机译：在许多脊椎动物中，生长激素（GH）作用降低与寿命延长有关。 GH受体（GHR）无效（GHR -'-）小鼠在GHR基因中具有破坏作用，是对胰岛素敏感，寿命长而肥胖的小鼠的充分研究的例子。但是，与其他GH作用降低的小鼠系不同，GH受体拮抗剂（GHA）转基因小鼠的GH作用降低，但显示出正常的寿命，而不是延长的寿命。了解为什么GHA小鼠与GHR小鼠具有许多生理属性，但为什么它们没有延长寿命，这将有助于提供有关GH如何影响衰老的线索。在这项研究中，我们检查了GHA小鼠和同窝仔对照的身体组成，葡萄糖稳态，循环脂肪因子和组织重量与年龄和性别相关的变化。与以前的GHR小鼠研究相比，GHA小鼠的脂肪含量随着年龄的增长而增加。肥胖增加导致脂肪因子发生显着变化。 GHA小鼠维持正常血糖水平;但是，老年男性GHA小鼠会出现高胰岛素血症。总体而言，与GHR'-小鼠相比，GHA小鼠经历了更为严重的肥胖症，伴有脂肪因子水平和葡萄糖稳态的改变，随着年龄的增长，肥胖变得更加夸张，并可能导致这些小鼠寿命的延长。

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