GH and IGF1: Roles in Energy Metabolism of Long-Living GH Mutant Mice
GH and IGF1: Roles in Energy Metabolism of Long-Living GH Mutant Mice
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DOI：
10.1093/gerona/gls086
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发表时间：
2012-06-01
影响因子：
5.1
通讯作者：
Bartke, Andrzej
中科院分区：
文献类型：
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作者：
Brown-Borg, Holly M.;Bartke, Andrzej
在解释超凡长寿的多种理论中，最有力的理论集中在生长激素(GH)、胰岛素样生长因子和胰岛素这三种合成蛋白激素的减少上。与野生型小鼠相比，GH突变小鼠的寿命延长了50%，并且在能量代谢的几个方面表现出显著的差异。线粒体代谢在没有生长激素的情况下被上调，而在生长激素转基因小鼠和用生长激素治疗的侏儒小鼠中，这些途径的多个方面受到抑制。侏儒小鼠的核心体温显著低于正常对照小鼠，而用间接量热法测量的Ames侏儒小鼠和Ghr-/-小鼠的全身新陈代谢水平却出人意料地高于正常对照组。脂联素是一种关键的抗炎细胞因子，它的升高也很可能有助于延长这些小鼠的寿命。因此，在生长激素突变小鼠中，与能量代谢相关的几个重要成分发生了变化，这些差异可能在衰老过程和延长寿命方面至关重要。
Of the multiple theories to explain exceptional longevity, the most robust of these has centered on the reduction of three anabolic protein hormones, growth hormone (GH), insulin-like growth factor, and insulin. GH mutant mice live 50% longer and exhibit significant differences in several aspects of energy metabolism as compared with wild-type mice. Mitochondrial metabolism is upregulated in the absence of GH, whereas in GH transgenic mice and dwarf mice treated with GH, multiple aspects of these pathways are suppressed. Core body temperature is markedly lower in dwarf mice, yet whole-body metabolism, as measured by indirect calorimetry, is surprisingly higher in Ames dwarf and Ghr-/- mice compared with normal controls. Elevated adiponectin, a key antiinflammatory cytokine, is also very likely to contribute to longevity in these mice. Thus, several important components related to energy metabolism are altered in GH mutant mice, and these differences are likely critical in aging processes and life-span extension.