Ikeno Yuji, Hubbard Gene B, Lee Shuko, Cortez Lisa A, Lew Christie M, Webb Celeste R, Berryman Darlene E, List Edward O, Kopchick John J, Bartke Andrzej
Barshop Institute for Longevity and Aging Studies, San Antonio, TX 78245-3207, USA.
J Gerontol A Biol Sci Med Sci. 2009 May;64(5):522-9. doi: 10.1093/gerona/glp017. Epub 2009 Feb 19.
Although studies of Ames and Snell dwarf mice have suggested possible important roles of the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis in aging and age-related diseases, the results cannot rule out the possibility of other hormonal changes playing an important role in the life extension exhibited by these dwarf mice. Therefore, growth hormone receptor/binding protein (GHR/BP) knockout (KO) mice would be valuable animals to directly assess the roles of somatotropic axis in aging and age-related diseases because the primary hormonal change is due to GH/IGF-1 deficiency. Our pathological findings showed GHR/BP KO mice to have a lower incidence and delayed occurrence of fatal neoplastic lesions compared with their wild-type littermates. These changes of fatal neoplasms are similar to the effects observed with calorie restriction and therefore could possibly be a major contributing factor to the extended life span observed in the GHR/BP KO mice.
尽管对艾姆斯侏儒小鼠和斯内尔侏儒小鼠的研究表明,生长激素(GH)/胰岛素样生长因子-1(IGF-1)轴在衰老及与年龄相关的疾病中可能发挥重要作用,但这些结果并不能排除其他激素变化在这些侏儒小鼠所表现出的寿命延长中起重要作用的可能性。因此,生长激素受体/结合蛋白(GHR/BP)基因敲除(KO)小鼠将是直接评估生长激素轴在衰老及与年龄相关疾病中作用的有价值的动物,因为主要的激素变化是由于GH/IGF-1缺乏所致。我们的病理学研究结果显示,与野生型同窝小鼠相比,GHR/BP基因敲除小鼠致命性肿瘤病变的发生率较低且发生时间延迟。这些致命性肿瘤的变化与热量限制所观察到的效果相似,因此可能是GHR/BP基因敲除小鼠寿命延长的一个主要促成因素。