Westbrook Reyhan, Bonkowski Michael S, Strader April D, Bartke Andrzej
Department of Internal Medicine, Division of Geriatric Research, Southern Illinois University School of Medicine, 801 North Rutledge Street, Springfield, IL 62794-9628, USA.
J Gerontol A Biol Sci Med Sci. 2009 Apr;64(4):443-51. doi: 10.1093/gerona/gln075. Epub 2009 Mar 13.
Growth hormone (GH) signaling influences longevity in mice, with decreased GH signaling associated with longer life span and increased GH signaling with shortened life span. A proposed mechanism through which GH signaling influences life span postulates that decreased GH signaling lowers metabolic rate, thus slowing aging by decreasing production of damaging free radicals. The influence of altered GH signaling on metabolism was tested by monitoring oxygen consumption (VO(2)), respiratory quotient (RQ), and heat production in long-lived GH receptor knockout (GHRKO) and Ames dwarf mice, and short-lived bovine GH-overexpressing transgenic (bGH TG) mice. Intriguingly, both GHRKO and Ames dwarf mice have increased VO(2) and heat per gram body weight, and decreased RQ, whereas bGH TG mice have decreased VO(2) and heat per gram body weight and increased RQ. In conclusion, decreased GH signaling associates with increased metabolism per body weight and may beneficially affect mitochondrial flexibility by increasing the capacity for fat oxidation; generally, GH excess produces opposite metabolic effects.
生长激素(GH)信号传导影响小鼠的寿命,GH信号传导降低与寿命延长相关,而GH信号传导增加与寿命缩短相关。一种关于GH信号传导影响寿命的机制假说认为,GH信号传导降低会降低代谢率,从而通过减少有害自由基的产生来减缓衰老。通过监测长寿的生长激素受体基因敲除(GHRKO)小鼠、艾姆斯侏儒小鼠以及短命的牛生长激素过表达转基因(bGH TG)小鼠的耗氧量(VO₂)、呼吸商(RQ)和产热情况,来测试改变的GH信号传导对代谢的影响。有趣的是,GHRKO小鼠和艾姆斯侏儒小鼠每克体重的VO₂和产热均增加,RQ降低,而bGH TG小鼠每克体重的VO₂和产热减少,RQ增加。总之,GH信号传导降低与每体重代谢增加相关,可能通过增加脂肪氧化能力对线粒体灵活性产生有益影响;一般而言,GH过量会产生相反的代谢效应。