Transgenic mice with a reduced core body temperature have an increased life span
Transgenic mice with a reduced core body temperature have an increased life span
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DOI：
10.1126/science.1132191
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发表时间：
2006-11-03
期刊：
影响因子：
56.9
通讯作者：
Bartfai, Tamas
中科院分区：
文献类型：
--
作者：
Conti, Bruno;Sanchez-Alavez, Manuel;Bartfai, Tamas
核心体温的降低被认为有助于增加寿命和卡路里限制（CR）所赋予的抗衰老作用。这一假设的验证一直很难在恒温动物，主要是由于缺乏实验模型。我们报告，转基因小鼠过表达解偶联蛋白2的下丘脑神经元（Hcrt-UCP 2）有升高的下丘脑温度。局部温度升高对中央恒温器的影响导致核心体温降低0.3 ℃至0.5 ℃。随意进食，Hcrt-UCP 2转基因小鼠的热量摄入与野生型同窝小鼠相同，但能量效率提高，中位寿命延长（雄性增加12%;雌性增加20%）。因此，适度的，持续的核心体温降低延长寿命的改变饮食或CR独立。
Reduction of core body temperature has been proposed to contribute to the increased life span and the antiaging effects conferred by calorie restriction (CR). Validation of this hypothesis has been difficult in homeotherms, primarily due to a lack of experimental models. We report that transgenic mice engineered to overexpress the uncoupling protein 2 in hypocretin neurons (Hcrt-UCP2) have elevated hypothalamic temperature. The effects of local temperature elevation on the central thermostat resulted in a 0.3 degrees to 0.5 degrees C reduction of the core body temperature. Fed ad libitum, Hcrt-UCP2 transgenic mice had the same caloric intake as their wild-type littermates but had increased energy efficiency and a greater median life span (12% increase in males; 20% increase in females). Thus, modest, sustained reduction of core body temperature prolonged life span independent of altered diet or CR.