Targeted expression of the human uncoupling protein 2 (hUCP2) to adult neurons extends life span in the fly
Targeted expression of the human uncoupling protein 2 (hUCP2) to adult neurons extends life span in the fly
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DOI：
10.1016/j.cmet.2005.01.005
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发表时间：
2005-02-01
期刊：
影响因子：
29
通讯作者：
Helfand, SL
中科院分区：
文献类型：
--
作者：
Fridell, YWC;Sánchez-Blanco, A;Helfand, SL
衰老的氧化应激假说预测，线粒体活性氧（ROS）生成的减少将减少氧化损伤并延长寿命。通过增加线粒体解偶联来增加线粒体质子泄漏依赖性 4 态呼吸是一种推测可减少线粒体 ROS 产生的干预措施。当人 UCP2 (hUCP2) 靶向成年果蝇神经元的线粒体时，我们发现 4 态呼吸增加，ROS 产生减少，氧化损伤减少，对自由基产生剂百草枯的抵抗力增强，并且在不影响生育能力或体力活动的情况下延长寿命。我们的结果表明，成年果蝇中 hUCP2 的神经元特异性表达可减少细胞氧化损伤，并足以延长寿命。
The oxidative stress hypothesis of aging predicts that a reduction in the generation of mitochondrial reactive oxygen species (ROS) will decrease oxidative damage and extend life span. Increasing mitochondrial proton leak-dependent state 4 respiration by increasing mitochondrial uncoupling is an intervention postulated to decrease mitochondrial ROS production. When human UCP2 (hUCP2) is targeted to the mitochondria of adult fly neurons, we find an increase in state 4 respiration, a decrease in ROS production, a decrease in oxidative damage, heightened resistance to the free radical generator paraquat, and an extension in life span without compromising fertility or physical activity. Our results demonstrate that neuronal-specific expression of hUCP2 in adult flies decreases cellular oxidative damage and is sufficient to extend life span.