An antidepressant that extends lifespan in adult Caenorhabditis elegans
An antidepressant that extends lifespan in adult Caenorhabditis elegans
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DOI：
10.1038/nature05991
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发表时间：
2007-11-22
期刊：
影响因子：
64.8
通讯作者：
Buck, Linda B.
中科院分区：
文献类型：
--
作者：
Petrascheck, Michael;Ye, Xiaolan;Buck, Linda B.
决定生物体寿命的机制在很大程度上仍然是一个谜（1）。衰老研究的一个目标是找到药物，当给予成年动物时，可以增加寿命和活力。为此，我们测试了88，000种化学物质延长秀丽隐杆线虫成虫寿命的能力。在这里，我们报告说，一种药物作为抗抑郁药在人类增加C。elegans寿命。在人类中，这种药物通过神经递质5-羟色胺阻断神经信号。In C.在线虫中，药物对寿命的影响会因突变而减少或消除，这些突变会影响5-羟色胺的合成、突触对5-羟色胺的再摄取，或影响两种G蛋白偶联受体中的任何一种：一种识别5-羟色胺，另一种检测另一种神经递质章鱼胺。体外研究表明，该药物在这两种受体上都是拮抗剂。在饮食限制动物或具有影响寿命的突变的动物上进行的药物测试表明，其对寿命的影响涉及与通过饮食限制延长寿命相关的机制。这些研究表明，通过阻断成年动物中与食物感知有关的某些类型的神经传递，可能导致感知到的（尽管不是真实的）饥饿状态，可以延长寿命。
The mechanisms that determine the lifespan of an organism are still largely a mystery(1). One goal of ageing research is to find drugs that would increase lifespan and vitality when given to an adult animal. To this end, we tested 88,000 chemicals for the ability to extend the lifespan of adult Caenorhabditis elegans nematodes. Here we report that a drug used as an antidepressant in humans increases C. elegans lifespan. In humans, this drug blocks neural signalling by the neurotransmitter serotonin. In C. elegans, the effect of the drug on lifespan is reduced or eradicated by mutations that affect serotonin synthesis, serotonin re-uptake at synapses, or either of two G-protein-coupled receptors: one that recognizes serotonin and the other that detects another neurotransmitter, octopamine. In vitro studies show that the drug acts as an antagonist at both receptors. Testing of the drug on dietary-restricted animals or animals with mutations that affect lifespan indicates that its effect on lifespan involves mechanisms associated with lifespan extension by dietary restriction. These studies indicate that lifespan can be extended by blocking certain types of neurotransmission implicated in food sensing in the adult animal, possibly leading to a state of perceived, although not real, starvation.