领导此次研究的是美国佛瑞德·哈金森癌症研究中心(Fred Hutchinson Cancer Research Center)的分子生物学家Linda Buck。她和同事花了5年的时间，从8.8万种化学制剂中挑选出了100多种，它们能够延长秀丽隐杆线虫的寿命。由于对这些制剂在生物体内的反应机理并不清楚，她们转而寻找具有相似作用的成品药物。结果发现，抗抑郁药脱尔烦能够将这种线虫的寿命延长三分之一以上。
Nature 450, 553-556 (22 November 2007) | doi:10.1038/nature05991; Received 31 July 2007; Accepted 11 October 2007
An antidepressant that extends lifespan in adult Caenorhabditis elegans
Michael Petrascheck1, Xiaolan Ye1 & Linda B. Buck1
Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109-1024, USA
Correspondence to: Linda B. Buck1 Correspondence and requests for materials should be addressed to L.B.B. (Email: lbuck@fhcrc.org).
Abstract
The mechanisms that determine the lifespan of an organism are still largely a mystery1. 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.
