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2007-11-23 9:09:14
Nature：抗抑郁药能延长线虫寿命 有助推动人类抗老化研究 三环丙米阻a受体释NE阻他受体镇静抗组胺治焦郁t1/2约8-19H副嗜睡
人们早已知道，限制卡路里摄入是延长有机体寿命的好方法。美国科学家近日研究发现，抗抑郁药脱尔烦（Tolvon）具有同样的功效，它能够将秀丽隐杆线虫（Caenorhabditis elegans）的寿命延长三分之一以上，即从三周延长到四周多。这为研究人类的抗老化问题提供了重要的参考。相关论文11月22日发表于《自然》（Nature）杂志上。
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。
实验中脱尔烦并没有使秀丽隐杆线虫的进食量减少，这表明它并不是通过实际降低卡路里摄入来延长寿命的。Buck说：“它们看起来很活跃，并不像非常饥饿的样子。”不过研究人员相信，脱尔烦延长寿命的机制与卡路里限制是一样的，即脱尔烦诱骗线虫大脑相信摄入了较少的卡路里，从而帮助延长了机体寿命。
美国哈佛大学的生物学家David Sinclair认为，对于人类的老化问题研究来说，找到能够延长线虫寿命的药物是重要的第一步。
不过Buck提醒说，她反对仅仅利用其小组的初步成果就预测，人类能从脱尔烦中得到相同的好处。下一步她和研究小组计划在小鼠身上进行类似实验，并且将更深入地研究已发现的100多种化学制剂，以探寻动物老化的原因及减缓这一过程的方法。（科学网 梅进/编译）（生物谷）
http://www.bioon.com/biology/genetics/316609.shtml
原始出处:
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.
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