众所周知节食在如线虫、酵母、果蝇与啮齿动物等多种模型生物中可以延长寿命，延迟衰老相关疾病发生。虽然在寿命延长中发挥作用的若干关键因素已被识别出来，但人们对于协调生物代谢反应的信号却知之甚少。
近日由美国佛罗里达州斯克里普斯研究院的科学家领导的一个研究小组证实一条调控营养吸收和能量平衡生物信号可影响线虫寿命的长短。这一研究发现在线发布在5月12日的《自然》（Nature）杂志上。
“这是我们第一次在线虫中鉴定出这些分子，并证实它们不仅可作为营养利用率的信号分子，并可最终影响线虫的寿命，”斯克里普斯研究院新陈代谢与老化系助理教授Matthew Gill博士说：“值得关注的是，在人类及线虫中都存在这些相同的分子，因此这些分子极有可能在两种生物体中发挥了相似的作用。”
在这篇文章中，科研人员鉴定出的是一类来自脂质的信号作用分子称为N-酰基乙醇胺（N-acylethanolamines ，NAEs)。过去的研究表明它能在哺乳动物中调控营养吸收和能量平衡。Gill及同事在新研究中证实节食可导致线虫中NAE的丰度显著下降，而仅仅NAE的缺乏就足以使得线虫寿命延长。
“众所周知当线虫处于节食状态时，它的寿命可延长40-50%。然而在新研究中我们惊奇地发现仅需要给予其中的一种NAE分子eicosapentaenoyl ethanolamide就可完全终止寿命的延长，”Gill说。
研究人员发现这种特异的NAE与哺乳动物中的内源性大麻素（endocannabinoid）非常相似。内源性大麻素可对多种不同的生理过程包括营养摄入和能量平衡、炎症以及神经功能起重要的调控作用。“现在我们在线虫中鉴别出了新型内源性大麻素系统的其他组分，从而为研究者们开展NAE与内源性大麻素的生理学研究提供了一个新的模式系统，”Gill说。
此外，研究人员还在新研究中确定了脂肪，NAE水平与寿命之间的联系。过去一些研究团体曾在啮齿动物中证实脂肪酸的利用率可影响NAE的水平。在新研究中Gill及同事们发现遗传工程修饰的线虫无法生成的某种多不饱和脂肪酸不仅与特异的NAEs水平下降有关，还可影响线虫的寿命。Gill表示新研究发现为推动科学家们开发出影响衰老及衰老相关疾病的药物指明了新方向。（生物谷Bioon.com）
生物谷推荐原文出处：
Nature DOI:10.1038/nature10007
N-acylethanolamine signalling mediates the effect of diet on lifespan in Caenorhabditis elegans
Mark Lucanic, Jason M. Held, Maithili C. Vantipalli, Ida M. Klang, Jill B. Graham, Bradford W. Gibson, Gordon J. Lithgow & Matthew S. Gill
Dietary restriction is a robust means of extending adult lifespan and postponing age-related disease in many species, including yeast, nematode worms, flies and rodents1, 2. Studies of the genetic requirements for lifespan extension by dietary restriction in the nematode Caenorhabditis elegans have implicated a number of key molecules in this process3, 4, 5, including the nutrient-sensing target of rapamycin (TOR) pathway6 and the Foxa transcription factor PHA-4 (ref. 7). However, little is known about the metabolic signals that coordinate the organismal response to dietary restriction and maintain homeostasis when nutrients are limited. The endocannabinoid system is an excellent candidate for such a role given its involvement in regulating nutrient intake and energy balance8. Despite this, a direct role for endocannabinoid signalling in dietary restriction or lifespan determination has yet to be demonstrated, in part due to the apparent absence of endocannabinoid signalling pathways in model organisms that are amenable to lifespan analysis9. N-acylethanolamines (NAEs) are lipid-derived signalling molecules, which include the mammalian endocannabinoid arachidonoyl ethanolamide. Here we identify NAEs in C. elegans, show that NAE abundance is reduced under dietary restriction and that NAE deficiency is sufficient to extend lifespan through a dietary restriction mechanism requiring PHA-4. Conversely, dietary supplementation with the nematode NAE eicosapentaenoyl ethanolamide not only inhibits dietary-restriction-induced lifespan extension in wild-type worms, but also suppresses lifespan extension in a TOR pathway mutant. This demonstrates a role for NAE signalling in ageing and indicates that NAEs represent a signal that coordinates nutrient status with metabolic changes that ultimately determine lifespan.
