眾所周知節(jié)食在如線蟲、酵母,、果蠅與嚙齒動(dòng)物等多種模型生物中可以延長壽命,，延遲衰老相關(guān)疾病發(fā)生。雖然在壽命延長中發(fā)揮作用的若干關(guān)鍵因素已被識(shí)別出來,，但人們對(duì)于協(xié)調(diào)生物代謝反應(yīng)的信號(hào)卻知之甚少,。
近日由美國佛羅里達(dá)州斯克里普斯研究院的科學(xué)家領(lǐng)導(dǎo)的一個(gè)研究小組證實(shí)一條調(diào)控營養(yǎng)吸收和能量平衡生物信號(hào)可影響線蟲壽命的長短。這一研究發(fā)現(xiàn)在線發(fā)布在5月12日的《自然》（Nature）雜志上,。
“這是我們第一次在線蟲中鑒定出這些分子,，并證實(shí)它們不僅可作為營養(yǎng)利用率的信號(hào)分子，并可最終影響線蟲的壽命,，”斯克里普斯研究院新陳代謝與老化系助理教授Matthew Gill博士說：“值得關(guān)注的是,，在人類及線蟲中都存在這些相同的分子，因此這些分子極有可能在兩種生物體中發(fā)揮了相似的作用,。”
在這篇文章中,，科研人員鑒定出的是一類來自脂質(zhì)的信號(hào)作用分子稱為N-酰基乙醇胺（N-acylethanolamines ,，NAEs),。過去的研究表明它能在哺乳動(dòng)物中調(diào)控營養(yǎng)吸收和能量平衡。Gill及同事在新研究中證實(shí)節(jié)食可導(dǎo)致線蟲中NAE的豐度顯著下降,，而僅僅NAE的缺乏就足以使得線蟲壽命延長,。
“眾所周知當(dāng)線蟲處于節(jié)食狀態(tài)時(shí)，它的壽命可延長40-50%,。然而在新研究中我們驚奇地發(fā)現(xiàn)僅需要給予其中的一種NAE分子eicosapentaenoyl ethanolamide就可完全終止壽命的延長,，”Gill說。
研究人員發(fā)現(xiàn)這種特異的NAE與哺乳動(dòng)物中的內(nèi)源性大麻素（endocannabinoid）非常相似,。內(nèi)源性大麻素可對(duì)多種不同的生理過程包括營養(yǎng)攝入和能量平衡,、炎癥以及神經(jīng)功能起重要的調(diào)控作用。“現(xiàn)在我們?cè)诰€蟲中鑒別出了新型內(nèi)源性大麻素系統(tǒng)的其他組分,，從而為研究者們開展NAE與內(nèi)源性大麻素的生理學(xué)研究提供了一個(gè)新的模式系統(tǒng),，”Gill說。
此外,，研究人員還在新研究中確定了脂肪,，NAE水平與壽命之間的聯(lián)系,。過去一些研究團(tuán)體曾在嚙齒動(dòng)物中證實(shí)脂肪酸的利用率可影響NAE的水平。在新研究中Gill及同事們發(fā)現(xiàn)遺傳工程修飾的線蟲無法生成的某種多不飽和脂肪酸不僅與特異的NAEs水平下降有關(guān),，還可影響線蟲的壽命,。Gill表示新研究發(fā)現(xiàn)為推動(dòng)科學(xué)家們開發(fā)出影響衰老及衰老相關(guān)疾病的藥物指明了新方向。（生物谷Bioon.com）
生物谷推薦原文出處：
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.
