Aversion to an offending smell can be an indicator of the organism’s capacity to protect itself from harmful substances and live longer. This at least is what happens in the case of nematodes of the species Caenorhabditis elegans.
对难闻气味的厌恶可以表明生物体保护自身免受有害物质侵害并延长寿命的能力。至少对于秀丽隐杆线虫来说是这样的。
Although nematodes (roundworms or threadworms) do not look remotely like humans, for about 50 years they have been used as a model for biological studies. The advantages include a simple nervous system, few cells and genes, many of which have the same functions as our own, and a short lifespan averaging 17 days, which is ideal for research on aging.
尽管线虫（蛔虫或线虫）看起来与人类相差甚远，但大约 50 年来它们一直被用作生物学研究的模型。其优点包括神经系统简单，细胞和基因少，其中许多与我们的功能相同，寿命短，平均17天，非常适合衰老研究。
An article published in the journal Nature Aging reports the findings of a study showing that odorant molecules secreted by pathogenic bacteria not only produced an aversive response in C. elegans, which retreated to avoid the threat but also triggered a neural circuit that induced a response in other tissues of the nematode.
《自然衰老》杂志上发表的一篇文章报道了一项研究结果，该研究结果表明，病原菌分泌的气味分子不仅使秀丽隐杆线虫产生厌恶反应，使秀丽隐杆线虫后退以躲避威胁，而且还触发了一个神经回路，从而诱发了线虫其他组织的反应。
This response includes more efficient processing of toxic proteins, and control of the aggregation of these and other proteins produced by the worms. The relevance of this is that in humans a buildup of these proteins is one of the factors associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s.
这种反应包括更有效地处理有毒蛋白质，以及控制这些蠕虫产生的蛋白质和其他蛋白质的聚集。其相关性在于，在人类中，这些蛋白质的积累是与阿尔茨海默症和帕金森症等神经退行性疾病相关的因素之一。
“They can sense danger in the environment by smell, heightening their stress responses even before they locate any pathogenic bacteria. Smell also prevents aggregation of proteins involved in disease, potentially extending their lifespan,” said Evandro Araújo de Souza, first author of the article.
“它们可以通过气味感知环境中的危险，甚至在发现任何致病细菌之前就增强应激反应。气味还可以防止与疾病相关的蛋白质聚集，从而有可能延长它们的寿命，”该文章的第一作者 Evandro Araújo de Souza 说道。
The study was part of his postdoctoral research at the Neurobiology Division of the Medical Research Council Laboratory of Molecular Biology (MRC-LMB) in Cambridge in the United Kingdom.
这项研究是他在英国剑桥医学研究委员会分子生物学实验室 (MRC-LMB) 神经生物学部博士后研究的一部分。
Souza is one of 32 scientists selected for FAPESP’s Project Generation, which supports research based on bold ideas conducted by early-career researchers with outstanding potential. In September, he embarked on the next stage of the study at the State University of Campinas’s Institute of Biology (IB-UNICAMP) in Brazil, where he will conduct the project “Mechanisms of regulation of proteostasis in peripheral tissues by the nervous system”.
Souza 是入选 FAPESP Project Generation 的 32 名科学家之一，该项目支持具有杰出潜力的早期职业研究人员基于大胆想法进行的研究。 9月，他在巴西坎皮纳斯州立大学生物研究所（IB-UNICAMP）开始了下一阶段的研究，在那里他将开展“神经系统调节外周组织蛋白质稳态的机制”项目。
Scenting danger
In the study, nematodes exposed to 1-undecene, an odorant molecule, lived longer than those that had no contact with the odor secreted by bacteria. Responses to the stimulus could be seen in the intestine, evidencing the existence of a circuit connecting olfactory perception to the rest of the body.
气味危险
在这项研究中，接触1-十一碳烯（一种气味分子）的线虫比那些没有接触细菌分泌的气味的线虫寿命更长。在肠道中可以看到对刺激的反应，证明存在连接嗅觉和身体其他部位的回路。
“These findings suggest that manipulating perceptions of chemical substances could one day be a route to intervention in neurodegenerative and age-related diseases. However, more research is needed to establish whether similar cell signaling pathways and mechanisms also operate in humans,” said Rebecca Taylor, a researcher at MRC-LMB and last author of the article.
“这些发现表明，操纵对化学物质的感知有一天可能成为干预神经退行性疾病和年龄相关疾病的一种途径。然而，还需要更多的研究来确定类似的细胞信号传导途径和机制是否也适用于人类，”MRC-LMB 的研究员、该文章的最后作者Rebecca Taylor 说道。
According to the researchers, other studies had already shown that mice have a neural circuit linking brain to liver when these animals smell certain kinds of food, and it makes sense to hypothesize that the mammalian nervous system could trigger a response by other organs when stimulated, as is the case in nematodes.
研究人员表示，其他研究已经表明，当小鼠闻到某些食物的气味时，它们的大脑和肝脏之间有一个神经回路连接起来，并且推测哺乳动物的神经系统在受到刺激时可能会引发其他器官的反应，这是有道理的。就像线虫的情况一样。
“If we find a molecule that can mediate this circuit connecting the perception of odor to the organism’s response, we could have a promising route to develop novel treatments,” Souza said.
Souza说：“如果我们找到一种分子可以介导将气味感知与生物体反应联系起来的回路，那么我们就有了一条开发新疗法的有希望的途径。”
Partially revealed circuit
In the study, the nematodes were placed on different plates from those containing the odorants to demonstrate that it was not direct contact between the worms and the substances that caused aversion but only their smell.
部分被揭露的回路
在这项研究中，线虫被放置在与含有气味剂的盘子不同的盘子上，以证明引起厌恶的并不是线虫与物质的直接接触，而是它们的气味。
The odorants used were those secreted by pathogenic bacteria such as Pseudomonas aeruginosa and Staphylococcus aureus, which are harmful to nematodes. Three of these compounds including 1-undecene were associated with aversive responses in C. elegans. The researchers decided to focus on 1-undecene in subsequent experiments as it induced aversion without being toxic.
使用的气味剂是铜绿假单胞菌、金黄色葡萄球菌等病原菌分泌的气味剂，对线虫有害。其中三种化合物（包括 1-十一碳烯）与秀丽隐杆线虫的厌恶反应相关。研究人员决定在后续实验中将重点放在 1-十一碳烯上，因为它会引起厌恶，但没有毒性。
When they analyzed the worms exposed to the substance, they observed activation of the endoplasmic reticulum unfolded protein response (UPRER) in the intestine. This is a defense the organism uses to trigger repair mechanisms or eliminate defective proteins.
当他们分析接触该物质的线虫时，他们观察到肠道中内质网未折叠蛋白反应（UPRER）的激活。这是生物体用来触发修复机制或消除有缺陷的蛋白质的防御机制。
In worms with mutations in two genes that regulate the UPRER (ire-1 and xbp-1), the response was not activated by 1-undecene, showing that this cellular signaling pathway was essential to activation of UPRER by the substance. Other experiments confirmed this result.
在两个调节 UPRER 的基因（ire-1 和 xbp-1）发生突变的线虫中，1-十一碳烯不会激活该反应，表明该细胞信号传导途径对于该物质激活 UPRER 至关重要。其他实验也证实了这一结果。
Another group of mutant nematodes exposed to 1-undecene failed to produce neurotransmitters such as serotonin, dopamine and glutamate, among others, but the researchers were unable to identify a role for any of these molecules.
另一组暴露于 1-十一碳烯的突变线虫未能产生神经递质，如血清素、多巴胺和谷氨酸等，但研究人员无法确定这些分子的作用。
Next, they focused on DAF-7, a protein and gene equivalent to transforming growth factor-beta (TGF-β) in mammals, where it plays an important role in the neural circuits that govern behavior such as aversion to pathogens.
接下来，他们关注了 DAF-7，这是一种相当于哺乳动物转化生长因子-β (TGF-β) 的蛋白质和基因，它在控制诸如厌恶病原体等行为的神经回路中发挥着重要作用。
When production of DAF-7 was inhibited, odorant-induced UPRER was not activated, evidencing its role in this response. “We now know the route we need to follow, especially because the protein has an equivalent in humans,” Souza said.
当 DAF-7 的产生受到抑制时，气味剂诱导的 UPRER 不会被激活，这证明了它在这种反应中的作用。Souza说：“我们现在知道了需要遵循的路线，特别是因为这种蛋白质在人类中具有等效的蛋白质。”