Chemosensation and longevity in C. elegans

线虫的化学感应和长寿

• 批准号: 10374859
• 负责人: Shawn Xu
• 金额: $ 36.89万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10374859
• 关键词: Address; Affect; Aging; Alzheimer' s Disease; Animal Behavior; Animals; Behavior; CD2 Antigens; Caenorhabditis elegans; Chemicals; Communication; Cues; Data; Disease; Dopamine; Environmental Risk Factor; Food; GTP-Binding Proteins; Genetic; Genetic Models; Homologous Gene; Intestines; Invertebrates; Longevity; Longevity Pathway; Mammals; Mediating; Modeling; Neurodegenerative Disorders; Neurons; Neurosciences; Norepinephrine; Nutrient; Octopamine; Odors; Organism; Pathway interactions; Perception; Physiological Processes; Play; Process; Protocols documentation; Regulation; Research; Risk; Role; Serotonin; Signal Transduction; Signaling Protein; System; Testing; Work; Yeasts; age related; dietary restriction; fly; healthspan; improved; insight; monoamine; neurotransmission; novel; octopamine receptor; relating to nervous system; sensor; tool

Chemical cues, such as odors and tastants, are best known to regulate animal behavior. Interestingly, such chemical cues not just regulate behavior, but also other types of critical physiological processes such as longevity. While chemosensory regulation of behavior has been extensively characterized, much less effort has been devoted to investigating how chemical cues regulate longevity. Food is a primary environmental factor that affects aging. Dietary restriction (DR) represents one of the most effective means to extend lifespan in all tested organisms. How dietary restriction (DR) promotes longevity has been a subject of intensive research; however, the underlying mechanisms are far from clear. Previous effort has mostly focused on characterizing how food nutrients regulate longevity. It should be noted that in addition to nutrients, other components are also found in food. One notable example is the odors associated with food. However, though the mechanisms by which nutrient signaling regulates lifespan has been extensively characterized, much less is known about the role of food odors in longevity. As such, it remains largely unclear whether, to what extent, and how food odors regulates longevity. It is also unclear how the chemosensory system is involved. As odors are integral components of food, addressing this question will help us to achieve a better understanding of how DR promotes longevity. It will also help us to understand how the chemosensory system regulates longevity. C. elegans is a nice genetic model for aging research. Thus far, nearly all the major longevity pathways were first discovered in invertebrate models such as worms, flies and yeast, and subsequently were found to be evolutionarily conserved in mammals. This, together with a short lifespan (~3 weeks) and facile genetics, makes C. elegans a highly valuable model for aging research. We found that food odors regulate DR longevity in C. elegans, and that the chemosensory system plays a key role in mediating the effect of food-derived odors on DR longevity. Here, we propose to investigate the underlying neural and genetic mechanisms. To do so, we will use a combination of neuroscience and aging research tools. As longevity mechanisms tend to be evolutionarily conserved from worms to mammals, the proposed work will provide novel insights into DR- dependent longevity in other organisms.

众所周知，化学信号，例如气味和促味剂，可以调节动物行为。有趣的是，这样的 化学信号不仅调节行为，还调节其他类型的关键生理过程，例如 长寿。虽然行为的化学感应调节已被广泛表征，但研究的努力却少得多。 一直致力于研究化学信号如何调节寿命。食物是首要环境因素 从而影响衰老。饮食限制（DR）是延长寿命的最有效方法之一 被测试的生物体。饮食限制（DR）如何促进长寿一直是深入研究的课题。 然而，其根本机制尚不清楚。之前的努力主要集中在表征 食物营养素如何调节寿命。需要注意的是，除了营养成分外，还有其他成分。 也存在于食物中。一个值得注意的例子是与食物相关的气味。然而，尽管机制 营养信号调节寿命的机制已被广泛表征，但人们知之甚少 食物气味在长寿中的作用。因此，目前尚不清楚食品是否、在何种程度上以及如何 气味调节寿命。目前还不清楚化学感应系统是如何参与的。由于气味是不可或缺的 食品成分，解决这个问题将有助于我们更好地理解 DR 如何 促进长寿。它还将帮助我们了解化学感应系统如何调节寿命。 C. 线虫是衰老研究的一个很好的遗传模型。到目前为止，几乎所有主要的长寿途径都是首先的 在蠕虫、苍蝇和酵母等无脊椎动物模型中发现，随后被发现 在哺乳动物中进化上保守。再加上寿命短（约 3 周）和简单的遗传， 使线虫成为衰老研究中非常有价值的模型。我们发现食物气味调节 DR 寿命 在线虫中，化学感应系统在介导食物气味的影响中发挥着关键作用 关于 DR 寿命。在这里，我们建议研究潜在的神经和遗传机制。为此，我们 将结合使用神经科学和衰老研究工具。由于长寿机制往往是 从蠕虫到哺乳动物，这项工作在进化上是保守的，拟议的工作将为DR-提供新的见解 依赖其他生物体的长寿。