Chemosensation of death conspecifics modulates neural signaling and lifespan in Caenorhabditis elegans

项目摘要 所有动物都依赖感觉系统来检测和响应环境和行为线索。在大多数 动物，这种感觉信息被不同的感觉神经元感知和处理，使动物能够 做出适当的反应，以最大限度地提高健康和寿命。然而，详细了解底层 感觉神经系统调节寿命和衰老的线索和机制在很大程度上 未知解决这些知识差距对于全面了解 感官知觉对寿命调节的影响。我的项目的目标是识别神经元， 对死亡同种的感知调节人类行为和寿命的信号机制 秀丽隐杆线虫我用C. elegans表明接触死亡同种 导致1）厌恶行为和2）缩短寿命。我的研究还表明死去的同类 嗅觉神经元可以检测到死亡信号。我的核心假设是， 由死亡同种释放的细胞内代谢物被两栖类嗅觉神经元AWB识别 和/或ASH，促进GPCR依赖性信号级联，导致观察到的厌恶行为， 寿命缩短目标1的目的是确定所需的感觉神经元、间神经元和运动神经元， 足以使C.优雅目标2将定义翻译死亡的分子机制 行为变化和寿命缩短的感知。这项研究将提供新的 基本知识到作用的感官知觉的调节老化。这可能代表了 探索利用感官知觉的新治疗靶点的第一步-衰老 关系

PROJECT ABSTRACT All animals rely on sensory systems to detect and respond to environmental and behavioral cues. In most animals, this sensory information is perceived and processed by different sensory neurons, allowing animals to respond appropriately to maximize health- and lifespan. However, a detailed understanding of the underlying cues and mechanisms by which the sensory nervous system regulates lifespan and aging remains largely unknown. Addressing these gaps in knowledge is imperative to obtain a comprehensive understanding of the impact of sensory perception on lifespan regulation. The goal of my project is to identify the neurons and signaling mechanisms by which the perception of dead conspecifics regulates behavior and lifespan in Caenorhabditis elegans. My preliminary work using C. elegans shows that exposure to dead conspecifics result in 1) aversive behavior and 2) shortened lifespan. My studies also suggest that dead conspecifics release “death cues” that are detected by olfactory neurons. My central hypothesis is that detection of intracellular metabolites released by dead conspecifics are recognized by amphid olfactory neurons AWB and/or ASH, promoting a GPCR-dependent signaling cascade leading to the observed aversive behavior and lifespan shortening. The objective of Aim 1 is to identify the sensory, inter-, and motor neurons required and sufficient for death perception in C. elegans. Aim 2 will define the molecular mechanisms translating death perception to behavioral changes and shortened lifespans. The proposed research will provide new fundamental knowledge into the role of sensory perception in the regulation of aging. This may represent the first step towards uncovering novel therapeutic targets capitalizing on the sensory perception – aging relationship.