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

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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.