The sensory system acts with a neuromedin U signaling pathway to mediate food type-dependent effects on lifespan

In order to survive, the animal uses its sensory system to interpret the complexity of its environment.
Interestingly, a subset of sensory neurons, which function in taste or olfaction, has been found to
influence the lifespan of C. elegans and Drosophila. Although the mechanisms by which these neurons
affect lifespan are unknown, the nature of these neurons suggest that the sensory influence on lifespan
is mediated by food-derived cues. This thesis shows that sensory neurons recognize different food types
to affect C. elegans lifespan through a mechanism distinct from that of calorie restriction, which is
commonly studied by restricting the levels of food intake. Moreover, this work identifies a neuropeptide
signaling pathway, the neuromedin U pathway, which acts with the sensory system to affect C. elegans
lifespan in response to specific food-derived cues, such as the lipopolysaccharide (LPS) structure of its
E. coli bacterial food source. The neuromedin U neuropeptide receptor nmur-1, which is expressed in
sensory neurons, interneurons and the somatic gonad, shortens lifespan on E. coli food sources that have
short LPS. In contrast, a neuromedin U ligand precursor, nlp-44, which is expressed in only two pairs of
sensory neurons, lengthens lifespan in a food source-dependent manner. Genetic epistasis analysis suggests
that nlp-44 might encode ligands that act downstream of or in parallel to nmur-1. Since C. elegans has
three other members of the neuromedin U receptor (NMUR) family, future studies are needed to determine
whether nlp 44 encodes different peptide ligands that could then act on several NMUR proteins, including
NMUR-1. The identification of a neuromedin U pathway that mediates the sensory recognition of food quality
provides a genetic framework to elucidate further the mechanisms that underlie this sensory influence on
lifespan. In addition, the observation that a neuropeptide signaling pathway promotes the sensory
influence on lifespan raises the intriguing possibility that other neuropeptides might also affect
lifespan in response to other types of sensory cues. These neuropeptide pathways might thus integrate
different sensory information with signaling pathways already known to regulate lifespan.