Subsets of sensory neurons, which can detect specific food-derived gustatory and olfactory cues (1), have been shown to have distinct effects on the lifespan of C. elegans. This is consistent with the observation that different bacterial food sources have also been shown to modulate C. elegans lifespan (2). Since the effects on lifespan of these food sources can be mediated by different types of cells (1,3-5), it is possible that their diverse effects are also promoted by different genes that act in a food source-dependent manner. These food source-dependent genes would presumably be unlike the many longevity genes, such as the insulin/IGF-1 receptor
daf-2, that have been shown to affect lifespan consistently on different food sources, and thus act in a food source-independent manner. We reasoned that some of the food source-dependent lifespan-influencing genes presumably encode signaling molecules, like neuropeptides, which are secreted from neuronal and/or non-neuronal cells in response to food-derived cues, and the receptors for such peptide signals. Among several neuropeptide and neuropeptide receptor genes that we tested for food source-dependent lifespan phenotypes, we identified
nmur-1, a homolog of the mammalian neuromedin U receptors, which shortens C. elegans lifespan only on some E. coli food sources but not on others. Notably, the lifespan-influencing effect of
nmur-1, which is expressed in the somatic gonad, sensory neurons and interneurons, requires the lipopolysaccharide (LPS) structure of its live E. coli food source. Furthermore, we found that the
nmur-1 food source-dependent regulation of lifespan can be uncoupled from its food source-dependent regulation of feeding rate, development and reproduction. Together our data suggest that
nmur-1 plays a role in processing information from different food sources to influence C. elegans lifespan and other aspects of its physiology. References: (1) Alcedo and Kenyon, 2004, Neuron 41, 45-55. (2) Garsin et al., 2003, Science 300, 1921. (3) Apfeld and Kenyon, 1998, Cell 95, 199-210. (4) Wolkow et al., 2000, Science 290, 147-150. (5) Libina et al., 2003, Cell 115, 489-502.