Diet affects nearly every aspect of animal life, such as development, metabolism, behavior and aging, both directly by supplying nutrients and indirectly through gut microbiota. C. elegans feeds on bacteria, and like other animals, different bacterial diets induce distinct dietary responses in the worm. However, the lack of certain critical tools hampers the use of worms as a model for dietary signaling. Here, we genetically-engineered the E. coli strain OP50, the standard laboratory diet for C. elegans, making it compatible for double-stranded RNA production. Together with the other bacterial strain HT115, we are able to feed worms different diets while delivering RNAi to interrogate the genetic basis underlying diet-dependent differential modulation of development, metabolism, behavior, and aging. Using comparative RNAi combined with mutant experiemnts, we found that mTORC2, but not mTORC1, modulates a wide range of C. elegans life traits including lifespan in a diet-dependent manner. In addition, neuropeptide signaling may also play important roles in the diet-dependent C. elegans behaviors. Taken together, our results show that neuroendocrine and mTOR pathways are involved in mediating differential dietary responses. This genetic tool (RNAi-competent OP50
(xu363)) will greatly facilitate the use of C. elegans as a model for dietary signaling.