mTORC1 drives protein synthesis, but our understanding of how it might control other growth-related processes is limited. Using a systems biology approach, we have determined that mTORC1 broadly regulates mRNA splicing. Through this evolutionarily conserved pathway, mTORC1 extends its regulation of protein synthesis, and expands its reach to control many other growth and metabolism parameters. Our findings illuminate how mTORC1 influences growth, development, disease, and the maintenance of gene expression fidelity during aging.

We find in C. elegans that another key element in DR is modulation of a conserved innate immunity pathway that is controlled by p38 signaling. This essential immunometabolic pathway responds to nutrients as well as pathogens, and must be downregulated for lifespan extension from DR or reduced IIS (rIIS). Unexpectedly, through tissue-non-autonomous action of the DAF-16/FOXO transcription factor, rIIS decreases feeding, and induces a DR-like state that lowers immune activity. Our findings predict that nutrient regulation of immunity will be important for longevity in higher organisms, and reveal an unexpected appetite regulatory function of FOXO.