During periods of fasting the liver produces ketone bodies, which the peripheral tissues can use as a source of energy. Here it is shown that fasting inhibits multi-component mTOR complex 1 (mTORC1) in the liver. Inhibition of mTORC1 is required for activation of PPARα, a master regulator that switches on genes involved in ketogenesis. Livers from aged mice have increased mTORC1 signalling, reduced PPARα activity, and reduced ketone production. The observation that mTORC1 promotes an ageing phenotype in the liver fits well with the observation that inhibition of this pathway increases lifespan in several organisms.
- Shomit Sengupta
- Timothy R. Peterson
- David M. Sabatini
