mTORC1 controls fasting-induced ketogenesis and its modulation by ageing

During periods of fasting, the liver breaks down fatty acids to produce acetone and other ketone bodies that the peripheral tissues can use as a source of energy. A study of the role in the liver of mTORC1, the target of the immunosuppressant rapamycin, shows that fasting inhibits the activity of multicomponent mTORC1. Inhibition of mTORC1 is required for activation of PPAR, a master regulator that switches on genes involved in ketogenesis. Livers from aged mice have increased mTORC1 signalling, reduced PPAR 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.