While this previous work demonstrates an important effect of isoleucine on metabolism and aging, the impact of restricting either leucine or valine on healthy aging and lifespan has not been investigated. Although leucine activates mTORC1, a central regulator of metabolism and aging22,23, restriction of leucine in our hands provides minimal metabolic benefits, and leucine supplementation has been found to not impact lifespan21,24,25. By contrast, recent work shows that valine is associated with cancer, inflammation, insulin resistance and glucotoxicity in mouse and cell culture models26,27,28,29. Further, dietary restriction of valine alone reverses diet-induced obesity and restores glucoregulatory control in C57BL/6J male mice21,25.