Caloric restriction mimetics: towards a molecular definition

Caloric restriction can promote health and extend the lifespan of model organisms, and diverse classes of compounds that mimic the biochemical and functional effects of caloric restriction have attracted considerable interest as potential pharmacotherapies for diseases such as diabetes and obesity. Kroemer, Madeo and colleagues propose a unifying definition of caloric restriction mimetics as agents that induce autophagy by promoting protein deacetylation, which could have implications for their development as drugs. Caloric restriction, be it constant or intermittent, is reputed to have health-promoting and lifespan-extending effects. Caloric restriction mimetics (CRMs) are compounds that mimic the biochemical and functional effects of caloric restriction. In this Opinion article, we propose a unifying definition of CRMs as compounds that stimulate autophagy by favouring the deacetylation of cellular proteins. This deacetylation process can be achieved by three classes of compounds that deplete acetyl coenzyme A (AcCoA; the sole donor of acetyl groups), that inhibit acetyl transferases (a group of enzymes that acetylate lysine residues in an array of proteins) or that stimulate the activity of deacetylases and hence reverse the action of acetyl transferases. A unifying definition of CRMs will be important for the continued development of this class of therapeutic agents.