Caloric restriction mimetics: towards a molecular definition

Nat Rev Drug Discov. 2014 Oct;13(10):727-40. doi: 10.1038/nrd4391. Epub 2014 Sep 12.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetyl Coenzyme A / metabolism
  • Acetylation / drug effects
  • Acetyltransferases / antagonists & inhibitors
  • Animals
  • Autophagy / drug effects
  • Caloric Restriction / methods*
  • Drug Design*
  • Humans


  • Acetyl Coenzyme A
  • Acetyltransferases