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

Caloric restriction mimetics: towards a molecular definition.

Author information

1
Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
2
Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, F-75006 Paris, France and the Université Paris Descartes, Sorbonne Paris Cité, F-75006 Paris, France.
3
Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, F-75006 Paris, France; the Université Paris Descartes, Sorbonne Paris Cité, F-75006 Paris, France; the Pôle de Biologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Labex Immuno-Oncology, F-75015 Paris, France; and the Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, F-94805 Villejuif, France.

Abstract

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.

PMID:
25212602
DOI:
10.1038/nrd4391
[Indexed for MEDLINE]

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