A discovery platform for the identification of caloric restriction mimetics with broad health-improving effects.


Journal

Autophagy
ISSN: 1554-8635
Titre abrégé: Autophagy
Pays: United States
ID NLM: 101265188

Informations de publication

Date de publication:
01 2020
Historique:
pubmed: 7 11 2019
medline: 25 11 2020
entrez: 7 11 2019
Statut: ppublish

Résumé

The age-related decline in organismal fitness results in vulnerability to pathologies and eventual lethal decay. One way to counteract cellular aging and to delay and/or prevent the onset of age-related maladies is the reduction of calorie intake or the institution of fasting regimens. Caloric restriction mimetics (CRMs) have the ability to imitate the health-promoting and lifespan-extending effects of caloric restriction without the need for dietary restriction. CRMs induce an increase in autophagic flux in response to the deacetylation of cellular proteins in the absence of cytotoxicity. Here we report the development of a high-throughput discovery platform for novel CRMs that uses systems biology approaches, in vitro validation and functional tests employing in vivo disease models. This workflow led to the identification of 3,4-dimethoxychalcone (3,4-DC) as a novel CRM that stimulated TFEB (transcription factor EB)- and TFE3 (transcription factor E3)-dependent macroautophagy/autophagy. 3,4-DC showed cardioprotective effects and stimulated anticancer immunosurveillance in the context of immunogenic chemotherapy.

Identifiants

pubmed: 31690168
doi: 10.1080/15548627.2019.1688984
pmc: PMC6984457
doi:

Substances chimiques

Transcription Factors 0
Acetyl Coenzyme A 72-89-9

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

188-189

Références

EMBO Mol Med. 2019 Nov 7;11(11):e10469
pubmed: 31609086

Auteurs

Oliver Kepp (O)

Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138, Paris, France.
Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Center, Villejuif, France.
Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

Guo Chen (G)

Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138, Paris, France.
Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Center, Villejuif, France.
Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
College of Life Sciences, Nankai University, Tianjin, China.

Didac Carmona-Gutierrez (D)

Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.

Frank Madeo (F)

Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.
Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
BioTechMed Graz, Graz, Austria.

Guido Kroemer (G)

Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138, Paris, France.
Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Center, Villejuif, France.
Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Pôle de Biologie, Hôpital Européen Georges Pompidou, Paris, France.
Suzhou Institute for Systems Medicine, Chinese Academy of Sciences, Suzhou, China.
Karolinska Institutet, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.

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Classifications MeSH