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

Authors
  • Kepp, Oliver1, 2, 3
  • Chen, Guo1, 2, 3, 4
  • Carmona-Gutierrez, Didac5
  • Madeo, Frank5, 6, 7
  • Kroemer, Guido1, 2, 3, 8, 9, 10
  • 1 Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138, Paris, France. , (France)
  • 2 Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Center, Villejuif, France. , (France)
  • 3 Université Paris Descartes, Sorbonne Paris Cité, Paris, France. , (France)
  • 4 College of Life Sciences, Nankai University, Tianjin, China. , (China)
  • 5 Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria. , (Austria)
  • 6 Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria. , (Austria)
  • 7 BioTechMed Graz, Graz, Austria. , (Austria)
  • 8 Pôle de Biologie, Hôpital Européen Georges Pompidou, Paris, France. , (France)
  • 9 Suzhou Institute for Systems Medicine, Chinese Academy of Sciences, Suzhou, China. , (China)
  • 10 Karolinska Institutet, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden. , (Sweden)
Type
Published Article
Journal
Autophagy
Publisher
Landes Bioscience
Publication Date
Nov 07, 2019
Pages
1–2
Identifiers
DOI: 10.1080/15548627.2019.1688984
PMID: 31690168
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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.

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