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The flavonoid 4,4′-dimethoxychalcone promotes autophagy-dependent longevity across species

  • Carmona-Gutierrez, Didac Institute of Molecular Biosciences, NAWI Graz, University of Graz,Austria
  • Zimmermann, Andreas Institute of Molecular Biosciences, NAWI Graz, University of Graz,Austria - Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Austria
  • Kainz, Katharina Institute of Molecular Biosciences, NAWI Graz, University of Graz,Austria
  • Pietrocola, Federico 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 - Université Pierre et Marie Curie, Paris, France
  • Chen, Guo 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 - Université Pierre et Marie Curie, Paris, France
  • Maglioni, Silvia IUF - Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany
  • Schiavi, Alfonso IUF - Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany
  • Nah, Jihoon Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Newark, USA
  • Mertel, Sara Institute for Biology/Genetics, Freie Universität Berlin, Germany
  • Beuschel, Christine B. Institute for Biology/Genetics, Freie Universität Berlin, Germany
  • Castoldi, Francesca 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 - Université Pierre et Marie Curie, Paris, France - Sotio a.c, Prague, Czech Republic
  • Sica, Valentina 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 - Université Pierre et Marie Curie, Paris, France
  • Trausinger, Gert Joanneum Research Forschungsgesellschaft m.b.H., HEALTH, Institute for Biomedicine and Health Sciences, Graz, Austria
  • Raml, Reingard Joanneum Research Forschungsgesellschaft m.b.H., HEALTH, Institute for Biomedicine and Health Sciences, Graz, Austria
  • Sommer, Cornelia Institute of Molecular Biosciences, NAWI Graz, University of Graz,Austria
  • Schroeder, Sabrina Institute of Molecular Biosciences, NAWI Graz, University of Graz,Austria
  • Hofer, Sebastian J. Institute of Molecular Biosciences, NAWI Graz, University of Graz,Austria
  • Bauer, Maria A. Institute of Molecular Biosciences, NAWI Graz, University of Graz,Austria
  • Pendl, Tobias Institute of Molecular Biosciences, NAWI Graz, University of Graz,Austria
  • Tadic, Jelena Institute of Molecular Biosciences, NAWI Graz, University of Graz,Austria
  • Dammbrueck, Christopher Institute of Molecular Biosciences, NAWI Graz, University of Graz,Austria
  • Hu, Zehan Department of Cardiology, Medical University of Graz, Austria
  • Ruckenstuhl, Christoph Institute of Molecular Biosciences, NAWI Graz, University of Graz,Austria
  • Eisenberg, Tobias Institute of Molecular Biosciences, NAWI Graz, University of Graz,Austria
  • Durand, Sylvere 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.
  • Bossut, Noélie 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.
  • Aprahamian, Fanny 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.
  • Abdellatif, Mahmoud Department of Cardiology, Medical University of Graz, Austria
  • Sedej, Simon Department of Cardiology, Medical University of Graz, Austria - BioTechMed Graz, Austria
  • Enot, David P. 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.
  • Wolinski, Heimo Institute of Molecular Biosciences, NAWI Graz, University of Graz,Austria
  • Dengjel, Jörn Department of Biology, Université de Fribourg, Switzerland
  • Kepp, Oliver 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 - Université Pierre et Marie Curie, Paris, France
  • Magnes, Christoph Joanneum Research Forschungsgesellschaft m.b.H., HEALTH, Institute for Biomedicine and Health Sciences, Graz, Austria
  • Sinner, Frank Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Austria - Joanneum Research Forschungsgesellschaft m.b.H., HEALTH, Institute for Biomedicine and Health Sciences, Graz, Austria
  • Pieber, Thomas R. Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Austria - Joanneum Research Forschungsgesellschaft m.b.H., HEALTH, Institute for Biomedicine and Health Sciences, Graz, Austria
  • Sadoshima, Junichi Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Newark, USA
  • Ventura, Natascia IUF - Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany - Institute for Clinical Chemistry and Laboratory Diagnostic, Medical Faculty of the Heinrich Heine University, Düsseldorf, Germany
  • Sigrist, Stephan J. Institute for Biology/Genetics, Freie Universität Berlin, Germany - NeuroCure, Charité, Berlin, Germany
  • Kroemer, Guido 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 - Université Pierre et Marie Curie, Paris, France - Pôle de Biologie, Hôpital Européen Georges Pompidou, Paris, France - Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden
  • Madeo, Frank Institute of Molecular Biosciences, NAWI Graz, University of Graz,Austria - BioTechMed Graz, Austria
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    19.02.2019
Published in:
  • Nature Communications. - 2019, vol. 10, no. 1, p. 651
English Ageing constitutes the most important risk factor for all major chronic ailments, including malignant, cardiovascular and neurodegenerative diseases. However, behavioural and pharmacological interventions with feasible potential to promote health upon ageing remain rare. Here we report the identification of the flavonoid 4,4′- dimethoxychalcone (DMC) as a natural compound with anti-ageing properties. External DMC administration extends the lifespan of yeast, worms and flies, decelerates senescence of human cell cultures, and protects mice from prolonged myocardial ischaemia. Concomitantly, DMC induces autophagy, which is essential for its cytoprotective effects from yeast to mice. This pro-autophagic response induces a conserved systemic change in metabolism, operates independently of TORC1 signalling and depends on specific GATA transcription factors. Notably, we identify DMC in the plant Angelica keiskei koidzumi, to which longevity- and health-promoting effects are ascribed in Asian traditional medicine. In summary, we have identified and mechanistically characterised the conserved longevity-promoting effects of a natural anti-ageing drug.
Faculty
Faculté des sciences et de médecine
Department
Département de Biologie
Language
  • English
Classification
Biological sciences
License
License undefined
Identifiers
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https://folia.unifr.ch/unifr/documents/307747
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