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

Carmona-Gutierrez, Didac; Zimmermann, Andreas; Kainz, Katharina; Pietrocola, Federico; Chen, Guo; Maglioni, Silvia; Schiavi, Alfonso; Nah, Jihoon; Mertel, Sara; Beuschel, Christine B.; Castoldi, Francesca; Sica, Valentina; Trausinger, Gert; Raml, Reingard; Sommer, Cornelia; Schroeder, Sabrina; Hofer, Sebastian J.; Bauer, Maria A.; Pendl, Tobias; Tadic, Jelena; Dammbrueck, Christopher; Hu, Zehan; Ruckenstuhl, Christoph; Eisenberg, Tobias; Durand, Sylvere; Bossut, Noélie; Aprahamian, Fanny; Abdellatif, Mahmoud; Sedej, Simon; Enot, David P.; Wolinski, Heimo; Dengjel, Jörn; Kepp, Oliver; Magnes, Christoph; Sinner, Frank; Pieber, Thomas R.; Sadoshima, Junichi; Ventura, Natascia; Sigrist, Stephan J.; Kroemer, Guido; Madeo, Frank

doi:10.1038/s41467-019-08555-w

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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

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