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

D. Carmona-Gutierrez, A. Zimmermann, K. Kainz, F. Pietrocola, G. Chen, S. Maglioni, A. Schiavi, J. Nah, S. Mertel, CB. Beuschel, F. Castoldi, V. Sica, G. Trausinger, R. Raml, C. Sommer, S. Schroeder, SJ. Hofer, MA. Bauer, T. Pendl, J. Tadic, C....

. 2019 ; 10 (1) : 651. [pub] 20190219

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc19027801

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.

Department of Biology Université de Fribourg Chemin du Musée 10 1700 Fribourg Switzerland

Department of Cardiology Medical University of Graz Graz 8036 Austria

Department of Cardiology Medical University of Graz Graz 8036 Austria BioTechMed Graz Graz 8010 Austria

Department of Cell Biology and Molecular Medicine Rutgers New Jersey Medical School Newark NJ USA

Division of Endocrinology and Diabetology Department of Internal Medicine Medical University of Graz Graz 8036 Austria Joanneum Research Forschungsgesellschaft m b H HEALTH Institute for Biomedicine and Health Sciences Graz 8010 Austria

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

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

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

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 17000 Prague Czech Republic

Institute for Biology Genetics Freie Universität Berlin Berlin 14195 Germany

Institute for Biology Genetics Freie Universität Berlin Berlin 14195 Germany NeuroCure Charité Berlin 10117 Germany

Institute of Molecular Biosciences NAWI Graz University of Graz Graz 8010 Austria

Institute of Molecular Biosciences NAWI Graz University of Graz Graz 8010 Austria BioTechMed Graz Graz 8010 Austria

Institute of Molecular Biosciences NAWI Graz University of Graz Graz 8010 Austria Division of Endocrinology and Diabetology Department of Internal Medicine Medical University of Graz Graz 8036 Austria

IUF Leibniz Research Institute for Environmental Medicine Düsseldorf 40225 Germany

IUF Leibniz Research Institute for Environmental Medicine Düsseldorf 40225 Germany Institute for Clinical Chemistry and Laboratory Diagnostic Medical Faculty of the Heinrich Heine University Moorenstrasse 5 40225 Düsseldorf Germany

Joanneum Research Forschungsgesellschaft m b H HEALTH Institute for Biomedicine and Health Sciences Graz 8010 Austria

Citace poskytuje Crossref.org

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