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.

BioTechMed Graz Graz 8010 Austria

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 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

Equipe 11 labellisée Ligue contre le Cancer Centre de Recherche des Cordeliers INSERM U 1138 Paris France

Institute for Biology Genetics Freie Universität Berlin Berlin 14195 Germany

Institute for Clinical Chemistry and Laboratory Diagnostic Medical Faculty of the Heinrich Heine University Moorenstrasse 5 40225 Düsseldorf Germany

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

IUF Leibniz Research Institute for Environmental Medicine Düsseldorf 40225 Germany

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

Karolinska Institute Department of Women's and Children's Health Karolinska University Hospital Stockholm Sweden

Metabolomics and Cell Biology Platforms Gustave Roussy Comprehensive Cancer Center Villejuif France

NeuroCure Charité Berlin 10117 Germany

Pôle de Biologie Hôpital Européen Georges Pompidou Paris France

Sotio a c 17000 Prague Czech Republic

Université Paris Descartes Sorbonne Paris Cité Paris France

Université Pierre et Marie Curie Paris France

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Microb Cell. 2019 May 06;6(5):212-216. doi: 10.15698/mic2019.05.676. PubMed

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Autophagy. 2019 Sep;15(9):1662-1664. doi: 10.1080/15548627.2019.1632623. PubMed

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