4,4’Dimethoxychalcone: a natural flavonoid that promotes health through autophagy-dependent and -independent effects

Zimmermann, Andreas; Kainz, Katharina; Hofer, Sebastian J.; Bauer, Maria A.; Schroeder, Sabrina; Dengjel, Jörn; Pietrocola, Federico; Kepp, Oliver; Ruckenstuhl, Christoph; Eisenberg, Tobias; Sigrist, Stephan J.; Madeo, Frank; Carmona-Gutierrez, Didac; Kroemer, Guido

doi:10.1080/15548627.2019.1632623

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Journal article

4,4’Dimethoxychalcone: a natural flavonoid that promotes health through autophagy-dependent and -independent effects

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 - Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Austria
Hofer, Sebastian J. Institute of Molecular Biosciences, NAWI Graz, University of Graz, Austria - BioTechMed Graz, Austria
Bauer, Maria A. Institute of Molecular Biosciences, NAWI Graz, University of Graz, Austria
Schroeder, Sabrina Institute of Molecular Biosciences, NAWI Graz, University of Graz, Austria
Dengjel, Jörn Department of Biology, Université de Fribourg, Switzerland
Pietrocola, Federico Institute for Research in Biomedicine, Barcelona, Spain
Kepp, Oliver Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France - Metabolomics and Cell Biology Platforms, Villejuif, France - Université Paris Descartes, Sorbonne Paris Cité, Paris, France - Université Pierre et Marie Curie, Paris, France
Ruckenstuhl, Christoph Institute of Molecular Biosciences, NAWI Graz, University of Graz, Austria
Eisenberg, Tobias Institute of Molecular Biosciences, NAWI Graz, University of Graz, Austria - BioTechMed Graz, Austria - Central Lab Gracia, NAWI Graz, University of Graz, Austria - BioHealth Graz, Graz, Austria
Sigrist, Stephan J. Institute for Biology/Genetics, Freie Universität Berlin, Germany
Madeo, Frank Institute of Molecular Biosciences, NAWI Graz, University of Graz, Austria - Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Austria - BioTechMed Graz, Austria - BioHealth Graz, Graz, Austria
Carmona-Gutierrez, Didac Institute of Molecular Biosciences, NAWI Graz, University of Graz, Austria
Kroemer, Guido Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France - Metabolomics and Cell Biology Platforms, Villejuif, France - Université Paris Descartes, Sorbonne Paris Cité, 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 - Suzhou Institute for Systems Biology, Chinese Academy of Sciences, Suzhou, China

02.09.2019

Published in:

Autophagy. - 2019, vol. 15, no. 9, p. 1662–1664

English The age-induced deterioration of the organism results in detrimental and ultimately lethal pathologies. The process of aging itself involves a plethora of different mechanisms that should be subverted concurrently to delay and/or prevent age- related maladies. We have identified a natural compound, 4,4ʹ-dimethoxychalcone (DMC), which promotes longevity in yeast, worms and flies, and protects mice from heart injury and liver toxicity. Interestingly, both the DMC-mediated lifespan extension and the cardioprotection depend on macroautophagy/autophagy whereas hepatoprotection does not. DMC induces autophagy by inhibiting specific GATA transcription factors (TFs), independently of the TORC1 kinase pathway. The autophagy-independent beneficial effects of DMC might involve its antioxidative properties. DMC treatment results in a phylogenetically conserved, systemic impact on the metabolome, which is most prominently characterized by changes in cellular amino acid composition. Altogether, DMC exerts multiple, geroprotective effects by igniting distinct pathways, and thus represents a potential pharmacological agent that delays aging through multipronged effects.

Faculty

Faculté des sciences et de médecine

Department

Département de Biologie

Language