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
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    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
  • English
Classification
Biology
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/307922
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