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

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

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    Résumé

    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.

    langue originaleAnglais
    Pages (de - à)1662-1664
    Nombre de pages3
    journalAutophagy
    Volume15
    Numéro de publication9
    Les DOIs
    étatPublié - 2 sept. 2019

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