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 2019-09-02 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. application/pdf https://folia.unifr.ch/global/documents/307922 https://folia.unifr.ch/documents/307922/files/den_dnf.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1080/15548627.2019.1632623 info:eu-repo/semantics/openAccess License undefined Autophagy. - 2019, vol. 15, no. 9, p. 1662–1664 info:eu-repo/classification/udc/57 4,4’Dimethoxychalcone: a natural flavonoid that promotes health through autophagy-dependent and -independent effects http://purl.org/coar/resource_type/c_6501