The flavonoid 4,4′-dimethoxychalcone promotes autophagy-dependent longevity across species

Didac Carmona-Gutierrez, Andreas Zimmermann, Katharina Kainz, Federico Pietrocola, Guo Chen, Silvia Maglioni, Alfonso Schiavi, Jihoon Nah, Sara Mertel, Christine B. Beuschel, Francesca Castoldi, Valentina Sica, Gert Trausinger, Reingard Raml, Cornelia Sommer, Sabrina Schroeder, Sebastian J. Hofer, Maria A. Bauer, Tobias Pendl, Jelena TadicChristopher Dammbrueck, Zehan Hu, Christoph Ruckenstuhl, Tobias Eisenberg, Sylvere Durand, Noélie Bossut, Fanny Aprahamian, Mahmoud Abdellatif, Simon Sedej, David P. Enot, Heimo Wolinski, Jörn Dengjel, Oliver Kepp, Christoph Magnes, Frank Sinner, Thomas R. Pieber, Junichi Sadoshima, Natascia Ventura, Stephan J. Sigrist, Guido Kroemer, Frank Madeo

    Research output: Contribution to journalArticlepeer-review

    110 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Article number651
    JournalNature Communications
    Volume10
    Issue number1
    DOIs
    Publication statusPublished - 1 Dec 2019

    Cite this