Author/Editor		Carmona-Gutierrez, Didac; Zimmermann, Andreas; Kainz, Katharina; Pietrocola, Federico; Chen, Guo; Maglioni, Silvia; Schiavi, Alfonso; Nah, Jihoon; Mertel, Sara; Beuschel, Christine B; Castoldi, Francesca; Sedej, Simon
Title		The flavonoid 4,4'-dimethoxychalcone promotes autophagy-dependent longevity across species
Type		članek
Vol. and No.		, št. Vol. 10
Publication year		2019
Volume		str. 1-17
ISSN		2041-1723 - Nature communications
Language		eng
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.
Descriptors		Aging Neurodegenerative Diseases Cardiovascular Diseases drug effects physiology