Journal
NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-08555-w
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Funding
- Austrian Science Fund FWF [SFB-LIPOTOX F3007, F3012, W1226, P29203, P29262, P27893]
- Austrian Federal Ministry of Education, Science and Research
- University of Graz
- FWF [W 1226]
- (DK Metabolic and Cardiovascular Disease) at the University of Graz [FWF W1226]
- NAWI Graz
- BioTechMed-Graz flagship project EPIAge
- Ligue contre le Cancer (equipe labelisee)
- Agence National de la Recherche (ANR) -Projets blancs
- ANR
- ERA-Net for Research on Rare Diseases
- Association pour la recherche sur le cancer (ARC)
- Canceropole Ile-de-France
- Institut National du Cancer (INCa)
- Inserm (HTE)
- Institut Universitaire de France
- Fondation pour la Recherche Medicale (FRM)
- European Commission (ArtForce)
- European Research Council (ERC)
- Fondation Carrefour
- LeDucq Foundation
- LabEx Immuno-Oncology
- Seerave Foundation
- SIRIC Stratified Oncology Cell DNA Repair and Tumour Immune Elimination (SOCRATE)
- SIRIC Cancer Research and Personalised Medicine (CARPEM)
- Paris Alliance of Cancer Research Institutes (PACRI)
- Deutsche Forschungsgemeinschaft (DFG)
- Bundesministerium fur Bildung und Forschung (BMBF)
- Austrian Science Fund (FWF) [P27893, P29203, P29262, W1226] Funding Source: Austrian Science Fund (FWF)
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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.
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