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Carmona-Gutierrez, D; Zimmermann, A; Kainz, K; Pietrocola, F; Chen, G; Maglioni, S; Schiavi, A; Nah, J; Mertel, S; Beuschel, CB; Castoldi, F; Sica, V; Trausinger, G; Raml, R; Sommer, C; Schroeder, S; Hofer, SJ; Bauer, MA; Pendl, T; Tadic, J; Dammbrueck, C; Hu, Z; Ruckenstuhl, C; Eisenberg, T; Durand, S; Bossut, N; Aprahamian, F; Abdellatif, M; Sedej, S; Enot, DP; Wolinski, H; Dengjel, J; Kepp, O; Magnes, C; Sinner, F; Pieber, TR; Sadoshima, J; Ventura, N; Sigrist, SJ; Kroemer, G; Madeo, F.
The flavonoid 4,4'-dimethoxychalcone promotes autophagy-dependent longevity across species.
Nat Commun. 2019; 10(1):651-651
Doi: 10.1038/s41467-019-08555-w
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- Co-authors Med Uni Graz
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Abdellatif Mahmoud
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Pieber Thomas
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Sedej Simon
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Sinner Frank Michael
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- Abstract:
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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.
- Find related publications in this database (using NLM MeSH Indexing)
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Aging - drug effects
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Aging - physiology
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Angelica - chemistry
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Animals -
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Autophagy - drug effects
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Caenorhabditis elegans - drug effects
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Cation Transport Proteins - genetics
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Cell Death - drug effects
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Cell Line - drug effects
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Drosophila melanogaster - drug effects
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Flavonoids - administration & dosage
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Flavonoids - pharmacology
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GATA Transcription Factors - drug effects
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Gene Expression Regulation - drug effects
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Humans -
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Longevity - drug effects
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Longevity - physiology
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Male -
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Mechanistic Target of Rapamycin Complex 1 - metabolism
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Medicine, East Asian Traditional -
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Mice -
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Mice, Inbred C57BL -
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Myocardial Ischemia - drug therapy
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Plant Extracts - pharmacology
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Saccharomyces cerevisiae - drug effects
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Saccharomyces cerevisiae - metabolism
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Saccharomyces cerevisiae Proteins - genetics
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Signal Transduction -
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Sirolimus - pharmacology
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Transcription Factors - drug effects
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Transcription Factors - genetics