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 Tadic; Christopher 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

doi:10.1038/s41467-019-08555-w

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

Résultats de recherche: Contribution à un journal › Article › Revue par des pairs

102 Citations (Scopus)

Résumé

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.

langue originale	Anglais
Numéro d'article	651
journal	Nature Communications
Volume	10
Numéro de publication	1
Les DOIs	https://doi.org/10.1038/s41467-019-08555-w
état	Publié - 1 déc. 2019

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10.1038/s41467-019-08555-w

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Carmona-Gutierrez, D., Zimmermann, A., Kainz, K., Pietrocola, F., Chen, G., Maglioni, S., Schiavi, A., Nah, J., Mertel, S., Beuschel, C. B., Castoldi, F., Sica, V., Trausinger, G., Raml, R., Sommer, C., Schroeder, S., Hofer, S. J., Bauer, M. A., Pendl, T., ... Madeo, F. (2019). The flavonoid 4,4′-dimethoxychalcone promotes autophagy-dependent longevity across species. Nature Communications, 10(1), Article 651. https://doi.org/10.1038/s41467-019-08555-w

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

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.",

author = "Didac Carmona-Gutierrez and Andreas Zimmermann and Katharina Kainz and Federico Pietrocola and Guo Chen and Silvia Maglioni and Alfonso Schiavi and Jihoon Nah and Sara Mertel and Beuschel, {Christine B.} and Francesca Castoldi and Valentina Sica and Gert Trausinger and Reingard Raml and Cornelia Sommer and Sabrina Schroeder and Hofer, {Sebastian J.} and Bauer, {Maria A.} and Tobias Pendl and Jelena Tadic and Christopher Dammbrueck and Zehan Hu and Christoph Ruckenstuhl and Tobias Eisenberg and Sylvere Durand and No{\'e}lie Bossut and Fanny Aprahamian and Mahmoud Abdellatif and Simon Sedej and Enot, {David P.} and Heimo Wolinski and J{\"o}rn Dengjel and Oliver Kepp and Christoph Magnes and Frank Sinner and Pieber, {Thomas R.} and Junichi Sadoshima and Natascia Ventura and Sigrist, {Stephan J.} and Guido Kroemer and Frank Madeo",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41467-019-08555-w",

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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 2019, 'The flavonoid 4,4′-dimethoxychalcone promotes autophagy-dependent longevity across species', Nature Communications, VOL. 10, Numéro 1, 651. https://doi.org/10.1038/s41467-019-08555-w

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T1 - The flavonoid 4,4′-dimethoxychalcone promotes autophagy-dependent longevity across species

AU - Carmona-Gutierrez, Didac

AU - Zimmermann, Andreas

AU - Kainz, Katharina

AU - Pietrocola, Federico

AU - Chen, Guo

AU - Maglioni, Silvia

AU - Schiavi, Alfonso

AU - Nah, Jihoon

AU - Mertel, Sara

AU - Beuschel, Christine B.

AU - Castoldi, Francesca

AU - Sica, Valentina

AU - Trausinger, Gert

AU - Raml, Reingard

AU - Sommer, Cornelia

AU - Schroeder, Sabrina

AU - Hofer, Sebastian J.

AU - Bauer, Maria A.

AU - Pendl, Tobias

AU - Tadic, Jelena

AU - Dammbrueck, Christopher

AU - Hu, Zehan

AU - Ruckenstuhl, Christoph

AU - Eisenberg, Tobias

AU - Durand, Sylvere

AU - Bossut, Noélie

AU - Aprahamian, Fanny

AU - Abdellatif, Mahmoud

AU - Sedej, Simon

AU - Enot, David P.

AU - Wolinski, Heimo

AU - Dengjel, Jörn

AU - Kepp, Oliver

AU - Magnes, Christoph

AU - Sinner, Frank

AU - Pieber, Thomas R.

AU - Sadoshima, Junichi

AU - Ventura, Natascia

AU - Sigrist, Stephan J.

AU - Kroemer, Guido

AU - Madeo, Frank

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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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AN - SCOPUS:85061697282

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VL - 10

JO - Nature Communications

JF - Nature Communications

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