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1. Dietary spermidine improves cognitive function

Author

Schroeder, Sabrina, Hofer, Sebastian J., Zimmermann, Andreas, Pechlaner, Raimund, Dammbrueck, Christopher, Pendl, Tobias, Marcello, G. Mark, Pogatschnigg, Viktoria, Bergmann, Martina, Müller, Melanie, Gschiel, Verena, Ristic, Selena, Tadic, Jelena, Iwata, Keiko, Richter, Gesa, Farzi, Aitak, Üçal, Muammer, Schäfer, Ute, Poglitsch, Michael, Royer, Philipp, Mekis, Ronald, Agreiter, Marlene, Tölle, Regine C., Sótonyi, Péter, Willeit, Johann, Mairhofer, Barbara, Niederkofler, Helga, Pallhuber, Irmgard, Rungger, Gregorio, Tilg, Herbert, Defrancesco, Michaela, Marksteiner, Josef, Sinner, Frank, Magnes, Christoph, Pieber, Thomas R., Holzer, Peter, Kroemer, Guido, Carmona-Gutierrez, Didac, Scorrano, Luca, Dengjel, Jörn, Madl, Tobias, Sedej, Simon, Sigrist, Stephan J., Rácz, Bence, Kiechl, Stefan, Eisenberg, Tobias, and Madeo, Frank

Published
2021
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2. Chemical activation of SAT1 corrects diet-induced metabolic syndrome

Author

Castoldi, Francesca, Hyvönen, Mervi T., Durand, Sylvère, Aprahamian, Fanny, Sauvat, Allan, Malik, Shoaib A., Baracco, Elisa Elena, Vacchelli, Erika, Opolon, Paule, Signolle, Nicolas, Lefevre, Déborah, Bossut, Noelie, Eisenberg, Tobias, Dammbrueck, Christopher, Pendl, Tobias, Kremer, Margerie, Lachkar, Sylvie, Einer, Claudia, Michalke, Bernhard, Zischka, Hans, Madeo, Frank, Keinänen, Tuomo A., Maiuri, Maria Chiara, Pietrocola, Federico, and Kroemer, Guido

Published
2020
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3. Alternate Day Fasting Improves Physiological and Molecular Markers of Aging in Healthy, Non-obese Humans

Author

Stekovic, Slaven, Hofer, Sebastian J., Tripolt, Norbert, Aon, Miguel A., Royer, Philipp, Pein, Lukas, Stadler, Julia T., Pendl, Tobias, Prietl, Barbara, Url, Jasmin, Schroeder, Sabrina, Tadic, Jelena, Eisenberg, Tobias, Magnes, Christoph, Stumpe, Michael, Zuegner, Elmar, Bordag, Natalie, Riedl, Regina, Schmidt, Albrecht, Kolesnik, Ewald, Verheyen, Nicolas, Springer, Anna, Madl, Tobias, Sinner, Frank, de Cabo, Rafael, Kroemer, Guido, Obermayer-Pietsch, Barbara, Dengjel, Jörn, Sourij, Harald, Pieber, Thomas R., and Madeo, Frank

Published
2019
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4. Acetyl-CoA carboxylase 1–dependent lipogenesis promotes autophagy downstream of AMPK

Author

Gross, Angelina S., Zimmermann, Andreas, Pendl, Tobias, Schroeder, Sabrina, Schoenlechner, Hannes, Knittelfelder, Oskar, Lamplmayr, Laura, Santiso, Ana, Aufschnaiter, Andreas, Waltenstorfer, Daniel, Ortonobes Lara, Sandra, Stryeck, Sarah, Kast, Christina, Ruckenstuhl, Christoph, Hofer, Sebastian J., Michelitsch, Birgit, Woelflingseder, Martina, Müller, Rolf, Carmona-Gutierrez, Didac, Madl, Tobias, Büttner, Sabrina, Fröhlich, Kai-Uwe, Shevchenko, Andrej, and Eisenberg, Tobias

Published
2019
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6. 3,4‐Dimethoxychalcone induces autophagy through activation of the transcription factors TFE3 and TFEB

Author

Chen, Guo, Xie, Wei, Nah, Jihoon, Sauvat, Allan, Liu, Peng, Pietrocola, Federico, Sica, Valentina, Carmona‐Gutierrez, Didac, Zimmermann, Andreas, Pendl, Tobias, Tadic, Jelena, Bergmann, Martina, Hofer, Sebastian J, Domuz, Lana, Lachkar, Sylvie, Markaki, Maria, Tavernarakis, Nektarios, Sadoshima, Junichi, Madeo, Frank, Kepp, Oliver, and Kroemer, Guido

Published
2019
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7. The flavonoid 4,4′-dimethoxychalcone promotes autophagy-dependent longevity across species

Author

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

Published
2019
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8. Regulation of Autophagy by Cytosolic Acetyl-Coenzyme A

Author

Mariño, Guillermo, Pietrocola, Federico, Eisenberg, Tobias, Kong, Yongli, Malik, Shoaib Ahmad, Andryushkova, Aleksandra, Schroeder, Sabrina, Pendl, Tobias, Harger, Alexandra, Niso-Santano, Mireia, Zamzami, Naoufal, Scoazec, Marie, Durand, Silvère, Enot, David P., Fernández, Álvaro F., Martins, Isabelle, Kepp, Oliver, Senovilla, Laura, Bauvy, Chantal, Morselli, Eugenia, Vacchelli, Erika, Bennetzen, Martin, Magnes, Christoph, Sinner, Frank, Pieber, Thomas, López-Otín, Carlos, Maiuri, Maria Chiara, Codogno, Patrice, Andersen, Jens S., Hill, Joseph A., Madeo, Frank, and Kroemer, Guido

Published
2014
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9. Nucleocytosolic Depletion of the Energy Metabolite Acetyl-Coenzyme A Stimulates Autophagy and Prolongs Lifespan

Author

Eisenberg, Tobias, Schroeder, Sabrina, Andryushkova, Aleksandra, Pendl, Tobias, Küttner, Victoria, Bhukel, Anuradha, Mariño, Guillermo, Pietrocola, Federico, Harger, Alexandra, Zimmermann, Andreas, Moustafa, Tarek, Sprenger, Adrian, Jany, Evelyne, Büttner, Sabrina, Carmona-Gutierrez, Didac, Ruckenstuhl, Christoph, Ring, Julia, Reichelt, Wieland, Schimmel, Katharina, Leeb, Tina, Moser, Claudia, Schatz, Stefanie, Kamolz, Lars-Peter, Magnes, Christoph, Sinner, Frank, Sedej, Simon, Fröhlich, Kai-Uwe, Juhasz, Gabor, Pieber, Thomas R., Dengjel, Jörn, Sigrist, Stephan J., Kroemer, Guido, and Madeo, Frank

Published
2014
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10. Cardioprotection and lifespan extension by the natural polyamine spermidine

Author

Eisenberg, Tobias, Abdellatif, Mahmoud, Schroeder, Sabrina, Primessnig, Uwe, Stekovic, Slaven, Pendl, Tobias, Harger, Alexandra, Schipke, Julia, Zimmermann, Andreas, Schmidt, Albrecht, Tong, Mingming, Ruckenstuhl, Christoph, Dammbrueck, Christopher, Gross, Angelina S, Herbst, Viktoria, Magnes, Christoph, Trausinger, Gert, Narath, Sophie, Meinitzer, Andreas, Hu, Zehan, Kirsch, Alexander, Eller, Kathrin, Carmona-Gutierrez, Didac, Büttner, Sabrina, Pietrocola, Federico, Knittelfelder, Oskar, Schrepfer, Emilie, Rockenfeller, Patrick, Simonini, Corinna, Rahn, Alexandros, Horsch, Marion, Moreth, Kristin, Beckers, Johannes, Fuchs, Helmut, Gailus-Durner, Valerie, Neff, Frauke, Janik, Dirk, Rathkolb, Birgit, Rozman, Jan, de Angelis, Martin Hrabe, Moustafa, Tarek, Haemmerle, Guenter, Mayr, Manuel, Willeit, Peter, von Frieling-Salewsky, Marion, Pieske, Burkert, Scorrano, Luca, Pieber, Thomas, Pechlaner, Raimund, Willeit, Johann, Sigrist, Stephan J, Linke, Wolfgang A, Mühlfeld, Christian, Sadoshima, Junichi, Dengjel, Joern, Kiechl, Stefan, Kroemer, Guido, Sedej, Simon, and Madeo, Frank

Subjects
Polyamines -- Research, Cardiovascular diseases -- Research, Biological sciences, Health
Abstract

Aging is associated with an increased risk of cardiovascular disease and death. Here we show that oral supplementation of the natural polyamine spermidine extends the lifespan of mice and exerts cardioprotective effects, reducing cardiac hypertrophy and preserving diastolic function in old mice. Spermidine feeding enhanced cardiac autophagy, mitophagy and mitochondrial respiration, and it also improved the mechano-elastical properties of cardiomyocytes in vivo, coinciding with increased titin phosphorylation and suppressed subclinical inflammation. Spermidine feeding failed to provide cardioprotection in mice that lack the autophagy-related protein Atg5 in cardiomyocytes. In Dahl salt-sensitive rats that were fed a high-salt diet, a model for hypertension-induced congestive heart failure, spermidine feeding reduced systemic blood pressure, increased titin phosphorylation and prevented cardiac hypertrophy and a decline in diastolic function, thus delaying the progression to heart failure. In humans, high levels of dietary spermidine, as assessed from food questionnaires, correlated with reduced blood pressure and a lower incidence of cardiovascular disease. Our results suggest a new and feasible strategy for protection against cardiovascular disease., Author(s): Tobias Eisenberg [1, 2]; Mahmoud Abdellatif [3]; Sabrina Schroeder [1]; Uwe Primessnig [3, 4]; Slaven Stekovic [1]; Tobias Pendl [1]; Alexandra Harger [1, 5]; Julia Schipke [6, 7]; Andreas [...]

Published
2016
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11. Fine-Tuning Cardiac Insulin-Like Growth Factor 1 Receptor Signaling to Promote Health and Longevity

Author

Abdellatif, Mahmoud, primary, Trummer-Herbst, Viktoria, additional, Heberle, Alexander Martin, additional, Humnig, Alina, additional, Pendl, Tobias, additional, Durand, Sylvère, additional, Cerrato, Giulia, additional, Hofer, Sebastian J., additional, Islam, Moydul, additional, Voglhuber, Julia, additional, Ramos Pittol, José Miguel, additional, Kepp, Oliver, additional, Hoefler, Gerald, additional, Schmidt, Albrecht, additional, Rainer, Peter P., additional, Scherr, Daniel, additional, von Lewinski, Dirk, additional, Bisping, Egbert, additional, McMullen, Julie R., additional, Diwan, Abhinav, additional, Eisenberg, Tobias, additional, Madeo, Frank, additional, Thedieck, Kathrin, additional, Kroemer, Guido, additional, and Sedej, Simon, additional

Published
2022
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13. Nicotinamide for the treatment of heart failure with preserved ejection fraction

Author

Abdellatif, Mahmoud, Trummer-Herbst, Viktoria, Koser, Franziska, Durand, Sylvere, Adao, Rui, Vasques-Novoa, Francisco, Freundt, Johanna K., Voglhuber, Julia, Pricolo, Maria-Rosaria, Kasa, Michael, Turk, Clara, Aprahamian, Fanny, Herrero-Galan, Elias, Hofer, Sebastian J., Pendl, Tobias, Rech, Lavinia, Kargl, Julia, Anto-Michel, Nathaly, Ljubojevic-Holzer, Senka, Schipke, Julia, Brandenberger, Christina, Auer, Martina, Schreiber, Renate, Koyani, Chintan N., Heinemann, Akos, Zirlik, Andreas, Schmidt, Albrecht, von Lewinski, Dirk, Scherr, Daniel, Rainer, Peter P., von Maltzahn, Julia, Muhlfeld, Christian, Kruger, Marcus, Frank, Sasa, Madeo, Frank, Eisenberg, Tobias, Prokesch, Andreas, Leite-Moreira, Adelino F., Lourenco, Andre P., Alegre-Cebollada, Jorge, Kiechl, Stefan, Linke, Wolfgang A., Kroemer, Guido, Sedej, Simon, Abdellatif, Mahmoud, Trummer-Herbst, Viktoria, Koser, Franziska, Durand, Sylvere, Adao, Rui, Vasques-Novoa, Francisco, Freundt, Johanna K., Voglhuber, Julia, Pricolo, Maria-Rosaria, Kasa, Michael, Turk, Clara, Aprahamian, Fanny, Herrero-Galan, Elias, Hofer, Sebastian J., Pendl, Tobias, Rech, Lavinia, Kargl, Julia, Anto-Michel, Nathaly, Ljubojevic-Holzer, Senka, Schipke, Julia, Brandenberger, Christina, Auer, Martina, Schreiber, Renate, Koyani, Chintan N., Heinemann, Akos, Zirlik, Andreas, Schmidt, Albrecht, von Lewinski, Dirk, Scherr, Daniel, Rainer, Peter P., von Maltzahn, Julia, Muhlfeld, Christian, Kruger, Marcus, Frank, Sasa, Madeo, Frank, Eisenberg, Tobias, Prokesch, Andreas, Leite-Moreira, Adelino F., Lourenco, Andre P., Alegre-Cebollada, Jorge, Kiechl, Stefan, Linke, Wolfgang A., Kroemer, Guido, and Sedej, Simon

Abstract

Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent and intractable form of cardiac decompensation commonly associated with diastolic dysfunction. Here, we show that diastolic dysfunction in patients with HFpEF is associated with a cardiac deficit in nicotinamide adenine dinucleotide (NAD(+)). Elevating NAD(+) by oral supplementation of its precursor, nicotinamide, improved diastolic dysfunction induced by aging (in 2-year-old C57BL/6J mice), hypertension (in Dahl salt-sensitive rats), or cardiometabolic syndrome (in ZSF1 obese rats). This effect was mediated partly through alleviated systemic comorbidities and enhanced myocardial bioenergetics. Simultaneously, nicotinamide directly improved cardiomyocyte passive stiffness and calcium-dependent active relaxation through increased deacetylation of titin and the sarcoplasmic reticulum calcium adenosine triphosphatase 2a, respectively. In a long-term human cohort study, high dietary intake of naturally occurring NAD(+) precursors was associated with lower blood pressure and reduced risk of cardiac mortality. Collectively, these results suggest NAD(+) precursors, and especially nicotinamide, as potential therapeutic agents to treat diastolic dysfunction and HFpEF in humans.

Published
2021

14. Alternate Day Fasting Improves Physiological and Molecular Markers of Aging in Healthy, Non-obese Humans

Author

Stekovic, Slaven, Hofer, Sebastian J., Tripolt, Norbert, Aon, Miguel A., Royer, Philipp, Pein, Lukas, Stadler, Julia T., Pendl, Tobias, Prietl, Barbara, Url, Jasmin, Schroeder, Sabrina, Tadic, Jelena, Eisenberg, Tobias, Magnes, Christoph, Stumpe, Michael, Zuegner, Elmar, Bordag, Natalie, Riedl, Regina, Schmidt, Albrecht, Kolesnik, Ewald, Verheyen, Nicolas, Springer, Anna, Madl, Tobias, Sinner, Frank, de Cabo, Rafael, Kroemer, Guido, Obermayer-Pietsch, Barbara, Dengjel, Jörn, Sourij, Harald, Pieber, Thomas R., and Madeo, Frank

Published
2020
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15. Nicotinamide for the treatment of heart failure with preserved ejection fraction

Author

Abdellatif, Mahmoud, primary, Trummer-Herbst, Viktoria, additional, Koser, Franziska, additional, Durand, Sylvère, additional, Adão, Rui, additional, Vasques-Nóvoa, Francisco, additional, Freundt, Johanna K., additional, Voglhuber, Julia, additional, Pricolo, Maria-Rosaria, additional, Kasa, Michael, additional, Türk, Clara, additional, Aprahamian, Fanny, additional, Herrero-Galán, Elías, additional, Hofer, Sebastian J., additional, Pendl, Tobias, additional, Rech, Lavinia, additional, Kargl, Julia, additional, Anto-Michel, Nathaly, additional, Ljubojevic-Holzer, Senka, additional, Schipke, Julia, additional, Brandenberger, Christina, additional, Auer, Martina, additional, Schreiber, Renate, additional, Koyani, Chintan N., additional, Heinemann, Akos, additional, Zirlik, Andreas, additional, Schmidt, Albrecht, additional, von Lewinski, Dirk, additional, Scherr, Daniel, additional, Rainer, Peter P., additional, von Maltzahn, Julia, additional, Mühlfeld, Christian, additional, Krüger, Marcus, additional, Frank, Saša, additional, Madeo, Frank, additional, Eisenberg, Tobias, additional, Prokesch, Andreas, additional, Leite-Moreira, Adelino F., additional, Lourenço, André P., additional, Alegre-Cebollada, Jorge, additional, Kiechl, Stefan, additional, Linke, Wolfgang A., additional, Kroemer, Guido, additional, and Sedej, Simon, additional

Published
2021
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16. Nutritional Aspects of Spermidine

Author

Madeo, Frank, primary, Hofer, Sebastian J., additional, Pendl, Tobias, additional, Bauer, Maria A., additional, Eisenberg, Tobias, additional, Carmona-Gutierrez, Didac, additional, and Kroemer, Guido, additional

Published
2020
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17. Journal of Biological Chemistry / Acetyl-CoA carboxylase 1-dependent lipogenesis promotes autophagy downstream of AMPK

Author

Gross, Angelina S., Zimmermann, Andreas, Pendl, Tobias, Schröder, Sabrina, Schoenlechner, Hannes, Knittelfelder, Oskar, Gross, Angelina S., Zimmermann, Andreas, Pendl, Tobias, Schröder, Sabrina, Schoenlechner, Hannes, and Knittelfelder, Oskar

Abstract

Autophagy, a membrane-dependent catabolic process, ensures survival of aging cells and depends on the cellular energetic status. Acetyl-CoA carboxylase 1 (Acc1) connects central energy metabolism to lipid biosynthesis and is rate-limiting for the de novo synthesis of lipids. However, it is unclear how de novo lipogenesis and its metabolic consequences affect autophagic activity. Here, we show that in aging yeast, autophagy levels highly depend on the activity of Acc1. Constitutively active Acc1 (acc1S/A) or a deletion of the Acc1 negative regulator, Snf1 (yeast AMPK), shows elevated autophagy levels, which can be reversed by the Acc1 inhibitor soraphen A. Vice versa, pharmacological inhibition of Acc1 drastically reduces cell survival and results in the accumulation of Atg8-positive structures at the vacuolar membrane, suggesting late defects in the autophagic cascade. As expected, acc1S/A cells exhibit a reduction in acetate/acetyl-CoA availability along with elevated cellular lipid content. However, concomitant administration of acetate fails to fully revert the increase in autophagy exerted by acc1S/A. Instead, administration of oleate, while mimicking constitutively active Acc1 in WT cells, alleviates the vacuolar fusion defects induced by Acc1 inhibition. Our results argue for a largely lipid-dependent process of autophagy regulation downstream of Acc1. We present a versatile genetic model to investigate the complex relationship between acetate metabolism, lipid homeostasis, and autophagy and propose Acc1-dependent lipogenesis as a fundamental metabolic path downstream of Snf1 to maintain autophagy and survival during cellular aging.

Published
2019
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18. Cardioprotection and lifespan extension by the natural polyamine spermidine

Author

Eisenberg, Tobias, Abdellatif, Mahmoud, Zimmermann, Andreas, Schroeder, Sabrina, Pendl, Tobias, Harger, Alexandra, Stekovic, Slaven, Schipke, Julia, Magnes, Christoph, Schmidt, Albrecht, Ruckenstuhl, Christoph, Dammbrueck, Christopher, Gross, Angelina S., Herbst, Viktoria, Carmona-Gutierrez, Didac, Pietrocola, Federico, Pieber, Thomas R., Sigrist, Stephan J., Linke, Wolfgang A., Mühlfeld, Christian, Sadoshima, Junichi, Dengjel, Joern, Kiechl, Stefan, Kroemer, Guido, Sedej, Simon, and Madeo, Frank

Subjects
Mice, Inbred C57BL, autophagy, hypertension, Rats, Inbred Dahl, cardiovascular disease, polyamine, Spermidine, aging, Animals, Humans, Models, Biological, Autophagic Puncta
Abstract

Loss of cardiac macroautophagy/autophagy impairs heart function, and evidence accumulates that an increased autophagic flux may protect against cardiovascular disease. We therefore tested the protective capacity of the natural autophagy inducer spermidine in animal models of aging and hypertension, which both represent major risk factors for the development of cardiovascular disease. Dietary spermidine elicits cardioprotective effects in aged mice through enhancing cardiac autophagy and mitophagy. In salt-sensitive rats, spermidine supplementation also delays the development of hypertensive heart disease, coinciding with reduced arterial blood pressure. The high blood pressure-lowering effect likely results from improved global arginine bioavailability and protection from hypertension-associated renal damage. The polyamine spermidine is naturally present in human diets, though to a varying amount depending on food type and preparation. In humans, high dietary spermidine intake correlates with reduced blood pressure and decreased risk of cardiovascular disease and related death. Altogether, spermidine represents a cardio- and vascular-protective autophagy inducer that can be readily integrated in common diets.

Published
2017

19. N ‐acetylaspartate availability is essential for juvenile survival on fat‐free diet and determines metabolic health

Author

Hofer, Dina C., primary, Zirkovits, Gabriel, additional, Pelzmann, Helmut J., additional, Huber, Katharina, additional, Pessentheiner, Ariane R., additional, Xia, Wenmin, additional, Uno, Kyosuke, additional, Miyazaki, Toh, additional, Kon, Kanta, additional, Tsuneki, Hiroshi, additional, Pendl, Tobias, additional, Zoughbi, Wael Al, additional, Madreiter‐Sokolowski, Corina T., additional, Trausinger, Gert, additional, Abdellatif, Mahmoud, additional, Schoiswohl, Gabriele, additional, Schreiber, Renate, additional, Eisenberg, Tobias, additional, Magnes, Christoph, additional, Sedej, Simon, additional, Eckhardt, Matthias, additional, Sasahara, Masakiyo, additional, Sasaoka, Toshiyasu, additional, Nitta, Atsumi, additional, Hoefler, Gerald, additional, Graier, Wolfgang F., additional, Kratky, Dagmar, additional, Auwerx, Johan, additional, and Bogner‐Strauss, Juliane G., additional

Published
2019
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20. 3,4‐Dimethoxychalcone induces autophagy through activation of the transcription factors TFE 3 and TFEB

Author

Chen, Guo, primary, Xie, Wei, additional, Nah, Jihoon, additional, Sauvat, Allan, additional, Liu, Peng, additional, Pietrocola, Federico, additional, Sica, Valentina, additional, Carmona‐Gutierrez, Didac, additional, Zimmermann, Andreas, additional, Pendl, Tobias, additional, Tadic, Jelena, additional, Bergmann, Martina, additional, Hofer, Sebastian J, additional, Domuz, Lana, additional, Lachkar, Sylvie, additional, Markaki, Maria, additional, Tavernarakis, Nektarios, additional, Sadoshima, Junichi, additional, Madeo, Frank, additional, Kepp, Oliver, additional, and Kroemer, Guido, additional

Published
2019
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21. Guidelines and recommendations on yeast cell death nomenclature

Author

Carmona-Gutierrez, Didac, Bauer, Maria Anna, Zimmermann, Andreas, Aguilera, Andres, Austriaco, Nicanor, Ayscough, Kathryn, Balzan, Rena, Bar-Nun, Shoshana, Barrientos, Antonio, Belenky, Peter, Blondel, Marc, Braun, Ralf J., Breitenbach, Michael, Burhans, William C., Büttner, Sabrina, Cavalieri, Duccio, Chang, Michael, Cooper, Katrina F., Corte-Real, Manuela, Costa, Vitor, Cullin, Christophe, Dawes, Ian, Dengjel, Jorn, Dickman, Martin B., Eisenberg, Tobias, Fahrenkrog, Birthe, Fasel, Nicolas, Frohlich, Kai-Uwe, Gargouri, Ali, Giannattasio, Sergio, Goffrini, Paola, Gourlay, Campbell W., Grant, Chris M., Greenwood, Michael T., Guaragnella, Nicoletta, Heger, Thomas, Heinisch, Juergen, Herker, Eva, Herrmann, Johannes M., Hofer, Sebastian, Jimenez-Ruiz, Antonio, Jungwirth, Helmut, Kainz, Katharina, Kontoyiannis, Dimitrios P., Ludovico, Paula, Manon, Stephen, Martegani, Enzo, Mazzoni, Cristina, Megeney, Lynn A., Meisinger, Chris, Nielsen, Jens, Nystrom, Thomas, Osiewacz, Heinz D., Outeiro, Tiago F., Park, Hay-Oak, Pendl, Tobias, Petranovic, Dina, Picot, Stephane, Polcic, Peter, Powers, Ted, Ramsdale, Mark, Rinnerthaler, Mark, Rockenfeller, Patrick, Ruckenstuhl, Christoph, Schaffrath, Raffael, Segovia, Maria, Severin, Fedor F., Sharon, Amir, Sigrist, Stephan J., Sommer-Ruck, Cornelia, Sousa, Maria Joao, Thevelein, Johan M., Thevissen, Karin, Titorenko, Vladimir, Toledano, Michel B., Tuite, Mick, Voegtle, F. -Nora, Westermann, Benedikt, Winderickx, Joris, Wissing, Silke, Woelfl, Stefan, Zhang, Zhaojie J., Zhao, Richard Y., Zhou, Bing, Galluzzi, Lorenzo, Kroemer, Guido, Madeo, Frank, Carmona-Gutierrez, Didac, Bauer, Maria Anna, Zimmermann, Andreas, Aguilera, Andres, Austriaco, Nicanor, Ayscough, Kathryn, Balzan, Rena, Bar-Nun, Shoshana, Barrientos, Antonio, Belenky, Peter, Blondel, Marc, Braun, Ralf J., Breitenbach, Michael, Burhans, William C., Büttner, Sabrina, Cavalieri, Duccio, Chang, Michael, Cooper, Katrina F., Corte-Real, Manuela, Costa, Vitor, Cullin, Christophe, Dawes, Ian, Dengjel, Jorn, Dickman, Martin B., Eisenberg, Tobias, Fahrenkrog, Birthe, Fasel, Nicolas, Frohlich, Kai-Uwe, Gargouri, Ali, Giannattasio, Sergio, Goffrini, Paola, Gourlay, Campbell W., Grant, Chris M., Greenwood, Michael T., Guaragnella, Nicoletta, Heger, Thomas, Heinisch, Juergen, Herker, Eva, Herrmann, Johannes M., Hofer, Sebastian, Jimenez-Ruiz, Antonio, Jungwirth, Helmut, Kainz, Katharina, Kontoyiannis, Dimitrios P., Ludovico, Paula, Manon, Stephen, Martegani, Enzo, Mazzoni, Cristina, Megeney, Lynn A., Meisinger, Chris, Nielsen, Jens, Nystrom, Thomas, Osiewacz, Heinz D., Outeiro, Tiago F., Park, Hay-Oak, Pendl, Tobias, Petranovic, Dina, Picot, Stephane, Polcic, Peter, Powers, Ted, Ramsdale, Mark, Rinnerthaler, Mark, Rockenfeller, Patrick, Ruckenstuhl, Christoph, Schaffrath, Raffael, Segovia, Maria, Severin, Fedor F., Sharon, Amir, Sigrist, Stephan J., Sommer-Ruck, Cornelia, Sousa, Maria Joao, Thevelein, Johan M., Thevissen, Karin, Titorenko, Vladimir, Toledano, Michel B., Tuite, Mick, Voegtle, F. -Nora, Westermann, Benedikt, Winderickx, Joris, Wissing, Silke, Woelfl, Stefan, Zhang, Zhaojie J., Zhao, Richard Y., Zhou, Bing, Galluzzi, Lorenzo, Kroemer, Guido, and Madeo, Frank

Abstract

Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cellular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing. Here, we propose unified criteria for the definition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death routines that are relevant for the biology of (at least some species of) yeast. As this area of investigation advances rapidly, changes and extensions to this set of recommendations will be implemented in the years to come. Nonetheless, we strongly encourage the authors, reviewers and editors of scientific articles to adopt these collective standards in order to establish an accurate framework for yeast cell death research and, ultimately, to accelerate the progress of this vibrant field of research.

Published
2018
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22. Guidelines and recommendations on yeast cell death nomenclature

Author

Carmona-Gutierrez, D, Bauer, M, Zimmermann, A, Aguilera, A, Austriaco, N, Ayscough, K, Balzan, R, Bar-Nun, S, Barrientos, A, Belenky, P, Blondel, M, Braun, R, Breitenbach, M, Burhans, W, Buettner, S, Cavalieri, D, Chang, M, Cooper, K, Côrte-Real, M, Costa, V, Cullin, C, Dawes, I, Dengjel, J, Dickman, M, Eisenberg, T, Fahrenkrog, B, Fasel, N, Froehlich, K, Gargouri, A, Giannattasio, S, Goffrini, P, Gourlay, C, Grant, C, Greenwood, M, Guaragnella, N, Heger, T, Heinisch, J, Herker, E, Herrmann, J, Hofer, S, Jiménez-Ruiz, A, Jungwirth, H, Kainz, K, Kontoyiannis, D, Ludovico, P, Manon, S, Martegani, E, Mazzoni, C, Megeney, L, Meisinger, C, Nielsen, J, Nystroem, T, Osiewacz, H, Outeiro, T, Park, H, Pendl, T, Petranovic, D, Picot, S, Polčic, P, Powers, T, Ramsdale, M, Rinnerthaler, M, Rockenfeller, P, Ruckenstuhl, C, Schaffrath, R, Segovia, M, Severin, F, Sharon, A, Sigrist, S, Sommer-Ruck, C, Sousa, M, Thevelein, J, Thevissen, K, Titorenko, V, Toledano, M, Tuite, M, Voegtle, F, Westermann, B, Winderickx, J, Wissing, S, Woelfl, S, Zhang, Z, Zhao, R, Zhou, B, Galluzzi, L, Kroemer, G, Madeo, F, Carmona-Gutierrez, Didac, Bauer, Maria Anna, Zimmermann, Andreas, Aguilera, Andrés, Austriaco, Nicanor, Ayscough, Kathryn, Balzan, Rena, Bar-Nun, Shoshana, Barrientos, Antonio, Belenky, Peter, Blondel, Marc, Braun, Ralf J., Breitenbach, Michael, Burhans, William C., Buettner, Sabrina, Cavalieri, Duccio, Chang, Michael, Cooper, Katrina F., Côrte-Real, Manuela, Costa, Vítor, Cullin, Christophe, Dawes, Ian, Dengjel, Jörn, Dickman, Martin B., Eisenberg, Tobias, Fahrenkrog, Birthe, Fasel, Nicolas, Froehlich, Kai-Uwe, Gargouri, Ali, Giannattasio, Sergio, Goffrini, Paola, Gourlay, Campbell W., Grant, Chris M., Greenwood, Michael T., Guaragnella, Nicoletta, Heger, Thomas, Heinisch, Juergen, Herker, Eva, Herrmann, Johannes M., Hofer, Sebastian, Jiménez-Ruiz, Antonio, Jungwirth, Helmut, Kainz, Katharina, Kontoyiannis, Dimitrios P., Ludovico, Paula, Manon, Stéphen, Martegani, Enzo, Mazzoni, Cristina, Megeney, Lynn A., Meisinger, Chris, Nielsen, Jens, Nystroem, Thomas, Osiewacz, Heinz D., Outeiro, Tiago F., Park, Hay-Oak, Pendl, Tobias, Petranovic, Dina, Picot, Stephane, Polčic, Peter, Powers, Ted, Ramsdale, Mark, Rinnerthaler, Mark, Rockenfeller, Patrick, Ruckenstuhl, Christoph, Schaffrath, Raffael, Segovia, Maria, Severin, Fedor F., Sharon, Amir, Sigrist, Stephan J., Sommer-Ruck, Cornelia, Sousa, Maria João, Thevelein, Johan M., Thevissen, Karin, Titorenko, Vladimir, Toledano, Michel B., Tuite, Mick, Voegtle, F. -Nora, Westermann, Benedikt, Winderickx, Joris, Wissing, Silke, Woelfl, Stefan, Zhang, Zhaojie J., Zhao, Richard Y., Zhou, Bing, Galluzzi, Lorenzo, Kroemer, Guido, Madeo, Frank, Carmona-Gutierrez, D, Bauer, M, Zimmermann, A, Aguilera, A, Austriaco, N, Ayscough, K, Balzan, R, Bar-Nun, S, Barrientos, A, Belenky, P, Blondel, M, Braun, R, Breitenbach, M, Burhans, W, Buettner, S, Cavalieri, D, Chang, M, Cooper, K, Côrte-Real, M, Costa, V, Cullin, C, Dawes, I, Dengjel, J, Dickman, M, Eisenberg, T, Fahrenkrog, B, Fasel, N, Froehlich, K, Gargouri, A, Giannattasio, S, Goffrini, P, Gourlay, C, Grant, C, Greenwood, M, Guaragnella, N, Heger, T, Heinisch, J, Herker, E, Herrmann, J, Hofer, S, Jiménez-Ruiz, A, Jungwirth, H, Kainz, K, Kontoyiannis, D, Ludovico, P, Manon, S, Martegani, E, Mazzoni, C, Megeney, L, Meisinger, C, Nielsen, J, Nystroem, T, Osiewacz, H, Outeiro, T, Park, H, Pendl, T, Petranovic, D, Picot, S, Polčic, P, Powers, T, Ramsdale, M, Rinnerthaler, M, Rockenfeller, P, Ruckenstuhl, C, Schaffrath, R, Segovia, M, Severin, F, Sharon, A, Sigrist, S, Sommer-Ruck, C, Sousa, M, Thevelein, J, Thevissen, K, Titorenko, V, Toledano, M, Tuite, M, Voegtle, F, Westermann, B, Winderickx, J, Wissing, S, Woelfl, S, Zhang, Z, Zhao, R, Zhou, B, Galluzzi, L, Kroemer, G, Madeo, F, Carmona-Gutierrez, Didac, Bauer, Maria Anna, Zimmermann, Andreas, Aguilera, Andrés, Austriaco, Nicanor, Ayscough, Kathryn, Balzan, Rena, Bar-Nun, Shoshana, Barrientos, Antonio, Belenky, Peter, Blondel, Marc, Braun, Ralf J., Breitenbach, Michael, Burhans, William C., Buettner, Sabrina, Cavalieri, Duccio, Chang, Michael, Cooper, Katrina F., Côrte-Real, Manuela, Costa, Vítor, Cullin, Christophe, Dawes, Ian, Dengjel, Jörn, Dickman, Martin B., Eisenberg, Tobias, Fahrenkrog, Birthe, Fasel, Nicolas, Froehlich, Kai-Uwe, Gargouri, Ali, Giannattasio, Sergio, Goffrini, Paola, Gourlay, Campbell W., Grant, Chris M., Greenwood, Michael T., Guaragnella, Nicoletta, Heger, Thomas, Heinisch, Juergen, Herker, Eva, Herrmann, Johannes M., Hofer, Sebastian, Jiménez-Ruiz, Antonio, Jungwirth, Helmut, Kainz, Katharina, Kontoyiannis, Dimitrios P., Ludovico, Paula, Manon, Stéphen, Martegani, Enzo, Mazzoni, Cristina, Megeney, Lynn A., Meisinger, Chris, Nielsen, Jens, Nystroem, Thomas, Osiewacz, Heinz D., Outeiro, Tiago F., Park, Hay-Oak, Pendl, Tobias, Petranovic, Dina, Picot, Stephane, Polčic, Peter, Powers, Ted, Ramsdale, Mark, Rinnerthaler, Mark, Rockenfeller, Patrick, Ruckenstuhl, Christoph, Schaffrath, Raffael, Segovia, Maria, Severin, Fedor F., Sharon, Amir, Sigrist, Stephan J., Sommer-Ruck, Cornelia, Sousa, Maria João, Thevelein, Johan M., Thevissen, Karin, Titorenko, Vladimir, Toledano, Michel B., Tuite, Mick, Voegtle, F. -Nora, Westermann, Benedikt, Winderickx, Joris, Wissing, Silke, Woelfl, Stefan, Zhang, Zhaojie J., Zhao, Richard Y., Zhou, Bing, Galluzzi, Lorenzo, Kroemer, Guido, and Madeo, Frank

Abstract

Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cellular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing. Here, we propose unified criteria for the definition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death routines that are relevant for the biology of (at least some species of) yeast. As this area of investigation advances rapidly, changes and extensions to this set of recommendations will be implemented in the years to come. Nonetheless, we strongly encourage the authors, reviewers and editors of scientific articles to adopt these collective standards in order to establish an accurate framework for yeast cell death research and, ultimately, to accelerate the progress of this vibrant field of research.

Published
2018

25. Safety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline

Author

Schwarz, Claudia, primary, Stekovic, Slaven, additional, Wirth, Miranka, additional, Benson, Gloria, additional, Royer, Philipp, additional, Sigrist, Stephan J, additional, Pieber, Thomas, additional, Dammbrueck, Christopher, additional, Magnes, Christoph, additional, Eisenberg, Tobias, additional, Pendl, Tobias, additional, Bohlken, Jens, additional, Köbe, Theresa, additional, Madeo, Frank, additional, and Flöel, Agnes, additional

Published
2018
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26. Guidelines and recommendations on yeast cell death nomenclature

Author

Carmona-Gutierrez, Didac, primary, Bauer, Maria Anna, additional, Zimmermann, Andreas, additional, Aguilera, Andrés, additional, Austriaco, Nicanor, additional, Ayscough, Kathryn, additional, Balzan, Rena, additional, Bar-Nun, Shoshana, additional, Barrientos, Antonio, additional, Belenky, Peter, additional, Blondel, Marc, additional, Braun, Ralf J., additional, Breitenbach, Michael, additional, Burhans, William C., additional, Buettner, Sabrina, additional, Cavalieri, Duccio, additional, Chang, Michael, additional, Cooper, Katrina F., additional, Côrte-Real, Manuela, additional, Costa, Vítor, additional, Cullin, Christophe, additional, Dawes, Ian, additional, Dengjel, Jörn, additional, Dickman, Martin B., additional, Eisenberg, Tobias, additional, Fahrenkrog, Birthe, additional, Fasel, Nicolas, additional, Froehlich, Kai-Uwe, additional, Gargouri, Ali, additional, Giannattasio, Sergio, additional, Goffrini, Paola, additional, Gourlay, Campbell W., additional, Grant, Chris M., additional, Greenwood, Michael T., additional, Guaragnella, Nicoletta, additional, Heger, Thomas, additional, Heinisch, Juergen, additional, Herker, Eva, additional, Herrmann, Johannes M., additional, Hofer, Sebastian, additional, Jiménez-Ruiz, Antonio, additional, Jungwirth, Helmut, additional, Kainz, Katharina, additional, Kontoyiannis, Dimitrios P., additional, Ludovico, Paula, additional, Manon, Stéphen, additional, Martegani, Enzo, additional, Mazzoni, Cristina, additional, Megeney, Lynn A., additional, Meisinger, Chris, additional, Nielsen, Jens, additional, Nystroem, Thomas, additional, Osiewacz, Heinz D., additional, Outeiro, Tiago F., additional, Park, Hay-Oak, additional, Pendl, Tobias, additional, Petranovic, Dina, additional, Picot, Stephane, additional, Polčic, Peter, additional, Powers, Ted, additional, Ramsdale, Mark, additional, Rinnerthaler, Mark, additional, Rockenfeller, Patrick, additional, Ruckenstuhl, Christoph, additional, Schaffrath, Raffael, additional, Segovia, Maria, additional, Severin, Fedor F., additional, Sharon, Amir, additional, Sigrist, Stephan J., additional, Sommer-Ruck, Cornelia, additional, Sousa, Maria João, additional, Thevelein, Johan M., additional, Thevissen, Karin, additional, Titorenko, Vladimir, additional, Toledano, Michel B., additional, Tuite, Mick, additional, Voegtle, F.-Nora, additional, Westermann, Benedikt, additional, Winderickx, Joris, additional, Wissing, Silke, additional, Woelfl, Stefan, additional, Zhang, Zhaojie J., additional, Zhao, Richard Y., additional, Zhou, Bing, additional, Galluzzi, Lorenzo, additional, Kroemer, Guido, additional, and Madeo, Frank, additional

Published
2018
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27. Dietary spermidine for lowering high blood pressure

Author

Eisenberg, Tobias, Abdellatif, Mahmoud, Zimmermann, Andreas, Schroeder, Sabrina, Pendl, Tobias, Harger, Alexandra, Stekovic, Slaven, Schipke, Julia, Magnes, Christoph, Schmidt, Albrecht, Ruckenstuhl, Christoph, Dammbrueck, Christopher, Gross, Angelina S., Herbst, Viktoria, Carmona-Gutierrez, Didac, Pietrocola, Federico, Pieber, Thomas R., Sigrist, Stephan J., Linke, Wolfgang A., Mühlfeld, Christian, Sadoshima, Junichi, Dengjel, Jörn, Kiechl, Stefan, Kroemer, Guido, Sedej, Simon, Madeo, Frank, Eisenberg, Tobias, Abdellatif, Mahmoud, Zimmermann, Andreas, Schroeder, Sabrina, Pendl, Tobias, Harger, Alexandra, Stekovic, Slaven, Schipke, Julia, Magnes, Christoph, Schmidt, Albrecht, Ruckenstuhl, Christoph, Dammbrueck, Christopher, Gross, Angelina S., Herbst, Viktoria, Carmona-Gutierrez, Didac, Pietrocola, Federico, Pieber, Thomas R., Sigrist, Stephan J., Linke, Wolfgang A., Mühlfeld, Christian, Sadoshima, Junichi, Dengjel, Jörn, Kiechl, Stefan, Kroemer, Guido, Sedej, Simon, and Madeo, Frank

Abstract

Loss of cardiac macroautophagy/autophagy impairs heart function, and evidence accumulates that an increased autophagic flux may protect against cardiovascular disease. We therefore tested the protective capacity of the natural autophagy inducer spermidine in animal models of aging and hypertension, which both represent major risk factors for the development of cardiovascular disease. Dietary spermidine elicits cardioprotective effects in aged mice through enhancing cardiac autophagy and mitophagy. In salt-sensitive rats, spermidine supplementation also delays the development of hypertensive heart disease, coinciding with reduced arterial blood pressure. The high blood pressure-lowering effect likely results from improved global arginine bioavailability and protection from hypertension-associated renal damage. The polyamine spermidine is naturally present in human diets, though to a varying amount depending on food type and preparation. In humans, high dietary spermidine intake correlates with reduced blood pressure and decreased risk of cardiovascular disease and related death. Altogether, spermidine represents a cardio- and vascular- protective autophagy inducer that can be readily integrated in common diets.

Published
2017

28. Dietary spermidine for lowering high blood pressure

Author

Eisenberg, Tobias, primary, Abdellatif, Mahmoud, additional, Zimmermann, Andreas, additional, Schroeder, Sabrina, additional, Pendl, Tobias, additional, Harger, Alexandra, additional, Stekovic, Slaven, additional, Schipke, Julia, additional, Magnes, Christoph, additional, Schmidt, Albrecht, additional, Ruckenstuhl, Christoph, additional, Dammbrueck, Christopher, additional, Gross, Angelina S., additional, Herbst, Viktoria, additional, Carmona-Gutierrez, Didac, additional, Pietrocola, Federico, additional, Pieber, Thomas R., additional, Sigrist, Stephan J., additional, Linke, Wolfgang A., additional, Mühlfeld, Christian, additional, Sadoshima, Junichi, additional, Dengjel, Joern, additional, Kiechl, Stefan, additional, Kroemer, Guido, additional, Sedej, Simon, additional, and Madeo, Frank, additional

Published
2017
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31. Acetyl-coenzyme A

Author

Schroeder, Sabrina, primary, Pendl, Tobias, additional, Zimmermann, Andreas, additional, Eisenberg, Tobias, additional, Carmona-Gutierrez, Didac, additional, Ruckenstuhl, Christoph, additional, Mariño, Guillermo, additional, Pietrocola, Federico, additional, Harger, Alexandra, additional, Magnes, Christoph, additional, Sinner, Frank, additional, Pieber, Thomas R, additional, Dengjel, Jörn, additional, Sigrist, Stephan J, additional, Kroemer, Guido, additional, and Madeo, Frank, additional

Published
2014
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32. A histone point mutation that switches on autophagy

Author

Eisenberg, Tobias, primary, Schroeder, Sabrina, additional, Büttner, Sabrina, additional, Carmona-Gutierrez, Didac, additional, Pendl, Tobias, additional, Andryushkova, Aleksandra, additional, Mariño, Guillermo, additional, Pietrocola, Federico, additional, Harger, Alexandra, additional, Zimmermann, Andreas, additional, Magnes, Christoph, additional, Sinner, Frank, additional, Sedej, Simon, additional, Pieber, Thomas R, additional, Dengjel, Jörn, additional, Sigrist, Stephan, additional, Kroemer, Guido, additional, and Madeo, Frank, additional

Published
2014
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33. Dietary spermidine for lowering high blood pressure

Author

Eisenberg, Tobias, Abdellatif, Mahmoud, Zimmermann, Andreas, Schroeder, Sabrina, Pendl, Tobias, Harger, Alexandra, Stekovic, Slaven, Schipke, Julia, Magnes, Christoph, Schmidt, Albrecht, Ruckenstuhl, Christoph, Dammbrueck, Christopher, Gross, Angelina S., Herbst, Viktoria, Carmona-Gutierrez, Didac, Pietrocola, Federico, Pieber, Thomas R., Sigrist, Stephan J., Linke, Wolfgang A., Mühlfeld, Christian, Sadoshima, Junichi, Dengjel, Jörn, Kiechl, Stefan, Kroemer, Guido, Sedej, Simon, Madeo, Frank, Eisenberg, Tobias, Abdellatif, Mahmoud, Zimmermann, Andreas, Schroeder, Sabrina, Pendl, Tobias, Harger, Alexandra, Stekovic, Slaven, Schipke, Julia, Magnes, Christoph, Schmidt, Albrecht, Ruckenstuhl, Christoph, Dammbrueck, Christopher, Gross, Angelina S., Herbst, Viktoria, Carmona-Gutierrez, Didac, Pietrocola, Federico, Pieber, Thomas R., Sigrist, Stephan J., Linke, Wolfgang A., Mühlfeld, Christian, Sadoshima, Junichi, Dengjel, Jörn, Kiechl, Stefan, Kroemer, Guido, Sedej, Simon, and Madeo, Frank

Abstract

Loss of cardiac macroautophagy/autophagy impairs heart function, and evidence accumulates that an increased autophagic flux may protect against cardiovascular disease. We therefore tested the protective capacity of the natural autophagy inducer spermidine in animal models of aging and hypertension, which both represent major risk factors for the development of cardiovascular disease. Dietary spermidine elicits cardioprotective effects in aged mice through enhancing cardiac autophagy and mitophagy. In salt-sensitive rats, spermidine supplementation also delays the development of hypertensive heart disease, coinciding with reduced arterial blood pressure. The high blood pressure-lowering effect likely results from improved global arginine bioavailability and protection from hypertension-associated renal damage. The polyamine spermidine is naturally present in human diets, though to a varying amount depending on food type and preparation. In humans, high dietary spermidine intake correlates with reduced blood pressure and decreased risk of cardiovascular disease and related death. Altogether, spermidine represents a cardio- and vascular- protective autophagy inducer that can be readily integrated in common diets.

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

Author

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

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.

35. Assessing autophagic flux in yeast.

Author

Kainz K, Pendl T, Madeo F, and Carmona-Gutierrez D

Subjects
Autophagy, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae Proteins
Abstract

Competing Interests: Conflict of interest D.C-G. and F.M. are the scientific co-founders of Samsara Therapeutics, a company that develops novel pharmacological autophagy inducers. T.P. has equity interests in Samsara Therapeutics. F.M. and D.C-G. have equity interests in TLL (The Longevity Labs), a company that develops natural food extracts.

Published
2021
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36. Acetyl-coenzyme A: a metabolic master regulator of autophagy and longevity.

Author

Schroeder S, Pendl T, Zimmermann A, Eisenberg T, Carmona-Gutierrez D, Ruckenstuhl C, Mariño G, Pietrocola F, Harger A, Magnes C, Sinner F, Pieber TR, Dengjel J, Sigrist SJ, Kroemer G, and Madeo F

Subjects
Animals, Cell Nucleus metabolism, Cytosol metabolism, Humans, Mice, Models, Biological, Saccharomyces cerevisiae cytology, Saccharomyces cerevisiae metabolism, Acetyl Coenzyme A metabolism, Autophagy, Longevity, Metabolic Networks and Pathways
Abstract

As the major lysosomal degradation pathway, autophagy represents the guardian of cellular homeostasis, removing damaged and potentially harmful material and replenishing energy reserves in conditions of starvation. Given its vast physiological importance, autophagy is crucially involved in the process of aging and associated pathologies. Although the regulation of autophagy strongly depends on nutrient availability, specific metabolites that modulate autophagic responses are poorly described. Recently, we revealed nucleo-cytosolic acetyl-coenzyme A (AcCoA) as a phylogenetically conserved inhibitor of starvation-induced and age-associated autophagy. AcCoA is the sole acetyl-group donor for protein acetylation, explaining why pharmacological or genetic manipulations that modify the concentrations of nucleo-cytosolic AcCoA directly affect the levels of protein acetylation. The acetylation of histones and cytosolic proteins inversely correlates with the rate of autophagy in yeast and mammalian cells, respectively, despite the fact that the routes of de novo AcCoA synthesis differ across phyla. Thus, we propose nucleo-cytosolic AcCoA to act as a conserved metabolic rheostat, linking the cellular metabolic state to the regulation of autophagy via effects on protein acetylation.

Published
2014
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37. Metabolites in aging and autophagy.

Author

Schroeder S, Zimmermann A, Carmona-Gutierrez D, Eisenberg T, Ruckenstuhl C, Andryushkova A, Pendl T, Harger A, and Madeo F

Abstract

Competing Interests: Conflict of interest: The authors declare no conflict of interest.

Published
2014
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