Cell Reports (Apr 2021)
Dietary spermidine improves cognitive function
- Sabrina Schroeder,
- Sebastian J. Hofer,
- Andreas Zimmermann,
- Raimund Pechlaner,
- Christopher Dammbrueck,
- Tobias Pendl,
- G. Mark Marcello,
- Viktoria Pogatschnigg,
- Martina Bergmann,
- Melanie Müller,
- Verena Gschiel,
- Selena Ristic,
- Jelena Tadic,
- Keiko Iwata,
- Gesa Richter,
- Aitak Farzi,
- Muammer Üçal,
- Ute Schäfer,
- Michael Poglitsch,
- Philipp Royer,
- Ronald Mekis,
- Marlene Agreiter,
- Regine C. Tölle,
- Péter Sótonyi,
- Johann Willeit,
- Barbara Mairhofer,
- Helga Niederkofler,
- Irmgard Pallhuber,
- Gregorio Rungger,
- Herbert Tilg,
- Michaela Defrancesco,
- Josef Marksteiner,
- Frank Sinner,
- Christoph Magnes,
- Thomas R. Pieber,
- Peter Holzer,
- Guido Kroemer,
- Didac Carmona-Gutierrez,
- Luca Scorrano,
- Jörn Dengjel,
- Tobias Madl,
- Simon Sedej,
- Stephan J. Sigrist,
- Bence Rácz,
- Stefan Kiechl,
- Tobias Eisenberg,
- Frank Madeo
Affiliations
- Sabrina Schroeder
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria; BioTechMed-Graz, 8010 Graz, Austria
- Sebastian J. Hofer
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria; BioTechMed-Graz, 8010 Graz, Austria; Field of Excellence BioHealth, University of Graz, 8010 Graz, Austria
- Andreas Zimmermann
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria; Field of Excellence BioHealth, University of Graz, 8010 Graz, Austria
- Raimund Pechlaner
- Department of Neurology, Medical University of Innsbruck, 6020 Innsbruck, Austria
- Christopher Dammbrueck
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria
- Tobias Pendl
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria
- G. Mark Marcello
- Department of Anatomy and Histology, University of Veterinary Medicine Budapest, 1078 Budapest, Hungary
- Viktoria Pogatschnigg
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria
- Martina Bergmann
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria
- Melanie Müller
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria
- Verena Gschiel
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria
- Selena Ristic
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria
- Jelena Tadic
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria; Field of Excellence BioHealth, University of Graz, 8010 Graz, Austria
- Keiko Iwata
- Veneto Institute of Molecular Medicine, 35129 Padova, Italy; Research Center for Child Mental Development, University of Fukui, 910-1193 Fukui, Japan
- Gesa Richter
- Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging Molecular Biology and Biochemistry Medical University of Graz, 8010 Graz, Austria
- Aitak Farzi
- Otto Loewi Research Center (for Vascular Biology, Immunology and Inflammation), Division of Pharmacology, Medical University of Graz (MUG), 8010 Graz, Austria
- Muammer Üçal
- Department of Neurosurgery, RU Experimental Neurotraumatology, Medical University Graz, 8036 Graz, Austria
- Ute Schäfer
- Department of Neurosurgery, RU Experimental Neurotraumatology, Medical University Graz, 8036 Graz, Austria
- Michael Poglitsch
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria
- Philipp Royer
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria
- Ronald Mekis
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria
- Marlene Agreiter
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria
- Regine C. Tölle
- Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland
- Péter Sótonyi
- Department of Anatomy and Histology, University of Veterinary Medicine Budapest, 1078 Budapest, Hungary
- Johann Willeit
- Department of Neurology, Medical University of Innsbruck, 6020 Innsbruck, Austria
- Barbara Mairhofer
- Department of Psychiatry, Bruneck Hospital, 39031 Bruneck, Italy
- Helga Niederkofler
- Department of Psychiatry, Bruneck Hospital, 39031 Bruneck, Italy
- Irmgard Pallhuber
- Department of Psychiatry, Bruneck Hospital, 39031 Bruneck, Italy
- Gregorio Rungger
- Department of Neurology, Bruneck Hospital, 39031 Bruneck, Italy
- Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Medical University of Innsbruck, 6020 Innsbruck, Austria
- Michaela Defrancesco
- Department of Psychiatry, Psychotherapy and Psychosomatics, Medical University of Innsbruck, 6020 Innsbruck, Austria
- Josef Marksteiner
- Department of Psychiatry and Psychotherapy A, Hall State Hospital, 6060 Hall in Tirol, Austria
- Frank Sinner
- HEALTH-Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft mbH, 8010 Graz, Austria; Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria
- Christoph Magnes
- HEALTH-Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft mbH, 8010 Graz, Austria
- Thomas R. Pieber
- BioTechMed-Graz, 8010 Graz, Austria; HEALTH-Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft mbH, 8010 Graz, Austria; Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria
- Peter Holzer
- Otto Loewi Research Center (for Vascular Biology, Immunology and Inflammation), Division of Pharmacology, Medical University of Graz (MUG), 8010 Graz, Austria
- Guido Kroemer
- Equipe Labellisée par la Ligue Contre le Cancer, Université Paris Descartes, Université Paris Diderot, Université Sorbonne Paris Cité, INSERM U1138, Centre de Recherche des Cordeliers, 75006 Paris, France; Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, 94 805 Villejuif, France; Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, 75015 Paris, France; Suzhou Institute for Systems Biology, Chinese Academy of Sciences, 215123 Suzhou, China; Department of Women’s and Children’s Health, Karolinska University Hospital, 171 77 Stockholm, Sweden
- Didac Carmona-Gutierrez
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria
- Luca Scorrano
- Veneto Institute of Molecular Medicine, 35129 Padova, Italy
- Jörn Dengjel
- Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland
- Tobias Madl
- BioTechMed-Graz, 8010 Graz, Austria; Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging Molecular Biology and Biochemistry Medical University of Graz, 8010 Graz, Austria
- Simon Sedej
- BioTechMed-Graz, 8010 Graz, Austria; Department of Cardiology, Medical University of Graz, 8036 Graz, Austria; Faculty of Medicine, University of Maribor, 2000 Maribor, Slovenia
- Stephan J. Sigrist
- Institute of Biology/Genetics, Freie Universität Berlin, 14195 Berlin, Germany
- Bence Rácz
- Department of Anatomy and Histology, University of Veterinary Medicine Budapest, 1078 Budapest, Hungary
- Stefan Kiechl
- Department of Neurology, Medical University of Innsbruck, 6020 Innsbruck, Austria; VASCage, Research Centre on Vascular Ageing and Stroke, 6020 Innsbruck, Austria; Corresponding author
- Tobias Eisenberg
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria; BioTechMed-Graz, 8010 Graz, Austria; Field of Excellence BioHealth, University of Graz, 8010 Graz, Austria; Corresponding author
- Frank Madeo
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria; BioTechMed-Graz, 8010 Graz, Austria; Field of Excellence BioHealth, University of Graz, 8010 Graz, Austria; Corresponding author
- Journal volume & issue
-
Vol. 35,
no. 2
p. 108985
Abstract
Summary: Decreased cognitive performance is a hallmark of brain aging, but the underlying mechanisms and potential therapeutic avenues remain poorly understood. Recent studies have revealed health-protective and lifespan-extending effects of dietary spermidine, a natural autophagy-promoting polyamine. Here, we show that dietary spermidine passes the blood-brain barrier in mice and increases hippocampal eIF5A hypusination and mitochondrial function. Spermidine feeding in aged mice affects behavior in homecage environment tasks, improves spatial learning, and increases hippocampal respiratory competence. In a Drosophila aging model, spermidine boosts mitochondrial respiratory capacity, an effect that requires the autophagy regulator Atg7 and the mitophagy mediators Parkin and Pink1. Neuron-specific Pink1 knockdown abolishes spermidine-induced improvement of olfactory associative learning. This suggests that the maintenance of mitochondrial and autophagic function is essential for enhanced cognition by spermidine feeding. Finally, we show large-scale prospective data linking higher dietary spermidine intake with a reduced risk for cognitive impairment in humans.
