Dietary spermidine improves cognitive function.

Aging / genetics Animals Autophagy-Related Protein 7 / genetics Brain / cytology Cognition / drug effects Cognitive Dysfunction / genetics Dietary Supplements Drosophila melanogaster / drug effects Female Gene Expression Regulation Humans Learning / drug effects Male Mice Mitochondria / drug effects Neurons / drug effects Oxidative Phosphorylation / drug effects Protein Kinases / genetics Signal Transduction Spatial Memory / drug effects Spermidine / pharmacology Ubiquitin-Protein Ligases / genetics
Pink1 aging autophagy cognitive function dietary spermidine memory mitochondria mitophagy

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
13 04 2021
Historique:
received: 03 06 2019
revised: 08 02 2021
accepted: 22 03 2021
entrez: 14 4 2021
pubmed: 15 4 2021
medline: 15 2 2022
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.celrep.2021.108985 PMID: 33852843
pubmed: 33852843
pii: S2211-1247(21)00299-0
doi: 10.1016/j.celrep.2021.108985
pii:
doi:

Substances chimiques

Ubiquitin-Protein Ligases EC 2.3.2.27
parkin protein EC 2.3.2.27
Protein Kinases EC 2.7.-
PTEN-induced putative kinase EC 2.7.11.1
ATG7 protein, human EC 6.2.1.45
Autophagy-Related Protein 7 EC 6.2.1.45
Spermidine U87FK77H25

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

108985

Subventions

Organisme : Austrian Science Fund FWF
ID : W 1226
Pays : Austria

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests F.M., S.J.S., and D.C.-G. have equity interests in The Longevity Labs (TLL), a company founded in 2016 that develops natural food extracts. T.E. has equity interests in and conducts paid consultancies for TLL. G.K. holds research contracts with Bayer Healthcare, Genentech, GlaxoSmithKline, Institut Mérieux, Kaleido Biosciences, Lytix Biopharma, NuCana, Oncolinx, PharmaMar, Samsara Therapeutics, SOTIO, and Tioma Therapeutics. G.K. is on the Board of Directors of the Bristol Myers Squibb Foundation France. G.K. is a scientific cofounder of everImmune, a biotech company that develops immunostimulatory bacteria, and Therafast Bio. F.M. and T.E. are inventors on a pending patent application related to this work.

Auteurs

Sabrina Schroeder (S)

Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria; BioTechMed-Graz, 8010 Graz, Austria.

Sebastian J Hofer (SJ)

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 (A)

Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria; Field of Excellence BioHealth, University of Graz, 8010 Graz, Austria.

Raimund Pechlaner (R)

Department of Neurology, Medical University of Innsbruck, 6020 Innsbruck, Austria.

Christopher Dammbrueck (C)

Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria.

Tobias Pendl (T)

Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria.

G Mark Marcello (GM)

Department of Anatomy and Histology, University of Veterinary Medicine Budapest, 1078 Budapest, Hungary.

Viktoria Pogatschnigg (V)

Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria.

Martina Bergmann (M)

Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria.

Melanie Müller (M)

Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria.

Verena Gschiel (V)

Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria.

Selena Ristic (S)

Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria.

Jelena Tadic (J)

Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria; Field of Excellence BioHealth, University of Graz, 8010 Graz, Austria.

Keiko Iwata (K)

Veneto Institute of Molecular Medicine, 35129 Padova, Italy; Research Center for Child Mental Development, University of Fukui, 910-1193 Fukui, Japan; Department of Biology, University of Padova, 35121 Padova, Italy.

Gesa Richter (G)

Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging Molecular Biology and Biochemistry Medical University of Graz, 8010 Graz, Austria.

Aitak Farzi (A)

Otto Loewi Research Center (for Vascular Biology, Immunology and Inflammation), Division of Pharmacology, Medical University of Graz (MUG), 8010 Graz, Austria.

Muammer Üçal (M)

Department of Neurosurgery, RU Experimental Neurotraumatology, Medical University Graz, 8036 Graz, Austria.

Ute Schäfer (U)

Department of Neurosurgery, RU Experimental Neurotraumatology, Medical University Graz, 8036 Graz, Austria.

Michael Poglitsch (M)

Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria.

Philipp Royer (P)

Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria.

Ronald Mekis (R)

Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria.

Marlene Agreiter (M)

Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria.

Regine C Tölle (RC)

Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland.

Péter Sótonyi (P)

Department of Anatomy and Histology, University of Veterinary Medicine Budapest, 1078 Budapest, Hungary.

Johann Willeit (J)

Department of Neurology, Medical University of Innsbruck, 6020 Innsbruck, Austria.

Barbara Mairhofer (B)

Department of Psychiatry, Bruneck Hospital, 39031 Bruneck, Italy.

Helga Niederkofler (H)

Department of Psychiatry, Bruneck Hospital, 39031 Bruneck, Italy.

Irmgard Pallhuber (I)

Department of Psychiatry, Bruneck Hospital, 39031 Bruneck, Italy.

Gregorio Rungger (G)

Department of Neurology, Bruneck Hospital, 39031 Bruneck, Italy.

Herbert Tilg (H)

Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Medical University of Innsbruck, 6020 Innsbruck, Austria.

Michaela Defrancesco (M)

Department of Psychiatry, Psychotherapy and Psychosomatics, Medical University of Innsbruck, 6020 Innsbruck, Austria.

Josef Marksteiner (J)

Department of Psychiatry and Psychotherapy A, Hall State Hospital, 6060 Hall in Tirol, Austria.

Frank Sinner (F)

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 (C)

HEALTH-Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft mbH, 8010 Graz, Austria.

Thomas R Pieber (TR)

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 (P)

Otto Loewi Research Center (for Vascular Biology, Immunology and Inflammation), Division of Pharmacology, Medical University of Graz (MUG), 8010 Graz, Austria.

Guido Kroemer (G)

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 (D)

Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria.

Luca Scorrano (L)

Veneto Institute of Molecular Medicine, 35129 Padova, Italy; Department of Biology, University of Padova, 35121 Padova, Italy.

Jörn Dengjel (J)

Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland.

Tobias Madl (T)

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 (S)

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 (SJ)

Institute of Biology/Genetics, Freie Universität Berlin, 14195 Berlin, Germany.

Bence Rácz (B)

Department of Anatomy and Histology, University of Veterinary Medicine Budapest, 1078 Budapest, Hungary.

Stefan Kiechl (S)

Department of Neurology, Medical University of Innsbruck, 6020 Innsbruck, Austria; VASCage, Research Centre on Vascular Ageing and Stroke, 6020 Innsbruck, Austria. Electronic address: stefan.kiechl@i-med.ac.at.

Tobias Eisenberg (T)

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. Electronic address: tobias.eisenberg@uni-graz.at.

Frank Madeo (F)

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. Electronic address: frank.madeo@uni-graz.at.

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Classifications MeSH

questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Vieillissement › Dietary spermidine improves cognitive function.
questionsmedicales.fr › Eucaryotes › Animaux › Dietary spermidine improves cognitive function.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines associées à l'autophagie › Protéine-7 associée à l'autophagie › Dietary spermidine improves cognitive function.
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Dietary spermidine improves cognitive function.
questionsmedicales.fr › Phénomènes psychologiques › Processus mentaux › Cognition › Dietary spermidine improves cognitive function.
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Troubles de la cognition › Dysfonctionnement cognitif › Dietary spermidine improves cognitive function.
questionsmedicales.fr › Aliments et boissons › Aliments › Compléments alimentaires › Dietary spermidine improves cognitive function.
questionsmedicales.fr › Eucaryotes › Animaux › Invertébrés › Arthropodes › Insectes › Pterygota › Neoptera › Holometabola › Diptera › Drosophilidae › Drosophila › Drosophila melanogaster › Dietary spermidine improves cognitive function.
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Dietary spermidine improves cognitive function.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Dietary spermidine improves cognitive function.
questionsmedicales.fr › Phénomènes psychologiques › Psychologie appliquée › Apprentissage › Dietary spermidine improves cognitive function.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Dietary spermidine improves cognitive function.
questionsmedicales.fr › Cellules › Structures cellulaires › Fractions subcellulaires › Mitochondries › Dietary spermidine improves cognitive function.
questionsmedicales.fr › Cellules › Neurones › Dietary spermidine improves cognitive function.
questionsmedicales.fr › Métabolisme › Phosphorylation › Phosphorylation oxydative › Dietary spermidine improves cognitive function.
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Phosphotransferases › Phosphotransferases (Alcohol Group Acceptor) › Protein kinases › Dietary spermidine improves cognitive function.
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Dietary spermidine improves cognitive function.
questionsmedicales.fr › Phénomènes psychologiques › Processus mentaux › Mémoire › Mémoire spatiale › Dietary spermidine improves cognitive function.
questionsmedicales.fr › Composés chimiques organiques › Amines › Polyamines › Spermidine › Dietary spermidine improves cognitive function.
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Ligases › Ubiquitin-protein ligase complexes › Ubiquitin-protein ligases › Dietary spermidine improves cognitive function.