Schroeder 2021 Cell Rep

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Schroeder S, Hofer SJ, Zimmermann A, Pechlaner R, Dammbrueck C, Pendl T, Marcello GM, Pogatschnigg V, Bergmann M, Mueller M, Gschiel V, Ristic S, Tadic J, Iwata K, Richter G, Farzi A, Uecal M, Schaefer U, Poglitsch M, Royer P, Mekis R, Agreiter M, Toelle RC, Sotonyi P, Willeit J, Mairhofer B, Niederkofler H, Pallhuber I, Rungger G, Tilg H, Defrancesco M, Marksteiner J, Sinner F, Magnes C, Pieber TR, Holzer P, Kroemer G, Carmona-Gutierrez D, Scorrano L, Dengjel J, Madl T, Sedej S, Sigrist SJ, Racz B, Kiechl S, Eisenberg T, Madeo F (2021) Dietary spermidine improves cognitive function. Cell Rep 35:108985.

» PMID: 33852843 Open Access

Schroeder Sabrina, Hofer Sebastian J, Zimmermann Andreas, Pechlaner Raimund, Dammbrueck Christopher, Pendl Tobias, Marcello G Mark, Pogatschnigg Viktoria, Bergmann Martina, Mueller Melanie, Gschiel Verena, Ristic Selena, Tadic Jelena, Iwata Keiko, Richter Gesa, Farzi Aitak, Uecal Muammer, Schaefer Ute, Poglitsch Michael, Royer Philipp, Mekis Ronald, Agreiter Marlene, Toelle Regine C, Sotonyi Peter, 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 Joern, Madl Tobias, Sedej Simon, Sigrist Stephan J, Racz Bence, Kiechl Stefan, Eisenberg Tobias, Madeo Frank (2021) Cell Rep

Abstract: 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.

Keywords: Pink1, Aging, Autophagy, Cognitive function, Dietary spermidine, Memory, Mitochondria, Mitophagy Bioblast editor: Reiswig R


Labels: MiParea: Respiration, Exercise physiology;nutrition;life style, Pharmacology;toxicology  Pathology: Aging;senescence 

Organism: Mouse, Drosophila  Tissue;cell: Nervous system  Preparation: Homogenate 


Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, NS, ROX 


2021-07