Dietary spermidine improves cognitive function
Publication from Health
Bioanalytik und Metabolomics
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
Cell Reports , 4/2021
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.