Dietary spermidine improves cognitive function

• DOI: 10.1016/j.celrep.2021.108985
• Publication Date: 2021-04-15T14:27:35Z
• Authors: Sabrina Schroeder; Sebastian J. Hofer; Andreas Zimmermann; Raimund Pechlaner; Christopher Dammb...; Tobias Pendl; G. Mark Marcello; Viktoria Pogatsch...; 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-Gut...; Luca Scorrano; Jörn Dengjel; Tobias Madl; Simon Sedej; Stephan J. Sigrist; Bence Rácz; Stefan Kiechl; Tobias Eisenberg; Frank Madeo
• Keywords: Polyamine; Cognitive Decline

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 lifespan-extending effects dietary spermidine, natural autophagy-promoting polyamine. Here, we show that spermidine passes blood-brain barrier in mice increases hippocampal eIF5A hypusination mitochondrial function. Spermidine feeding aged affects behavior homecage environment tasks, improves spatial learning, respiratory competence. In Drosophila aging model, boosts capacity, an effect requires autophagy regulator Atg7 mitophagy mediators Parkin Pink1. Neuron-specific Pink1 knockdown abolishes spermidine-induced improvement olfactory associative learning. This suggests maintenance autophagic function essential for enhanced cognition by feeding. Finally, large-scale prospective data linking higher intake with reduced risk impairment humans.