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 RoyerRonald 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

    Research output: Contribution to journalArticlepeer-review

    115 Citations (Scopus)

    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.

    Original languageEnglish
    Article number108985
    JournalCell Reports
    Volume35
    Issue number2
    DOIs
    Publication statusPublished - 13 Apr 2021

    Keywords

    • Pink1
    • aging
    • autophagy
    • cognitive function
    • dietary spermidine
    • memory
    • mitochondria
    • mitophagy

    Cite this