Dietary spermidine improves cognitive function

被引：139

作者：

Schroeder, Sabrina ^{[1
,2
]}

Hofer, Sebastian J. ^{[1
,2
,3
]}

Zimmermann, Andreas ^{[1
,2
]}

Pechlaner, Raimund ^{[4
]}

Dammbrueck, Christopher ^{[1
]}

Pendl, Tobias ^{[1
]}

Marcello, G. Mark ^{[5
]}

Pogatschnigg, Viktoria ^{[1
]}

Bergmann, Martina ^{[1
]}

Mueller, Melanie ^{[1
]}

Gschiel, Verena ^{[1
]}

Ristic, Selena ^{[1
]}

Tadic, Jelena ^{[1
,3
]}

Iwata, Keiko ^{[6
,7
,27
]}

Richter, Gesa ^{[8
]}

Farzi, Aitak ^{[9
]}

Uecal, Muammer ^{[10
]}

Schaefer, Ute ^{[10
]}

Poglitsch, Michael ^{[1
]}

Royer, Philipp ^{[1
]}

Mekis, Ronald ^{[1
]}

Agreiter, Marlene ^{[1
]}

Toelle, Regine C. ^{[11
]}

Sotonyi, Peter ^{[5
]}

Willeit, Johann ^{[4
]}

Mairhofer, Barbara ^{[12
]}

Niederkofler, Helga ^{[12
]}

Pallhuber, Irmgard ^{[12
]}

Rungger, Gregorio ^{[13
]}

Tilg, Herbert ^{[14
]}

Defrancesco, Michaela ^{[15
]}

Marksteiner, Josef ^{[16
]}

Sinner, Frank ^{[17
,18
]}

Magnes, Christoph ^{[17
]}

Pieber, Thomas R. ^{[2
,17
,18
]}

Holzer, Peter ^{[9
]}

Kroemer, Guido ^{[19
,20
,21
,22
]}

Carmona-Gutierrez, Didac ^{[1
]}

Scorrano, Luca ^{[6
,27
]}

Dengjel, Joem ^{[11
]}

Madl, Tobias ^{[2
,8
]}

Sedej, Simon ^{[2
,23
,24
]}

Sigrist, Stephan J. ^{[25
]}

Racz, Bence ^{[5
]}

Kiechl, Stefan ^{[4
,26
]}

Eisenberg, Tobias ^{[1
,2
,3
]}

Madeo, Frank ^{[1
,2
,3
]}

机构：

[1] Karl Franzens Univ Graz, Inst Mol Biosci, NAWI Graz, A-8010 Graz, Austria

[2] Karl Franzens Univ Graz, BioTechMed Graz, A-8010 Graz, Austria

[3] Karl Franzens Univ Graz, Field Excellence BioHlth, A-8010 Graz, Austria

[4] Med Univ Innsbruck, Dept Neurol, A-6020 Innsbruck, Austria

[5] Univ Vet Med Budapest, Dept Anat & Histol, H-1078 Budapest, Hungary

[6] Veneto Inst Mol Med, I-35129 Padua, Italy

[7] Univ Fukui, Res Ctr Child Mental Dev, Fukui 9101193, Japan

[8] Metab & Aging Mol Biol & Biochem Med Univ Graz, Gottfried Schatz Res Ctr Cell Signaling, A-8010 Graz, Austria

[9] Med Univ Graz Mug, Otto Loewi Res Ctr Vasc Biol Immunol & Inflammat, Div Pharmacol, A-8010 Graz, Austria

[10] Med Univ Graz, Dept Neurosurg, RU Expt Neurotraumatol, A-8036 Graz, Austria

[11] Univ Fribourg, Dept Biol, Chemin Musee 10, CH-1700 Fribourg, Switzerland

[12] Bruneck Hosp, Dept Psychiat, I-39031 Brunico, Italy

[13] Bruneck Hosp, Dept Neurol, I-39031 Brunico, Italy

[14] Med Univ Innsbruck, Dept Internal Med 1 Gastroenterol Hepatol Endocri, A-6020 Innsbruck, Austria

[15] Med Univ Innsbruck, Dept Psychiat Psychotherapy & Psychosomat, A-6020 Innsbruck, Austria

[16] Hall State Hosp, Dept Psychiat & Psychotherapy A, A-6060 Hall In Tirol, Austria

[17] Joanneum Res Forschungsgesell MbH, Inst Biomed & Hlth Sci, HEALTH, A-8010 Graz, Austria

[18] Med Univ Graz, Dept Internal Med, Div Endocrinol & Diabetol, A-8036 Graz, Austria

[19] Univ Paris 05, Univ Paris Diderot, Univ Sorbonne Paris Cite,INSERM U1138, Equipe Labellisee Ligue Canc,Ctr Rech Cordeliers, F-75006 Paris, France

[20] Inst Gustave Roussy, Metabol & Cell Biol Platforms, F-94805 Villejuif, France

[21] Chinese Acad Sci, Suzhou Inst Syst Biol, Suzhou 215123, Peoples R China

[22] Karolinska Univ Hosp, Dept Womens & Childrens Hlth, S-17177 Stockholm, Sweden

[23] Med Univ Graz, Dept Cardiol, A-8036 Graz, Austria

[24] Univ Maribor, Fac Med, Maribor 2000, Slovenia

[25] Free Univ Berlin, Inst Biol Genet, D-14195 Berlin, Germany

[26] Res Ctr Vasc Ageing & Stroke, VASCage, A-6020 Innsbruck, Austria

[27] Univ Padua, Dept Biol, I-35121 Padua, Italy

来源：

CELL REPORTS | 2021年 / 35卷 / 02期

基金：

奥地利科学基金会;

关键词：

ALZHEIMERS-DISEASE; MEMORY IMPAIRMENT; BINDING PROTEIN; GLYCEMIC INDEX; AUTOPHAGY; RISK; AGE; MITOPHAGY; STRESS; NEURODEGENERATION;

D O I：

10.1016/j.celrep.2021.108985

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：24

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