Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria; BioTechMed-Graz, 8010 Graz, Austria.
Institute of Molecular Biosciences, NAWI Graz, University of Graz, 8010 Graz, Austria; BioTechMed-Graz, 8010 Graz, Austria; Field of Excellence BioHealth, University of Graz, 8010 Graz, Austria.
Cell Rep. 2021 Apr 13;35(2):108985. doi: 10.1016/j.celrep.2021.108985.
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.
认知表现下降是大脑衰老的标志，但潜在的机制和潜在的治疗途径仍知之甚少。最近的研究揭示了饮食亚精胺的健康保护和延长寿命的作用，亚精胺是一种天然的自噬促进多胺。在这里，我们表明饮食亚精胺可以穿过血脑屏障进入小鼠体内，并增加海马 eIF5A 过度甲基化和线粒体功能。在老年小鼠中进行亚精胺喂养会影响其在家庭环境任务中的行为，改善空间学习能力，并增加海马的呼吸能力。在果蝇衰老模型中，亚精胺可提高线粒体呼吸能力，这种作用需要自噬调节剂 Atg7 和线粒体自噬介质 Parkin 和 Pink1。神经元特异性 Pink1 敲低可消除亚精胺诱导的嗅觉联想学习的改善。这表明，维持线粒体和自噬功能对于亚精胺喂养增强认知至关重要。最后，我们展示了大规模前瞻性数据，表明较高的饮食亚精胺摄入量与人类认知障碍风险降低相关。
