Institute for Biology/Genetics, Freie Universität Berlin, Berlin 14195, Germany; NeuroCure Cluster of Excellence, Charité Universitätmedizin Berlin, Berlin 10117, Germany.
Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., Dortmund 44139, Germany.
Cell Rep. 2021 Apr 13;35(2):108941. doi: 10.1016/j.celrep.2021.108941.
Mitochondrial function declines during brain aging and is suspected to play a key role in age-induced cognitive decline and neurodegeneration. Supplementing levels of spermidine, a body-endogenous metabolite, has been shown to promote mitochondrial respiration and delay aspects of brain aging. Spermidine serves as the amino-butyl group donor for the synthesis of hypusine (N-[4-amino-2-hydroxybutyl]-lysine) at a specific lysine residue of the eukaryotic translation initiation factor 5A (eIF5A). Here, we show that in the Drosophila brain, hypusinated eIF5A levels decline with age but can be boosted by dietary spermidine. Several genetic regimes of attenuating eIF5A hypusination all similarly affect brain mitochondrial respiration resembling age-typical mitochondrial decay and also provoke a premature aging of locomotion and memory formation in adult Drosophilae. eIF5A hypusination, conserved through all eukaryotes as an obviously critical effector of spermidine, might thus be an important diagnostic and therapeutic avenue in aspects of brain aging provoked by mitochondrial decline.
随着大脑衰老，线粒体功能下降，被怀疑在年龄相关认知能力下降和神经退行性变中发挥关键作用。补充亚精胺，一种内源性代谢物，可以促进线粒体呼吸，延缓大脑衰老的某些方面。亚精胺作为氨基丁基供体，用于在真核翻译起始因子 5A (eIF5A) 的特定赖氨酸残基上合成hypusine (N-[4-氨基-2-羟基丁基]-赖氨酸)。在这里，我们发现在果蝇大脑中，hypusinated eIF5A 水平随年龄增长而下降，但可以通过饮食中的亚精胺来提高。几种削弱 eIF5A hypusination 的遗传方法都类似地影响大脑线粒体呼吸，类似于典型的年龄相关线粒体衰减，也会引发成年果蝇运动和记忆形成的过早衰老。eIF5A hypusination 通过所有真核生物保守，作为亚精胺的一个明显关键效应物，因此可能是由线粒体衰退引起的大脑衰老的一个重要诊断和治疗途径。
