精胺对空腹介导的自噬和长寿至关重要

IF 17.3 1区 生物学 Q1 CELL BIOLOGY Nature Cell Biology Pub Date : 2024-08-08 DOI:10.1038/s41556-024-01468-x
Sebastian J. Hofer, Ioanna Daskalaki, Martina Bergmann, Jasna Friščić, Andreas Zimmermann, Melanie I. Mueller, Mahmoud Abdellatif, Raffaele Nicastro, Sarah Masser, Sylvère Durand, Alexander Nartey, Mara Waltenstorfer, Sarah Enzenhofer, Isabella Faimann, Verena Gschiel, Thomas Bajaj, Christine Niemeyer, Ilias Gkikas, Lukas Pein, Giulia Cerrato, Hui Pan, YongTian Liang, Jelena Tadic, Andrea Jerkovic, Fanny Aprahamian, Christine E. Robbins, Nitharsshini Nirmalathasan, Hansjörg Habisch, Elisabeth Annerer, Frederik Dethloff, Michael Stumpe, Franziska Grundler, Françoise Wilhelmi de Toledo, Daniel E. Heinz, Daniela A. Koppold, Anika Rajput Khokhar, Andreas Michalsen, Norbert J. Tripolt, Harald Sourij, Thomas R. Pieber, Rafael de Cabo, Mark A. McCormick, Christoph Magnes, Oliver Kepp, Joern Dengjel, Stephan J. Sigrist, Nils C. Gassen, Simon Sedej, Tobias Madl, Claudio De Virgilio, Ulrich Stelzl, Markus H. Hoffmann, Tobias Eisenberg, Nektarios Tavernarakis, Guido Kroemer, Frank Madeo
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引用次数: 0

摘要

限制热量摄入和间歇性禁食可以延长模式生物的寿命和健康期限,改善人类健康。天然多胺亚精胺同样与自噬增强、老年保护以及降低心血管和神经退行性疾病的发病率有关。在这里,我们想知道热量限制和禁食对细胞和生理的影响是否取决于多胺代谢。我们发现,在酵母、苍蝇、小鼠和人类志愿者体内,不同的禁食或热量限制方案会导致亚精胺水平升高。通过基因或药物阻断内源性亚精胺的合成可减少酵母、线虫和人类细胞中禁食诱导的自噬。此外,在体内扰乱多胺通路会减弱禁食对延长寿命和健康寿命的影响,以及对心脏和抗关节炎的保护作用。从机理上讲,亚精胺通过诱导自噬和降低翻译调节因子eIF5A的作用来介导这些效应。总之,多胺-羟化轴是一个系统发育保守的代谢控制中枢,可用于禁食介导的自噬增强和长寿。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Spermidine is essential for fasting-mediated autophagy and longevity
Caloric restriction and intermittent fasting prolong the lifespan and healthspan of model organisms and improve human health. The natural polyamine spermidine has been similarly linked to autophagy enhancement, geroprotection and reduced incidence of cardiovascular and neurodegenerative diseases across species borders. Here, we asked whether the cellular and physiological consequences of caloric restriction and fasting depend on polyamine metabolism. We report that spermidine levels increased upon distinct regimens of fasting or caloric restriction in yeast, flies, mice and human volunteers. Genetic or pharmacological blockade of endogenous spermidine synthesis reduced fasting-induced autophagy in yeast, nematodes and human cells. Furthermore, perturbing the polyamine pathway in vivo abrogated the lifespan- and healthspan-extending effects, as well as the cardioprotective and anti-arthritic consequences of fasting. Mechanistically, spermidine mediated these effects via autophagy induction and hypusination of the translation regulator eIF5A. In summary, the polyamine–hypusination axis emerges as a phylogenetically conserved metabolic control hub for fasting-mediated autophagy enhancement and longevity. Hofer et al. show that fasting promotes the synthesis of spermidine, which stimulates eIF5A hypusination to induce autophagy and increase lifespan in various species in a conserved manner.
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来源期刊
Nature Cell Biology
Nature Cell Biology 生物-细胞生物学
CiteScore
28.40
自引率
0.90%
发文量
219
审稿时长
3 months
期刊介绍: Nature Cell Biology, a prestigious journal, upholds a commitment to publishing papers of the highest quality across all areas of cell biology, with a particular focus on elucidating mechanisms underlying fundamental cell biological processes. The journal's broad scope encompasses various areas of interest, including but not limited to: -Autophagy -Cancer biology -Cell adhesion and migration -Cell cycle and growth -Cell death -Chromatin and epigenetics -Cytoskeletal dynamics -Developmental biology -DNA replication and repair -Mechanisms of human disease -Mechanobiology -Membrane traffic and dynamics -Metabolism -Nuclear organization and dynamics -Organelle biology -Proteolysis and quality control -RNA biology -Signal transduction -Stem cell biology
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