• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

亚精胺对于禁食介导的自噬和长寿是必不可少的。

Spermidine is essential for fasting-mediated autophagy and longevity.

机构信息

Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.

Field of Excellence BioHealth, University of Graz, Graz, Austria.

出版信息

Nat Cell Biol. 2024 Sep;26(9):1571-1584. doi: 10.1038/s41556-024-01468-x. Epub 2024 Aug 8.

DOI:10.1038/s41556-024-01468-x
PMID:39117797
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11392816/
Abstract

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.

摘要

热量限制和间歇性禁食可以延长模型生物的寿命和健康寿命，并改善人类健康。天然多胺亚精胺同样与自噬增强、保护衰老和降低心血管和神经退行性疾病的发病率有关，跨越物种界限。在这里，我们想知道热量限制和禁食的细胞和生理后果是否取决于多胺代谢。我们报告说，在酵母、苍蝇、老鼠和人类志愿者中，禁食或热量限制的不同方案会增加亚精胺的水平。遗传或药理学阻断内源性亚精胺合成会减少酵母、线虫和人类细胞中禁食诱导的自噬。此外，体内干扰多胺途径会消除禁食的延长寿命和健康寿命的作用，以及对心脏的保护和抗关节炎的影响。从机制上讲，亚精胺通过自噬诱导和翻译调节因子 eIF5A 的 hypusination 来介导这些作用。总之，多胺-hypusination 轴作为一种进化保守的代谢控制枢纽，用于调节禁食诱导的自噬增强和长寿。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/d7fd574c4f88/41556_2024_1468_Fig16_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/b158510a83c5/41556_2024_1468_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/f63548289bbb/41556_2024_1468_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/e4dc3af4fb0c/41556_2024_1468_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/c1a0bd234d2a/41556_2024_1468_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/aa76685d6bd3/41556_2024_1468_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/b83ca8490bb7/41556_2024_1468_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/7e021c7bce8a/41556_2024_1468_Fig7_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/97fa1922f93e/41556_2024_1468_Fig8_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/f306c75dfbf2/41556_2024_1468_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/d7139bb61184/41556_2024_1468_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/0c28182e6864/41556_2024_1468_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/098f524ba993/41556_2024_1468_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/7898bd1482ff/41556_2024_1468_Fig13_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/70d3c0e36a7c/41556_2024_1468_Fig14_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/d6a60d466bde/41556_2024_1468_Fig15_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/d7fd574c4f88/41556_2024_1468_Fig16_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/b158510a83c5/41556_2024_1468_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/f63548289bbb/41556_2024_1468_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/e4dc3af4fb0c/41556_2024_1468_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/c1a0bd234d2a/41556_2024_1468_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/aa76685d6bd3/41556_2024_1468_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/b83ca8490bb7/41556_2024_1468_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/7e021c7bce8a/41556_2024_1468_Fig7_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/97fa1922f93e/41556_2024_1468_Fig8_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/f306c75dfbf2/41556_2024_1468_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/d7139bb61184/41556_2024_1468_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/0c28182e6864/41556_2024_1468_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/098f524ba993/41556_2024_1468_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/7898bd1482ff/41556_2024_1468_Fig13_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/70d3c0e36a7c/41556_2024_1468_Fig14_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/d6a60d466bde/41556_2024_1468_Fig15_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e93/11392816/d7fd574c4f88/41556_2024_1468_Fig16_ESM.jpg

相似文献

1
Spermidine is essential for fasting-mediated autophagy and longevity.亚精胺对于禁食介导的自噬和长寿是必不可少的。
Nat Cell Biol. 2024 Sep;26(9):1571-1584. doi: 10.1038/s41556-024-01468-x. Epub 2024 Aug 8.
2
A surge in endogenous spermidine is essential for rapamycin-induced autophagy and longevity.内源性亚精胺的激增对于雷帕霉素诱导的自噬和长寿是必不可少的。
Autophagy. 2024 Dec;20(12):2824-2826. doi: 10.1080/15548627.2024.2396793. Epub 2024 Sep 12.
3
Polyamines Control eIF5A Hypusination, TFEB Translation, and Autophagy to Reverse B Cell Senescence.多胺控制 eIF5A 翻译后修饰、TFEB 翻译和自噬以逆转 B 细胞衰老。
Mol Cell. 2019 Oct 3;76(1):110-125.e9. doi: 10.1016/j.molcel.2019.08.005. Epub 2019 Aug 29.
4
Induction of autophagy by spermidine promotes longevity.亚精胺诱导自噬可促进长寿。
Nat Cell Biol. 2009 Nov;11(11):1305-14. doi: 10.1038/ncb1975. Epub 2009 Oct 4.
5
Can autophagy promote longevity?自噬能促进长寿吗？
Nat Cell Biol. 2010 Sep;12(9):842-6. doi: 10.1038/ncb0910-842.
6
Autophagy mediates pharmacological lifespan extension by spermidine and resveratrol.自噬介导了亚精胺和白藜芦醇对寿命的药理学延长作用。
Aging (Albany NY). 2009 Dec 23;1(12):961-70. doi: 10.18632/aging.100110.
7
eIF5A hypusination, boosted by dietary spermidine, protects from premature brain aging and mitochondrial dysfunction.eIF5A 亚精胺化作用受到膳食精胺的促进，可预防大脑早衰和线粒体功能障碍。
Cell Rep. 2021 Apr 13;35(2):108941. doi: 10.1016/j.celrep.2021.108941.
8
Spermidine-induced hypusination preserves mitochondrial and cognitive function during aging.亚精胺诱导的假尿嘧啶化在衰老过程中维持线粒体和认知功能。
Autophagy. 2021 Aug;17(8):2037-2039. doi: 10.1080/15548627.2021.1933299. Epub 2021 Jun 9.
9
Herpesvirus-induced spermidine synthesis and eIF5A hypusination for viral episomal maintenance.疱疹病毒诱导的精脒合成和 eIF5A 高丝氨酸化以维持病毒的附加体。
Cell Rep. 2022 Aug 16;40(7):111234. doi: 10.1016/j.celrep.2022.111234.
10
The spermidine analogue GC7 (N1-guanyl-1,7-diamineoheptane) induces autophagy through a mechanism not involving the hypusination of eIF5A.亚精胺类似物GC7（N1-胍基-1,7-二氨基庚烷）通过一种不涉及真核翻译起始因子5A（eIF5A）羟腐赖氨酸化的机制诱导自噬。
Amino Acids. 2014 Dec;46(12):2767-76. doi: 10.1007/s00726-014-1821-0. Epub 2014 Sep 14.

引用本文的文献

1
Engineered spermidine-secreting Saccharomyces boulardii ameliorates colitis and colon cancer in mice.工程化分泌亚精胺的布拉酵母菌可改善小鼠的结肠炎和结肠癌。
Sci Rep. 2025 Aug 30;15(1):31959. doi: 10.1038/s41598-025-16736-5.
2
Understanding and improving vaccine efficacy in older adults.了解并提高老年人的疫苗效力。
Nat Aging. 2025 Aug;5(8):1455-1470. doi: 10.1038/s43587-025-00939-6. Epub 2025 Aug 14.
3
Antioxidants and Reactive Oxygen Species: Shaping Human Health and Disease Outcomes.抗氧化剂与活性氧：塑造人类健康与疾病结局

本文引用的文献

1
Hallmarks of cardiovascular ageing.心血管衰老的特征
Nat Rev Cardiol. 2023 Nov;20(11):754-777. doi: 10.1038/s41569-023-00881-3. Epub 2023 May 16.
2
Peripheral modulation of antidepressant targets MAO-B and GABAAR by harmol induces mitohormesis and delays aging in preclinical models.通过哈默诱导的抗抑郁药靶点 MAO-B 和 GABAAR 的外周调节作用，可引发线粒体激素和延缓临床前模型的衰老。
Nat Commun. 2023 May 15;14(1):2779. doi: 10.1038/s41467-023-38410-y.
3
Mechanisms of spermidine-induced autophagy and geroprotection.亚精胺诱导自噬及老年保护作用的机制。
Int J Mol Sci. 2025 Aug 4;26(15):7520. doi: 10.3390/ijms26157520.
4
Protective effects of S-adenosyl methionine on oxidative stress and tissue damage in STZ-induced diabetic rats.S-腺苷甲硫氨酸对链脲佐菌素诱导的糖尿病大鼠氧化应激和组织损伤的保护作用。
Amino Acids. 2025 Jul 31;57(1):38. doi: 10.1007/s00726-025-03471-4.
5
Intermittent fasting and a no-sugar diet for Long COVID symptoms: a randomized crossover trial.间歇性禁食和无糖饮食对新冠长期症状的影响：一项随机交叉试验。
Sci Rep. 2025 Jul 29;15(1):27563. doi: 10.1038/s41598-025-07461-0.
6
Polyamines stimulate the protein synthesis of the translation initiation factor eIF5A2, participating in mRNA decoding, distinct from eIF5A1.多胺刺激翻译起始因子eIF5A2的蛋白质合成，参与mRNA解码，与eIF5A1不同。
J Biol Chem. 2025 Jul 4;301(8):110453. doi: 10.1016/j.jbc.2025.110453.
7
An overview of contemporary theories of ageing.当代衰老理论综述。
Nat Cell Biol. 2025 Jul 1. doi: 10.1038/s41556-025-01698-7.
8
Metabolites as agents and targets for cancer immunotherapy.代谢产物作为癌症免疫治疗的作用物和靶点。
Nat Rev Drug Discov. 2025 Jun 26. doi: 10.1038/s41573-025-01227-z.
9
An insulin-sensitive Drosophila insulin-like receptor mutant remodels methionine metabolism to extend lifespan.一个对胰岛素敏感的果蝇胰岛素样受体突变体重塑甲硫氨酸代谢以延长寿命。
PLoS Genet. 2025 Jun 16;21(6):e1011640. doi: 10.1371/journal.pgen.1011640. eCollection 2025 Jun.
10
Enhanced γ-aminobutyric acid levels promote degeneration of silk glands following spermidine supplementation in Bombyx mori.在补充亚精胺后，家蚕体内γ-氨基丁酸水平升高会促进丝腺退化。
Amino Acids. 2025 Jun 13;57(1):33. doi: 10.1007/s00726-025-03462-5.
Nat Aging. 2022 Dec;2(12):1112-1129. doi: 10.1038/s43587-022-00322-9. Epub 2022 Dec 22.
4
Spermidine activates mitochondrial trifunctional protein and improves antitumor immunity in mice.亚精胺激活线粒体三功能蛋白并改善小鼠的抗肿瘤免疫。
Science. 2022 Oct 28;378(6618):eabj3510. doi: 10.1126/science.abj3510.
5
Fine-Tuning Cardiac Insulin-Like Growth Factor 1 Receptor Signaling to Promote Health and Longevity.精细调节心脏胰岛素样生长因子 1 受体信号以促进健康和长寿。
Circulation. 2022 Jun 21;145(25):1853-1866. doi: 10.1161/CIRCULATIONAHA.122.059863. Epub 2022 May 26.
6
Circadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice.限时进食起始时间与生物钟同步可延长雄性 C57BL/6J 小鼠寿命。
Science. 2022 Jun 10;376(6598):1192-1202. doi: 10.1126/science.abk0297. Epub 2022 May 5.
7
Polyamines in cancer: integrating organismal metabolism and antitumour immunity.多胺在癌症中的作用：整合机体代谢与抗肿瘤免疫。
Nat Rev Cancer. 2022 Aug;22(8):467-480. doi: 10.1038/s41568-022-00473-2. Epub 2022 Apr 27.
8
Intermittent and periodic fasting, longevity and disease.间歇性禁食和周期性禁食、长寿与疾病。
Nat Aging. 2021 Jan;1(1):47-59. doi: 10.1038/s43587-020-00013-3. Epub 2021 Jan 14.
9
Mitochondrial protein import determines lifespan through metabolic reprogramming and de novo serine biosynthesis.线粒体蛋白的输入通过代谢重编程和从头合成丝氨酸来决定寿命。
Nat Commun. 2022 Feb 3;13(1):651. doi: 10.1038/s41467-022-28272-1.
10
Autophagy in healthy aging and disease.自噬在健康衰老和疾病中的作用。
Nat Aging. 2021 Aug;1(8):634-650. doi: 10.1038/s43587-021-00098-4. Epub 2021 Aug 12.