草酰乙酸盐补充通过 AMPK/FOXO 依赖途径增加秀丽隐杆线虫的寿命。
Oxaloacetate supplementation increases lifespan in Caenorhabditis elegans through an AMPK/FOXO-dependent pathway.
机构信息
Departments of Pharmacology and Neurosciences, UCSD School of Medicine, University of California-San Diego, La Jolla, CA 92130, USA.
出版信息
Aging Cell. 2009 Dec;8(6):765-8. doi: 10.1111/j.1474-9726.2009.00527.x. Epub 2009 Sep 30.
Abstract
Reduced dietary intake increases lifespan in a wide variety of organisms. It also retards disease progression. We tested whether dietary supplementation of citric acid cycle metabolites could mimic this lifespan effect. We report that oxaloacetate supplementation increased lifespan in Caenorhabditis elegans. The increase was dependent on the transcription factor, FOXO/DAF-16, and the energy sensor, AMP-activated protein kinase, indicating involvement of a pathway that is also required for lifespan extension through dietary restriction. These results demonstrate that supplementation of the citric acid cycle metabolite, oxaloacetate, influences a longevity pathway, and suggest a tractable means of introducing the health-related benefits of dietary restriction.
摘要
减少饮食摄入可以延长多种生物的寿命。它还可以延缓疾病的发展。我们测试了柠檬酸循环代谢物的饮食补充是否可以模拟这种寿命效应。我们报告说，草酰乙酸补充剂可以延长秀丽隐杆线虫的寿命。这种增加依赖于转录因子 FOXO/DAF-16 和能量传感器 AMP 激活蛋白激酶，表明涉及到一条途径，该途径也需要通过饮食限制来延长寿命。这些结果表明，柠檬酸循环代谢物草酰乙酸的补充会影响长寿途径，并为引入饮食限制的健康益处提供了一种可行的方法。
相似文献
1
Oxaloacetate supplementation increases lifespan in Caenorhabditis elegans through an AMPK/FOXO-dependent pathway.草酰乙酸盐补充通过 AMPK/FOXO 依赖途径增加秀丽隐杆线虫的寿命。
Aging Cell. 2009 Dec;8(6):765-8. doi: 10.1111/j.1474-9726.2009.00527.x. Epub 2009 Sep 30.
2
An AMPK-FOXO pathway mediates longevity induced by a novel method of dietary restriction in C. elegans.一条AMPK-FOXO信号通路介导了秀丽隐杆线虫中一种新型饮食限制方法所诱导的寿命延长。
Curr Biol. 2007 Oct 9;17(19):1646-56. doi: 10.1016/j.cub.2007.08.047. Epub 2007 Sep 27.
3
Towards understanding the lifespan extension by reduced insulin signaling: bioinformatics analysis of DAF-16/FOXO direct targets in Caenorhabditis elegans.探索胰岛素信号通路减弱导致寿命延长的机制：秀丽隐杆线虫中DAF-16/FOXO直接靶标的生物信息学分析
Oncotarget. 2016 Apr 12;7(15):19185-92. doi: 10.18632/oncotarget.8313.
4
Different dietary restriction regimens extend lifespan by both independent and overlapping genetic pathways in C. elegans.不同的饮食限制方案通过独立和重叠的遗传途径延长线虫的寿命。
Aging Cell. 2009 Apr;8(2):113-27. doi: 10.1111/j.1474-9726.2009.00459.x. Epub 2009 Feb 23.
5
5'-AMP-Activated Protein Kinase Signaling in Caenorhabditis elegans.秀丽隐杆线虫中的5'-AMP激活蛋白激酶信号传导
Exp Suppl. 2016;107:375-388. doi: 10.1007/978-3-319-43589-3_15.
6
DAF-16/FoxO directly regulates an atypical AMP-activated protein kinase gamma isoform to mediate the effects of insulin/IGF-1 signaling on aging in Caenorhabditis elegans.DAF-16/FoxO直接调控一种非典型的AMP激活蛋白激酶γ亚型，以介导胰岛素/胰岛素样生长因子-1信号通路对秀丽隐杆线虫衰老的影响。
PLoS Genet. 2014 Feb 6;10(2):e1004109. doi: 10.1371/journal.pgen.1004109. eCollection 2014 Feb.
7
Mechanisms of amino acid-mediated lifespan extension in Caenorhabditis elegans.氨基酸介导的秀丽隐杆线虫寿命延长的机制。
BMC Genet. 2015 Feb 3;16(1):8. doi: 10.1186/s12863-015-0167-2.
8
d-Allulose, a stereoisomer of d-fructose, extends Caenorhabditis elegans lifespan through a dietary restriction mechanism: A new candidate dietary restriction mimetic.D-阿洛酮糖，D-果糖的一种立体异构体，通过饮食限制机制延长秀丽隐杆线虫的寿命：一种新的饮食限制模拟物候选物。
Biochem Biophys Res Commun. 2017 Dec 2;493(4):1528-1533. doi: 10.1016/j.bbrc.2017.09.147. Epub 2017 Sep 28.
9
Tart Cherry Increases Lifespan in by Altering Metabolic Signaling Pathways.酸樱桃通过改变代谢信号通路延长 的寿命。
Nutrients. 2020 May 20;12(5):1482. doi: 10.3390/nu12051482.
10
Elucidating the Mechanism of Weissella-dependent Lifespan Extension in Caenorhabditis elegans.阐明魏斯氏菌依赖的秀丽隐杆线虫寿命延长机制。
Sci Rep. 2015 Nov 25;5:17128. doi: 10.1038/srep17128.
引用本文的文献
1
The C. elegans glutamate transporters GLT-4 and GLT-5 regulate protein expression, behavior, and lifespan.秀丽隐杆线虫的谷氨酸转运体GLT-4和GLT-5调节蛋白质表达、行为和寿命。
Neurochem Int. 2025 Jun;186:105966. doi: 10.1016/j.neuint.2025.105966. Epub 2025 Mar 25.
2
Longevity Humans Have Youthful Erythrocyte Function and Metabolic Signatures.长寿人群具有年轻的红细胞功能和代谢特征。
Aging Cell. 2025 May;24(5):e14482. doi: 10.1111/acel.14482. Epub 2025 Feb 9.
3
RESTORE ME: a RCT of oxaloacetate for improving fatigue in patients with myalgic encephalomyelitis/chronic fatigue syndrome.恢复自我：一项关于草酰乙酸改善肌痛性脑脊髓炎/慢性疲劳综合征患者疲劳症状的随机对照试验。
Front Neurol. 2024 Nov 27;15:1483876. doi: 10.3389/fneur.2024.1483876. eCollection 2024.
4
AMPK: The energy sensor at the crossroads of aging and cancer.AMPK：衰老与癌症交叉路口的能量传感器。
Semin Cancer Biol. 2024 Nov;106-107:15-27. doi: 10.1016/j.semcancer.2024.08.002. Epub 2024 Aug 26.
5
Novel Approaches to the Establishment of Local Microenvironment from Resorbable Biomaterials in the Brain In Vitro Models.新型可吸收生物材料在体外脑模型中建立局部微环境的方法。
Int J Mol Sci. 2023 Sep 28;24(19):14709. doi: 10.3390/ijms241914709.
6
Mitochondrial aconitase suppresses immunity by modulating oxaloacetate and the mitochondrial unfolded protein response.线粒体乌头酸酶通过调节草酰乙酸和线粒体未折叠蛋白反应来抑制免疫。
Nat Commun. 2023 Jun 22;14(1):3716. doi: 10.1038/s41467-023-39393-6.
7
A metabolomic signature of decelerated physiological aging in human plasma.人类血浆中生理衰老减速的代谢组学特征。
Geroscience. 2023 Dec;45(6):3147-3164. doi: 10.1007/s11357-023-00827-0. Epub 2023 May 31.
8
A Glutamate Scavenging Protocol Combined with Deanna Protocol in SOD1-G93A Mouse Model of ALS.使用谷氨酸清除方案联合 Deanna 方案治疗 SOD1-G93A 肌萎缩侧索硬化症模型。
Nutrients. 2023 Apr 10;15(8):1821. doi: 10.3390/nu15081821.
9
The metabolite alpha-ketobutyrate extends lifespan by promoting peroxisomal function in C. elegans.代谢产物α-酮戊二酸通过促进秀丽隐杆线虫过氧化物酶体的功能来延长寿命。
Nat Commun. 2023 Jan 16;14(1):240. doi: 10.1038/s41467-023-35899-1.
10
Testing the evidence that lifespan-extending compound interventions are conserved across laboratory animal model species.测试证据表明，延长寿命的化合物干预措施在实验室动物模型物种中是保守的。
Geroscience. 2023 Jun;45(3):1401-1409. doi: 10.1007/s11357-022-00722-0. Epub 2023 Jan 13.
本文引用的文献
1
Optimizing dietary restriction for genetic epistasis analysis and gene discovery in C. elegans.优化用于秀丽隐杆线虫遗传上位性分析和基因发现的饮食限制。
PLoS One. 2009;4(2):e4535. doi: 10.1371/journal.pone.0004535. Epub 2009 Feb 20.
2
Signalling through RHEB-1 mediates intermittent fasting-induced longevity in C. elegans.通过RHEB-1发出的信号介导了秀丽隐杆线虫中间歇禁食诱导的长寿。
Nature. 2009 Feb 5;457(7230):726-30. doi: 10.1038/nature07583. Epub 2008 Dec 14.
3
The malate-aspartate NADH shuttle components are novel metabolic longevity regulators required for calorie restriction-mediated life span extension in yeast.苹果酸-天冬氨酸NADH穿梭系统组件是酵母中热量限制介导的寿命延长所需的新型代谢寿命调节因子。
Genes Dev. 2008 Apr 1;22(7):931-44. doi: 10.1101/gad.1648308.
4
Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress.葡萄糖限制通过诱导线粒体呼吸和增加氧化应激来延长秀丽隐杆线虫的寿命。
Cell Metab. 2007 Oct;6(4):280-93. doi: 10.1016/j.cmet.2007.08.011.
5
An AMPK-FOXO pathway mediates longevity induced by a novel method of dietary restriction in C. elegans.一条AMPK-FOXO信号通路介导了秀丽隐杆线虫中一种新型饮食限制方法所诱导的寿命延长。
Curr Biol. 2007 Oct 9;17(19):1646-56. doi: 10.1016/j.cub.2007.08.047. Epub 2007 Sep 27.
6
Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival.营养敏感型线粒体NAD+水平决定细胞存活。
Cell. 2007 Sep 21;130(6):1095-107. doi: 10.1016/j.cell.2007.07.035.
7
Two neurons mediate diet-restriction-induced longevity in C. elegans.两个神经元介导了秀丽隐杆线虫中饮食限制诱导的长寿。
Nature. 2007 May 31;447(7144):545-9. doi: 10.1038/nature05904.
8
The permeability of mitochondria to oxaloacetate and malate.线粒体对草酰乙酸和苹果酸的通透性。
Biochem J. 1968 May;107(5):659-67. doi: 10.1042/bj1070659.
9
Aging networks in Caenorhabditis elegans: AMP-activated protein kinase (aak-2) links multiple aging and metabolism pathways.秀丽隐杆线虫中的衰老网络：AMP 活化蛋白激酶（aak-2）连接多种衰老和代谢途径。
Aging Cell. 2006 Apr;5(2):119-26. doi: 10.1111/j.1474-9726.2006.00205.x.
10
The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans.AMP 激活的蛋白激酶 AAK-2 将能量水平和胰岛素样信号与秀丽隐杆线虫的寿命联系起来。
Genes Dev. 2004 Dec 15;18(24):3004-9. doi: 10.1101/gad.1255404. Epub 2004 Dec 1.
Zotero 插件