通过设计延缓衰老：NAD及sirtuin激活化合物的兴起
Slowing ageing by design: the rise of NAD and sirtuin-activating compounds.
作者信息
Bonkowski Michael S, Sinclair David A
机构信息
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Department of Pharmacology, The University of New South Wales, Sydney 2052, Australia.
出版信息
Nat Rev Mol Cell Biol. 2016 Nov;17(11):679-690. doi: 10.1038/nrm.2016.93. Epub 2016 Aug 24.
Abstract
The sirtuins (SIRT1-7) are a family of nicotinamide adenine dinucleotide (NAD)-dependent deacylases with remarkable abilities to prevent diseases and even reverse aspects of ageing. Mice engineered to express additional copies of SIRT1 or SIRT6, or treated with sirtuin-activating compounds (STACs) such as resveratrol and SRT2104 or with NAD precursors, have improved organ function, physical endurance, disease resistance and longevity. Trials in non-human primates and in humans have indicated that STACs may be safe and effective in treating inflammatory and metabolic disorders, among others. These advances have demonstrated that it is possible to rationally design molecules that can alleviate multiple diseases and possibly extend lifespan in humans.
摘要
沉默调节蛋白（SIRT1 - 7）是一类依赖烟酰胺腺嘌呤二核苷酸（NAD）的去酰基酶家族，具有预防疾病甚至逆转衰老某些方面的显著能力。经过基因工程改造以表达额外拷贝的SIRT1或SIRT6的小鼠，或用白藜芦醇和SRT2104等沉默调节蛋白激活化合物（STACs）或NAD前体处理的小鼠，其器官功能、身体耐力、抗病能力和寿命都有所改善。在非人类灵长类动物和人类中进行的试验表明，STACs在治疗炎症和代谢紊乱等疾病方面可能是安全有效的。这些进展表明，合理设计能够缓解多种疾病并可能延长人类寿命的分子是有可能的。
相似文献
1
Slowing ageing by design: the rise of NAD and sirtuin-activating compounds.通过设计延缓衰老：NAD及sirtuin激活化合物的兴起
Nat Rev Mol Cell Biol. 2016 Nov;17(11):679-690. doi: 10.1038/nrm.2016.93. Epub 2016 Aug 24.
2
Small-molecule allosteric activators of sirtuins.沉默调节蛋白的小分子变构激活剂。
Annu Rev Pharmacol Toxicol. 2014;54:363-80. doi: 10.1146/annurev-pharmtox-010611-134657. Epub 2013 Oct 16.
3
Sirtuin activators and inhibitors.Sirtuin 激活剂和抑制剂。
Biofactors. 2012 Sep-Oct;38(5):349-59. doi: 10.1002/biof.1032. Epub 2012 Jun 25.
4
Sirtuins and NAD in the Development and Treatment of Metabolic and Cardiovascular Diseases.沉默调节蛋白与烟酰胺腺嘌呤二核苷酸在代谢和心血管疾病的发生发展及治疗中的作用
Circ Res. 2018 Sep 14;123(7):868-885. doi: 10.1161/CIRCRESAHA.118.312498.
5
Resveratrol and novel potent activators of SIRT1: effects on aging and age-related diseases.白藜芦醇与新型高效SIRT1激活剂：对衰老及衰老相关疾病的影响
Nutr Rev. 2008 Oct;66(10):591-6. doi: 10.1111/j.1753-4887.2008.00109.x.
6
Sirtuin activators.沉默调节蛋白激活剂
Expert Opin Ther Pat. 2009 Apr;19(4):403-14. doi: 10.1517/13543770902762893.
7
Small molecule SIRT1 activators for the treatment of aging and age-related diseases.小分子 SIRT1 激活剂治疗衰老和与年龄相关的疾病。
Trends Pharmacol Sci. 2014 Mar;35(3):146-54. doi: 10.1016/j.tips.2013.12.004. Epub 2014 Jan 16.
8
9
10
Sirtuins: novel targets for metabolic disease.沉默调节蛋白：代谢性疾病的新型靶点。
Curr Opin Investig Drugs. 2008 Apr;9(4):371-8.
引用本文的文献
1
Rhapontigenin attenuates neurodegeneration in a parkinson's disease model by downregulating mtDNA-cGAS-STING-NF-κB-mediated neuroinflammation via PINK1/DRP1-dependent microglial mitophagy.rhapontigenin通过PINK1/DRP1依赖性小胶质细胞线粒体自噬下调mtDNA-cGAS-STING-NF-κB介导的神经炎症，从而减轻帕金森病模型中的神经退行性变。
Cell Mol Life Sci. 2025 Sep 6;82(1):337. doi: 10.1007/s00018-025-05873-9.
2
REV-ERBα regulates brain NAD levels and tauopathy via an NFIL3-CD38 axis.REV-ERBα通过NFIL3-CD38轴调节大脑中的烟酰胺腺嘌呤二核苷酸水平和tau蛋白病。
Nat Aging. 2025 Sep 1. doi: 10.1038/s43587-025-00950-x.
3
Roles of SIRT3 in aging and aging-related diseases.SIRT3在衰老及衰老相关疾病中的作用。
Int J Biol Sci. 2025 Jul 28;21(11):5135-5163. doi: 10.7150/ijbs.115518. eCollection 2025.
4
Sirtuins as mediators and targets of arsenic toxicity: unraveling signaling pathway crosstalk.沉默调节蛋白作为砷毒性的介质和靶点：揭示信号通路间的相互作用
Arch Toxicol. 2025 Aug 22. doi: 10.1007/s00204-025-04158-1.
5
Sirtuins mediate the reduction of age-related oxidative damage in the cochlea under a cocoa-rich diet.在富含可可的饮食条件下，沉默调节蛋白介导耳蜗中与年龄相关的氧化损伤的减少。
Geroscience. 2025 Aug 20. doi: 10.1007/s11357-025-01847-8.
6
Immunosenescence: signaling pathways, diseases and therapeutic targets.免疫衰老：信号通路、疾病与治疗靶点。
Signal Transduct Target Ther. 2025 Aug 6;10(1):250. doi: 10.1038/s41392-025-02371-z.
7
Recent progress in stem cell and immune cell-based interventions for aging and age-related disorders.基于干细胞和免疫细胞的衰老及年龄相关疾病干预措施的最新进展。
Front Aging. 2025 Jul 22;6:1638168. doi: 10.3389/fragi.2025.1638168. eCollection 2025.
8
Role of mitochondria in physiological activities, diseases, and therapy.线粒体在生理活动、疾病及治疗中的作用。
Mol Biomed. 2025 Jun 19;6(1):42. doi: 10.1186/s43556-025-00284-5.
9
Nobiletin potentially reduce lipid accumulation by up-regulating the SIRT1-AMPK signaling pathway in HepG2 hepatocarcinoma cells.诺米林可能通过上调HepG2肝癌细胞中的SIRT1-AMPK信号通路来减少脂质积累。
Mol Biol Rep. 2025 May 25;52(1):503. doi: 10.1007/s11033-025-10587-z.
10
Impacts of systemic milieu on cerebrovascular and brain aging: insights from heterochronic parabiosis, blood exchange, and plasma transfer experiments.全身环境对脑血管和脑衰老的影响：来自异时联体共生、血液交换和血浆转移实验的见解
Geroscience. 2025 May 23. doi: 10.1007/s11357-025-01657-y.
本文引用的文献
1
CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism.CD38通过一种依赖SIRT3的机制决定与年龄相关的NAD下降和线粒体功能障碍。
Cell Metab. 2016 Jun 14;23(6):1127-1139. doi: 10.1016/j.cmet.2016.05.006.
2
Sirtuin functions and modulation: from chemistry to the clinic.沉默调节蛋白的功能与调控：从化学到临床
Clin Epigenetics. 2016 May 25;8:61. doi: 10.1186/s13148-016-0224-3. eCollection 2016.
3
SIRT6 Suppresses Pancreatic Cancer through Control of Lin28b.SIRT6 通过调控 Lin28b 抑制胰腺癌。
Cell. 2016 Jun 2;165(6):1401-1415. doi: 10.1016/j.cell.2016.04.033. Epub 2016 May 12.
4
NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice.NAD⁺ 补充可改善线粒体和干细胞功能，并延长小鼠寿命。
Science. 2016 Jun 17;352(6292):1436-43. doi: 10.1126/science.aaf2693. Epub 2016 Apr 28.
5
A Randomized, Placebo-Controlled Study of SRT2104, a SIRT1 Activator, in Patients with Moderate to Severe Psoriasis.一项关于SIRT1激活剂SRT2104治疗中重度银屑病患者的随机、安慰剂对照研究。
PLoS One. 2015 Nov 10;10(11):e0142081. doi: 10.1371/journal.pone.0142081. eCollection 2015.
6
Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart.心脏缺乏转铁蛋白受体的小鼠中的致死性心肌病
Cell Rep. 2015 Oct 20;13(3):533-545. doi: 10.1016/j.celrep.2015.09.023. Epub 2015 Oct 8.
7
The multifaceted functions of sirtuins in cancer.Sirtuins 在癌症中的多方面功能。
Nat Rev Cancer. 2015 Oct;15(10):608-24. doi: 10.1038/nrc3985. Epub 2015 Sep 18.
8
A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease.一项关于白藜芦醇治疗阿尔茨海默病的随机、双盲、安慰剂对照试验。
Neurology. 2015 Oct 20;85(16):1383-91. doi: 10.1212/WNL.0000000000002035. Epub 2015 Sep 11.
9
Nicotinamide N-methyltransferase regulates hepatic nutrient metabolism through Sirt1 protein stabilization.烟酰胺N-甲基转移酶通过稳定Sirt1蛋白来调节肝脏营养代谢。
Nat Med. 2015 Aug;21(8):887-94. doi: 10.1038/nm.3882. Epub 2015 Jul 13.
10
Crystallographic structure of a small molecule SIRT1 activator-enzyme complex.小分子 SIRT1 激活剂-酶复合物的晶体结构。
Nat Commun. 2015 Jul 2;6:7645. doi: 10.1038/ncomms8645.
Zotero 插件