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Caloric restriction, sirtuins, and cardiovascular diseases

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中华医学杂志(英文版) 2024年第8期137卷 2024 Mar 25页

作者： Wei Ziyu Yang Bo Wang Huiyu Lv Shuangjie Chen Houzao Liu Depei State Key Laboratory of Common Mechanism Research for Major Diseases Department of Biochemistry and Molecular Biology Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100005 China

Caloric restriction (CR) is a well-established dietary intervention known to extend healthy lifespan and exert positive effects on aging-related diseases, including cardiovascular conditions. sirtuins, a family of nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases, have emerged as key regulators of cellular metabolism, stress responses, and the aging process, serving as energy status sensors in response to CR. However, the mechanism through which CR regulates Sirtuin function to ameliorate cardiovascular disease remains unclear. This review not only provided an overview of recent research investigating the interplay between sirtuins and CR, specifically focusing on their potential implications for cardiovascular health, but also provided a comprehensive summary of the benefits of CR for the cardiovascular system mediated directly via sirtuins. CR has also been shown to have considerable impact on specific metabolic organs, leading to the production of small molecules that enter systemic circulation and subsequently regulate Sirtuin activity within the cardiovascular system. The direct and indirect effects of CR offer a potential mechanism for Sirtuin modulation and subsequent cardiovascular protection. Understanding the interplay between CR and sirtuins will provide new insights for the development of interventions to prevent and treat cardiovascular diseases.

关键词： Caloric restriction sirtuins Cardiovascular diseases Healthy lifestyle Dietary

sirtuins家族和线粒体未折叠蛋白反应在疾病中的研究进展

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安徽医科大学学报 2024年第3期59卷 559-562页

作者：徐常玮(综述) 张涓(综述) 申亮亮(综述) 吴元明(审校) 张静(审校) 延安大学医学院医学研究实验中心延安716099 空军军医大学生物化学与分子生物学实验室西安710038 陕西省临床遗传学重点实验室西安710032

线粒体未折叠蛋白反应(UPRmt)是一种适应性细胞内应激机制,通过促进编码线粒体伴侣蛋白和蛋白酶的基因转录来响应应激信号。随着研究的深入,UPRmt在疾病中的作用机制已逐渐明确。沉默信息调节因子(sirtuins)是一类进化上高度保守的NAD+... 详细信息

线粒体未折叠蛋白反应(UPRmt)是一种适应性细胞内应激机制,通过促进编码线粒体伴侣蛋白和蛋白酶的基因转录来响应应激信号。随着研究的深入,UPRmt在疾病中的作用机制已逐渐明确。沉默信息调节因子(sirtuins)是一类进化上高度保守的NAD+依赖性组蛋白去酰基酶,是多种生物过程中的关键信号通路。近年来sirtuins在衰老和代谢中的多种调节功能相继报道,也有研究明确了UPRmt和sirtuins家族之间存在着重要联系。该文总结了sirtuins与UPRmt的最新研究成果,并归纳了两者在衰老、肿瘤以及代谢性疾病中的作用机制,阐明了sirtuins与UPRmt在疾病中的研究进展。

关键词： sirtuins 线粒体未折叠蛋白反应衰老肿瘤线粒体代谢性疾病

沉默信息调节因子sirtuins在牙周炎中的作用

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中国组织工程研究 2024年第11期28卷 1737-1742页

作者：孙金熠王勤英李英孟茂花陈河林曾筱舒佳玉李文杰罗云彩董强贵州医科大学口腔医学院/贵州医科大学附属口腔医院贵州省贵阳市550004

背景:牙周炎是以牙菌斑生物膜为主要致病物质的炎症性、破坏性疾病,发生于牙龈、牙周膜、牙槽骨和牙骨质。细菌复合体的抗原及其分泌的毒素、酶等直接导致牙周组织的破坏,并引发宿主的免疫反应,使机体组织受到间接损害。沉默信息调节因... 详细信息

背景:牙周炎是以牙菌斑生物膜为主要致病物质的炎症性、破坏性疾病,发生于牙龈、牙周膜、牙槽骨和牙骨质。细菌复合体的抗原及其分泌的毒素、酶等直接导致牙周组织的破坏,并引发宿主的免疫反应,使机体组织受到间接损害。沉默信息调节因子(sirtuins,SIRTs)在抗衰老、抗氧化应激、调节炎症、介导细胞自噬等方面发挥重要作用,与牙周炎的发生和发展也有着密切的关系。目的:针对sirtuins在牙周炎中的研究概况做一综述。方法:由第一作者应用计算机在PubMed、Web of Science、中国知网和万方数据库检索涉及sirtuins在牙周炎中的相关研究,以“sirtuins,Sirtuin1-7,periodontitis”为英文检索词,“沉默信息调节因子,沉默信息调节因子1-7,牙周炎”为中文检索词,经过筛选后纳入57篇文献进行综述分析。结果与结论:①SIRT1、SIRT2、SIRT3、SIRT6参与调控了牙周炎的发生与发展;②SIRT1:抑制SIRT1表达可能是牙周炎治疗靶点;SIRT1的过表达对牙周炎症有抑制作用,保护牙周组织;SIRT1的激活剂可减轻牙周组织的炎症,并可改善牙周炎引起的全身组织病变;③SIRT2:参与烟酰胺磷酸核糖转移酶介导的牙周炎症,SIRT2在牙周疾病的治疗和转归中发挥一定的作用;④SIRT3:可改善年龄相关的牙周病;天麻素可通过SIRT3的上调促进牙周膜干细胞成骨分化;SIRT3的激活剂通过调节细胞自噬水平,降低牙周炎对牙周和肾脏组织的破坏程度;⑤SIRT6:可抑制牙周组织炎症反应,抑制成牙骨质细胞的分化和矿化;SIRT6对根尖周炎的预后有利;⑥SIRT4、SIRT5、SIRT7与牙周炎的关系鲜有报道。

关键词： sirtuins 牙周炎氧化应激去乙酰化牙槽骨吸收

葡萄糖转运蛋白GLUT1/4和sirtuins在糖尿病大鼠视网膜中的表达

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眼科新进展 2024年第4期44卷 270-274页

作者：白文帆郭玉伏等弟罗明秀芦晓红姚青宁夏医科大学基础医学院生物化学与分子生物学系宁夏回族自治区银川市750004

目的探讨葡萄糖转运蛋白GLUT1/4和sirtuins在糖尿病大鼠视网膜中的表达。方法取8周龄健康雄性SD大鼠20只随机分为正常对照组和糖尿病组,糖尿病组大鼠按照60 mg·kg^(-1)的剂量采用一次性腹腔注射链脲佐菌素诱导糖尿病模型,正常对照组... 详细信息

目的探讨葡萄糖转运蛋白GLUT1/4和sirtuins在糖尿病大鼠视网膜中的表达。方法取8周龄健康雄性SD大鼠20只随机分为正常对照组和糖尿病组,糖尿病组大鼠按照60 mg·kg^(-1)的剂量采用一次性腹腔注射链脲佐菌素诱导糖尿病模型,正常对照组大鼠注射等量的溶剂。每隔2周检测大鼠体重和血糖。造模后12周,应用彩色多普勒超声检测大鼠视网膜中央动脉(CRA)血流参数;使用戊巴比妥钠麻醉大鼠后摘取眼球,采用HE染色观察大鼠视网膜组织的病理变化,免疫组织化学染色、Western blot和qRT-PCR分别检测大鼠视网膜中GLUT1/4和sirtuins mRNA的表达情况。结果造模后12周,与正常对照组相比,糖尿病组大鼠CRA的收缩期峰值流速和舒张末期流速均显著降低(均为P0.05)。造模后12周HE染色结果显示,正常对照组大鼠视网膜组织各层结构清晰,细胞排列紧密、规则,未发现明显的病理改变;糖尿病组大鼠视网膜组织厚度变薄,各层界限模糊,结构紊乱,细胞数量减少。造模后12周免疫组织化学染色结果显示,在大鼠视网膜中,GLUT1主要位于视网膜色素上皮层,GLUT4位于神经节细胞层、内丛状层及光感受器层;Western blot检测结果显示,糖尿病组大鼠视网膜中GLUT1及GLUT4蛋白相对表达量均低于正常对照组(均为Psirtuins的表达发生改变,GLUT1/4和sirtuins可能参与了DR的发生与发展。

关键词：糖尿病视网膜病变葡萄糖转运蛋白 sirtuins 视网膜中央动脉

Sodium-glucose cotransporter-2 inhibitors protect tissues via cellular and mitochondrial pathways:Experimental and clinical evidence

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World Journal of Experimental Medicine 2024年第2期14卷 46-52页

作者： Raúl Lelio Sanz Sebastián García Menéndez Felipe Inserra Leon Ferder Walter Manucha Department of Pathology Facultad de Ciencias MédicasUniversidad Nacional de CuyoMendoza 5500Argentina Department of Pharmacology Instituto de Medicina y Biología Experimental de CuyoCentro Científico TecnológicoMendoza 5500Argentina Department of Nephrology Universidad de MaimónidesCiudad Autónoma de Buenos Aires C1405Argentina Department of Cardiology Universidad de MaimónidesCiudad Autónoma de Buenos Aires C1405Argentina

Mitochondrial dysfunction is a key driver of cardiovascular disease(CVD)in metabolic syndrome and diabetes.This dysfunction promotes the production of reactive oxygen species(ROS),which cause oxidative stress and inflammation.Angiotensin II,the main mediator of the renin-angiotensin-aldosterone system,also contributes to CVD by promoting ROS production.Reduced activity of sirtuins(SIRTs),a family of proteins that regulate cellular metabolism,also worsens oxidative stress.Reduction of energy production by mitochondria is a common feature of all metabolic disorders.High SIRT levels and 5’adenosine monophosphate-activated protein kinase signaling stimulate hypoxia-inducible factor 1 beta,which promotes ketosis.Ketosis,in turn,increases autophagy and mitophagy,processes that clear cells of debris and protect against damage.Sodiumglucose cotransporter-2 inhibitors(SGLT2i),a class of drugs used to treat type 2 diabetes,have a beneficial effect on these mechanisms.Randomized clinical trials have shown that SGLT2i improves cardiac function and reduces the rate of cardiovascular and renal events.SGLT2i also increase mitochondrial efficiency,reduce oxidative stress and inflammation,and strengthen tissues.These findings suggest that SGLT2i hold great potential for the treatment of CVD.Furthermore,they are proposed as anti-aging drugs;however,rigorous research is needed to validate these preliminary findings.

关键词： Sodium-glucose cotransporter-2 inhibitors Cardiovascular diseases sirtuins Oxidative stress Inflammation Mitochondrial dysfunction

sirtuins are not conserved longevity genes

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Life Metabolism 2022年第2期1卷 122-133页

作者： Charles Brenner Department of Diabetes&Cancer Metabolism Beckman Research Institute of City of HopeDuarteCA 91010 USA

It is central to biology that sequence conservation suggests functional conservation.Animal longevity is an emergent property of selected traits that integrates capacities to perform physical and mental functions after reproductive maturity.Though the yeast SIR2 gene was nominated as a longevity gene based on extended replicative longevity of old mother cells,this is not a selected trait:SIR2 is selected against in chronological aging and the direct targets of SIR2 in replicative lifespan are not conserved.Though it would be difficult to imagine how a gene that advantages 1 in 5 million yeast cells could have anticipated causes of aging in animals,overexpression of SIR2 homologs was tested in invertebrates for longevity.Because artifactual positive results were reported years before they were sorted out and because it was not known that SIR2 functions as a pro-aging gene in yeast chronological aging and in flies subject to amino acid deprivation,a global pursuit of longevity phenotypes was driven by a mixture of framing bias,confirmation bias,and hype.Review articles that propagate these biases are so rampant that few investigators have considered how weak the case ever was for sirtuins as longevity genes.Acknowledging that a few positive associations between sirtuins and longevity have been identified after thousands of person-years and billions of dollars of effort,we review the data and suggest rejection of the notions that sirtuins(i)have any specific connection to lifespan in animals and(ii)are primary mediators of the beneficial effects of NAD repletion.

关键词： sirtuins longevity model organism publication bias resveratrol nicotinamide adenine dinucleotide

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足细胞自噬机制和靶向信号通路相关研究进展

重庆医学 2024年第3期53卷 445-450页

作者：陈立柳敏娜赵欣怡席春生中国人民解放军联勤保障部队第九四〇医院肾脏内科兰州730000 甘肃中医药大学第一临床学院兰州730000

足细胞作为一种高分化细胞,具有高度自噬活性。维持细胞内动态平衡降解,可减缓慢性肾脏疾病进展,保护受损的足细胞免受不可逆转的损伤。足细胞自噬水平高于其他类型的肾脏细胞,足细胞自噬的激活与雷帕霉素靶蛋白(mTOR)和腺苷5’-单磷酸... 详细信息

足细胞作为一种高分化细胞,具有高度自噬活性。维持细胞内动态平衡降解,可减缓慢性肾脏疾病进展,保护受损的足细胞免受不可逆转的损伤。足细胞自噬水平高于其他类型的肾脏细胞,足细胞自噬的激活与雷帕霉素靶蛋白(mTOR)和腺苷5’-单磷酸活化蛋白激酶(AMPK)、sirtuins、丝裂原活化蛋白激酶(MAPK)等相关通路有关,这些通路在足细胞功能的各种关键途径中具有至关重要作用。目前发现,足细胞自噬已成为改善足细胞损伤的有力治疗靶点。该文阐述了自噬在足细胞损伤中的功能作用,以及在基础实验和临床肾小球疾病调节方面的最新数据,以期为临床提供科学指导。

关键词：足细胞自噬信号通路雷帕霉素靶蛋白腺苷5’-单磷酸活化蛋白激酶 sirtuins 丝裂原活化蛋白激酶

sirtuins and nonalcoholic fatty liver disease

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World Journal of Gastroenterology 2016年第46期22卷 10084-10092页

作者： Fatiha Nassir Jamal A Ibdah Research Service Harry S Truman Memorial VA Hospital University of Missouri Department of Medicine Division of Gastroenterology and Hepatology University of Missouri

Mammalian sirtuins are seven members belonging to the silent information regulator 2 family, a group of Class Ⅲ histone/protein deacetylases. sirtuins(SIRT 1-7) have different subcellular localization and function and they regulate cellular protein function through various posttranslational modifications. SIRT1 and 3, the most studied sirtuins, use the product of cellular metabolism nicotinamide adenine dinucleotide as a cofactor to post-translationally deacetylate cellular proteins and consequently link the metabolic status of the cell to protein function. sirtuins have been shown to play a key role in the development and rescue of various metabolic diseases including non-alcoholic fatty liver disease(NAFLD). NAFLD is currently the most chronic liver disease due mainly to high-calorie consumption and lower physical activity. No pharmacological approach is available to treat NAFLD, the current recommended treatment are lifestyle modification such as weight loss through calorie restriction and exercise. Recent studies have shown downregulation of sirtuins in human as well as animal models of NAFLD indicating an important role of sirtuins in the dynamic pathophysiology of NAFLD. In this review, we highlight the recent knowledge on sirtuins, their role in NAFLD and their unique potential role as novel therapeutic target for NAFLD treatment.

关键词： SIRT1 SIRT3 sirtuins 非酒精的脂肪肝疾病

sirtuins Function as the Modulators in Aging-related Diseases in Common or Respectively

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Chinese Medical Journal 2015年第12期128卷 1671-1678页

作者： Qi-Lin Wang Shang-Jing Guo School of Life Science Liaocheng University Liaocheng Shandong 252059 China School of Pharmacy Liaocheng University Liaocheng Shandong 252059 China

INTRODUCTIONAccording to the demographics, the world population over 60 years will double from 605 million to 2 billion people between 2000 and 2050. Aging is a complex process in which the organism and its ability to... 详细信息

关键词： Aging-related Disease Deacetylase Hypoxia Inducible Factor-1α NAD＋ Peroxisome Proliferator-activated Receptor-γ Coactivator- 1α sirtuins