自噬调控衰老的研究进展

随着机体老化,组织器官可发生不可逆退行性改变,这些变化与疾病和死亡密切相关。自噬是细胞内一种重要的分解代谢过程,在维持细胞稳态和促进长寿中起重要作用,机体衰老后,其自噬调节能力也随之下降。本文综述了自噬与衰老相关疾病的关系,明确自噬调控衰老的相关分子机制可能为治疗衰老相关疾病提供新的靶点。     

自噬与衰老关系的研究进展

正衰老是一种自然的、不可避免的生命过程,是一种复杂的自然现象,主要表现为机体结构和功能的衰退以及适应性和抵抗力的降低。衰老的进行性发展可引发多种疾病,使国家疾病负担日益加重,这已成为我国乃至全世界面临的重大问题。细胞自噬被认为与衰老有着密切的联系,通过干预细胞自噬改善衰老状态已成为近年研究的新方向。1衰老的概述及其相关学说衰老是机体各种生化反应及体内外诸多因素综合作用的结果,表现为机体各器官、组织和细胞结构的退     

细胞自噬和衰老及衰老相关疾病

细胞自噬和衰老及衰老相关疾病密切相关。从自噬角度延缓衰老和治疗衰老相关疾病的方法包括使用自噬诱导剂、抗氧化剂和热量限制。本文就自噬和衰老及衰老相关疾病的关系及机制方面做一综述,以提高临床医师的认识。     

自噬在糖尿病心肌病的作用机制研究

自噬是真核细胞中普遍存在的一种物质降解途径,通过自噬溶酶体介导,清除自身多余或受损的细胞器,以维持细胞内物质的再循环并调节内环境稳态,对机体生长、发育和衰老均起重要作用。研究发现,自噬影响心血管功能,与心血管疾病的病理生理进程密切相关。本文从自噬的信号转导途径,自噬与糖尿病心肌的关系及其可能的机制的进行探讨,希望从自噬的角度对糖尿病心肌病的发生、发展过程进行阐述,为治疗糖尿病心肌病提供理论依据。     

自噬与肝脏脂代谢

细胞自噬是利用溶酶体降解受损的细胞器、未折叠蛋白来维持细胞内稳态,在机体生长、发育和衰老中均起重要作用.研究表明,自噬可能与肝脏脂肪合成及分解相关.固醇调节元件结合蛋白通路、转录因子、激素与营养因素可能会影响自噬,从而改变脂代谢.     

转化生长因子β信号通路调控血管衰老的作用机制研究进展

血管衰老是增龄相关性心血管疾病的主要危险因素，纤维化、钙化、慢性炎症、自噬水平下降、端粒缩短是血管衰老的重要诱因。转化生长因子β(TGF-β)是调节细胞生长和分化的重要细胞因子，其作为衰老相关分泌表型的成员在老龄机体内表达显著上调。在血管衰老进程中，TGF-β信号通路能够通过对血管纤维化、血管钙化、细胞自噬、炎症反应、端粒长度、端粒酶活性以及新型长寿靶点的调控影响血管衰老，从而在血管衰老相关疾病中发挥作用。     

ROS调节mTOR信号通路参与自噬的研究进展

自噬是真核细胞中普遍存在的一种物质降解途径,通过自噬溶酶体介导,清除自身多余或受损的细胞器,参与正常细胞内稳态的维护,对机体生长、发育和衰老均起重要作用。哺乳动物雷帕霉素靶蛋白(mTOR)是一种丝/苏氨酸蛋白质激酶,接受并整合细胞内外的各种信号,是调节蛋白质翻译与细胞生长等多种生理活动的中心信号分子。而活性氧类(ROS)作为第2信使分子,可介导多种细胞信号通路并发挥广泛的生理效应。研究发现,在自噬的过程中,ROS可通过一定的途径激活或抑制mTOR通路,但其调节机制极其复杂。本文就自噬过程中ROS与mTOR之间相互调节机制的研究进展进行综述。     

寄生虫感染与宿主细胞自噬相互作用研究进展

自噬是一种真核细胞特有的生命现象,是一种保守的细胞内降解系统。通常所说的自噬是通过双层膜包裹细胞质成分形成自噬体,随后与溶酶体融合,从而降解细胞自身物质的过程。自噬可以由饥饿诱导,也可以由包括寄生虫在内的各种病原体所诱导。当机体感染胞内寄生虫时,宿主细胞可以通过自噬清除寄生虫。然而,寄生虫也进化出自身防御机制,能够利用宿主细胞自噬促进自身发育生长。本文综述了目前国内外关于寄生虫感染与宿主细胞自噬相互影响的研究进展,深入探讨自噬作用对防治寄生虫感染和抗虫药物研发具有重要意义。     

细胞自噬对衰老的调节

细胞内损伤物质的积累是所有衰老细胞的普遍特征,能导致生命有机体生存能力降低.细胞自噬能够降解受损蛋白质和衰老或损伤细胞器等细胞结构,是细胞内主要的异化途径,参与衰老以及与衰老相关的各种病理过程.近年来研究发现,衰老进程中,细胞自噬活动下调,而对各种长寿突变体的研究表明自噬活动是寿命延长所必需的,多种自噬相关基因或蛋白直接受长寿途径的调节[1~5],这些发现都支持细胞自噬是各种真核生物衰老非常重要的调节机制.     

自噬与2型糖尿病

自噬是机体处于物质与能量代谢障碍时主要防御机制之一,在维持胰岛β细胞结构功能、改善IR等方面有重要作用。某些治疗T2DM药物也参与自噬途径调节。本文就近年关于自噬对T2DM影响的相关研究进行综述。     

自噬在代谢综合征相关的心血管老化中的作用机制

代谢综合征是一组表型复杂的代谢紊乱症候群,发病率居高不下.代谢性综合征病理相关的肥胖、胰岛素抵抗、糖尿病、高血压及脂代谢异常促进心血管过早老化.自噬溶酶体途径可降解心血管老化过程中产生的功能异常的蛋白质和细胞器,参与代谢综合征相关的心血管过早老化的发生发展.为寻找各种代谢性疾病下心血管老化治疗的新策略,掌握代谢应激情况...     

细胞自噬与心血管疾病中炎症反应的相关性

细胞自噬既是保守的细胞防御机制,也是程序性细胞死亡(即调亡)机制,其可维持细胞自身内环境的稳态。心血管疾病多伴有炎症反应并与细胞自噬密切相关。新近研究表明:一方面,自噬可以通过清除堆积蛋白和保持线粒体稳态对抗心血管疾病的炎症反应,此效应可能与抑制炎症小体以及钙蛋白酶依赖的白介素-1α的活性有关;另一方面,自噬在某些情况下也可促进炎症反应,自噬相关蛋白和高尔基体重组-堆叠蛋白参与了自噬的促炎效应。以本文简要综述细胞自噬在心血管疾病炎症反应中的作用,探讨自噬与炎症反应的相关分子机制,为心血管疾病中炎症反应的治疗提供新的思路。     

哺乳动物雷帕霉素靶蛋白介导的自噬在心血管疾病中作用的研究进展

自噬是生物进化过程中高度保守、依赖溶酶体的胞内降解途径。在心血管系统中,基础水平的自噬是维持心脏结构和功能稳态的一种机制;在应激状态下,自噬适度激活可保护心肌细胞免受应激损伤,而过度激活则会加重心肌损伤,从而参与多种心血管疾病的病理生理过程。生物体内存在多种自噬调控机制,其中哺乳动物雷帕霉素靶蛋白是自噬的关键负调控因子,研究其介导的自噬在心血管疾病中的作用机制,有助于探索临床预防和治疗心血管疾病的新靶点。     

Network pharmacology-based screening of the active ingredients and mechanisms of Huangqi against aging

Studies have shown that Huangqi (HQ) has anti-aging efficacy. However, its active ingredients and mechanisms for anti-aging are still unclear. In this study, we will systematically screen the active ingredients of HQ and explore the possible mechanism of HQ in prevention from aging through network pharmacology technology.The main active ingredients of HQ were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The possible targets were predicted by TCMSP. The related targets for aging were obtained from GeneCards (The Human Gene Database) and Online Mendelian Inheritance in Man (OMIM) database. The common targets of HQ and aging were obtained using R 3.6.3 software. The protein–protein interaction (PPI) network and the ingredient-target-disease network were constructed using Cytoscape 3.7.2 software for visualization. In addition, the Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation of potential targets were performed using R 3.6.3 software.Based on the screening conditions, 16 active ingredients and 28 drug targets were obtained. The PPI network contained 29 proteins, including PTGS2, AR, NOS2, and so on. GO functional enrichment analysis obtained 40 GO items (P < .05). KEGG pathway enrichment analysis obtained 110 aging related pathways (P < .05), including hypoxia inducible factor 1 signaling pathway, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway in diabetic complication, among others.Sixteen effective ingredients of HQ and 28 targets against aging were identified through network pharmacology. Multiple pathways were involved in the effect of HQ on preventing aging.     

Effect of free radicals and antioxidant on the vascular wall

Free radicals pay an important role in the pathogenesis of atherosclerosis by their direct toxic action on the vascular endothelium as well as by antioxidant of low density lipoproteins (LDL) which subsequently increase their atherogenic potential. Natural antioxidants interrupt the chain-like increase of radicals and thus also the risk of oxidation stress. The majority of epidemiological data indicate that an increased intake of fruit, vegetables and other foods of plant origin reduces the risk of cardiovascular disease. On the other hand, several so far not completed long-term intervention studies with some antioxidant vitamins (e. g. vitamin E, beta-carotene) don't provide such unequivocal results. This indicated that fruit and vegetables contain other protective substances, other than vitamins, some which were identified so far. It is beyond doubt than even the intake of very large amounts of antioxidant vitamins does not ensure in humans exposed to the potent action of several traditional cardiovascular risk factors (hypertension, high LDL-cholesterol, smoking) unequivocal protection against ischaemic heart disease. On the other hand, it is probable that chronic antioxidant deficiency enhances the risk of development of pathological changes of the vascular system. So far the problem has yet been resolved whether to recommend within the framework of cardiovascular disease prevention to the public at large daily consumption of preparations containing natural antioxidants. The final word on the effectiveness of antioxidants in the prevention of cardiovascular disease will be provided by extensive intervention studies which are at present under way, the results of which will be available within the few years.     

Nef performance in macrophages: the master orchestrator of viral persistence and spread

Following transmission of human immunodeficiency virus (HIV) into a new host, cells of the monocyte/macrophage lineage play a central role in host invasion and viral replication. In particular, macrophages survive infection and support long-standing viral replication, contributing to viral persistence within the host and representing a viral reservoir in vivo. On the other hand, HIV Nef protein is a small though versatile molecule that plays an unquestioned key role in viral pathogenesis. In macrophages, Nef is able to modulate cell surface receptor expression, to intersect intracellular signaling pathways and to augment the release of pro-inflammatory and chemotactic molecules. In addition, Nef can alter macrophage phagocytic capacity, autophagy machinery and metabolism. Altogether, these Nef activities support viral replication and persistence in this cell type while at the same time favor viral dissemination. Here, we will review the newest findings describing how monocytes/macrophages natural pathways are altered by Nef protein, highlighting how viral and host biology are perturbed in consequence.     

Too much or not enough of a good thing — The Janus faces of autophagy in cardiac fuel and protein homeostasis

Cells respond to changes in their environment and in their intracellular milieu by altering specific pathways of protein synthesis and degradation. Autophagy is a highly conserved catabolic process involved in the degradation of long-lived proteins, damaged organelles, and subcellular structures. The process is orchestrated by the autophagy related protein (Atg) to form the double-membrane structure autophagosomes, which then fuse with lysosomes to generate autophagolysosomes where subcellular contents are degraded for a variety of cellular processes. Alterations in autophagy play an important role in diseases including cancer, neurodegenerative diseases, aging, metabolic diseases, inflammation and cardiovascular diseases. In the latter, dysregulated autophagy is speculated to contribute to the onset and development of atherosclerosis, ischemia/reperfusion injury, cardiomyopathy, diabetes mellitus, and hypertension. Autophagy may be both adaptive and beneficial for cell survival, or maladaptive and detrimental for the cell. Basal autophagy plays an essential role in the maintenance of cellular homeostasis whereas excessive autophagy may lead to autophagic cell death. The point and counterpoint discussion highlights adaptive vs. maladaptive autophagy. In this review, we discuss the molecular control of autophagy, focusing particularly on the regulation of physiologic vs. defective autophagy.     

自噬在病理刺激下导致的心室重构中的作用

尽管目前心血管领域的研究较前几十年已经取得了较大进展,但是心力衰竭仍然是导致心血管疾病死亡率居高不下的主要原因。心室重构是指心血管系统对某些生理刺激(如妊娠和剧烈运动)和病理刺激(如心肌梗死、压力超负荷)的一个结构和功能重塑的过程,其特征是心室的逐渐扩张、心肌肥大、心肌纤维化,最终导致心力衰竭。自噬是溶酶体介导的蛋白质和细胞器降解的高度保守机制,在维持细胞稳态中起着至关重要的作用。越来越多证据表明,自噬在心血管系统中,尤其在心室重构方面起着重要作用。本文就自噬在心室重构中的作用的研究进展进行阐述。     

Role of cell death in the progression of heart failure

All multicellular organisms develop during evolution the highly regulated and interconnected pathways of cell death. This complex network contributes to the pathogenesis of various cardiovascular disorders including ischemia/reperfusion injury, myocardial infarction, heart failure, dysrhythmias and atherosclerosis. Chronic cardiac remodeling response and transition to overt HF have been associated with modestly increased apoptosis, although the actual burden of chronic cell loss attributable to apoptosis is not clear. Central mediators of cardiomyocyte survival and death are the mitochondrial organelles. Based on its morphological characteristics, cell death can be classified into three major types: apoptosis, necrosis and autophagy. Recently, a new pathway of regulated necrosis, necroptosis, has also been reported in the failing heart. The mitochondrial (intrinsic) and the death-receptor-mediated (extrinsic) converge at mitochondria inducing release of mitochondrial apoptogens to initiate the caspase cascade and eventually degradation of the doomed cardiomyocyte. Activation of death receptors can initiate not only extrinsic apoptotic pathway, but also necrosis. On the other hand, autophagy, which is characterized by the massive formation of lysosomal-derived vesicles, containing degenerating cytoplasmic contents, is primarily a survival response to nutrient deprivation, and a selective form of autophagy, mitophagy, is also a protective mechanism that allows to eliminate damaged mitochondria and thereby to attenuate mitochondria-mediated apoptosis and necrosis in the myocardium. Further insight into the molecular mechanisms underlying cell death will increase the efficiency and repertoire of therapeutic interventions available in cardiovascular disease.