前景可观的senolytics延缓衰老的研究进展

细胞衰老呈现不可逆的永久性细胞周期停滞的状态,它可以促进组织在发育过程中和损伤后的重塑,但也会导致老年生物体组织再生潜力和功能的下降,以及炎症和肿瘤的发生。研究发现,清除衰老细胞可以延缓衰老相关疾病的发生。因此,探究衰老细胞的分子特征与探索清除衰老细胞的新药成为衰老研究领域的热点。近年来,人们发现一类称为senolytics的小分子化合物能特异性靶向衰老细胞并帮助清除衰老细胞,从而延长哺乳动物的寿命及健康寿命。该文对衰老细胞的分子特征、作为衰老相关疾病的治疗靶点及具有senolytics活性的化合物作用机制和潜在应用进行了综述。     

细胞衰老信号通路中NF-κB作用的研究进展CSCD

生物体衰老是一个非常复杂的过程。研究发现核转录因子(NF-κB)在细胞衰老中具有重要作用,对于细胞衰老的研究具有重要意义。本文综述了近几年来NF-κB与细胞衰老的相关研究,包括NF-κB作用机制、衰老相关信号通路与NF-κB的串流(crosstalk),深入探讨NF-κB与衰老的关系可为阐明衰老的分子机制及延缓衰老提供新的思路。     

细胞衰老信号通路中NF-κB作用的研究进展

生物体衰老是一个非常复杂的过程。研究发现核转录因子(NF-κB)在细胞衰老中具有重要作用,对于细胞衰老的研究具有重要意义。本文综述了近几年来NF-κB与细胞衰老的相关研究,包括NF-κB作用机制、衰老相关信号通路与NF-κB的串流(crosstalk),深入探讨NF-κB与衰老的关系可为阐明衰老的分子机制及延缓衰老提供新的思路。     

生物衰老的主要分子机制概述

衰老是一种包括生理性衰老和病理性衰老的正常自然规律,与其他生物过程一样,受一些信号通路和分子机制的调控。研究发现调控生物衰老机制的信号通路之间存在相互作用。综述了胰岛素通路、雷帕霉素通路及Sirtuins家族这3种与自噬相关的延缓衰老的经典信号通路,总结了氧化应激、细胞衰老、免疫衰老等影响机体衰老的主要原因及方式,希望在此基础上发现新的互作通路,探索出更多新颖的分子机制和方法以预防、延缓或减轻多种与衰老相关的疾病。     

miRNAs与衰老相关信号通路的研究进展

miRNAs是一类负调控基因表达的内源性非编码小分子RNA,在细胞衰老过程中发挥重要作用. 细胞衰老是指可增殖细胞在各种应激下出现细胞周期阻滞,并且丧失增殖能力,进入一种不可逆的、相对稳定的状态. p53、p21、p16、SIRT1、胰岛素/IGF-1及mTOR等蛋白是衰老相关信号通路中的重要分子,参与细胞衰老过程. 研究表明,miRNAs可以通过调控这些衰老相关蛋白所在的信号通路,促进或延缓细胞衰老. 本文综述细胞衰老相关的miRNAs,以及它们对衰老相关信号通路的影响,为深化认识衰老和衰老相关疾病的分子机制奠定基础.     

益生菌抗衰老作用机制研究进展

衰老会引起机体诸多不良的生理变化并增加对疾病的易感性,明确引发衰老的机制对于寻找其干预措施至关重要。研究发现,自由基氧化应激、炎症性衰老、免疫衰老、肠道菌群失调是引发衰老的相关机制。益生菌被报道具有潜在的延缓衰老作用,比较分析了常用益生菌抗衰老评价模型,并从衰老引发机制出发,重点综述了益生菌对肠道菌群的调节机制和抗衰老相关信号通路的影响,旨为进一步研究益生菌抗衰老作用提供新思路。     

衰老的分子机制与干预研究的最新进展

随着全球老龄化时代的到来,衰老和衰老相关疾病带来的健康问题日益突出。如何最大限度地维持老龄人口健康、干预衰老相关疾病并延缓衰老的发生对于医疗系统、科研机构乃至整个社会都是巨大的挑战。目前,对于衰老的分子机制研究已经有长足的进步,对于衰老进程的生物学和遗传学机制已有突破性的认识,对于衰老相关疾病的发病机制也有了深刻的理解。但这些研究成果还远远达不到能够延缓人类衰老并遏制衰老相关疾病的发生的要求。该文将从衰老的分子机制和干预手段这两个方面入手,综述衰老的理论研究和实际应用中的主要成果和最新进展。     

衰老机制及延缓衰老活性物质研究进展

关于衰老机制的研究及根据衰老机制寻找延缓衰老的药物已成为当前医药领域研究的热点之一,并取得了一定的进展。文章就延缓衰老的天然活性物质及延缓衰老作用机制的研究进展进行简要综述,并对研究衰老的主要模型做简要总结。     

运动调节内质网应激和线粒体自噬防治衰老相关疾病研究进展

随着我国逐渐步入老龄化社会,衰老及其相关疾病的预防和治疗措施已成为研究的热点问题。机体老化引起老年人常见的慢性疾病如阿尔茨海默病、心血管疾病、肌肉减少症和骨质疏松等是影响老年人身体健康和造成死亡的重要威胁。内质网和线粒体是机体蛋白质合成和能量供应的主要细胞器,对于细胞内稳态调节起主导作用,在机体老化过程中细胞内的动态平衡被打破,从而加剧各器官老化,并且伴随着衰老相关疾病发生。而运动作为一种有效的非药物干预手段,对于延缓衰老预防衰老相关疾病的发生起到保护作用。本文从内质网应激、线粒体自噬两个方面入手,综述了衰老相关疾病阿尔兹海默病、心血管疾病、肌肉减少症以及骨质疏松等的相关分子机制,并且阐述运动干预之后各疾病相关分子机制变化,进一步论述了衰老机体中运动调节内质网应激和线粒体自噬及运动干预后发挥保护效应的分子机制,拟为运动延缓机体衰老及预防老年性相关疾病的发生提供新的思路和理论依据。     

线粒体功能相关的抗衰老天然产物活性分子

近年来,衰老分子生物学及衰老药物学的研究取得了长足进展,寻找能延缓衰老的活性小分子物质正成为衰老研究领域的重点及热点。一方面,多种天然产物特别是传统中药对疾病防治及人体健康有重大益处,天然产物活性小分子在延缓衰老方面的作用引起了业内的极大关注。另一方面,线粒体功能在衰老调控中的重要性正被广泛重视和认可。本文综述了近年被报道的靶向线粒体功能的主要抗衰老天然产物(包括单一组分和提取物),可为进一步开发利用天然产物提供理论基础和研发方向。     

Imaging mass spectrometry: principle and application

Imaging mass spectrometry (IMS) is two-dimensional mass spectrometry to visualize the spatial distribution of biomolecules, which does not need either separation or purification of target molecules, and enables us to monitor not only the identification of unknown molecules but also the localization of numerous molecules simultaneously. Among the ionization techniques, matrix assisted laser desorption/ionization (MALDI) is one of the most generally used for IMS, which allows the analysis of numerous biomolecules ranging over wide molecular weights. Proper selection and preparation of matrix is essential for successful imaging using IMS. Tandem mass spectrometry, which is referred to MSⁿ, enables the structural analysis of a molecule detected by the first step of IMS. Applications of IMS were initially developed for studying proteins or peptides. At present, however, targets of IMS research have expanded to the imaging of small endogenous metabolites such as lipids, exogenous drug pharmacokinetics, exploring new disease markers, and other new scientific fields. We hope that this new technology will open a new era for biophysics.     

Depolymerization of hyaluronan by sonication

High molecular weight hyaluronan (M _r 400 000) obtained from human umbilical cord was depolymerized by sonication for 10 h into small molecules and finally into molecules of constant size (M _r 11 000). The molecular size of the depolymerized hyaluronan was unaltered even under different conditions of sonication. After sonication, the main sugar residues at the reducing and non-reducing termini of depolymerized hyaluronan wereN-acetylglucosamine (86%) and glucuronic acid (98%), respectively. Hyaluronans derived from rooster comb (M _r 1×10⁶) andStreptococcus zooepidemicus (M _r 1.2×10⁶) were deploymerized into molecules of different but characteristic sizes by sonication. On the other hand, neither chondroitin sulfate nor glycogen was depolymerized by sonication. These results suggest that high molecular weight hyaluronan may have some weak linkages related toN-acetylglucosamine in the chain, which are extremely sensitive to sonication. At present, however, the nature of these linkages is still unclear.Abbreviations HA hyaluronan - PA 2-aminopyridine     

调控骨骼形成的信号通路

骨骼形成后会处于不断的分解与重建中.通过骨骼形成与骨骼吸收之间的动态平衡来维持骨量.如果二者间的平衡被打破,骨吸收大于骨形成时,骨量会减少,骨骼微环境随之发生改变,脆性增加,进而引发骨质疏松、骨折等疾病.其中,骨骼形成是成骨细胞的重要功能.成骨细胞由间充质干细胞(mesenchymal stem cells,MSCs)...     

HBx参与肝细胞癌发生发展调控的分子机制

肝细胞癌 (hepatocellular carcinoma, HCC)是我国最常见的恶性肿瘤之一,而HBV慢性感染是肝癌发生的主要原因.乙型肝炎病毒(HBV)中X基因编码的一种多功能蛋白(HBx),参与众多重要生物学过程的调控,并促进肝细胞癌的发生. 早期研究表明,HBx在HCC发生过程中发挥重要的调控功能,但其确切分子机制尚未完全明确. 近几年,HBx参与生物学过程的分子机制研究有了较快的进展. 有趣的是,研究发现,HBx在不同的细胞系以及HBV感染的不同阶段发挥促抑凋亡的双重作用,HBx还参与细胞自噬的调控. 此外,在HBx参与细胞增殖及肿瘤侵袭和转移等方面,也产生了一些新的认识. 本文将从HBx对肝细胞凋亡、自噬和增殖的调控及其对肝癌细胞转移和侵袭的调控等方面,对HBx参与肝细胞癌发生发展调控机制做一综述.     

Dietary antiaging phytochemicals and mechanisms associated with prolonged survival

Aging is well-known an inevitable process that is influenced by genetic, lifestyle and environmental factors. However, the exact mechanisms underlying the aging process are not well understood. Increasing evidence shows that aging is highly associated with chronic increase in reactive oxygen species (ROS), accumulation of a low-grade proinflammatory phenotype and reduction in age-related autophagy, suggesting that these factors may play important roles in promoting aging. Indeed, reduction of ROS and low-grade inflammation and promotion of autophagy by calorie restriction or other dietary manipulation can extend lifespan in a wide spectrum of model organisms. Interestingly, recent studies show that some food-derived small molecules, also called phytochemicals, can extend lifespan in various animal species. In this paper, we review several recently identified potential antiaging phytochemicals that have been studied in cells, animals and humans and further highlight the cellular and molecular mechanisms underlying the antiaging actions by these molecules.     

热量限制及其模拟物的延衰作用

热量限制是一种有效的延缓衰老的方法,它不仅能延长实验动物的寿命,还能推迟和减少多种老龄相关疾病的发生,但长期严格的热量限制对人类较难实施,因此类似的人体试验相对较少。基于对热量限制抗衰老作用机制的研究促使了热量限制模拟物的出现,使得热量限制这种延衰策略在人类施行成为可能。本文介绍了热量限制延衰机制的最新研究进展,并根据热量限制模拟物作用机制的不同,分别对下游型热量限制模拟物AMPK激活剂、m TOR抑制剂和Sirtuins激活剂,及上游型热量限制模拟物2-脱氧葡萄糖、D-葡糖胺和壳聚糖进行综述。     

琥珀酸对酵母细胞转录组的影响

寻找抗衰老活性小分子并研究其作用机制是衰老药物学研究的重点和热点。本文报道了一种新的抗衰老活性小分子琥珀酸,发现琥珀酸可以显著延缓芽殖酵母细胞的衰老并增强细胞的压力抗性。随后,利用DNA Microarray技术及生物信息学手段较系统分析了琥珀酸处理对基因表达谱、基因本体聚类及相关信号通路的影响。结果显示,琥珀酸处理对细胞转录组产生了显著影响,共导致3 485个基因的差异表达(P 0.05),其中1 335个基因显著上调,2 150个基因显著下调。进一步对基因本体聚类及信号通路分析显示,线粒体及核糖体生物合成相关的分子功能、细胞组分、生物学过程和信号通路可能是琥珀酸作用的主要靶点,其他可能的作用靶点还包括蛋白酶体、细胞内吞、过氧化物酶体代谢及细胞自噬等。本研究为进一步阐明琥珀酸介导的寿命及压力调控机制提供了理论参考和研究线索。     

Antimicrobial peptides: an overview of a promising class of therapeutics

Antibiotic resistance is increasing at a rate that far exceeds the pace of new development of drugs. Antimicrobial peptides, both synthetic and from natural sources, have raised interest as pathogens become resistant against conventional antibiotics. Indeed, one of the major strengths of this class of molecules is their ability to kill multidrug-resistant bacteria. Antimicrobial peptides are relatively small (6 to 100 aminoacids), amphipathic molecules of variable length, sequence and structure with activity against a wide range of microorganisms including bacteria, protozoa, yeast, fungi, viruses and even tumor cells. They usually act through relatively non-specific mechanisms resulting in membranolytic activity but they can also stimulate the innate immune response. Several peptides have already entered pre-clinical and clinical trials for the treatment of catheter site infections, cystic fibrosis, acne, wound healing and patients undergoing stem cell transplantation. We review the advantages of these molecules in clinical applications, their disadvantages including their low in vivo stability, high costs of production and the strategies for their discovery and optimization.     

M2 Macrophage Derived Extracellular Vesicle-Mediated Transfer of MiR-186-5p Promotes Colon Cancer Progression by Targeting DLC1

Colon cancer (CC) is one of the most common malignances in digestive tract. M2-polarized macrophages within the tumor microenvironment could facilitate CC cell growth by transferring molecules via extracellular vesicles, but the mechanisms are not fully elucidated. The current study aims to identify the possible effectors in M2 macrophage-derived extracellular vesicles (M2-EVs) and reveal related molecular mechanisms. In our study, we validated the promotion effects of M2-EVs on the proliferation and motility of CC cells, which was found to be dependent on the EVs enclosed molecules by a mild EVs digestion assay. Then we found that miR-186-5p was enriched in M2-EVs and was responsible for the tumor promoting functions of M2-EVs. Furthermore, mechanism investigation revealed M2-EVs transferring miR-186-5p inhibited DLC1 expression by targeting its 3''UTR, and restored DLC1 successfully neutralized the tumor-promoting effects of M2-EVs transferring miR-186-5p via inhibiting the β-catenin pathway. Our study revealed that M2-EVs facilitates the growth and motility of CC cells by delivering the enclosed miR-186-5p, which directly targets DLC1 mRNAs and facilitates their degradation, which could provide a potential biomarker and therapeutic target for CC.