端粒生物学的某些进展—衰老与癌症

端粒生物学的某些进展———衰老与癌症广州铁路中心医院医学美容整形科（广州５１００８０）惠俐中山医科大学病理学教研室（广州５１００８９）王连唐ＳｏｍｅａｄｖａｎｃｅｏｆｔｅｌｏｍｅｒｅｂｉｏｌｏｇｙｉｎｓｅｎｅｓｃｅｎｃｅａｎｄｃａｎｃｅｒＨＵＩＬｉ，...     

衰老的分子机制

衰老是人类生命过程中的必然规律,但并不意味着人类在自身衰老方面无所作为,长期以来,人类都梦想着延缓衰老,延长寿命,近年来在细胞生物学和分子生物学迅速发展的推动下,衰老机理研究已取得重大进展,抗衰老研究已成为生命科学和医学领域的前沿课题,本文对近年来在衰老领域的最新进展作一综述。     

端粒、端粒酶与人类衰老和肿瘤

近年来,不少学者注意到染色体端粒(telomere)的长度和端粒酶(telomerase)活性与细胞的衰老、细胞的永生化以及细胞的恶性变有着密切的关系,显示它们在细胞的增殖调控中起着重要的作用,本文仅对此作一综述.     

学历较低的人衰老得快

一项新的研究显示,学历较低的人衰老得快。     

端粒（酶）同癌症与衰老关系的研究进展

端粒是真核生物染色体的天然末端，具有稳定染色体结构，避免遗传信息在复制过程中丢失的作用。端粒酶是端粒复制成必须的一种特殊的ＤＮＡ聚合酶，在大多数的正常人体细胞中没有活性。在近年来的研究中，人们发现“衰老的端粒缩短”，而且在约８５％的肿瘤细胞中检测到了端粒酶活性。这些事实提示人们：端粒、端粒酶同癌症与衰老之间存在相关性。     

端粒(酶)同癌症与衰老关系的研究进展

端粒是真核生物染色体的天然末端,具有稳定染色体结构,避免遗传信息在复制过程中丢失的作用.端粒酶是端粒复制所必须的一种特殊的DNA聚合酶,在大多数的正常人体细胞中没有活性.在近年来的研究中,人们发现“衰老者的端粒缩短”,而且在约85％的肿瘤细胞中检测到了端粒酶活性.这些事实提示人们:端粒、端粒酶同癌症与衰老之间存在相关性.     

中药抑制间充质干细胞衰老的作用及机制

背景：间充质干细胞的衰老严重影响其临床应用并且是衰老相关疾病发生的主要诱因之一,中药具有良好的抗衰老作用,可抑制间充质干细胞衰老从而促进其在组织工程中的应用并防治衰老相关疾病。目的：综述中药抑制间充质干细胞衰老的作用及机制。方法：检索中国知网和PubMed数据库2012-2022年关于中药抑制间充质干细胞衰老的文献,以“中药,间充质干细胞,衰老”为中文检索词,以“traditional chinese medicines,mesenchymal stem cells (MSCs),aging”为英文检索词,最终共纳入92篇文献进行分析。结果与结论：(1)文章总结了当前间充质干细胞衰老的5个主要机制：包括DNA损伤、端粒缩短、氧化应激、自噬障碍及线粒体功能障碍。(2)文章梳理了衰老间充质干细胞的表型特征,主要包括细胞体积增大、增殖和多向分化能力下降、β-半乳糖苷酶活性增加、p21及p16通路激活等。(3)文章总结了当前中药抑制间充质干细胞衰老的主要机制,包括抑制Wnt通路激活、抑制线粒体活性氧产生、促进沉默信息调节因子2同系物1、磷脂酰肌醇3-激酶/蛋白激酶B、腺苷酸活化蛋白激酶及核因子...     

端粒与端粒酶:运动延缓衰老的端粒机制

背景:端粒是人体细胞染色体末端的特殊结构,与衰老有非常密切的关系;科学运动可以提高端粒酶活性,保护端粒结构,从而影响人体的身体健康;端粒变短,机体疾病发病率增加,存活率降低,因此,端粒常被认为是细胞衰老的生物学标志物,是触发衰老的“生物钟”。目的:基于端粒系统和衰老的关系,总结分析运动对端粒、端粒酶的影响,探讨运动延缓衰老的端粒理论机制,为运动抗衰老、运动健康促进提供理论依据和参考。方法:以“端粒,端粒酶,运动,衰老”为中文检索词,以“telomeres,telomerase,exercise,senescence”为英文检索词;查阅中国知网、Pub Med、Web of science数据库,初步筛选运动调控端粒延缓衰老的相关文献,在全文阅读后共纳入89篇文献进行分析。结果与结论:不同运动对端粒的影响具有差异性;运动与端粒长度存在正相关、无相关和倒U型关系,与端粒酶活性存在年龄偏移性;适宜运动可以减缓端粒缩短的速度,防止端粒过度消耗,延缓或预防与年龄相关的疾病发生,延长寿命,但其机制一直未阐明。     

端粒、端粒酶、衰老与癌变

端粒和端粒酶与细胞增殖密切相关，在衰老和癌变过程中发挥重要作用。端粒的结构和长度变化、端粒酶的表达水平在众多相关蛋白所组成的复杂调控网络的作用下保持平衡。端粒酶也通过非端粒依赖性机制发挥细胞保护作用，可以促进干细胞激活和增殖。     

Autism: recent molecular genetic advances

Autism (MIM 209850) is a severe neuropsychiatric disorder of unknown aetiology with profound consequences for patients and their families. Strong evidence from twin and family studies indicates the importance of genetic factors in the development of idiopathic autism, although it is clear that these influences are complex. This review focuses on recent molecular investigations to identify susceptibility loci implicated in autistic disorder.     

细胞胀亡的分子机制研究进展

Oncosis is another form of cell death, which is different from apoptosis. The review will discuss the recent advances of oncosis on pathological morphology, nuclear biochemical changes and molecular mechanisms.     

Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis

Rationale: Idiopathic pulmonary fibrosis (IPF) is one of the most aggressive forms of idiopathic interstitial pneumonia. Some miRNAs may be associated with IPF and may affect the occurrence and development of IPF in various pathways. Many miRNAs and genes that may be involved in the development of IPF have been discovered using chip and high throughput technologies.Methods: We analyzed one miRNA and four mRNA databases. We identified hub genes and pathways related to IPF using GO, KEGG enrichment analysis, gene set variation analysis (GSVA), PPI network construction, and hub gene analysis. A comprehensive analysis of differentially expressed miRNAs (DEMs), predicted miRNA target genes, and differentially expressed genes (DEGs) led to the creation of a miRNA-mRNA regulatory network in IPF.Results: We found 203 DEGs and 165 DEMs that were associated with IPF. The findings of enrichment analyses showed that these DEGs were mainly involved in antimicrobial humoral response, antimicrobial humoral immune response mediated by antimicrobial peptide, extracellular matrix organization, cell killing, and organ or tissue specific immune response. The VEGFA, CDH5, and WNT3A genes overlapped between hub genes and the miRNA-mRNA regulatory network. The miRNAs including miR-199b-5p, miR-140-5p, miR-199a-5p, miR-125A-5p, and miR-107 that we predicted would regulate the VEGFA, CDH5, and WNT3A genes, which were also associated with IPF or other fibrosis-related diseases. GSVA indicated that metabolic processes of UTP and IMP, immune response, regulation of Th2 cell cytokine production, and positive regulation of NK cell-mediated immunity are associated with the pathogenesis and treatment of IPF. These pathways also interact with VEGFA, CDH5, and WNT3A.Conclusion: These findings provide a new research direction for the diagnosis and treatment of IPF.     

New models for new perspectives in the biology of senescence

This essay presents examples of life history patterns that are not often discussed. Life spans range nearly a million-fold between different species of higher animals and plants and must be species characteristics under considerable genetic control. A comparative approach to senescence reveals a vast variety in temporal organization, both among species as well as between and within populations that may vary over as large ranges of scale and qualitative characteristics as do morphological and biochemical variations. Species comparisons across many levels of biological organization involving the life histories of many species besides the usual few mammals, insects, and nematodes importantly expand the view of mechanisms that limit life spans. The presumption that age-correlated changes are all adverse to some degree and that most components of an organism should decay as the life span is approached is reevaluated.     

Genetic variations in the CLU and PICALM genes are associated with cognitive function in the oldest old

Recently, two large, and independent genome wide association studies of late-onset Alzheimer's disease (AD) established association with the same rs11136000 variation in the clusterin (CLU) gene. In addition, one variation, rs3851179, in the phosphatidylinositol binding clathrin assembly protein (PICALM) gene and one variation, rs6656401, in the complement component (3b/4b) receptor 1 (CR) gene were associated with AD. Here, we replicate these associations with cognitive functioning in 1380 individuals from the Danish (1905) birth cohort study of the oldest old (92-93 years at intake) using measures of Mini Mental State Examination (MMSE) and a cognitive composite score. We found a significant association between the highly frequent CLU rs11136000 T allele (38%) and better performance on the cognitive composite score (p = 0.016) explaining 0.5% of the mean variation in cognitive composite score, and for men a significant association between the highly frequent PICALM rs3851179 A allele (38%). Better performance was found (p = 0.024), explaining 1.4% of the mean variation in cognitive composite score in men. These alleles correspond to the minor alleles initially found more frequent in controls than in cases of AD.     

重组腺病毒介导的p16INK4a表达诱导A549细胞衰老的研究

目的 构建E1区缺失的复制缺陷型5型重组腺病毒载体，探讨p16INK4a基因对肺癌细胞株A549细胞增殖与衰老的影响。方法 通过脂质体介导，将pAdCMV-p16INK4a与pJM17共转染人5型腺病毒E1基因转化的人胚肾细胞系293细胞，同源重组产生腺病毒空斑，用双重PCR筛选出携带p16INK4a基因的重组腺病毒并感染肺癌细胞A549，用免疫组化及Western blot检测腺病毒载体介导的基因转移效率和蛋白表达水平，分别用X-gal染色和TRAP-ELISA检测A549细胞中衰老相关β-半乳糖苷酶及端粒酶活性。结果 腺病毒载体可将95％以上的p16INK4a基因转移到A549中，受感染细胞有外源p16INK4a蛋白表达，其生长受到明显抑制，即p16INK4a基因能诱导A549细胞表达衰老相关β-半乳糖苷酶，并抑制细胞中的端粒酶活性。结论 复制缺陷型重组腺病毒，能有效地介导外源基因的转移与表达，可用于基因免疫和基因治疗；p16INK4a基因能抑制肺癌细胞A549生长并诱导其发生复制性衰老。     

Cystic fibrosis: recent advances in genetics and molecular biology

Cystic fibrosis (CF) is the most common lethal hereditary disease of Caucasians, occurring once for every 2,000 live births. One out of 20 persons in the United States white population is a heterozygous carrier. An autosomal recessive pattern of inheritance is well established. The disease affects the respiratory and digestive tracts most severely. Despite the clearcut hereditary nature of the disease, insight into the biochemistry of CF has been almost totally lacking until very recently. New evidence strongly indicates that abnormal chloride ion transportation underlies the clinical manifestations. Recent advances in molecular genetics have established that the CF disease gene is located on the long arm of chromosome 7. Several restriction fragment length polymorphisms (RFLP) markers are closely linked to the CF gene. These markers permit antenatal testing of samples from fetuses at risk for CF with a high probability of disease prediction. One laboratory has isolated a desoxyribonucleic acid (DNA) sequence from chromosome 7 which is a candidate for the CF gene itself. A protein called the CF antigen is coded by a gene on chromosome 1. Patients with CF and carriers have abnormally high serum levels of this protein. In the normal state, the product of the CF gene on chromosome 7 may interact with the product of the gene on chromosome 1, enabling its normal catabolism and function. The structure of the CF antigen suggests that it may regulate ion transport.     

脑缺血损伤的分子机制研究进展

脑缺血疾病具有发病率高、死亡率高的特点 ,严重危害人类健康。尽管近几十年来对脑缺血进行了大量的研究[2 8- 3 0 ] ,但急性脑缺血的预后仍相当差。究其原因是由于脑缺血损伤的机制十分复杂 ,缺乏有效的干预手段。它的复杂性主要表现在 :脑缺血类型的复杂性 (包括局灶的或全脑的 ,完全的或不完全的 ,短暂的或永久的 )和脑缺血损伤分子机制在时空变化上的复杂性以及各作用因子间相互影响的复杂性。因此 ,迄今为止没有一种机制能完全阐明脑缺血的损伤机制。现认为参与脑缺血损伤的分子机制有兴奋性氨基酸的释放、钙离子稳态失衡、自由基的形…