共查询到19条相似文献,搜索用时 78 毫秒
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端粒DNA与细胞的衰老,死亡 总被引:1,自引:0,他引:1
端粒DNA与细胞的衰老、死亡白丽荣(河北衡水师专生物系,053000)端粒DNA是真核生物染色体的天然末端,它的生物学功能是保持染色体稳定。近年来研究发现,端粒DNA决定了细胞寿命,并与细胞的自然凋亡及癌化有关。端粒(Telomere)是指真核细胞线... 相似文献
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端粒是真核细胞染色体末端的一种保护性结构,在维持染色体末端稳定性等方面起重要作用。端粒被认为是细胞衰老的生物钟。研究证明端粒的长度随着人体的衰老呈进行性缩短。近年来,分子流行病学研究表明端粒的长度与人的寿命呈负相关。越来越多的相关研究发现,端粒的长度与许多衰老相关的疾病密切相关。原发性高血压(esential hypertension,EH)、冠状动脉粥样硬化(coronary atherosclerosis,CA)、心力衰竭(heart failure,HF)和脑卒中(stroke)等心脑血管疾病的发生发展过程中都伴有端粒长度的改变。影响端粒长度的因素有很多,包括遗传因素和非遗传因素,其中有关端粒长度和非遗传因素的关系还不确定。另外,端粒是否可以作为衰老及其相关疾病的预测因子还没有定论。本文现就端粒在人类疾病中的相关研究进展作一简要综述。 相似文献
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端粒(酶)的结构功能及其与衰老和癌症的关系 总被引:7,自引:0,他引:7
端粒是真核生物线性染色体末端由重复DNA序列和蛋白质结合形成的复合结构。在哺乳动物中,其特殊的环形结构与多种结合蛋白形成了端粒功能的基础。端粒酶具有逆转录酶特性和维持端粒长度的功能,其活性与恶性肿瘤的发生密切相关。衰老是大多数真核细胞分裂到一定次数后必然走上的道路,端粒的缩短是其中重要的调控因素,并在早衰症患者中表现出异常。癌细胞的恶性化过程中,端粒酶的激活是一重要步骤,此过程可受到多水平多途径的调节。癌症和衰老相互联系,端粒酶可能在两者交错的网络中体现了这一联系。 相似文献
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在对山羊体细胞进行外源基因转染过程中,无论电击法或脂质体法所得到的细胞克隆都有细胞过快衰老的现象。山羊体细胞转基因后出现细胞体积增大、细胞核膨大并逐步分裂成多核、细胞质空泡化和吐核等衰老的表型特征。转基因后衰老细胞的染色体核型正常,但经细胞染色体端粒长度的Southern检测发现,转基因衰老细胞比原代胎儿成纤维细胞染色体端粒长度减少了2.56 kb,超出了正常传代40代的细胞的衰老速度,但转基因衰老细胞仍能支持核移植克隆胚胎的早期发育。 相似文献
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Francesca Cipressa Sabrina Romano Silvia Centonze Petra I. zur Lage Fiammetta Vernì Patrizio Dimitri Maurizio Gatti Giovanni Cenci 《Genetics》2013,195(1):147-158
Drosophila telomeres are elongated by the transposition of telomere-specific retrotransposons rather than telomerase activity. Proximal to the terminal transposon array, Drosophila chromosomes contain several kilobases of a complex satellite DNA termed telomere-associated sequences (TASs). Reporter genes inserted into or next to the TAS are silenced through a mechanism called telomere position effect (TPE). TPE is reminiscent of the position effect variegation (PEV) induced by Drosophila constitutive heterochromatin. However, most genes that modulate PEV have no effect on TPE, and systematic searches for TPE modifiers have so far identified only a few dominant suppressors. Surprisingly, only a few of the genes required to prevent telomere fusion have been tested for their effect on TPE. Here, we show that with the exception of the effete (eff; also called UbcD1) mutant alleles, none of the tested mutations at the other telomere fusion genes affects TPE. We also found that mutations in eff, which encodes a class I ubiquitin-conjugating enzyme, act as suppressors of PEV. Thus, eff is one of the rare genes that can modulate both TPE and PEV. Immunolocalization experiments showed that Eff is a major constituent of polytene chromosomes. Eff is enriched at several euchromatic bands and interbands, the TAS regions, and the chromocenter. Our results suggest that Eff associates with different types of chromatin affecting their abilities to regulate gene expression. 相似文献
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Amel Chebel Serge Bauwens Luc-Marie Gerland Aurélie Belleville Iwona Urbanowicz Aude Roborel de Climens Yves Tourneur Wei Wen Chien Régine Catallo Gilles Salles Eric Gilson Martine Ffrench 《Aging cell》2009,8(1):52-64
Normal lymphocytes represent examples of somatic cells that are able to induce telomerase activity when stimulated. As previously reported, we showed that, during lymphocyte long-term culture and repeated stimulations, the appearance of senescent cells is associated with telomere shortening and a progressive drop in telomerase activity. We further showed that this shortening preferentially occured at long telomeres and was interrupted at each stimulation by a transitory increase in telomere length. In agreement with the fact that telomere uncapping triggers lymphocyte senescence, we observed an increase in γ-H2AX and 53BP1 foci as well as in the percentage of cells exhibiting DNA damage foci in telomeres. Such a DNA damage response may be related to the continuous increase of p16 ink4a upon cell stimulation and cell aging. Remarkably, at each stimulation, the expression of shelterin genes, such as hTRF1 , hTANK1 , hTIN2 , hPOT1 and hRAP1 , was decreased. We propose that telomere dysfunction during lymphocyte senescence caused by iterative stimulations does not only result from an excessive telomere shortening, but also from a decrease in shelterin content. These observations may be relevant for T-cell biology and aging. 相似文献
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The absence of telomerase in many eukaryotes leads to the gradual shortening of telomeres, causing replicative senescence. In humans, this proliferation barrier constitutes a tumor suppressor mechanism and may be involved in cellular aging. Yet the heterogeneity of the senescence phenotype has hindered the understanding of its onset. Here we investigated the regulation of telomere length and its control of senescence heterogeneity. Because the length of the shortest telomeres can potentially regulate cell fate, we focus on their dynamics in Saccharomyces cerevisiae. We developed a stochastic model of telomere dynamics built on the protein-counting model, where an increasing number of protein-bound telomeric repeats shift telomeres into a nonextendable state by telomerase. Using numerical simulations, we found that the length of the shortest telomere is well separated from the length of the others, suggesting a prominent role in triggering senescence. We evaluated this possibility using classical genetic analyses of tetrads, combined with a quantitative and sensitive assay for senescence. In contrast to mitosis of telomerase-negative cells, which produces two cells with identical senescence onset, meiosis is able to segregate a determinant of senescence onset among the telomerase-negative spores. The frequency of such segregation is in accordance with this determinant being the length of the shortest telomere. Taken together, our results substantiate the length of the shortest telomere as being the key genetic marker determining senescence onset in S. cerevisiae. 相似文献
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Although exposure to stressors is known to increase disease susceptibility and accelerate ageing, evidence is accumulating that these effects can span more than one generation. Stressors experienced by parents have been reported to negatively influence the longevity of their offspring and even grand offspring. The mechanisms underlying these long-term, cross-generational effects are still poorly understood, but we argue here that telomere dynamics are likely to play an important role. In this review, we begin by surveying the current connections between stress and telomere dynamics. We then lay out the evidence that exposure to stressors in the parental generation influences telomere dynamics in offspring and potentially subsequent generations. We focus on evidence in mammalian and avian studies and highlight several promising areas where our understanding is incomplete and future investigations are critically needed. Understanding the mechanisms that link stress exposure across generations requires interdisciplinary studies and is essential to both the biomedical community seeking to understand how early adversity impacts health span and evolutionary ecologists interested in how changing environmental conditions are likely to influence age-structured population dynamics. 相似文献
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K. Muniyappa K. Mary Kironmai 《Critical reviews in biochemistry and molecular biology》2013,48(4):297-336
Telomeres are the termini of linear eukaryotic chromosomes consisting of tandem repeats of DNA and proteins that bind to these repeat sequences. Telomeres ensure the complete replication of chromosome ends, impart protection to ends from nucleolytic degradation, end-to-end fusion, and guide the localization of chromosomes within the nucleus. In addition, a combination of genetic, biochemical, and molecular biological approaches have implicated key roles for telomeres in diverse cellular processes such as regulation of gene expression, cell division, cell senescence, and cancer. This review focuses on recent advances in our understanding of the organization of telomeres, telomere replication, proteins that bind telomeric DNA, and the establishment of telomere length equilibrium. 相似文献
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亚硒酸钠对肝细胞L-02端粒酶活性和端粒长度的作用 总被引:3,自引:0,他引:3
通过研究硒对端粒酶活性和端粒长度的作用 ,探讨硒抗衰老的生物学机制。实验以人肝细胞株L 0 2为研究对象 ,分别补充 0 .5和 2 .5 μmol L亚硒酸钠 ,采用端粒重复序列扩增 焦磷酸根酶联发光法、逆转录聚合酶链式反应法及流式荧光原位杂交法 ,分别检测细胞的端粒酶活性、人端粒酶逆转录酶催化亚基基因 (hTERT)的表达及端粒长度的变化。结果表明 :常规培养的肝细胞株L 0 2的端粒酶活性和hTERT基因表达水平均较低。补充 0 .5和2 .5 μmol L亚硒酸钠三周后细胞生长状况良好、端粒酶活性和hTERT基因表达水平显著性增高 ,且呈一定的剂量 效应关系。细胞补充亚硒酸钠四周后端粒长度显著增长。说明营养浓度的亚硒酸钠可通过提高端粒酶活性和增长端粒长度来减缓L 0 2肝细胞衰老、延长细胞寿命。 相似文献