A Study of Radiation-Induced Telomere Instability Using Multiplex Ligation-Dependent Probe Amplification (MLPA)

The integrity of the chromosomes for two WIL2-derived lymphoblastoid cell lines (TK6 and WTK1) in the presence and absence of ionizing radiation was analyzed by Multiplex Ligation-Dependent Probe Amplification (MLPA). The TK6 cell line has the native p53 tumor-suppressor gene, whereas WTK1 cells contain a p53 mutation. Each cell line was isolated pre- and post-irradiation (2 and 3 Gy) and analyzed by MLPA. The impact of irradiation on these two cell lines was investigated using probes that target specific regions on chromosomes associated with subtelomeric regions. Results indicate that WTK1 and TK6 are impacted differently after irradiation, and that each cell line presents its own unique MLPA profile. The most notable differences are the appearance of a number of probes in the post-irradiated MLPA profile that are not present in the controls, and two unique probe signals only seen in WTK1 cells. These results build on our previous studies that indicate how different human cell lines can be affected by radiation in significantly different ways depending on the presence or absence of wild type p53.

Direct Correlation among Telomere Length, Cellular Aging, and Rejuvenation Effects of Honey Child Powder

Purpose: Telomere length (TL) is an indicator of age;however, hormonal influences complicate individual aging. It remains unclear whether TL shortening is a direct factor in both individual and cellular aging. Therefore, we examined the direct relationship between TL and cellular senescence at the cellular level. Methods: Telomerase activity, TL, and gene expression were measured in cultured human lung-, fetal-, and skin-derived fibroblasts, human skin keratinocytes, and telomerase reverse transcriptase (TERT) gene-immortalized cells using detection kits, Cawthon’s method, and reverse transcription-quantitative polymerase chain reaction, respectively. Novel substances that elongate telomeres were screened to confirm cell rejuvenation effects. Results: Long-term cell culture of TIG-1-20 normal human fibroblasts resulted in TL shortening, decreased division rate, and senescence progression, whereas in OUMS-36T-2 cells, TL elongation via TERT gene transfer increased the division rate, reduced endoplasmic reticulum stress, and upregulated genes associated with young individuals, indicating that cellular rejuvenation occurs via TL elongation. In addition, a honey child powder (HCP) extract was found through screening, and the HCP extract strongly suppressed the menin gene, resulting in increased telomerase activity and extended cell lifespan. Upon addition of the HCP extract to skin fibroblasts, gene expression of moisturizing components, including collagen, hyaluronic acid, and elastin, increased, and exhibited a rejuvenating effect with an increase in elastin amount. Conclusions: TL elongation or shortening is involved in cell proliferation rate and cellular aging, and TL elongation rejuvenates cells. In addition, HCP extract has a rejuvenating effect on cells and is expected to be a rejuvenating compound.

Comparative Analysis of the Antioxidant and Free-Radical Scavenging Activities of Different Water-Soluble Extracts of Green, Black and Oolong Tea Samples

Extracts of 40 green, black or oolong high quality tea samples from China, Japan or India among others, have been prepared according to the manufacturer instructions and assayed for total polyphenols content using the Folin-Ciocalteu phenol reagent. In addition, the antioxidant activity was assessed by the CUPRAC method and the free-radical scavenging activity was determined using the antioxidant-promoting decay of the stable free-radical DPPH. Caffeine and the most important catechins were identified using RP-HPLC previously validated method. Results from this study suggest that teas, even though they content similar amounts of caffeine, differ considerably in polyphenolic content and therefore in antioxidant and free-radical scavenging activities, depending on the part of the plant used and the process applied to the material for the preparation of the final tea presentation. Correlations among Folin-Ciocalteau’s reactivity of tea samples, the neocuproine reactivity, the DPPH decolourization and the HPLC analysis suggest that the antioxidant activity is due essentially to polyphenolic compounds present in teas, mainly EGCG. The best extraction method of tea powder was the one indicated by dealers. In general, the richest samples belong to green teas and the poorest samples belong to the black teas.

Nonisothermal Kinetics of Free-Radical Polymerization of 2,2-Dinitropropyl Methacrylate

The 2,2-dinitropropyl methacrylate（DNPMA） was synthesized by esterification of α-methacrylic acid with 2,2-dinitropropanol.The free-radical bulk polymerization of DNPMA in the presence of 2,2-azobisisobutyronitrile（AIBN） was investigated by differential scanning calorimetry（DSC） in the nonisothermal mode.Kissinger,Ozawa and Barrett methods were applied to determine the activation energy（Ea） and the reaction order of the free-radical polymerization.The results showed that the temperature of exothermic polymerization peaks increased with increasing heating rate.With increasing the molar ratio of monomer/initiator and the heating rate,the reaction order of nonisothermal polymerization was approximately equal to 1.The average Ea value from Kissinger and Ozawa methods（77.74±1.07 kJ/mol） was smaller than the value from the Barrett method（Ea=102.36 kJ/mol）.

The Study of Influence of Silica and Polyethilene Glycols Organic-Inorganic Compounds on Free-Radical Processes in Vitro

In this study investigation of influence of hybrid nanosilica-polyethylene glycols materials (molecular weight 1500, 6000 and 15000), prepared by sol-gel synthesis, on lipid peroxidation and antioxidant activity of human serum in vitro was performed. Methods included chemiluminescence analysis and quantitative malonic dialdehyde estimation. It was revealed that nanosilica-PEG materials with different molecular weight had certain biological activity. Powders of SiO2-PEG 1500 and SiO2-PEG 6000 manifest prooxidant effects, whereas mesoporous (calcine) powders produced antioxidant effects in blood serum in vitro.

Association between Dietary Collagen Consumption and Telomere Length: National Health and Nutrition Examination Survey

Background: Bioactive peptides derived from hydrolyzed collagen have broad physiological functions and beneficial effects on human health, ranging from reducing skin aging to modifying lipid metabolism. Telomere length shortening is an established biomarker of cellular aging. It is not known if collagen consumption is associated with telomere length protection. Our purpose was to investigate the relationship between dietary collagen consumption and telomere length in a nationally representative US adult population. Methods: We analyzed the data of 6173 adults aged 20 - 84 from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. Multivariable linear regression and a generalized additive model with smoothing plot were used to assess the association between the total collagen consumption and log-transformed leukocyte telomere length (LTL). Results: Compared with the lowest quartile of total collagen (Q1), we found that the second quartile of collagen (Q2) consumption (1.36 - 3.40 g/1000kcal) was positively associated with telomere length (β: 0.017;95% CI: 0.006, 0.028;P = 0.022) in the females while no association in the males (β: −0.003;95% CI: −0.019, 0.012;P = 0.678) and overall population (β: 0.008;95% CI: −0.002, 0.018;P = 0.141). The association in the females is nonlinear with an inflection point of 2.5 g/1000kcal (P for non-linearity: Conclusion: In conclusion, moderate dietary collagen has a positive and nonlinear association with telomere length in US females, while no significant associations were found in the males and the overall population.

EPAS1 prevents telomeric damage-induced senescence by enhancing transcription of TRF1,TRF2,and RAD50

Telomeres are nucleoprotein structures located at the end of each chromosome,which function in terminal protection and genomic stability.Telomeric damage is closely related to replicative senescence in vitro and physical aging in vivo.As relatively long-lived mammals based on body size,bats display unique telomeric patterns,including the upregulation of genes involved in alternative lengthening of telomeres(ALT),DNA repair,and DNA replication.At present,however,the relevant molecular mechanisms remain unclear.In this study,we performed cross-species comparison and identified EPAS1,a well-defined oxygen response gene,as a key telomeric protector in bat fibroblasts.Bat fibroblasts showed high expression of EPAS1,which enhanced the transcription of shelterin components TRF1 and TRF2,as well as DNA repair factor RAD50,conferring bat fibroblasts with resistance to senescence during long-term consecutive expansion.Based on a human single-cell transcriptome atlas,we found that EPAS1 was predominantly expressed in the human pulmonary endothelial cell subpopulation.Using in vitro-cultured human pulmonary endothelial cells,we confirmed the functional and mechanistic conservation of EPAS1 in telomeric protection between bats and humans.In addition,the EPAS1 agonist M1001 was shown to be a protective compound against bleomycin-induced pulmonary telomeric damage and senescence.In conclusion,we identified a potential mechanism for regulating telomere stability in human pulmonary diseases associated with aging,drawing insights from the longevity of bats.

Hematopoietic stem cell transplantation of aplastic anemia by relative with mutations and normal telomere length: A case report

BACKGROUND Immunosuppressive therapy and matched sibling donor hematopoietic stem cell transplantation(MSD-HSCT)are the preferred treatments for aplastic anemia(AA).CASE SUMMARY In this report,we describe a 43-year-old male patient with severe AA who carried BRIP1(also known as FANCJ),TINF2,and TCIRG1 mutations.Screening of the family pedigree revealed the same TINF2 mutation in his mother and older brother,with his older brother also carrying the BRIP1 variant and demonstrating normal telomere length and hematopoietic function.The patient was successfully treated with oral cyclosporine A,eltrombopag,and acetylcysteine,achieving remission 4 years after receiving MSD-HSCT from his older brother.CONCLUSION This case provides a valuable clinical reference for individuals with suspected pathogenic gene mutations,normal telomere length,and hematopoietic function,highlighting them as potential donors for patients with AA.

不同运动方式对人体DNA损伤、DNA甲基化和端粒长度的影响

背景:运动不仅是改善身体健康和心理健康的有效手段,还对代谢性和心脑血管等疾病的发生、发展具有良好的干预效果,其原因与表观遗传因素有关。目的:总结不同运动方式对人体DNA损伤、DNA甲基化和端粒长度的影响,并分析运动调控表观遗传修饰的可能机制,以期为运动改善机体功能提供参考。方法:以“运动,有氧训练,急性运动,无氧训练,抗阻训练,DNA损伤,DNA甲基化,端粒”为中文检索词,以“exercise,sport,aerobic exercise,anaerobic exercise,resistance training,acute exercise,DNA methylation,DNA damage,telomere”为英文检索词。在PubMed、Embase、Web of Science、中国知网数据库中进行检索,并根据纳入与排除标准筛选文献,最终纳入70篇文献。结果与结论:①长期有氧、抗阻和无氧运动均能改善DNA损伤,其原因与运动可以提高机体的抗氧化能力有关。而急性运动则会通过上调活性氧和活性氮氧化物的表达进而加剧DNA损伤程度;②急性运动、长期抗阻运动和无氧运动在降低DNA甲基化方面具有积极作用,其关键机制可能是运动诱导的活性氧使氧化型谷胱甘肽/还原型谷胱甘肽比值和DNA甲基化转移酶、10-11易位酶的表达发生了改变,进而对DNA甲基化产生调控作用;③与其他运动形式相比,长时间有氧运动可能更具有增加端粒长度的潜在价值,其中的生物学机制涉及炎症、氧化应激、DNA甲基化和微小RNA的表达调控;④基于当前文献可知,有氧运动持续2年以上可以增加端粒长度,未来的研究也应进一步明确最佳的运动持续时间。

莱姆病螺旋体端粒解离酶的表达纯化及其晶体衍射分析

【目的】对莱姆病螺旋体(Borrelia burgdorferi)端粒解离酶(telomere resolvase,ResT)进行原核可溶性表达纯化,并筛选高衍射度的ResT-DNA复合物晶体,为探究ResT-DNA复合物的结构和功能奠定基础。【方法】合成pET28 b-ResT表达质粒,构建原核表达载体pSUMO-ResT,分析ResT可溶性蛋白在BL21(DE3)、BL21(DE3)pLysS、BL21 Gold(DE3)pLysS、BL21 Codon Plus(DE3)、Rosetta(DE3)和Rosetta(DE3)pLysS中的表达量,获得最优的ResT原核表达菌株。基于AlphaFold预测的ResT蛋白模型,利用定点突变及ResT可溶性蛋白表达分析,获得高效可溶性表达ResT突变体。经Ni-NTA亲和层析、HiTrap Heparin HP亲和层析及分子筛层析对ResT突变体ResT(W94H)进行蛋白纯化。利用EMAS检测ResT(W94H)与DNA的结合能力。使用蛋白晶体接种(seeding)和交叉接种(cross-seeding)方法,利用多种商业化结晶试剂盒筛选并优化ResT-DNA复合物的结晶条件,对复合物晶体进行X射线衍射分析。【结果】BL21 Gold(DE3)pLysS菌株是ResT最佳的高效可溶性表达菌株,W94H突变体比野生型具有更强的可溶性表达。获得了高纯度(95%)且高质量浓度(15 mg/mL)的ResT(W94H),其能够与底物DNA形成稳定的ResT-DNA复合物。在18℃下,ResT-DNA最佳结晶条件是:PEG3350150 g/L、二甲苯二酸钠0.1 mol/L(pH 6.6)、NaCl 0.15 mol/L,ResT-DNA晶体分辨率最高为3.52,晶体空间群为P4。【结论】得到了高纯度ResT(W94H)蛋白,获得了ResT-DNA复合物晶体。

端粒长度与10种常见肌肉骨骼疾病的关系孟德尔随机化分析

背景:多项观察性研究表明,端粒长度与肌肉骨骼疾病之间存在潜在的关联,然而它们之间的潜在机制仍不清楚。目的:利用两样本孟德尔随机化分析来探索端粒长度与肌肉骨骼疾病之间的遗传因果关系。方法:从英国生物银行中获得端粒长度的全基因组关联研究汇总数据。从FinnGen财团中获得了关于10种常见肌肉骨骼疾病(骨坏死、骨髓炎、骨质疏松、类风湿关节炎、腰痛、椎管狭窄、痛风、肩周炎、强直性脊柱炎和下肢深静脉血栓)的全基因组关联研究汇总数据。使用逆方差加权、孟德尔随机化-Egger和加权中位数方法评估端粒长度与10种肌肉骨骼疾病的因果关系,逆方差加权作为主要的孟德尔随机化分析方法,并进行敏感性分析探讨结果稳健性。结果与结论:①逆方差加权法结果表明,遗传预测的端粒长度与类风湿关节炎(OR=0.78,95%CI:0.64-0.95,P=0.015)和骨坏死(OR=0.56,95%CI:0.36-0.90,P=0.016)风险之间存在负向因果关系,但未发现端粒长度与其他8种肌肉骨骼疾病之间存在因果关系(P均>0.05)。②敏感性分析结果表明因果关系稳健,孟德尔随机化-Egger截距分析未检测到潜在的水平多效性(P均>0.05)。③此项孟德尔随机化研究支持端粒长度对类风湿关节炎和骨坏死的保护作用的结论,然而,未来将需要更多的基础和临床研究来验证。

植物端粒DNA结合蛋白及端粒酶活性调控研究

植物衰老和种子劣变机理的研究一直是农业科学领域关注的热点。植物衰老会对农业产生巨大的负面影响,牧草提前衰老也会导致草地生产力下降,限制草产业的发展。由于种子劣变,全球每年约有25%的种子失去活力,导致巨额的经济损失,严重影响农业的健康发展。深入揭示植物衰老特性和调控机制,不仅对于阐明植物生态适应性及种群稳定性具有重要价值,而且对于延缓衰老技术和调控措施的选择具有重要实践意义。在模式植物拟南芥研究中发现,染色体端粒与植物衰老以及种子活力密切相关。端粒是染色体末端的重复DNA序列,由端粒DNA和结合蛋白组成。端粒结合蛋白是一组与端粒DNA结合的蛋白质,主要是帮助稳定端粒结构并保护端粒免受DNA修复系统的干扰,其次还参与了基因表达、DNA复制和染色体结构调节等许多生物学过程。端粒酶由端粒酶逆转录酶(TERT)和端粒酶RNA(TER)两个亚单位组成,端粒酶逆转录酶亚基参与线粒体功能以及相关基因表达调控,通过对端粒酶新功能的探索,有助于提高植物的抗逆性,从而延缓植物的衰老进程,为提高作物产量提供一条新的途径。近年来在植物中研究发现,端粒的动态变化与植物衰老存在相关性,植物端粒内稳态的维持机制仍存在许多问题,端粒长度以及端粒酶活性的动态变化与植物衰老以及种子老化的关系尚不清楚。基于此,本研究综述了端粒和端粒结合蛋白在植物生物学中的作用,重点论述了端粒和端粒结合蛋白调控端粒长度以及端粒酶活性的模式,为后续解析植物衰老以及种子劣变机理提供理论参考依据。

链霉菌中一类同源非典型端粒的克隆及分析

采用自连接-PCR的方法克隆和测序了Streptomyces cattleya DSM46488、Streptomyces mobaraensisDSM40847及Streptomyces davawensisJCM4913的端粒,序列比对发现,这3种端粒具有较高的序列相似性,前60个核苷酸的序列相似性达到了80%以上;在二级结构水平,这些端粒含有多个回文序列,其中,包含相同的回文序列I和II,但并不能通过折返形成超级发夹结构;Streptomyces cattleya DSM46488、StreptomycesmobaraensisDSM40847及Streptomyces davawensis JCM4913的端粒与线性质粒pSHJG1端粒及Streptomyces albus J1074染色体端粒均具有较高的序列相似性;系统发育分析显示它们与典型端粒及其他非典型端粒处于不同的进化分支,S.cattleyaDSM46488、S.mobaraensis DSM40847、S.davawensisJCM4913、S.albus J1074及S.hydroscopicussubsp.Jinggangensis 5008都编码同源的潜在末端蛋白-端粒相关蛋白,暗示了这类同源的非典型端粒系统广泛存在于链霉菌中。

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E2相关因子2通路激活、促进端粒酶反转录酶表达等。(4)目前在中药抑制间充质干细胞衰老的研究中以对骨髓间充质干细胞研究最多,效果较好。(5)左归丸、补肾调肝方、白藜芦醇及黄芪等中药均可通过促进衰老间充质干细胞增殖及成骨分化起到防治骨质疏松作用,但对中药通过抑制间充质干细胞衰老改善间充质干细胞旁分泌功能及防治其他衰老相关疾病的机制仍需进一步探究。

端粒酶抑制剂在胶质瘤治疗中的研究现状和发展前景

端粒(telomere)是人类染色体末端一段富含TTAGGG/AATCCC碱基对和3'单链的特殊结构,其末端由Shelterin蛋白复合体封闭。细胞每次分裂后,端粒都会缩短一部分,直到到达临界值,而此时将触发双链断裂(double-strand break,DSB),引起细胞死亡。为了保障细胞的长期生存,必须具备延长端粒的机制。在正常情况下,这个机制主要存在于人类干细胞中,涉及一种名为端粒酶(telomerase)的酶,端粒酶主要由催化亚基(hTERT)和RNA(hTR)两个部分组成。大多数肿瘤细胞中都检测到了端粒酶的表达,在胶质母细胞瘤中甚至高达80%的细胞都表现出高端粒酶活性,表明以端粒酶为肿瘤治疗的靶点是极具有前景的。该文主要讨论近年来出现的端粒酶抑制剂在胶质瘤治疗中的应用。

生殖细胞减数分裂端粒挂膜分子机制概述

减数分裂是生殖细胞形成配子的分裂方式,染色体端粒正确锚定在核膜上是这一重要生理过程顺利进行的前提。蛋白与蛋白的相互作用使端粒悬挂在生殖细胞的核膜上,以保证减数第一次分裂前期中染色体配对、联会和同源重组的正确进行。本文对目前已知的减数分裂端粒挂膜相关蛋白及复合物,包括端粒保护蛋白复合物(Shelterin)、减数分裂特异的核骨架和细胞质骨架连接复合物(LINC)、内核膜相关的TERB1-TERB2-MAJIN(TTM)复合物,以及SPDYA-CDK2复合体的结构和功能方面进行概括及综述。

颅内动脉瘤模型大鼠端粒长度与端粒结合蛋白基因表达变化

目的探讨颅内动脉瘤(IA)大鼠外周血端粒长度及其结合蛋白基因表达变化,初步探讨IA的潜在机制。方法将24只SD雌性大鼠随机等分为两组,即对照组和IA模型组(以下简称模型组)。模型组结扎左侧颈总动脉、结扎双侧肾动脉后支、切除双侧卵巢,并于造模后1周喂同时含8%氯化钠和3%L-甲硫氨酸的饲料。对照组则仅暴露左侧颈总动脉和双肾20 min后缝合皮肤,喂常规饲料。两组大鼠分别于造模前和造模后6个月时进行眶下静脉丛取血并提取外周血基因组DNA,检测相对端粒长度。造模后6个月时处死前测量血压及检测血清中雌二醇、同型半胱氨酸(Hcy)水平,提取外周血总RNA并检测6种端粒结合蛋白[端粒重复序列结合因子1(TRF1)、端粒重复序列结合因子2(TRF2)、端粒保护蛋白1(POT1)、肾上腺皮质增生蛋白同源异构体(TPP1)、TRF1相互作用核蛋白2(TIN2)、阻滞活化蛋白1(RAP1)]基因表达水平的变化。处死后通过血管铸型观察IA形成情况。结果造模后6个月时,模型组大鼠收缩压和血清Hcy水平均高于对照组(P<0.05),雌二醇水平低于对照组(P<0.05)。模型组与对照组大鼠初始(0个月时)外周血端粒长度比较,差异无统计学意义(P>0.05);造模后6个月时,模型组大鼠端粒长度明显短于对照组,差异有统计学意义(P<0.05)。造模后6个月时,模型组大鼠外周血的TRF2和TPP1基因表达水平明显高于对照组(P<0.05),而TRF1、POT1、TIN2和RAP1基因表达水平与对照组相比,差异均无统计学意义(P>0.05)。结论IA模型大鼠造模后6个月时,外周血端粒长度明显缩短,端粒结合蛋白TRF2和TPP1基因表达水平上调,这可能与IA的病因机制相关。

端粒-端粒酶在神经退行性疾病中的研究进展

神经退行性疾病多以β-淀粉样蛋白(β-amyloid,Aβ)、α-突触核蛋白(α-synuclein,α-syn)作为生物标记物来辅助临床进行诊断。近年来,人们发现染色体末端的端粒能够作为衡量生物衰老程度的指标,并发现端粒长度、端粒酶活性可能作为评估老年神经退行性疾病发病风险、疾病进展、不良预后的血液标记物,但目前相关国内外研究结果并不具有一致性。了解端粒相关生物标记物在年龄相关疾病中的作用,是可以帮助临床医生更好地了解疾病的发生发展机制。现就端粒-端粒酶系统在神经退行性疾病中的最新研究进展综述如下,以介绍端粒长度、端粒酶活性对神经退行性疾病的影响以及潜在作用机制。

端粒在获得性再生障碍性贫血克隆演化中的作用

1/3获得性再生障碍性贫血患者端粒长度存在缩短,且端粒越短的患者病程越长、越易复发、总体生存率越低,出现克隆演化的概率越大。端粒长度受到多方面因素的影响,包括端粒酶活性、端粒酶相关基因、端粒调控蛋白等。端粒缩短导致遗传信息不稳定,使获得性再生障碍性贫血患者出现克隆演化的概率增加。本文就端粒在获得性再生障碍性贫血克隆演化中的作用及影响端粒长度因素的最新研究进展作一综述。

依赖于端粒延长替代机制的胶质瘤临床前模型及应用现状

胶质瘤是中枢神经系统最常见的恶性肿瘤,主要起源于神经胶质细胞。由于胶质瘤具有高度侵袭性的特点,其死亡率在各种癌症中名列前茅。因此,新的治疗方法和新的药物开发对于胶质瘤的治疗意义十分重大。在大约30%的胶质瘤中,端粒的维持并不是通过端粒酶的激活延长的,而是通过端粒延长替代机制(ALT)来维持和延长端粒。然而,由于目前对于ALT胶质瘤细胞系以及临床前的ALT胶质瘤模型的研究还比较匮乏,从而制约了ALT胶质瘤的机制研究。因此,本篇综述在此探讨了目前发现的ALT胶质瘤细胞系及ALT胶质瘤动物模型,以及这些模型在临床前研究中发挥的作用和最新的进展。