The individual blood cell telomere attrition rate is telomere length dependent.
The individual blood cell telomere attrition rate is telomere length dependent.
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DOI：
10.1371/journal.pgen.1000375
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发表时间：
2009-02
期刊：
影响因子：
4.5
通讯作者：
Roos, Goran
中科院分区：
文献类型：
--
作者：
Nordfjall, Katarina;Svenson, Ulrika;Norrback, Karl-Fredrik;Adolfsson, Rolf;Lenner, Per;Roos, Goran
在人群研究中，与端粒相关的端粒缩短是外周血细胞的一个有据可查的特征，但尚不清楚这些数据在多大程度上可以转移到个体水平。采用实时荧光定量PCR技术，对959名个体间隔10年采集的两份血样进行了端粒长度（TL）检测。TL还测量了来自多代队列的13个家庭。正如预期的那样，我们发现随着时间的推移，TL呈年龄相关性下降（r =-0.164，P <0.001，n = 959）。 然而，大约三分之一的人在十年内表现出稳定或增加的TL。个体端粒磨损率与初始TL呈高度显著负相关（r =-0.752，P <0.001），表明磨损率在基线时端粒较长的个体中最明显。 相应地，年龄相关的端粒磨损率在年轻时端粒较长的家族中更显著（r =-0.691，P <0.001）。 在各种恶性肿瘤的诊断中已经报道了异常的血液TL，但是在本研究中，个体端粒磨损率或诊断前TL与后来的肿瘤发展之间没有关联。收集的数据强烈表明TL维持机制在体内发挥作用，为短端粒提供保护，正如之前在体外证明的那样。我们的研究结果可能会挑战的假设，个别TL可以预测可能的寿命或以后的肿瘤发展。在对人类血细胞的横断面研究中经常观察到年龄依赖性端粒缩短。端粒酶是一种能够延长端粒的酶，它在大多数肿瘤细胞中被激活，以使它们成为永生化。这是关于端粒长度的第一个纵向研究之一，在两次采集的人类血液样本中进行了研究，其间间隔约10年。一个有趣的发现是，第一份血液样本中的个体端粒长度与端粒磨损率高度相关。因此，在基线时显示最长端粒的个体显示端粒随时间缩短最快，反之亦然。在探索多代同堂群体时，在家庭层面也观察到了这一点。这些结果与端粒酶似乎优先作用于培养细胞中最短端粒的事实一致，并为一般端粒和细胞生物学提供了基础知识。由于队列中的一部分在第二次抽血后发生了肿瘤，我们有机会检查肿瘤患者与对照组相比端粒磨损率是否不同，但没有观察到这种迹象。然而，对于前列腺癌，诊断前短端粒长度≥ 9年似乎预测死亡。
Age-associated telomere shortening is a well documented feature of peripheral blood cells in human population studies, but it is not known to what extent these data can be transferred to the individual level. Telomere length (TL) in two blood samples taken at ∼10 years interval from 959 individuals was investigated using real-time PCR. TL was also measured in 13 families from a multigenerational cohort. As expected, we found an age-related decline in TL over time (r = –0.164, P<0.001, n = 959). However, approximately one-third of the individuals exhibited a stable or increased TL over a decade. The individual telomere attrition rate was inversely correlated with initial TL at a highly significant level (r = –0.752, P<0.001), indicating that the attrition rate was most pronounced in individuals with long telomeres at baseline. In accordance, the age-associated telomere attrition rate was more prominent in families with members displaying longer telomeres at a young age (r = –0.691, P<0.001). Abnormal blood TL has been reported at diagnosis of various malignancies, but in the present study there was no association between individual telomere attrition rate or prediagnostic TL and later tumor development. The collected data strongly suggest a TL maintenance mechanism acting in vivo, providing protection of short telomeres as previously demonstrated in vitro. Our findings might challenge the hypothesis that individual TL can predict possible life span or later tumor development. An age-dependent telomere shortening has been frequently observed in cross-sectional studies on human blood cells. Telomerase is an enzyme capable of lengthening telomeres, and it is activated in most tumor cells in order for them to become immortalized. This is one of the first longitudinal studies on telomere length, investigated in human blood samples taken at two occasions with approximately 10 years between them. An interesting finding was that the individual telomere length in the first blood sample was highly correlated with telomere attrition rate. Thus, individuals displaying the longest telomeres at baseline showed the most rapid telomere shortening over time and vice versa. This was also observed at the family level when exploring a multigenerational cohort. These results are in concordance with the fact that telomerase seems to preferentially act on the shortest telomeres in cultivated cells and provide fundamental knowledge for general telomere and cell biology. Because one part of the cohort developed tumors after the second blood draw, we had the opportunity to examine whether telomere attrition rate differed in tumor patients compared with controls, but no such indication was observed. However, for prostate cancer, short telomere length ≥9 years before diagnosis seemed to predict death.
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影响因子：
8.3
作者：
Jeanclos, E;Schork, NJ;Aviv, A
通讯作者：
Aviv, A
DOI：
10.1073/pnas.0501724102
发表时间：
2005-11-08
影响因子：
11.1
作者：
Nordfjäll, K;Larefalk, Å;Roos, G
通讯作者：
Roos, G
影响因子：
5.3
作者：
Iwama, H;Ohyashiki, K;Shay, JW
通讯作者：
Shay, JW
影响因子：
4.8
作者：
Ouellette, MM;Liao, M;Wright, WE
通讯作者：
Wright, WE
影响因子：
64.5
作者：
Hemann, MT;Strong, MA;Greider, CW
通讯作者：
Greider, CW