The rate of telomere sequence loss in human leukocytes varies with age
The rate of telomere sequence loss in human leukocytes varies with age
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DOI：
10.1073/pnas.95.10.5607
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发表时间：
1998-05-12
影响因子：
11.1
通讯作者：
Shannon, KM
中科院分区：
文献类型：
--
作者：
Frenck, RW;Blackburn, EH;Shannon, KM
之前已经注意到，在正常成人组织中，随着衰老，端粒重复序列逐渐丢失，并且该过程与细胞衰老有关。没有数据可以说明正常人类细胞在家庭中或生命早期的端粒缩短率。为了解决这些问题，我们测量了 12 个家庭的 75 名成员以及一组 5-48 个月大的无关健康儿童的外周血白细胞 (PBL) 端粒长度。在这里，我们报告了令人惊讶的观察结果，即不同年龄的端粒损耗率显着不同，幼儿的 PBL 中端粒重复序列迅速丢失（以每年 > 1 kilobase 的速度），随后在 4 岁和青年期之间出现明显的平台期，并在以后的生活中逐渐损耗。这些数据表明，造血细胞中端粒重复序列的丢失是一个动态过程，在幼儿和成人中受到不同的调节。我们的结果对当前正常体细胞中端粒序列如何丢失的模型具有影响，并表明 PBL 是研究如何控制这一过程的绝佳组织。
A gradual loss of telomeric repeat sequences with aging previously has been noted in normal adult tissues, and this process has been implicated in cell senescence. No data exist that address the rate of telomere shortening in normal human cells within families or early in life. To address these questions, we measured telomere lengths in peripheral blood leukocytes (PBLs) from 75 members of 12 families and in a group of unrelated healthy children who were 5-48 months old. Here we report the surprising observation that rates of telomere attrition vary markedly at different ages, Telomeric repeats are lost rapidly (at a rate of >1 kilobase per year) from the PBLs of young children, followed by an apparent plateau between age 4 and young adulthood, and by gradual attrition later in life. These data suggest that the loss of telomeric repeats in hematopoietic cells is a dynamic process that is differentially regulated in young children and adults. Our results have implications for current models of how telomeric sequences are lost in normal somatic cells and suggest that PBLs are an excellent tissue to investigate how this process is controlled.