Frenck R W, Blackburn E H, Shannon K M
Clinical Investigation Department, U.S. Naval Hospital, Oakland, CA 94627, University of California, San Francisco, CA 94143, USA.
Proc Natl Acad Sci U S A. 1998 May 12;95(10):5607-10. doi: 10.1073/pnas.95.10.5607.
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.
此前已注意到，在正常成人组织中，端粒重复序列会随着衰老而逐渐丢失，这一过程与细胞衰老有关。目前尚无关于家庭内部或生命早期正常人类细胞中端粒缩短速率的数据。为了解决这些问题，我们测量了12个家庭中75名成员外周血白细胞（PBL）的端粒长度，以及一组年龄在5至48个月的无亲缘关系健康儿童外周血白细胞的端粒长度。在此，我们报告一个惊人的发现：端粒损耗速率在不同年龄阶段存在显著差异。幼儿外周血白细胞中的端粒重复序列迅速丢失（每年超过1千碱基对），随后在4岁至青年期之间出现明显平稳期，而在生命后期则逐渐损耗。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控。我们的研究结果对当前关于正常体细胞中端粒序列如何丢失的模型具有启示意义，并表明外周血白细胞是研究该过程如何受到控制的理想组织。
