Analyses and comparisons of telomerase activity and telomere length in human T and B cells: insights for epidemiology of telomere maintenance.
Analyses and comparisons of telomerase activity and telomere length in human T and B cells: insights for epidemiology of telomere maintenance.
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DOI：
10.1016/j.jim.2009.09.012
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发表时间：
2010-01-31
影响因子：
2.2
通讯作者：
Blackburn, Elizabeth
中科院分区：
文献类型：
--
作者：
Lin, Jue;Epel, Elissa;Cheon, Joshua;Kroenke, Candyce;Sinclair, Elizabeth;Bigos, Marty;Wolkowitz, Owen;Mellon, Synthia;Blackburn, Elizabeth
端粒是保护真核生物染色体末端的DNA-蛋白质复合物。细胞端粒酶通过添加端粒DNA来抵消端粒缩短。越来越多的文献将较短的端粒长度和较低的端粒酶活性与各种年龄相关的疾病和较早的死亡率联系起来。因此，白细胞端粒长度（LTL）和端粒酶活性正在成为生物标志物和年龄相关疾病的促成因素。然而，没有临床研究直接检查端粒酶活性和端粒长度在不同的淋巴细胞亚型分离自相同的捐助者，这可以提供深入了解白细胞端粒维护的总结措施。我们报告了第一个在人类中检测端粒酶活性和端粒长度水平的定量数据，这些数据来自同一供体的四种淋巴细胞亚群--CD 4+、CD 8 + CD 28+和CD 8 + CD 28 − T细胞和B细胞，以及健康女性队列中的总PBMC。结果发现，B细胞的端粒酶活性最高，端粒长度最长; CD 4 + T细胞的端粒酶活性略高于CD 8 + CD 28 + T细胞，端粒长度相近。与早期报道的CD 8 + CD 28 −T细胞是复制性衰老细胞一致，它们具有最低的端粒酶活性和最短的端粒长度。此外，较高的CD 8 + CD 28 − T细胞百分比与较短的总PBMC TL相关（r =-0.26，p = 0.05）。有趣的是，来自同一个体的CD 4+和CD 8 + CD 28 + T细胞的端粒酶活性强烈相关（r = 0.55，r < 0.001），表明这两种细胞亚型中端粒酶活性调节的可能共同机制。这些数据将有助于理解白细胞老化及其与人类健康的关系。
Telomeres are the DNA–protein complexes that protect the ends of eukaryotic chromosomes. The cellular enzyme telomerase counteracts telomere shortening by adding telomeric DNA. A growing body of literature links shorter telomere length and lower telomerase activity with various age-related diseases and earlier mortality. Thus, leukocyte telomere length (LTL) and telomerase activity are emerging both as biomarkers and contributing factors for age-related diseases. However, no clinical study has directly examined telomerase activity and telomere length in different lymphocyte subtypes isolated from the same donors, which could offer insight into the summary measure of leukocyte telomere maintenance. We report the first quantitative data in humans examining both levels of telomerase activity and telomere length in four lymphocyte subpopulations from the same donors—CD4+, CD8+CD28+ and CD8+CD28− T cells and B cells, as well as total PBMCs—in a cohort of healthy women. We found that B cells had the highest telomerase activity and longest telomere length; CD4+ T cells had slightly higher telomerase activity than CD8+CD28+ T cells, and similar telomere length. Consistent with earlier reports that CD8+CD28−T cells are replicatively senescent cells, they had the lowest telomerase activity and shortest telomere length. In addition, a higher percentage of CD8+CD28− T cells correlated with shorter total PBMC TL (r = −0.26, p = 0.05). Interestingly, telomerase activities of CD4+ and CD8+CD28+ T cells from the same individual were strongly correlated (r = 0.55, r < 0.001), indicating possible common mechanisms for telomerase activity regulation in these two cell subtypes. These data will facilitate the understanding of leukocyte aging and its relationship to human health.
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