Age-associated telomere attrition of lymphocytes in vivo is co-ordinated with changes in telomerase activity, composition of lymphocyte subsets and health conditions.
Age-associated telomere attrition of lymphocytes in vivo is co-ordinated with changes in telomerase activity, composition of lymphocyte subsets and health conditions.
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DOI：
10.1042/cs20140481
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发表时间：
2015-03
期刊：
影响因子：
--
通讯作者：
Weng NP
中科院分区：
文献类型：
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作者：
Lin Y;Damjanovic A;Metter EJ;Nguyen H;Truong T;Najarro K;Morris C;Longo DL;Zhan M;Ferrucci L;Hodes RJ;Weng NP
端粒在维持染色体完整性和控制细胞复制方面是必不可少的。外周血单核细胞(PBMCs)端粒长度随年龄增长的情况从横断面研究中得到了很好的证明。但体内端粒长度的实际变化及其与个体内随年龄增长的致病因素的关系尚未完全解决。本文对216例20-90岁人群的外周血单核细胞、淋巴细胞和单核细胞的端粒长度进行了纵向分析，并进行了0、5和12年的随访。在5年和12年的随访中，分别有34%和46%的受试者PBMC端粒长度下降，56%和47%的受试者端粒长度无明显变化，10%和7%的受试者端粒长度增加。在任何特定的受试者中，T细胞、B细胞和单核细胞的端粒变化率是不同的。静息T细胞、B细胞和活化T细胞的端粒酶活性随年龄增长而下降。最后，随着年龄的增长，T细胞端粒磨损的很大一部分原因是端粒酶活性下降，幼稚细胞减少，以及生理条件的变化，如血糖和白细胞介素6水平的升高。这些发现表明，体内PBMCs端粒长度随年龄的变化在不同的个体和细胞类型中以不同的速率发生，揭示了T细胞端粒长度随年龄的变化受端粒酶活性、幼稚T细胞百分率和健康状况变化的影响。
Telomeres are essential in maintaining chromosome integrity and in controlling cellular replication. Attrition of telomere length in peripheral blood mononuclear cells (PBMCs) with age is well documented from cross-sectional studies. But the actual in vivo changes in telomere lengths and its relationship with the contributing factors within the individuals with age have not been fully addressed. In the present paper, we report a longitudinal analysis of telomere length in the PBMCs, lymphocytes and monocytes of 216 human subjects aged from 20–90 years assessed at 0-, 5- and 12-year follow-up. For the 5- and 12-year follow-up, telomere length in the PBMCs decreased in 34 % and 46 %, exhibited no detectable change in 56 % and 47 % and increased in 10 % and 7 % of the subjects respectively. The rate of telomere change was distinct for T-cells, B-cells and monocytes for any given subject. Telomerase activity declined with age in the resting T-cells and B-cells and the activated T-cells. Finally, a significant portion of telomere attrition in T-cells with age was explained by a decline in the telomerase activity, decreased naïve cells and the change in physiological conditions such as elevated blood glucose and interleukin (IL)-6 levels. These findings show that changes in the telomere length of the PBMCs with age in vivo occur at different rates in different individuals and cell types and reveal that changes in the telomere length in the T-cells with age is influenced by the telomerase activity, naïve T-cell percentage and changes in health conditions.