Department of Immunology, Imperial College, London Translational Medicine Group, Cranfield University, Beds, UK.
Clin Exp Immunol. 2010 Sep;161(3):497-503. doi: 10.1111/j.1365-2249.2010.04209.x.
As a result of age-associated thymic atrophy, T cell production declines with age. Some studies suggest that production undergoes an exponential decline starting at birth, while others consider the decline to be in a biphasic manner with a rapid reduction in output occurring before middle age followed by a phase in which output declines at a regular, albeit much slower, rate. Both approaches provide estimations of the time of termination of thymic output, but on the basis of limited amounts of data. We have analysed blood from more than 200 individuals between the ages of 58 and 104 years to determine changes in thymic output using signal-joint T cell receptor excision circles (sjTREC)/T cells as our measure. To reduce any potential geographical or nutritional bias we have obtained samples from five different European countries. Our results reveal that while the absolute number of T cells per microlitre of blood does not change significantly across the age range we tested, the values of sjTREC per microlitre show wide variation and reveal an age-associated decline in thymic output. In addition we show gender differences, with notably higher thymic output in females than males at each decade. More importantly, we noted a significant decline in sjTREC/T cell levels in those more than 90 years of age in both males and females. Our results provide information about the potential end-point for thymic output and suggest that sjTREC analysis may be a biomarker of effective ageing.
由于与年龄相关的胸腺萎缩，T 细胞的产生随着年龄的增长而下降。一些研究表明，从出生开始，T 细胞的产生呈指数下降，而另一些研究则认为下降呈双相方式，中年前 T 细胞产量迅速减少，然后进入一个以较慢但稳定的速度下降的阶段。这两种方法都提供了对胸腺输出终止时间的估计，但都是基于有限的数据。我们分析了 200 多名年龄在 58 岁至 104 岁之间的人的血液，使用信号接头 T 细胞受体切除环 (sjTREC)/T 细胞作为我们的测量指标，来确定胸腺输出的变化。为了减少任何潜在的地理或营养偏见，我们从五个不同的欧洲国家获得了样本。我们的结果表明，虽然我们测试的年龄范围内每微升血液中的 T 细胞绝对数量没有显著变化，但每微升 sjTREC 的值显示出广泛的变化，并显示出与年龄相关的胸腺输出下降。此外，我们还显示出性别差异，在每个十年中，女性的胸腺输出明显高于男性。更重要的是，我们注意到男性和女性中，90 岁以上的个体的 sjTREC/T 细胞水平显著下降。我们的结果提供了有关胸腺输出潜在终点的信息，并表明 sjTREC 分析可能是有效衰老的生物标志物。
