Expression profiling of immune-associated genes in peripheral blood mononuclear cells reveals baseline differences in co-stimulatory signalling between nonagenarians and younger controls: the vitality 90+ study
Expression profiling of immune-associated genes in peripheral blood mononuclear cells reveals baseline differences in co-stimulatory signalling between nonagenarians and younger controls: the vitality 90+ study
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DOI：
10.1007/s10522-010-9274-7
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发表时间：
2010-12-01
期刊：
影响因子：
4.5
通讯作者：
Hurme, Mikko
中科院分区：
文献类型：
--
作者：
Jylhava, Juulia;Eklund, Carita;Hurme, Mikko
人类免疫系统，特别是适应性分支，随着年龄的增长而大幅下降。已经描述了几种不同的免疫衰老事件，但关于免疫细胞功能中年龄相关的基线改变的数据有限。因此，通过使用TaqMan人类免疫阵列，我们对年轻个体（年龄22-37岁，n = 13）和90岁以上（n = 12）的外周血单核细胞中的免疫相关基因进行了初步的基因表达谱分析，后者是Vitality 90+研究的一部分。我们还分析了显著调控基因之间的相关性。结果显示，与对照组相比，90岁组CCR 7、CD 19、CD 28、CD 40 LG、ICOS、IL 4、IL 6和LTA的表达显著降低，而FN 1的表达显著升高。90岁组CCR 7与CD 19、CCR 7与ICOS、ICOS与CD 19、ICOS与CD 40 LG、CD 40 LG与CD 28的表达均呈显著正相关，而对照组无相关性。这些结果表明，获得性免疫的关键参与者，即完全淋巴细胞活化所需的因子在非常年老的个体中显著且协调地下调。然而，需要进一步的研究来建立这些变化与免疫衰老机制之间的关系。
The human immune system, especially the adaptive branch, substantially declines with ageing. Several distinct immunosenescent events have already been described, yet data regarding to age-associated baseline alterations in immune cell function is limited. Therefore, by using the TaqMan Human Immune Arrays we conducted a preliminary gene expression profiling of immune-related genes in the peripheral blood mononuclear cells of young individuals (aged 22-37 years, n = 13) and nonagenarians (n = 12), the latter being part of the Vitality 90+ Study. We also analysed the correlations between significantly regulated genes. The results revealed a significantly decreased expression of CCR7, CD19, CD28, CD40LG, ICOS, IL4, IL6 and LTA as well as significantly increased expression of FN1 in the nonagenarians as compared to the controls. Significant direct correlations were observed between the expression of CCR7 and CD19, CCR7 and ICOS, ICOS and CD19, ICOS and CD40LG, as well as CD40LG and CD28 in the nonagenarians but not in the controls. These results suggest that the key players of adaptive immunity i.e. the factors required for full lymphocyte activation are markedly and coordinately down-modulated in the very old individuals. Further research is, however, required to establish the relationship between these changes and the mechanisms of immunosenescence.