BACKGROUND Progressive T cell decline in aged humans is associated with a deficiency of naïve (TN) and central memory (TCM) T cells. We have previously reported increased Tumor necrosis factor-α (TNF-α)-induced apoptosis in TN and TCM T cells in aged humans; however, the molecular basis of increased apoptosis remains to be defined. Since expression of TNF receptors (TNFRs) was reported to be comparable in young and aged, we investigated signaling events downstream of TNFRs to understand the molecular basis of increased TNF-α-induced apoptosis in aged TN and TCM CD8+ cells. RESULTS The expression of TRAF-2 and RIP, phosphorylation of JNK, IKKα/β, and IκBα, and activation of NF-κB activation were significantly decreased in TN and TCM CD8+ cells from aged subjects as compared to young controls. Furthermore, expression of A20, Bcl-xL, cIAP1, and FLIP-L and FLIP-S was significantly decreased in TN and TCM CD8+ cells from aged subjects. CONCLUSIONS These data demonstrate that an impaired expression/function of molecules downstream TNFR signaling pathway that confer survival signals contribute to increased apoptosis of TN and TCM CD8+ cells in aged humans.

中文翻译：

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与老年人幼稚 (TN) 和中央记忆 (TCM) CD8+ T 细胞中 TNF-α 诱导的细胞凋亡增加相关的分子变化。

背景技术老年人中 T 细胞进行性衰退与幼稚 (TN) 和中枢记忆 (TCM) T 细胞的缺乏有关。我们之前曾报道过，在老年人中，肿瘤坏死因子-α (TNF-α) 诱导的 TN 和 TCM T 细胞凋亡增加；然而，细胞凋亡增加的分子基础仍有待确定。据报道，年轻人和老年人的 TNF 受体 (TNFR) 表达相当，因此我们研究了 TNFR 下游的信号转导事件，以了解老年 TN 和 TCM CD8+ 细胞中 TNF-α 诱导细胞凋亡增加的分子基础。结果 与年轻对照组相比，老年受试者的 TN 和 TCM CD8+ 细胞中 TRAF-2 和 RIP 的表达、JNK、IKKα/β 和 IκBα 的磷酸化以及 NF-κB 的激活均显着降低。此外，老年受试者的 TN 和 TCM CD8+ 细胞中 A20、Bcl-xL、cIAP1 以及 FLIP-L 和 FLIP-S 的表达显着降低。结论 这些数据表明，赋予生存信号的 TNFR 信号通路下游分子的表达/功能受损，导致老年人 TN 和 TCM CD8+ 细胞凋亡增加。