Zhou Lixing, Ge Meiling, Zhang Yan, Wu Xiaochu, Leng Mi, Gan Chunmei, Mou Yi, Zhou Jiao, Valencia C Alexander, Hao Qiukui, Zhu Bin, Dong Biao, Dong Birong
National Clinical Research Center for Geriatrics and Department of Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Front Pharmacol. 2022 Jun 2;13:877709. doi: 10.3389/fphar.2022.877709. eCollection 2022.
The immune system of centenarians remains active and young to prevent cancer and infections. Aging is associated with inflammaging, a persistent low-grade inflammatory state in which CD4 T cells play a role. However, there are few studies that have been done on the CD4 T cell subsets in centenarians. Herein, the changes in CD4 T cell subsets were investigated in centenarians. It was found that with aging, the old adults had higher levels of proinflammatory cytokines and lower levels of anti-inflammatory cytokines in plasma. The levels of CRP, IL-12, TNF-α, IFN-γ, IL-6 and IL-10 were further increased in centenarians compared to old adults. While the levels of IL-17A, IL-1β, IL-23 and TGF-β in centenarians were closer to those in young adults. The total CD4, CD8, Th17 and Treg cells from peripheral blood mononuclear cells (PBMCs) were similar among the three groups. It was observed that the ratio of Th17/Treg cells was elevated in old adults compared to young adults. The ratio was not further elevated in centenarians but rather decreased. In addition, the PBMCs differentiation assay showed that increased Th17 cells in centenarians tended to secrete fewer proinflammatory cytokines, while decreased Treg cells in centenarians were prone to secrete more anti-inflammatory cytokines. These observations suggested centenarians alleviated inflammaging by decreasing the ratio of Th17/Treg cells and changing them into anti-inflammatory secretory phenotypes, which provided a novel mechanism for anti-aging research.
百岁老人的免疫系统保持活跃且年轻化，以预防癌症和感染。衰老与炎症衰老相关，炎症衰老是一种持续性的低度炎症状态，CD4 T细胞在其中发挥作用。然而，针对百岁老人CD4 T细胞亚群的研究较少。在此，对百岁老人的CD4 T细胞亚群变化进行了研究。结果发现，随着年龄增长，老年人血浆中促炎细胞因子水平较高，抗炎细胞因子水平较低。与老年人相比，百岁老人的CRP、IL-12、TNF-α、IFN-γ、IL-6和IL-10水平进一步升高。而百岁老人的IL-17A、IL-1β、IL-23和TGF-β水平更接近年轻人。三组外周血单个核细胞（PBMC）中的总CD4、CD8、Th17和Treg细胞相似。观察到与年轻人相比，老年人的Th17/Treg细胞比例升高。百岁老人的该比例未进一步升高，反而降低。此外，PBMC分化试验表明，百岁老人中增加的Th17细胞倾向于分泌较少的促炎细胞因子，而减少的Treg细胞则易于分泌更多的抗炎细胞因子。这些观察结果表明，百岁老人通过降低Th17/Treg细胞比例并将其转变为抗炎分泌表型来减轻炎症衰老，这为抗衰老研究提供了一种新机制。
