Michael Harrison, South East Technological University - Waterford Campus: South East Technological University, Ireland,
J Frailty Aging. 2024;13(3):203-212. doi: 10.14283/jfa.2024.38.
There is a need to identify vascular and geroscience-relevant markers and mediators that can physiologically link ageing to vascular disease. There is evidence of specific T cell subsets, all influenced by age, that exert positive and negative effects on vascular health. CD31+, termed angiogenic T cells, have been linked to vascular repair whereas CD28null, termed senescent T cells, display pro-inflammatory and cytotoxic effector functions.
This study sought to determine the combined influence of increasing age and frailty status on these circulating CD31+ and CD28null T cell subsets.
This cross-sectional study recruited four different cohorts of men and women; young (20-30 years, n=22), older (65-75 years, n=17), robust non-frail (76+ years, n=17), and frail (76+ years, n=15) adults. Frailty was determined using the Fried Frailty method. T cell subsets were determined by whole blood flow cytometry based on the expression of CD3, CD4, CD8, CD31 and CD28. Cognitive impairment (CI) was measured via the Montreal Cognitive Assessment test.
Whether expressed as circulating counts or as a % of total T cells, there was a progressive decrease (p<0.05) in CD31+ T cells with increasing age but paradoxically higher values (p<0.05) in the frail compared to the robust non-frail group. These changes were similar in the CD4+ and CD8+ fractions. CD28null T cells were considerably higher (p<0.05) in the frail compared to the robust non-frail group, including in the CD8+ (47% vs 29%, p<0.05) and CD4+ (4% vs 1%, p<0.05) fractions. CD28null T cell percentage was also higher (p<0.05) in those with moderate CI compared to mild CI and normal function.
CD8+CD28null T cells are considerably elevated in frailty and with cognitive impairment and may serve as a useful target for intervention. Currently, the utility of CD31+ T cells as an ageing biomarker may be confined to healthy ageing cohorts.
需要识别与血管和衰老相关的标志物和介质，这些标志物和介质可以将衰老与血管疾病在生理学上联系起来。有证据表明，特定的 T 细胞亚群，都受到年龄的影响，对血管健康产生积极和消极的影响。CD31+，称为血管生成 T 细胞，与血管修复有关，而 CD28null，称为衰老 T 细胞，显示出促炎和细胞毒性效应功能。
本研究旨在确定年龄增长和虚弱状态对这些循环 CD31+和 CD28null T 细胞亚群的综合影响。
这项横断面研究招募了四组不同的男性和女性；年轻人（20-30 岁，n=22）、老年人（65-75 岁，n=17）、健壮非虚弱（76+岁，n=17）和虚弱（76+岁，n=15）成年人。采用弗莱德虚弱方法确定虚弱状态。T 细胞亚群通过基于 CD3、CD4、CD8、CD31 和 CD28 表达的全血流式细胞术确定。认知障碍（CI）通过蒙特利尔认知评估测试进行测量。
无论以循环计数还是以总 T 细胞的百分比表示，CD31+T 细胞随着年龄的增长而逐渐减少（p<0.05），但在虚弱组中，与健壮非虚弱组相比，CD31+T 细胞的值却更高（p<0.05）。这些变化在 CD4+和 CD8+亚群中是相似的。与健壮非虚弱组相比，CD28null T 细胞在虚弱组中明显更高（p<0.05），包括 CD8+（47%比 29%，p<0.05）和 CD4+（4%比 1%，p<0.05）亚群。与轻度认知障碍和正常功能相比，中度认知障碍患者的 CD28null T 细胞比例也更高（p<0.05）。
在虚弱和认知障碍患者中，CD8+CD28null T 细胞明显升高，可能成为干预的有用靶点。目前，CD31+T 细胞作为衰老生物标志物的用途可能仅限于健康衰老队列。
