The susceptibility of human CD4⁺ and CD8⁺ T cells to senesce differs, with CD8⁺ T cells acquiring an immunosenescent phenotype faster than the CD4⁺ T cell compartment. We show here that it is the inherent difference in mitochondrial content that drives this phenotype, with senescent human CD4⁺ T cells displaying a higher mitochondrial mass. The loss of mitochondria in the senescent human CD8⁺ T cells has knock‐on consequences for nutrient usage, metabolism and function. Senescent CD4⁺ T cells uptake more lipid and glucose than their CD8⁺ counterparts, leading to a greater metabolic versatility engaging either an oxidative or a glycolytic metabolism. The enhanced metabolic advantage of senescent CD4⁺ T cells allows for more proliferation and migration than observed in the senescent CD8⁺ subset. Mitochondrial dysfunction has been linked to both cellular senescence and aging; however, it is still unclear whether mitochondria play a causal role in senescence. Our data show that reducing mitochondrial function in human CD4⁺ T cells, through the addition of low‐dose rotenone, causes the generation of a CD4⁺ T cell with a CD8⁺‐like phenotype. Therefore, we wish to propose that it is the inherent metabolic stability that governs the susceptibility to an immunosenescent phenotype.

中文翻译：

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线粒体质量控制着人类T细胞衰老的程度。

人CD4 ⁺和CD8 ⁺ T细胞对衰老的敏感性不同，CD8 ⁺ T细胞比CD4 ⁺ T细胞区室更快地获得免疫衰老表型。我们在这里表明，驱动此表型的是线粒体含量的内在差异，衰老的人CD4 ⁺ T细胞显示出更高的线粒体质量。衰老的人类CD8 ⁺ T细胞中线粒体的丧失对养分的使用，代谢和功能产生连锁反应。衰老的CD4 ⁺ T细胞比其CD8 ⁺吸收更多的脂质和葡萄糖对应物，导致更大的新陈代谢多功能性参与氧化或糖酵解代谢。与衰老CD8 ⁺亚群相比，衰老CD4 ⁺ T细胞具有更高的代谢优势，可以实现更多的增殖和迁移。线粒体功能障碍与细胞衰老和衰老有关。然而，线粒体是否在衰老中起因果作用还不清楚。我们的数据表明，通过添加低剂量鱼藤酮来降低人CD4 ⁺ T细胞中的线粒体功能，会导致CD4 ⁺ T细胞与CD8 ⁺样表型。因此，我们希望提出，固有的代谢稳定性决定着对免疫衰老表型的敏感性。