Niemiro Grace M, Coletta Adriana M, Agha Nadia H, Mylabathula Preteesh Leo, Baker Forrest L, Brewster Abenaa M, Bevers Therese B, Fuentes-Mattei Enrique, Basen-Engquist Karen, Katsanis Emmanuel, Gilchrist Susan C, Simpson Richard J
Department of Pediatrics, The University of Arizona, Tucson, Arizona, USA.
The University of Arizona Cancer Center, Tucson, Arizona, USA.
Immun Ageing. 2022 Mar 23;19(1):17. doi: 10.1186/s12979-022-00266-z.
Immunosenescence is described as age-associated changes within the immune system that are responsible for decreased immunity and increased cancer risk. Physically active individuals have fewer 'senescent' and more naïve T-cells compared to their sedentary counterparts, but it is not known if exercise training can rejuvenate 'older looking' T-cell profiles. We determined the effects of 12-weeks supervised exercise training on the frequency of T-cell subtypes in peripheral blood and their relationships with circulating levels of the muscle-derived cytokines (i.e. 'myokines') IL-6, IL-7, IL-15 and osteonectin in older women at high risk of breast cancer. The intervention involved 3 sessions/week of either high intensity interval exercise (HIIT) or moderate intensity continuous exercise (MICT) and were compared to an untrained control (UC) group.
HIIT decreased total granulocytes, CD4+ T-cells, CD4+ naïve T-cells, CD4+ recent thymic emigrants (RTE) and the CD4:CD8 ratio after training, whereas MICT increased total lymphocytes and CD8 effector memory (EM) T-cells. The change in total T-cells, CD4+ naïve T-cells, CD4+ central memory (CM) T-cells and CD4+ RTE was elevated after MICT compared to HIIT. Changes in [Formula: see text] after training, regardless of exercise prescription, was inversely related to the change in highly differentiated CD8+ EMRA T-cells and positively related to changes in β2-adrenergic receptor (β2-AR) expression on CM CD4+ and CM CD8+ T-cells. Plasma myokine levels did not change significantly among the groups after training, but individual changes in IL-7 were positively related to changes in the number of β2-AR expressing CD4 naïve T cells in both exercise groups but not controls. Further, CD4 T-cells and CD4 naive T-cells were negatively related to changes in IL-6 and osteonectin after HIIT but not MICT, whereas CD8 EMRA T-cells were inversely related to changes in IL-15 after MICT but not HIIT.
Aerobic exercise training alters the frequency of peripheral T-cells associated with immunosenescence in middle aged/older women at high risk of breast cancer, with HIIT (pro-senescent) and MICT (anti-senescent) evoking divergent effects. Identifying the underlying mechanisms and establishing whether exercise-induced changes in peripheral T-cell numbers can alter the risk of developing breast cancer warrants investigation.
免疫衰老被描述为免疫系统中与年龄相关的变化,这些变化导致免疫力下降和癌症风险增加。与久坐不动的人相比,身体活跃的个体具有更少的“衰老”T细胞和更多的初始T细胞,但尚不清楚运动训练是否能使“看起来衰老”的T细胞谱恢复活力。我们确定了为期12周的有监督运动训练对高危乳腺癌老年女性外周血中T细胞亚型频率的影响,以及它们与肌肉衍生细胞因子(即“肌动蛋白”)白细胞介素-6、白细胞介素-7、白细胞介素-15和骨连接蛋白循环水平的关系。干预措施包括每周3次的高强度间歇运动(HIIT)或中等强度持续运动(MICT),并与未训练的对照组(UC)进行比较。
HIIT训练后总粒细胞、CD4 + T细胞、CD4 + 初始T细胞、CD4 + 近期胸腺迁出细胞(RTE)和CD4:CD8比值降低,而MICT训练后总淋巴细胞和CD8效应记忆(EM)T细胞增加。与HIIT相比,MICT训练后总T细胞、CD4 + 初始T细胞、CD4 + 中央记忆(CM)T细胞和CD4 + RTE的变化更大。训练后,无论运动处方如何,[公式:见正文]的变化与高分化CD8 + EMRA T细胞的变化呈负相关,与CM CD4 + 和CM CD8 + T细胞上β2 - 肾上腺素能受体(β2 - AR)表达的变化呈正相关。训练后各组血浆肌动蛋白水平无显著变化,但在两个运动组而非对照组中,白细胞介素-7的个体变化与表达β2 - AR的CD4初始T细胞数量的变化呈正相关。此外,HIIT训练后CD4 T细胞和CD4初始T细胞与白细胞介素-6和骨连接蛋白的变化呈负相关,而MICT训练后则无此关系;MICT训练后CD8 EMRA T细胞与白细胞介素-15的变化呈负相关,而HIIT训练后则无此关系。
有氧运动训练可改变高危乳腺癌中老年女性外周血中与免疫衰老相关的T细胞频率,HIIT(促衰老)和MICT(抗衰老)产生不同的效果。确定潜在机制以及运动诱导的外周T细胞数量变化是否能改变患乳腺癌的风险值得研究。