Grace M Niemiro1,2, Adriana M Coletta3,4, Nadia H Agha5, Preteesh Leo Mylabathula1,5,6, Forrest L Baker1,5,6, Abenaa M Brewster7, Therese B Bevers7, Enrique Fuentes-Mattei8, Karen Basen-Engquist9, Emmanuel Katsanis1,2,10, Susan C Gilchrist7,11, Richard J Simpson12,13,14,15,16,17. 1. Department of Pediatrics, The University of Arizona, Tucson, Arizona, USA. 2. The University of Arizona Cancer Center, Tucson, Arizona, USA. 3. Department of Health and Kinesiology, The University of Utah, Salt Lake City, Utah, USA. 4. Cancer Control and Population Sciences Program, Huntsman Cancer Institute, Salt Lake City, Utah, USA. 5. Department of Health and Human Performance, University of Houston, Houston, Texas, USA. 6. School of Nutritional Sciences and Wellness, The University of Arizona, Tucson, Arizona, USA. 7. Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 8. Department of Radiation Oncology Clinical Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 9. Department of Behavioral Science, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 10. Department of Immunobiology, The University of Arizona, Tucson, Arizona, USA. 11. Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 12. Department of Pediatrics, The University of Arizona, Tucson, Arizona, USA. rjsimpson@arizona.edu. 13. The University of Arizona Cancer Center, Tucson, Arizona, USA. rjsimpson@arizona.edu. 14. Department of Health and Human Performance, University of Houston, Houston, Texas, USA. rjsimpson@arizona.edu. 15. School of Nutritional Sciences and Wellness, The University of Arizona, Tucson, Arizona, USA. rjsimpson@arizona.edu. 16. Department of Behavioral Science, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. rjsimpson@arizona.edu. 17. Department of Immunobiology, The University of Arizona, Tucson, Arizona, USA. rjsimpson@arizona.edu.
Abstract
BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Oscar Okwudiri Onyema; Lore Decoster; Rose Njemini; Louis Nuvagah Forti; Ivan Bautmans; Marc De Waele; Tony Mets Journal: Anticancer Res Date: 2015-03 Impact factor: 2.480
Authors: Niharika A Duggal; Grace Niemiro; Stephen D R Harridge; Richard J Simpson; Janet M Lord Journal: Nat Rev Immunol Date: 2019-09 Impact factor: 53.106
Authors: Grace M Niemiro; Adriana M Coletta; Nadia H Agha; Preteesh Leo Mylabathula; Forrest L Baker; Abenaa M Brewster; Therese B Bevers; Enrique Fuentes-Mattei; Karen Basen-Engquist; Emmanuel Katsanis; Susan C Gilchrist; Richard J Simpson Journal: Immun Ageing Date: 2022-06-08 Impact factor: 9.701