Six weeks of strength endurance training decreases circulating senescence-prone T-lymphocytes in cytomegalovirus seropositive but not seronegative older women

Abstract

Background Ageing is associated with a decline in immune function termed immunosenescence. This process is characterized amongst others by less naive T-cells and more senescent phenotypes, which have been implicated in the pathogenesis of many age-related diseases. Thus far, reports regarding the long-term adaptation effects of exercise on T-cell phenotypes are scant and largely equivocal. These inconsistencies may be due to potential contributors to immunosenescence, particularly cytomegalovirus infection, which is considered a hallmark of T-cell senescence. Therefore, we sought to investigate the impact of cytomegalovirus serostatus on the distribution of peripheral T-cell subsets following long-term exercise in older women. Methods One hundred women (aged 65 years and above) were randomized to 3 times/weekly training at either intensive strength training (3 × 10 repetitions at 80% of one-repetition maximum, n = 31), strength endurance training (2 × 30 repetitions at 40% of one-repetition maximum, n = 33), or control (passive stretching exercise, n = 36) for 6 weeks. All training sessions were supervised by trained instructors to minimize the risk of injury and to ensure that the participants adhered to the training protocol throughout the entire range of motion. The T-cell percentages and absolute blood counts were determined before and after 6 weeks (24 h–48 h after the last training session) using flow cytometry and a haematology analyser. Cytomegalovirus antibodies were measured in serum using Architect iSystem and cytomegalovirus serostatus was balanced in the three intervention groups. C-reactive protein was measured using immunonephelometry. Results We report for the first time that 6 weeks of strength endurance training significantly decreased senescence-prone T-cells along with a small increase in the number of CD8– naive T-cells in blood. The absolute counts of senescent-like T-cells decreased by 44% (from 26.03 ± 35.27 to 14.66 ± 21.36 cells/μL, p < 0.01) and by 51% (from 6.55 ± 12.37 to 3.18 ± 6.83 cells/μL, p < 0.05) for the CD8+ and CD8– T-cell pools, respectively. Intriguingly, these changes were observed in cytomegalovirus seropositive, but not cytomegalovirus seronegative individuals. Conclusions In conclusion, the present study shows that strength endurance training leads to a reduction in circulating senescence-prone T-cells in cytomegalovirus seropositive older women. It remains to be established if monitoring of peripheral senescence-prone T-cells may have utility as cellular biomarkers of immunosenescence. Electronic supplementary material The online version of this article (10.1186/s12979-019-0157-8) contains supplementary material, which is available to authorized users.

Regular Exercise May Restore Certain Age-Related Alterations of Adaptive Immunity and Rebalance Immune Regulation

“…It has already confirmed that the ratio of HLA-DR + cells in CD4 and CD8 lymphocytes are increased in elderly individuals compared to young adults, however it is more pronounced in CD8 than in CD4 T cells. In vitro stimulation of both subset revealed that activated CD8 T cells gained more HLA-DR expression during culture (27). Therefore, we believe that the observed increase in the expression of HLA-DR was not solely the result of the elevation in total CD4 + Th cell proportions after the training program.…”

“…software (26). Data from previous studies with approximate changes in the percentages of different lymphocyte subpopulations during physical activity served as a basis to determine a medium effect size (Cohen's d z = 0.6) (27,28). Our calculation indicated that a sample size of at least 24 subjects were required to observe a statistically significant difference between matched data pairs with 0.8 statistical power at significance level of 0.05.…”

“…Recently, several studies investigated the mobilization of CD8 + T cell subsets during exercise and revealed that latedifferentiated or RA + effector memory Tc subset is exclusively decreased post-exercise period (47). It is established that this subpopulation expresses elevated b2-adrenergic receptor density and sensitivity which could explain their higher responsiveness to exercise, and it could be further augmented by cytomegalovirus seropositivity (27,48). Of note, the expression of a broad number of markers overlaps or associates with each other and results in the large heterogeneity of CD8 + T cells.…”

“…Accordingly, several studies suggest that CD62L -CD45RA + T EMRA cells rather show highly functional capacity than an acutely activated phenotype since these antigen-experienced subset gradually down-regulate the expression of several activation and co-stimulatory markers including CD27, CD38 and HLA-DR while produce high level of inflammatory IFN-g cytokine and cytotoxic enzymes (27,(49)(50)(51)(52). This late-differentiated effector phase has multiple characteristics of senescence, including the loss of proliferative capacity which could be measured by the increase of CD57 expression, the acquisition of typical markers of the NK cells such as CD85j, CD158b/j, KLRG1 and short telomere length (27,(51)(52)(53)(54). Moreover, these exercise-sensitive RA + effector-memory Tc cells are largely negative for skin specific cutaneous lymphocyte-associated antigen (CLA), thus their migration from the circulation could rather be directed by CXCR3 and CCR5 chemokines or site-specific homing molecules like a4b7 integrin toward tissues, including lungs or Peyer's patches (55).…”

Lifestyle exercise attenuates immunosenescence; flow cytometry analysis

“…Indeed, physical activity is a powerful intervention that has a great potential to improve immune and health outcomes in the older adults, the obese, and patients with cancer and chronic viral infections [ 10 , 34 ]. The benefits of regular physical activity undertaken by the older adults are much less documented than the effects of regular physical activity on the immune system in young individuals [ 36 ]. Randomized prospective trials were conducted to explain the effect of aerobic exercise on the immune system of the older adults, where Nieman et al [ 37 ] found that a 3-month moderate aerobic exercise programme did not cause a significant increase in T lymphocyte mitogenesis.…”