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      Lifestyle exercise attenuates immunosenescence; flow cytometry analysis

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          Abstract

          Background

          Interaction of physical activity and overall immune profile is very complex and depends on the intensity, duration and frequency of undertaken physical activity, the exposure to cytomegalovirus (CMV) infection and the age-related changes in the immune system. Daily physical activity, which particularly influences immunity, declines dramatically with age. Therefore, the aim of the study was to explain whether physical activity sustained throughout life can attenuate or reverse immunosenescence.

          Methods

          Ninety-nine older adults (60–90 years) were recruited for the study. According to the 6-min walk test (6WMT), the Åstrand-Ryhming bike test (VO 2max) and Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire, the individuals were classified as physically active ( n = 34) and inactive ( n = 20) groups. The analysis of T lymphocytes between active vs. inactive participants was performed using eight-parameter flow cytometry.

          Results

          Analysis of the baseline peripheral naïve and memory T lymphocytes showed a significant relationship of lifestyle exercise with the CD4/CD8 ratio. Above 50% of physically active participants demonstrated the CD4/CD8 ratio ≥ 1 or ≤ 2.5 contrary to the inactive group who showed the ratio < 1. The older adults with the result of 6WMT > 1.3 m/s and VO 2max > 35 mL/kg/min had a significantly higher CD4 +CD45RA + T lymphocyte percentage and also a higher ratio of CD4 +CD45RA +/CD4 +CD45RO +. Interestingly, in active older adults with IgG CMV + ( n = 30) the count of CD4 +CD45RA + T lymphocytes was higher than in the inactive group with IgG CMV + ( n = 20).

          Conclusion

          Based on the flow cytometry analysis, we concluded that lifestyle exercise could lead to rejuvenation of the immune system by increasing the percentage of naïve T lymphocytes or by reducing the tendency of the inverse CD4/CD8 ratio.

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          Most cited references54

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          An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease.

          Field walking tests are commonly employed to evaluate exercise capacity, assess prognosis and evaluate treatment response in chronic respiratory diseases. In recent years, there has been a wealth of new literature pertinent to the conduct of the 6-min walk test (6MWT), and a growing evidence base describing the incremental and endurance shuttle walk tests (ISWT and ESWT, respectively). The aim of this document is to describe the standard operating procedures for the 6MWT, ISWT and ESWT, which can be consistently employed by clinicians and researchers. The Technical Standard was developed by a multidisciplinary and international group of clinicians and researchers with expertise in the application of field walking tests. The procedures are underpinned by a concurrent systematic review of literature relevant to measurement properties and test conduct in adults with chronic respiratory disease. Current data confirm that the 6MWT, ISWT and ESWT are valid, reliable and responsive to change with some interventions. However, results are sensitive to small changes in methodology. It is important that two tests are conducted for the 6MWT and ISWT. This Technical Standard for field walking tests reflects current evidence regarding procedures that should be used to achieve robust results.
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            The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease.

            Regular exercise reduces the risk of chronic metabolic and cardiorespiratory diseases, in part because exercise exerts anti-inflammatory effects. However, these effects are also likely to be responsible for the suppressed immunity that makes elite athletes more susceptible to infections. The anti-inflammatory effects of regular exercise may be mediated via both a reduction in visceral fat mass (with a subsequent decreased release of adipokines) and the induction of an anti-inflammatory environment with each bout of exercise. In this Review, we focus on the known mechanisms by which exercise - both acute and chronic - exerts its anti-inflammatory effects, and we discuss the implications of these effects for the prevention and treatment of disease.
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              Enhancing CD8 T-cell memory by modulating fatty acid metabolism.

              CD8 T cells, which have a crucial role in immunity to infection and cancer, are maintained in constant numbers, but on antigen stimulation undergo a developmental program characterized by distinct phases encompassing the expansion and then contraction of antigen-specific effector (T(E)) populations, followed by the persistence of long-lived memory (T(M)) cells. Although this predictable pattern of CD8 T-cell responses is well established, the underlying cellular mechanisms regulating the transition to T(M) cells remain undefined. Here we show that tumour necrosis factor (TNF) receptor-associated factor 6 (TRAF6), an adaptor protein in the TNF-receptor and interleukin-1R/Toll-like receptor superfamily, regulates CD8 T(M)-cell development after infection by modulating fatty acid metabolism. We show that mice with a T-cell-specific deletion of TRAF6 mount robust CD8 T(E)-cell responses, but have a profound defect in their ability to generate T(M) cells that is characterized by the disappearance of antigen-specific cells in the weeks after primary immunization. Microarray analyses revealed that TRAF6-deficient CD8 T cells exhibit altered expression of genes that regulate fatty acid metabolism. Consistent with this, activated CD8 T cells lacking TRAF6 display defective AMP-activated kinase activation and mitochondrial fatty acid oxidation (FAO) in response to growth factor withdrawal. Administration of the anti-diabetic drug metformin restored FAO and CD8 T(M)-cell generation in the absence of TRAF6. This treatment also increased CD8 T(M) cells in wild-type mice, and consequently was able to considerably improve the efficacy of an experimental anti-cancer vaccine.
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                Author and article information

                Contributors
                a.zembron-lacny@cm.uz.zgora.pl
                Journal
                BMC Geriatr
                BMC Geriatr
                BMC Geriatrics
                BioMed Central (London )
                1471-2318
                22 March 2021
                22 March 2021
                2021
                : 21
                : 200
                Affiliations
                [1 ]GRID grid.28048.36, ISNI 0000 0001 0711 4236, Department of Applied and Clinical Physiology, , Collegium Medicum University of Zielona Gora, ; 28 Zyty Str., 65-046 Zielona Gora, Poland
                [2 ]GRID grid.28048.36, ISNI 0000 0001 0711 4236, Faculty of Computer, Electrical and Control Engineering, , Institute of Control and Computation Engineering University of Zielona Gora, ; Zielona Gora, Poland
                Author information
                http://orcid.org/0000-0001-7596-9850
                Article
                2128
                10.1186/s12877-021-02128-7
                7986285
                33752623
                3245ef57-5575-4219-93a2-2d41ace9698d
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 21 July 2020
                : 2 March 2021
                Funding
                Funded by: National Science Centre Poland
                Award ID: No 2016/21/N/NZ7/03329
                Award Recipient :
                Funded by: Funds for young investigators from the University of Zielona Gora
                Award ID: No 222267/E-545/S/2019
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2021

                Geriatric medicine
                lymphocytes t,obesity,physical activity,successful ageing
                Geriatric medicine
                lymphocytes t, obesity, physical activity, successful ageing

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