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Teodoro TH, Costa KPM, Prestes J, Campanholi J, Navalta J, Pereira GB. The effects of acute and chronic exercise on immune markers of TH1/TH2 cells in older adults: a systematic review. Front Physiol 2025; 16:1453747. [PMID: 40008210 PMCID: PMC11850391 DOI: 10.3389/fphys.2025.1453747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Accepted: 01/21/2025] [Indexed: 02/27/2025] Open
Abstract
Purpose Imbalance between Th1 and Th2 cells correlated with increased disease incidence, is well-documented in the older adult. Both acute and chronic exercise induce a transient shift in organic homeostasis, modulating the immune system and impacting the balance between Th1 and Th2 cells. This review investigates the impact of acute and chronic exercise on immune markers of Th1 and Th2 cells in the older adults. Methods This study was conducted as a systematic review, following PRISMA guidelines, databases including PubMed, Web of Science, Embase, Science Direct, and Scopus were searched until March 2024, identifying randomized controlled trials and prospective observational studies that examined the effects of acute and chronic exercise on intracellular and surface markers, cytokines, and immunoglobulins in older adults. Studies involving animal subjects, isolated cells, diseased patients, or exposure to medications and drugs were excluded. The quality of the selected studies was assessed using the Cochrane risk of bias tool (ROB2), with data organized and presented in tables and figures. Results Fourteen studies with 525 participants were included in the analysis. An acute session significantly increased serum IL-4, IL-6, and IL-10 levels immediately afterward, returning to baseline within 1 hour at moderate to high intensities. Chronic exercise at moderate to high intensities reduced serum TNF-α, IL-6, and the CD4/CD8 ratio, while increasing IL-10 levels after 24 weeks. Intracellular, other surface markers and cytokines, and immunoglobulins were not analyzed. Conclusion Chronic exercise decreases serum TNF-α and IL-6 levels, lowers the CD4/CD8 ratio, and increases IL-10 after 24 weeks, aiding Th1 and Th2 balance. Acute exercise temporarily increases serum IL-4, IL-6, and IL-10 levels, returning to baseline within an hour, indicating short-term immune modulation of Th1/Th2 balance. Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021244426, Identifier CRD42021244426.
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Affiliation(s)
- Thiago Henrique Teodoro
- Laboratory of Clinical Exercise Physiology, Department of Physiological Sciences, Federal University of São Carlos, São Carlos, Brazil
| | - Katerine Palharini Manfrin Costa
- Laboratory of Clinical Exercise Physiology, Department of Physiological Sciences, Federal University of São Carlos, São Carlos, Brazil
| | - Jonato Prestes
- Graduation Program on Physical Education, Catholic University of Brasilia, Brasília, Brazil
| | - José Campanholi
- Department of Morphology and Pathology, Federal University of São Carlos, São Carlos, Brazil
| | - James Navalta
- Department of Kinesiology and Nutrition Sciences, University of Nevada, Las Vegas, Las Vegas, NV, United States
| | - Guilherme Borges Pereira
- Laboratory of Clinical Exercise Physiology, Department of Physiological Sciences, Federal University of São Carlos, São Carlos, Brazil
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K V BM, Alagesan J. A Case Series Tries to Answer Whether Exercise Positively Influences Immunosenescence. Cureus 2023; 15:e51072. [PMID: 38269239 PMCID: PMC10806379 DOI: 10.7759/cureus.51072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Accepted: 12/25/2023] [Indexed: 01/26/2024] Open
Abstract
The immune system, the defense mechanism of the body, mainly consists of lymphocytes. The three primary subtypes of lymphocytes are natural killer cells (NK cells), bone marrow-derived lymphocytes (B-lymphocytes), and thymus-derived lymphocytes (T-lymphocytes). T-lymphocytes are mostly composed of CD (cluster of differentiation) cells, such as CD4+ and CD8+ subsets of CD cells. Immunosenescence is the term for the steady decline of the immune system with aging. There are alterations in the composition of various types of lymphocytes, especially in CD4 and CD8 T cells. The elderly are more vulnerable to infections due to immunosenescence, which raises morbidity and mortality rates. Physical exercises are believed to have the potential to alter immunosenescence and produce positive changes in immune cell composition. The extent of exercise-induced immune function changes was different in research studies owing to the differences in protocols, methodologies, testing procedures, ages, and gender compositions. The impact of an eight-week balance-based exercise intervention on immune biomarkers is investigated in this case series. In this case series, two elderly women residing in an institutional setting were exposed to an eight-week-long balanced-based supervised exercise intervention. The immunological biomarkers CD45, CD3, CD4, and CD8 were the outcome variables that were assessed. Data on the outcome variables was gathered both before and after the intervention. Using flow cytometry and single-platform technology, immune biomarkers were analyzed. Following the intervention, there was a rise in the CD45, CD3, CD4, and CD8 cell counts relative to the baseline data. The biomarkers showed only slight and statistically non-significant improvements.
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Affiliation(s)
- Binoy M K V
- Physiotherapy, Saveetha College of Physiotherapy, Saveetha Institute of Medical and Technical Sciences, Chennai, IND
| | - Jagatheesan Alagesan
- Physiotherapy, Saveetha College of Physiotherapy, Saveetha Institute of Medical and Technical Sciences, Chennai, IND
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Günbatar N, Bulduk B, Bezgin S, Oto G, Bayıroğlu F, Bulduk M. The Effect of Moderate-Intensity Physical Exercise on Some Serum Inflammation Markers and the Immune System in Rats Fed Intermittent Fasting with a High-Fat Diet. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1687. [PMID: 37763806 PMCID: PMC10537032 DOI: 10.3390/medicina59091687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 09/15/2023] [Accepted: 09/17/2023] [Indexed: 09/29/2023]
Abstract
Background and Objectives: This study aimed to investigate the impact of moderate-intensity physical exercise on serum inflammation markers and the immune system in rats that were fed a high-fat diet (HFD) with intermittent fasting. Materials and Methods: A total of 48 Wistar albino male rats were included in the study and divided into eight groups, each consisting of six rats. Group 1 served as the control group (CG), receiving a standard diet. Group 2 followed the standard nutrition program with intermittent fasting (CG + IF). Group 3 underwent exercise with a standard diet (CG + E). Group 4 underwent both a standard diet with intermittent fasting and exercise (CG + IF + E). Group 5 was fed a high-fat diet (HFD). Group 6 received a high-fat diet with intermittent fasting (HFD + IF). Group 7 followed a high-fat diet with exercise (HFD + E). Group 8 underwent both a high-fat diet with intermittent fasting and exercise (HFD + IF + E). The study lasted for 8 weeks. Results: The results of the analysis show that lymphocyte cell levels in groups HFD + IF, HFD + IF, and HFD + IF + E were higher compared to groups CG-HFD (p < 0.05). Additionally, B lymphocyte and monocyte cell levels were higher in group HFD + IF + E compared to groups CG, CG + IF, and CG + IF + E, as well as CG, CG + IF, and CG + E, respectively. TNF-α levels were significantly higher in group HFD compared to the other groups. Furthermore, IL 10 levels were higher in group HFD + IF + E compared to the other groups. Conclusions: These findings indicate that moderate exercise and intermittent fasting, particularly in groups fed a high-fat diet, increased anti-inflammatory cytokine levels, and certain immune system cell counts, while decreasing pro-inflammatory cytokine levels.
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Affiliation(s)
- Nizamettin Günbatar
- Van School of Health, Van YuzuncuYıl University, 65090 Van, Turkey; (B.B.); (S.B.); (M.B.)
| | - Bahattin Bulduk
- Van School of Health, Van YuzuncuYıl University, 65090 Van, Turkey; (B.B.); (S.B.); (M.B.)
| | - Selver Bezgin
- Van School of Health, Van YuzuncuYıl University, 65090 Van, Turkey; (B.B.); (S.B.); (M.B.)
| | - Gökhan Oto
- Department of Pharmacology, Van YuzuncuYıl University, 65090 Van, Turkey;
| | - Fahri Bayıroğlu
- Faculty of Medicine, Department of Physiology, Yıldırım Beyazıt University, 06200 Ankara, Turkey;
| | - Mehmet Bulduk
- Van School of Health, Van YuzuncuYıl University, 65090 Van, Turkey; (B.B.); (S.B.); (M.B.)
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Alawna M, Mohamed AA. An integrated intervention combining cognitive-behavioural stress management and progressive muscle relaxation improves immune biomarkers and reduces COVID-19 severity and progression in patients with COVID-19: A randomized control trial. Stress Health 2022; 38:978-988. [PMID: 35393715 PMCID: PMC9111066 DOI: 10.1002/smi.3151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Revised: 03/26/2022] [Accepted: 04/04/2022] [Indexed: 12/16/2022]
Abstract
COVID-19 is a world disaster. In response to COVID-19 quarantine, stress, anxiety, and depression may easily develop which negatively affect immunity and decrease the patient's response against the COVID-19 virus. This study investigated the effect of an integrated intervention combining cognitive-behavioural stress management (CBSM) and progressive muscle relaxation (PMRs) on immune biomarkers and disease severity and progression in patients with COVID-19 and the period to which these changes last. Thirty patients with mild or moderate COVID-19 were randomly distributed into intervention and control groups. The intervention group performed an integrated intervention combining CBSM and PMRs. There were three outcome measures including blood immune markers, salivary immunoglobulin A, and Wisconsin scale (WIS). Two-week post-intervention, there were significant differences between groups in the WIS total score, Leucocytes, Lymphocytes, Interleukin-6, and Immunoglobulin-A. While there were non-significant differences between both groups in Interleukin-10 and TNF-α. The significant differences between groups in the WIS total score, Leucocytes, Lymphocytes, Interleukin-6, and Immunoglobulin-A significantly continued 1 week as a follow-up. This study concluded that performing an integrated intervention combining CBSM and PMRs for 2 weeks significantly increases immune biomarkers mainly Leucocytes, Lymphocytes, Interleukin-10, and Interleukin-6 along with S-IgA. Also, this protocol significantly decreases disease severity and associated stress, anxiety, and depression; and enhances the quality of life in patients with COVID-19. The study was retrospectively registered with NCT04998708.
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Affiliation(s)
- Motaz Alawna
- Department of Health SciencesFaculty of Graduate SciencesArab American UniversityJeninPalestine
| | - Ayman A. Mohamed
- Department of Basic SciencesFaculty of Physical TherapyBeni‐Suef UniversityBeni SuefEgypt
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Farinha C, Ferreira JP, Serrano J, Santos H, Oliveiros B, Silva FM, Cascante-Rusenhack M, Teixeira AM. The impact of aquatic exercise programs on the systemic hematological and inflammatory markers of community dwelling elderly: A randomized controlled trial. Front Physiol 2022; 13:838580. [PMID: 36246130 PMCID: PMC9554228 DOI: 10.3389/fphys.2022.838580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Accepted: 09/05/2022] [Indexed: 11/18/2022] Open
Abstract
Evidence shows that physical exercise is important in maintaining an efficient immune system during ageing. However, there are few studies that test the impact of aquatic exercise programs on the immune system. This study aims to analyze the impact of different physical exercise programs in aquatic environment on the systemic hematological and inflammatory markers of community dwelling elderly. One hundred and two elderly were randomly allocated into four groups: a continuous aerobic exercise group (AerG) (n = 25, 71.44 ± 4.84 years); an interval aerobic exercise group (IntG) (n = 28, 72.64 ± 5.22 years); a combined exercise group (ComG) (n = 29, 71.90 ± 5.67 years); a control group (CG) (n = 20, 73.60 ± 5.25 years). The AerG, IntG and ComG participants took part in three different aquatic exercise programs over a 28-weeks period. The CG participants maintained their usual routines during the same time period. Blood samples were collected from all participants in order to access hematologic indicators, by means of cell count, and the inflammatory profile by ELISA. After 28 weeks, significant differences were found for several hematologic variables in the AerG, IntG and ComG with increases in mean corpuscular hemoglobulin (MCH), mean corpuscular hemoglobulin concentration (MCHC), and hemoglobulin (Hb). Decreases in TNF-α levels were found for all exercising groups. An increase in IL-10 levels, granulocytes to lymphocytes ratio (GLR) and a decrease in the TNF-α/IL-10 ratio, were found for the IntG. For the ComG decreases were also found for the TNF-α, IL-1ß/IL-1ra ratios. The present study suggests that aquatic exercise programs were able to improve the inflammatory profile of the participants. Those in the exercise intervention groups showed a shift towards lower pro-inflammatory levels while the non-exercising group showed the opposite behaviour. The IntG and the ComG aquatic exercise programs appeared to be more effective than the AerG program in decreasing chronic low-grade inflammation by mediating the production of higher levels of anti-inflammatory cytokines. However, the differences found between the exercising groups were small and may not have clinical significance.
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Affiliation(s)
- Carlos Farinha
- Research Unit for Sport and Physical Activity, University of Coimbra, Coimbra, Portugal
- Municipality of Sertã, Sertã, Portugal
- *Correspondence: Carlos Farinha,
| | - José Pedro Ferreira
- Research Unit for Sport and Physical Activity, University of Coimbra, Coimbra, Portugal
| | - João Serrano
- Sport, Health and Exercise Research Unit (SHERU), Polytechnic Institute of Castelo Branco, Castelo-Branco, Portugal
| | - Hélder Santos
- Polytechnic of Coimbra, ESTeSC, Clinical Physiology, Coimbra, Portugal
| | - Bárbara Oliveiros
- Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Fernanda M. Silva
- Research Unit for Sport and Physical Activity, University of Coimbra, Coimbra, Portugal
| | | | - Ana Maria Teixeira
- Research Unit for Sport and Physical Activity, University of Coimbra, Coimbra, Portugal
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Vasconcelos ABS, Aragão-Santos JC, de Resende-Neto AG, Rodrigues LS, Corrêa CB, Schimieguel DM, Camargo EA, de Paula Ramos S, Da Silva-Grigoletto ME. Effects of functional and combined training on subsets of memory T cells and functional fitness of postmenopausal women: A randomized controlled trial. Exp Gerontol 2022; 167:111898. [PMID: 35863693 DOI: 10.1016/j.exger.2022.111898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 06/21/2022] [Accepted: 07/13/2022] [Indexed: 11/27/2022]
Abstract
This study investigated the effects of functional (FT) and combined (CT) training on memory T cells and functional fitness of postmenopausal women. 108 participants were randomly allocated to the control (CG), FT and CT groups. Functional fitness was assessed through physical tests similar to daily activities, such as dressing on and taking off a t-shirt (DTTS), 10-meter walking and countermovement jump. The CCR7 and CD45RA surface markers were used to characterize the memory T cells. Regarding the frequency of memory T cells, both training protocols reduced the percentage of CD4+ Terminally Differentiated Effector Memory T Cells Re-Expressing CD45RA (TEMRA) (FT: -38.73 %, p = 0.0455; CT: -30.43 %, p = 0.0036) and CD8+ TEMRA cells (FT: -22.24 %, p < 0.0013; CT: -13.13 %, p = 0.0051). Also, both FT and CT increased the percentage of central memory (TCM) CD4+ (FT: +55.22 %, p = 0.0104; CT: +68.03 %, p = 0.0167) and CD8+ (FT: +142.00 %, p < 0.0001; CT: +83.76 %, p = 0.0001) T cells. Furthermore, FT and CT increased the percentages of CD8+ effector memory T cells (TEM) (FT: +63.58 %, p < 0.0001; CT: +14.12 %, p = 0.0041). Regarding functional fitness, both training protocols reduced the time required to perform the DTTS (FT: -19.71 %, p < 0.0001; CT: -14.69 %, p < 0.0001) and 10-m walk tests (FT: -13.05 %, p < 0.0001; CT: -12.83 %, p < 0.0001), in addition to improving jumping ability (FT: +29.97 %, p < 0.0001; CT: +20.00 %, p < 0.0001), both compared to the pre-test or to the CG. Therefore, both FT and CT seem to be equally effective alternatives for promoting the reduction of CD4+ and CD8+ TEMRA cells, increasing the frequency of TCM and TEM cells, and improving functional fitness of postmenopausal women.
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Affiliation(s)
- Alan Bruno Silva Vasconcelos
- Graduate Program in Physiological Sciences (PROCFIS), Federal University of Sergipe, São Cristóvão, Sergipe, Brazil; Functional Training Group (FTG), Department of Physical Education, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
| | - José Carlos Aragão-Santos
- Functional Training Group (FTG), Department of Physical Education, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil; Graduate Program in Health Sciences (PPGCS), Federal University of Sergipe, Aracaju, Sergipe, Brazil
| | - Antônio Gomes de Resende-Neto
- Functional Training Group (FTG), Department of Physical Education, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil; Graduate Program in Health Sciences (PPGCS), Federal University of Sergipe, Aracaju, Sergipe, Brazil
| | | | - Cristiane Bani Corrêa
- Graduate Program in Physiological Sciences (PROCFIS), Federal University of Sergipe, São Cristóvão, Sergipe, Brazil; Graduate Program in Health Sciences (PPGCS), Federal University of Sergipe, Aracaju, Sergipe, Brazil
| | | | - Enilton Aparecido Camargo
- Graduate Program in Physiological Sciences (PROCFIS), Federal University of Sergipe, São Cristóvão, Sergipe, Brazil; Graduate Program in Health Sciences (PPGCS), Federal University of Sergipe, Aracaju, Sergipe, Brazil
| | | | - Marzo Edir Da Silva-Grigoletto
- Graduate Program in Physiological Sciences (PROCFIS), Federal University of Sergipe, São Cristóvão, Sergipe, Brazil; Functional Training Group (FTG), Department of Physical Education, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil
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7
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Graff RM, Jennings K, LaVoy ECP, Warren VE, Macdonald BW, Park Y, Markofski MM. T-cells in response to acute cardiorespiratory or resistance exercise in physically active or physically inactive older adults: A randomized crossover study. J Appl Physiol (1985) 2022; 133:119-129. [PMID: 35616304 DOI: 10.1152/japplphysiol.00301.2021] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
T-cells often undergo age-related changes, but regular exercise training may offset these age-related changes. However, the majority of literature is derived from cardiorespiratory exercise studies. The purpose of this study was to examine the effects of acute cardiorespiratory exercise and acute resistance exercise on the T-cell response among physically active older adults (PA) compared to physically inactive older adults (PI). METHODS Twenty-four healthy older adults (PA n=12; PI n=12; mean ± SD; age (yrs) PA 62 ± 5, PI 64 ± 5; BMI (kg/m2) PA 23.9 ± 3.0, PI 25.6 ± 3.5) completed one bout each of matched intensity cardiorespiratory exercise and resistance exercise in a randomized order. Blood samples drawn pre-exercise, post-exercise, and 1h post-exercise (recovery) were analyzed by flow cytometry for T-cells and T-cell subsets. RESULTS Resistance exercise mobilized more T-cell subsets in PI (10 of the measured types, including total T-cells; CD45RA+ CD62L+, CD45RA- CD62L+, CD45RA- CD62L-, and CD45RA+ CD62L- T-cells), whereas cardiorespiratory exercise mobilized more subsets in PA (CD45RA+ CD62L- and CD57+ CD45RA+ CD62L- CD4+ T-cells). Both cardiorespiratory exercise and resistance exercise elicited a significant (p<0.05) mobilization of highly-differentiated (CD45RA+ CD62L-; CD57+ CD45RA+ CD62L-) CD8+ T-cells into the circulation post-exercise in both PA and PI groups. Furthermore, cardiorespiratory exercise resulted in a decrease in the number of circulating Th17 cells post-exercise, while resistance exercise increased Th17 cell mobilization compared to the cardiorespiratory exercise response. CONCLUSION There are differences between cardiorespiratory exercise and resistance exercise on the immune responses of T-cells, particularly in PI individuals.
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Affiliation(s)
- Rachel M Graff
- Department of Health and Human Performance, University of Houston, Houston, TX, United States
| | - Kristofer Jennings
- Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Emily C P LaVoy
- Department of Health and Human Performance, University of Houston, Houston, TX, United States
| | - Victoria E Warren
- Department of Health and Human Performance, University of Houston, Houston, TX, United States
| | - Brad W Macdonald
- Department of Health and Human Performance, University of Houston, Houston, TX, United States
| | - Yoonjung Park
- Department of Health and Human Performance, University of Houston, Houston, TX, United States
| | - Melissa M Markofski
- Department of Health and Human Performance, University of Houston, Houston, TX, United States
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Emery A, Moore S, Turner JE, Campbell JP. Reframing How Physical Activity Reduces The Incidence of Clinically-Diagnosed Cancers: Appraising Exercise-Induced Immuno-Modulation As An Integral Mechanism. Front Oncol 2022; 12:788113. [PMID: 35359426 PMCID: PMC8964011 DOI: 10.3389/fonc.2022.788113] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 01/14/2022] [Indexed: 12/13/2022] Open
Abstract
Undertaking a high volume of physical activity is associated with reduced risk of a broad range of clinically diagnosed cancers. These findings, which imply that physical activity induces physiological changes that avert or suppress neoplastic activity, are supported by preclinical intervention studies in rodents demonstrating that structured regular exercise commonly represses tumour growth. In Part 1 of this review, we summarise epidemiology and preclinical evidence linking physical activity or regular structured exercise with reduced cancer risk or tumour growth. Despite abundant evidence that physical activity commonly exerts anti-cancer effects, the mechanism(s)-of-action responsible for these beneficial outcomes is undefined and remains subject to ongoing speculation. In Part 2, we outline why altered immune regulation from physical activity - specifically to T cells - is likely an integral mechanism. We do this by first explaining how physical activity appears to modulate the cancer immunoediting process. In doing so, we highlight that augmented elimination of immunogenic cancer cells predominantly leads to the containment of cancers in a 'precancerous' or 'covert' equilibrium state, thus reducing the incidence of clinically diagnosed cancers among physically active individuals. In seeking to understand how physical activity might augment T cell function to avert cancer outgrowth, in Part 3 we appraise how physical activity affects the determinants of a successful T cell response against immunogenic cancer cells. Using the cancer immunogram as a basis for this evaluation, we assess the effects of physical activity on: (i) general T cell status in blood, (ii) T cell infiltration to tissues, (iii) presence of immune checkpoints associated with T cell exhaustion and anergy, (iv) presence of inflammatory inhibitors of T cells and (v) presence of metabolic inhibitors of T cells. The extent to which physical activity alters these determinants to reduce the risk of clinically diagnosed cancers - and whether physical activity changes these determinants in an interconnected or unrelated manner - is unresolved. Accordingly, we analyse how physical activity might alter each determinant, and we show how these changes may interconnect to explain how physical activity alters T cell regulation to prevent cancer outgrowth.
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Affiliation(s)
- Annabelle Emery
- Department for Health, University of Bath, Bath, United Kingdom
| | - Sally Moore
- Department of Haematology, Royal United Hospitals Bath NHS Foundation Trust, Bath, United Kingdom
| | - James E Turner
- Department for Health, University of Bath, Bath, United Kingdom
| | - John P Campbell
- Department for Health, University of Bath, Bath, United Kingdom
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Felismino ES, Santos JMB, Rossi M, Santos CAF, Durigon EL, Oliveira DBL, Thomazelli LM, Monteiro FR, Sperandio A, Apostólico JS, França CN, Amaral JB, Amirato GR, Vieira RP, Vaisberg M, Bachi ALL. Better Response to Influenza Virus Vaccination in Physically Trained Older Adults Is Associated With Reductions of Cytomegalovirus-Specific Immunoglobulins as Well as Improvements in the Inflammatory and CD8 + T-Cell Profiles. Front Immunol 2021; 12:713763. [PMID: 34712226 PMCID: PMC8546344 DOI: 10.3389/fimmu.2021.713763] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 09/21/2021] [Indexed: 12/26/2022] Open
Abstract
Chronic cytomegalovirus (CMV) infection is a trigger factor for the development of immunosenescence and negatively impacts the immune response to influenza virus vaccination (IVV) in older adults. However, the role of physical exercise training in this context is unknown. Thus, the aim of this study was to investigate whether the regular practice of combined exercise training can improve the specific antibody response to IVV in CMV-seropositive older adults. Eighty older adults were distributed into two groups-non-practitioners (NP, n = 31, age = 74.06 ± 6.4 years) and practitioners of combined exercise training (CET, n = 49, age = 71.7 ± 5.8 years)-for at least 12 months. Both volunteer groups were submitted to IVV and blood samples were collected before (pre) and 30 days after (post) the vaccination. Concerning the specific antibody response to IVV, higher serum levels of specific immunoglobulin A (IgA) were found in the CET group post- than pre-vaccination (p < 0.01), whereas higher levels of specific immunoglobulin M (IgM) were observed both in the NP (p < 0.05) and CET (p < 0.001) groups post-vaccination as compared to the pre-vaccination values. Serum levels of specific immunoglobulin G (IgG) for IVV and CMV, as well as interleukin 6 (IL-6) and IL-10, were similar between the time points evaluated. However, the IL-10/IL-6 ratio post-vaccination was higher (p < 0.05) in the CET group than that before vaccination. Negative correlations were observed between the specific IgG levels for IVV and CMV only in the CET group, both pre- and post-vaccination. In addition, negative correlations were found between IL-10 and specific IgG for CMV in all volunteer groups pre- and post-vaccination, whereas a positive correlation between IL-10 and specific-IgG for IVV pre- and post-vaccination was observed in the CET group. In addition, with the hemagglutination inhibition (HAI) assay, it was found that 32.2% of the NP group and 32.6% of the CET group were responders to IVV and displayed reductions in the CMV serostatus (p < 0.05 and p < 0.001, respectively) and increases in naive and effector CD8+ T cells post-vaccination (p < 0.01). However, only the responders from the CET group showed significant reductions in the ratio of effector to naive CD8+ T cells (p < 0.05) and increased IL-10 levels post-vaccination (p < 0.001). In summary, this study demonstrates that the improvement in the response to IVV in CMV-seropositive older adults was related to an anti-inflammatory status and enhancement of naive CD8+ T cells, particularly associated with regular practice of CET.
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Affiliation(s)
- Eduardo S. Felismino
- Post-Graduation Program in Health Science, University of Santo Amaro, São Paulo, Brazil
| | - Juliana M. B. Santos
- Post-Graduation Program in Sciences of Human Movement and Rehabilitation, Federal University of São Paulo, Santos, Brazil
| | - Marcelo Rossi
- Ear, Nose and Throat (ENT) Lab, Department of Otorhinolaryngology, Federal University of São Paulo, São Paulo, Brazil
| | - Carlos A. F. Santos
- Department of Medicine, Geriatry, Paulista School of Medicine (EPM), São Paulo, Brazil
| | - Edison L. Durigon
- Laboratory of Clinical and Molecular Virology, Department of Microbiology, Institute of Biomedical Science of University of São Paulo, São Paulo, Brazil
- Scientific Platform Pasteur–University of São Paulo, São Paulo, Brazil
| | - Danielle B. L. Oliveira
- Laboratory of Clinical and Molecular Virology, Department of Microbiology, Institute of Biomedical Science of University of São Paulo, São Paulo, Brazil
- Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - Luciano M. Thomazelli
- Laboratory of Clinical and Molecular Virology, Department of Microbiology, Institute of Biomedical Science of University of São Paulo, São Paulo, Brazil
| | - Fernanda R. Monteiro
- Ear, Nose and Throat (ENT) Lab, Department of Otorhinolaryngology, Federal University of São Paulo, São Paulo, Brazil
- Method Faculty of São Paulo, São Paulo, Brazil
| | | | - Juliana S. Apostólico
- Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, São Paulo, Brazil
| | - Carolina N. França
- Post-Graduation Program in Health Science, University of Santo Amaro, São Paulo, Brazil
| | - Jonatas B. Amaral
- Ear, Nose and Throat (ENT) Lab, Department of Otorhinolaryngology, Federal University of São Paulo, São Paulo, Brazil
| | - Gislene R. Amirato
- Ear, Nose and Throat (ENT) Lab, Department of Otorhinolaryngology, Federal University of São Paulo, São Paulo, Brazil
| | - Rodolfo P. Vieira
- Post-Graduation Program in Sciences of Human Movement and Rehabilitation, Federal University of São Paulo, Santos, Brazil
- Post-Graduation Program in Bioengineering, Universidade Brasil, São Paulo, Brazil
- Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), Sao Jose dos Campos, Brazil
| | - Mauro Vaisberg
- Ear, Nose and Throat (ENT) Lab, Department of Otorhinolaryngology, Federal University of São Paulo, São Paulo, Brazil
| | - André L. L. Bachi
- Post-Graduation Program in Health Science, University of Santo Amaro, São Paulo, Brazil
- Ear, Nose and Throat (ENT) Lab, Department of Otorhinolaryngology, Federal University of São Paulo, São Paulo, Brazil
- Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), Sao Jose dos Campos, Brazil
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10
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Mohamed AA, Alawna M. The effect of aerobic exercise on immune biomarkers and symptoms severity and progression in patients with COVID-19: A randomized control trial. J Bodyw Mov Ther 2021; 28:425-432. [PMID: 34776174 PMCID: PMC8339452 DOI: 10.1016/j.jbmt.2021.07.012] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 07/09/2021] [Accepted: 07/31/2021] [Indexed: 01/19/2023]
Abstract
BACKGROUND The World Health Organization in March 2020 has announced that COVID-19 is a world pandemic because the number of infected cases increases rapidly. however, there are several available vaccines, their protection is limited to a certain period. Thus, the role of modalities that improve immune functions should be performed to counter COVID-19 viral load and decrease mortality rates. OBJECTIVE To investigate the effect of aerobic exercise on immune biomarkers, disease severity, and progression in patients with COVID-19. DESIGN A randomized controlled study. PARTICIPANTS Thirty patients with COVID-19 participated in this study. Participants' age ranged from 24 to 45 years old. Participants had a mild or moderate COVID-19. Participants were assigned randomly into two groups, exercise and control groups. There were two main dependent variables including blood immune markers and severity of respiratory symptoms. INTERVENTIONS All participants performed 2 weeks of moderate-intensity aerobic exercise for 40 min/session, 3 sessions/week. The measurements were performed at baseline, and after 2-weeks. RESULTS At baseline measurements, there were non-significant differences between both groups in the Wisconsin scale total score, Leucocytes, Lymphocytes, Interleukin-6, Interleukin-10, Immunoglobulin-A, and TNF-α (P > .05). After the intervention, the Wisconsin scale (patient-oriented illness-specific quality-of-life) total score significantly decreased in the intervention group (P < .05); while, Leucocytes, Lymphocytes, and Immunoglobulin-A significantly increased in the intervention group (P < .05). CONCLUSION The current study indicated that 2 weeks of moderate-intensity aerobic exercise decreased the severity and progression of COVID-19 associated disorders and quality of life. Also, a 2-weeks of aerobic exercise positively affected immune function by increasing the amounts of Leucocytes, Lymphocytes, Immunoglobulin A.
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Affiliation(s)
- Ayman A Mohamed
- Department of Physiotherapy and Rehabilitation, School of Health Sciences, Istanbul Gelisim University, Istanbul, Turkey; Department of Basic Sciences, Faculty of Physical Therapy, Beni-Suef University, Beni Suef, Egypt
| | - Motaz Alawna
- Department of Physiotherapy and Rehabilitation, School of Health Sciences, Istanbul Gelisim University, Istanbul, Turkey; Department of Physiotherapy and Rehabilitation, Faculty of Allied Medical Sciences, Arab American University, Jenin, Palestine.
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11
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Donovan T, Bain AL, Tu W, Pyne DB, Rao S. Influence of Exercise on Exhausted and Senescent T Cells: A Systematic Review. Front Physiol 2021; 12:668327. [PMID: 34489717 PMCID: PMC8417807 DOI: 10.3389/fphys.2021.668327] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 07/29/2021] [Indexed: 11/17/2022] Open
Abstract
The impaired effector function of exhausted and senescent T cells is implicated in cancer progression and inadequate vaccine responses. Exercise has been shown to improve cancer therapy and vaccine efficacy, most likely by improving immune function. However, given inconsistent terminology and definitions, the interactions between exercise and exhausted and senescent T cells remain unclear. We therefore performed a systematic review to investigate the effect of exercise on senescent and exhausted CD8+ T cell populations clearly defined by protein surface markers. Thirty articles were included, with the majority (n = 24) reporting senescent T cell populations defined according to a variety of surface markers. Repeated exercise was shown to be beneficial through limiting the accumulation of senescent and exhausted CD8+ T cells. This outcome is likely related to exercise-induced preferential mobilization of senescent T cells promoting apoptosis in the peripheral blood compartment. Future studies need to determine the clinical relevance of this effect in cancer prevention and vaccine efficacy. Data regarding exercise and exhausted T cells are limited due to a lack of available high-quality studies. Future studies require the control of confounding variables such as sex and cytomegalovirus (CMV) status, and consistent definitions of exhausted and senescent T cell populations to improve comparisons between studies and interventions.
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Affiliation(s)
- Thomasina Donovan
- Research Institute for Sport and Exercise, University of Canberra, Canberra, ACT, Australia.,Australian Centre for Health Services Innovation and Centre for Healthcare Transformation, School of Public Health and Social Work, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia
| | - Amanda L Bain
- Gene Regulation and Translational Medicine Laboratory, Immunology Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
| | - Wenjuan Tu
- Gene Regulation and Translational Medicine Laboratory, Immunology Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
| | - David B Pyne
- Research Institute for Sport and Exercise, University of Canberra, Canberra, ACT, Australia
| | - Sudha Rao
- Gene Regulation and Translational Medicine Laboratory, Immunology Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
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12
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Functional and concurrent training do not impair immune function and improve functional fitness in postmenopausal women: A randomized controlled trial. Exp Gerontol 2021; 153:111504. [PMID: 34343632 DOI: 10.1016/j.exger.2021.111504] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 07/19/2021] [Accepted: 07/27/2021] [Indexed: 01/01/2023]
Abstract
PURPOSE To evaluate the effects of functional and concurrent training on immune function and functional fitness in postmenopausal women. MATERIALS AND METHODS A randomized controlled trial was performed on 108 women aged 60 or older who were randomly assigned among the groups: control group (CG: n = 40; 63.88 ± 3.64 years); functional training (FT: n = 32; 63.88 ± 3.79 years); and concurrent training (CT: n = 36; 64.83 ± 4.00 years). Immune function was measured by the expression of the T-lymphocyte function-related surface markers (CD28 and CD57). Functional fitness was assessed using physical tests similar to daily activities, i.e., five times sit to stand, timed up and go, and gallon-jug shelf-transfer. RESULTS Regarding immune function, there was only a time effect, without between-group differences. Specifically, FT and CT show a reduction and increase in CD4+ and CD8+ T cells, respectively, without impairment in the subpopulations analyzed, while CG showed a reduction in naive T cells (CD8+CD28+). For functional fitness tests, there was a time × group interaction effect for all tests, the FT and CT were superior to the CG, with FT showing differences after the fourth week, while the CT showed this effect after the eighth week of intervention. CONCLUSION FT and CT do not impair immune function and similarly improve functional fitness in postmenopausal women. CLINICAL TRIALS REGISTRY RBR-2d56bt.
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13
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Impact of exercise on the immune system and outcomes in hematologic malignancies. Blood Adv 2021; 4:1801-1811. [PMID: 32343800 DOI: 10.1182/bloodadvances.2019001317] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Accepted: 02/27/2020] [Indexed: 12/13/2022] Open
Abstract
Exercise is increasingly recognized as important to cancer care. The biology of how exercise improves outcomes is not well understood, however. Studies show that exercise favorably influences the immune system in healthy individuals (neutrophils, monocytes, natural killer cells, T cells, and a number of cytokines). Thus, exercise in patients with hematologic cancer could significantly improve immune function and tumor microenvironment. We performed a literature search and identified 7 studies examining exercise and the immune environment in hematologic malignancies. This review focuses on the role of exercise and physical activity on the immune system in hematologic malignancies and healthy adults.
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14
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Effects of Regular Physical Activity on the Immune System, Vaccination and Risk of Community-Acquired Infectious Disease in the General Population: Systematic Review and Meta-Analysis. Sports Med 2021; 51:1673-1686. [PMID: 33877614 PMCID: PMC8056368 DOI: 10.1007/s40279-021-01466-1] [Citation(s) in RCA: 144] [Impact Index Per Article: 36.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/31/2021] [Indexed: 12/17/2022]
Abstract
Background Regular physical activity is the prime modality for the prevention of numerous non-communicable diseases and has also been advocated for resilience against COVID-19 and other infectious diseases. However, there is currently no systematic and quantitative evidence synthesis of the association between physical activity and the strength of the immune system. Objective To examine the association between habitual physical activity and (1) the risk of community-acquired infectious disease, (2) laboratory‐assessed immune parameters, and (3) immune response to vaccination. Methods We conducted a systemic review and meta-analysis according to PRISMA guidelines. We searched seven databases (MEDLINE, Embase, Cochrane CENTRAL, Web of Science, CINAHL, PsycINFO, and SportDiscus) up to April 2020 for randomised controlled trials and prospective observational studies were included if they compared groups of adults with different levels of physical activity and reported immune system cell count, the concentration of antibody, risk of clinically diagnosed infections, risk of hospitalisation and mortality due to infectious disease. Studies involving elite athletes were excluded. The quality of the selected studies was critically examined following the Cochrane guidelines using ROB2 and ROBINS_E. Data were pooled using an inverse variance random-effects model. Results Higher level of habitual physical activity is associated with a 31% risk reduction (hazard ratio 0.69, 95% CI 0.61–0.78, 6 studies, N = 557,487 individuals) of community-acquired infectious disease and 37% risk reduction (hazard ratio 0.64, 95% CI 0.59–0.70, 4 studies, N = 422,813 individuals) of infectious disease mortality. Physical activity interventions resulted in increased CD4 cell counts (32 cells/µL, 95% CI 7–56 cells/µL, 24 studies, N = 1112 individuals) and salivary immunoglobulin IgA concentration (standardised mean difference 0.756, 95% CI 0.146–1.365, 7 studies, N = 435 individuals) and decreased neutrophil counts (704 cells/µL, 95% CI 68–1340, 6 studies, N = 704 individuals) compared to controls. Antibody concentration after vaccination is higher with an adjunct physical activity programme (standardised mean difference 0.142, 95% CI 0.021–0.262, 6 studies, N = 497 individuals). Conclusion Regular, moderate to vigorous physical activity is associated with reduced risk of community-acquired infectious diseases and infectious disease mortality, enhances the first line of defence of the immune system, and increases the potency of vaccination. Protocol registration The original protocol was prospectively registered with PROSPERO (CRD42020178825). Supplementary Information The online version contains supplementary material available at 10.1007/s40279-021-01466-1.
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15
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Effects of a 6 Week Low-Dose Combined Resistance and Endurance Training on T Cells and Systemic Inflammation in the Elderly. Cells 2021; 10:cells10040843. [PMID: 33917916 PMCID: PMC8068286 DOI: 10.3390/cells10040843] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 04/06/2021] [Accepted: 04/07/2021] [Indexed: 12/20/2022] Open
Abstract
With increasing age, the immune system undergoes a remodeling process, affecting the shift of T cell subpopulations and the development of chronic low-grade inflammation. Clinically, this is characterized by increased susceptibility to infections or development of several diseases. Since lifestyle factors can play a significant role in reducing the hallmarks of immune aging and inflammation, we investigated the effect of a 6 week low-dose combined resistance and endurance training program. Forty participants (70.3 ± 5.0 years) were randomly assigned to either a training (TG) or control group (CG) and performed a controlled low-threshold and care-oriented 6-week-long combined resistance and endurance training program. Changes in anthropometrics as well as strength capacity were measured. In subgroups of TG and CG, T cells and their subpopulations (CD4+, CD8+, naïve, central, effector memory, T-EMRA) were analyzed by flow cytometry. The changes of various plasma cytokines, chemokines, growth factors and adipokines were analyzed by luminex assays. The exercise program was followed by an increase in strength capacities. Participants of TG showed an increase of the CD4+/CD8+ T cell ratio over time (p < 0.05). Significant decreases in systemic levels of interleukin (IL-) 6, IL-8, IL-10 and vascular endothelial growth factor (VEGF) (p < 0.05) were observed for participants of TG over time. Even short-term and low-threshold training can reduce some of the hallmarks of immune aging in elderly and thus could be beneficial to stimulate immunity. The specific characteristics of the program make it easily accessible to older people, who may benefit in the longer term in terms of their immunocompetence.
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16
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Abdelbasset WK. Stay Home: Role of Physical Exercise Training in Elderly Individuals' Ability to Face the COVID-19 Infection. J Immunol Res 2020; 2020:8375096. [PMID: 33354578 PMCID: PMC7737455 DOI: 10.1155/2020/8375096] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Revised: 11/13/2020] [Accepted: 11/18/2020] [Indexed: 12/20/2022] Open
Abstract
Recently, the novel coronavirus epidemic occurred in China and spread worldwide to become a global pandemic. COVID-19 is a fatal viral infection causing death, particularly in aged individuals, due to impaired immunity. To date, no intervention is available to prevent COVID-19 and its manifestations. Physical exercise training generally has health benefits, and it assists in the prevention of several chronic diseases. Therefore, this review is aimed at exploring the role of physical exercise training in the face of COVID-19 in older adults and elderly individuals. From this point of view, this review suggests that physical exercise training plays a key role in promoting immune system regulation, delaying immunity dysfunction, reducing circulatory inflammation markers, and preventing sarcopenia and thus could prevent the risk of acquiring COVID-19 infection and reduce the complications of recommended self-isolation in older adults and elderly individuals. Additionally, immunity biomarkers were optimistically demonstrated in older adults following physical exercise training, thereby reducing mortality and morbidity rates. Finally, in accordance with recommendations to stay home and perform self-isolation to prevent the spread of COVID-19, all populations are strongly recommended to practice regular home exercise training at home to promote immune system functioning.
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Affiliation(s)
- Walid Kamal Abdelbasset
- Department of Health and Rehabilitation Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia
- Department of Physical Therapy, Kasr Al-Ainy Hospital, Cairo University, Giza, Egypt
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17
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Cao Dinh H, Njemini R, Onyema OO, Beyer I, Liberman K, De Dobbeleer L, Renmans W, Vander Meeren S, Jochmans K, Delaere A, Knoop V, Bautmans I. Strength Endurance Training but Not Intensive Strength Training Reduces Senescence-Prone T Cells in Peripheral Blood in Community-Dwelling Elderly Women. J Gerontol A Biol Sci Med Sci 2020; 74:1870-1878. [PMID: 30285092 DOI: 10.1093/gerona/gly229] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Indexed: 12/31/2022] Open
Abstract
Aging is characterized by a progressive decline in immune function known as immunosenescence. Although the causes of immunosenescence are likely to be multifactorial, an age-associated accumulation of senescent T cells and decreased naive T-cell repertoire are key contributors to the phenomenon. On the other hand, there is a growing consensus that physical exercise may improve immune response in aging. However, the optimum training modality required to obtain beneficial adaptations in older subjects is lacking. Therefore, we aimed to investigate the effects of exercise modality on T-cell phenotypes in older women. A total of 100 women (aged ≥ 65 years) were randomized to either intensive strength training (80% of one-repetition maximum ), strength endurance training (40% one-repetition maximum), or control (stretching exercise) for 2-3 times per week during 6 weeks. The T-cell percentages and absolute counts were determined using flow cytometry and a hematology analyzer. C-reactive protein was measured using immunonephelometry. We report for the first time that 6 weeks of strength endurance training significantly decreased the basal percentage and absolute counts of senescence-prone T cells, which was positively related to the number of training sessions performed. Conceivably, training protocols with many repetitions-at a sufficiently high external resistance-might assist the reduction of senescence-prone T cells in older women.
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Affiliation(s)
- Hung Cao Dinh
- Frailty in Ageing Research Group.,Gerontology Department, Vrije Universiteit Brussel
| | - Rose Njemini
- Frailty in Ageing Research Group.,Gerontology Department, Vrije Universiteit Brussel
| | - Oscar Okwudiri Onyema
- Frailty in Ageing Research Group.,Gerontology Department, Vrije Universiteit Brussel
| | - Ingo Beyer
- Frailty in Ageing Research Group.,Gerontology Department, Vrije Universiteit Brussel.,Head Gerontology (GERO) & Frailty in Ageing Research (FRIA) Departments
| | - Keliane Liberman
- Frailty in Ageing Research Group.,Gerontology Department, Vrije Universiteit Brussel
| | - Liza De Dobbeleer
- Frailty in Ageing Research Group.,Gerontology Department, Vrije Universiteit Brussel
| | - Wim Renmans
- Hematology Laboratory, Universitair Ziekenhuis Brussel, Belgium
| | | | | | - Andreas Delaere
- Frailty in Ageing Research Group.,Gerontology Department, Vrije Universiteit Brussel
| | - Veerle Knoop
- Frailty in Ageing Research Group.,Gerontology Department, Vrije Universiteit Brussel
| | - Ivan Bautmans
- Frailty in Ageing Research Group.,Gerontology Department, Vrije Universiteit Brussel.,Head Gerontology (GERO) & Frailty in Ageing Research (FRIA) Departments
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18
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Cohen G, Steinberg DM, Keinan-Boker L, Shaked O, Goshen A, Shimony T, Shohat T, Gerber Y. Leisure-Time Physical Activity and Cancer Risk Among Older Adults: A Cohort Study. Mayo Clin Proc Innov Qual Outcomes 2020; 4:115-125. [PMID: 32280920 PMCID: PMC7140136 DOI: 10.1016/j.mayocpiqo.2019.11.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Objective To examine the association between leisure-time physical activity (LTPA) and long-term cancer risk in a nationwide cohort of older adults. Participants and Methods The cohort comprised participants of a national survey conducted between July 2005 and December 2006, constituting a random sample of Israeli community-dwelling adults aged 65 years or older. Based on self-reported LTPA habits, participants were classified as sufficiently active, insufficiently active, or inactive according to published guidelines. Cancer diagnosis was assessed via the Israeli National Cancer Registry through September 2015. Inverse probability weighted hazard ratios for incident cancer, based on propensity score, were estimated for LTPA categories. Results Analysis included 1542 participants with no history of cancer at baseline (median [25th-75th percentile] age, 73 years [69-78 years]; 826 [53.6%] women). Inactive participants (n=641 [41.6%]) were more likely to be female, of lower socioeconomic status, and with higher body mass index and poorer perceived health compared with their insufficiently active (n=443 [28.7%]) and sufficiently active (n=458 [29.7%]) counterparts. In the propensity score–weighted synthetic sample, the distribution of measured baseline covariates was similar across LTPA categories. Over a median follow-up of 9 years, 254 new cancer cases (16.5%) were diagnosed. Leisure-time physical activity was inversely associated with incident cancer, with adjusted hazard ratios (95% CIs) of 0.66 (0.46-0.93) in insufficiently active and 0.59 (0.42-0.82) in sufficiently active participants compared with inactive individuals (P value for trend = .002). Conclusion Among older adults, engaging in LTPA, even at lower levels than officially recommended, may have a beneficial effect on primary prevention of cancer.
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Affiliation(s)
- Gali Cohen
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Stanley Steyer Institute for Cancer Epidemiology and Research, Tel Aviv University, Tel Aviv, Israel
| | - David M Steinberg
- Department of Statistics and Operations Research, School of Mathematical Sciences, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, Israel
| | - Lital Keinan-Boker
- Israel Center for Disease Control, Israel Ministry of Health, Tel Hashomer, Israel.,School of Public Health, University of Haifa, Haifa, Israel
| | - Or Shaked
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Abigail Goshen
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Tal Shimony
- Israel Center for Disease Control, Israel Ministry of Health, Tel Hashomer, Israel
| | - Tamar Shohat
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Israel Center for Disease Control, Israel Ministry of Health, Tel Hashomer, Israel
| | - Yariv Gerber
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Stanley Steyer Institute for Cancer Epidemiology and Research, Tel Aviv University, Tel Aviv, Israel
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19
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Soltani N, Marandi SM, Kazemi M, Esmaeil N. The Exercise Training Modulatory Effects on the Obesity-Induced Immunometabolic Dysfunctions. Diabetes Metab Syndr Obes 2020; 13:785-810. [PMID: 32256095 PMCID: PMC7090203 DOI: 10.2147/dmso.s234992] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Accepted: 02/18/2020] [Indexed: 12/13/2022] Open
Abstract
Reduced physical activity rate in people's lifestyle is a global concern associated with the prevalence of health disorders such as obesity and metabolic disturbance. Ample evidence has indicated a critical role of the immune system in the aggravation of obesity. The type, duration, and production of adipose tissue-released mediators may change subsequent inactive lifestyle-induced obesity, leading to the chronic systematic inflammation and monocyte/macrophage (MON/MФ) phenotype polarization. Preliminary adipose tissue expansion can be inhibited by changing the lifestyle. In this context, exercise training is widely recommended due to a definite improvement of energy balance and the potential impacts on the inflammatory signaling cascades. How exercise training affects the immune system has not yet been fully elucidated, because its anti-inflammatory, pro-inflammatory, or even immunosuppressive impacts have been indicated in the literature. A thorough understanding of the mechanisms triggered by exercise can suggest a new approach to combat meta-inflammation-induced metabolic diseases. In this review, we summarized the obesity-induced inflammatory pathways, the roles of MON/MФ polarization in adipose tissue and systemic inflammation, and the underlying inflammatory mechanisms triggered by exercise during obesity.
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Affiliation(s)
- Nakisa Soltani
- Department of Exercise Physiology, Faculty of Sport Sciences, University of Isfahan, Isfahan, Iran
| | - Sayed Mohammad Marandi
- Department of Exercise Physiology, Faculty of Sport Sciences, University of Isfahan, Isfahan, Iran
- Sayed Mohammad Marandi Department of Exercise Physiology, Faculty of Sport Sciences, University of Isfahan, Isfahan, IranTel +983137932358Fax +983136687572 Email
| | - Mohammad Kazemi
- Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Nafiseh Esmaeil
- Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
- Correspondence: Nafiseh Esmaeil Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan81744-176, IranTel +98 31 37929097Fax +98 3113 7929031 Email
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20
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Leiter O, Bernas SN, Seidemann S, Overall RW, Horenburg C, Kowal S, Kempermann G, Walker TL. The systemic exercise-released chemokine lymphotactin/XCL1 modulates in vitro adult hippocampal precursor cell proliferation and neuronal differentiation. Sci Rep 2019; 9:11831. [PMID: 31413355 PMCID: PMC6694144 DOI: 10.1038/s41598-019-48360-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Accepted: 08/01/2019] [Indexed: 12/23/2022] Open
Abstract
Physical exercise has well-established anti-inflammatory effects, with neuro-immunological crosstalk being proposed as a mechanism underlying the beneficial effects of exercise on brain health. Here, we used physical exercise, a strong positive modulator of adult hippocampal neurogenesis, as a model to identify immune molecules that are secreted into the blood stream, which could potentially mediate this process. Proteomic profiling of mouse plasma showed that levels of the chemokine lymphotactin (XCL1) were elevated after four days of running. We found that XCL1 treatment of primary cells isolated from both the dentate gyrus and the subventricular zone of the adult mice led to an increase in the number of neurospheres and neuronal differentiation in neurospheres derived from the dentate gyrus. In contrast, primary dentate gyrus cells isolated from XCL1 knockout mice formed fewer neurospheres and exhibited a reduced neuronal differentiation potential. XCL1 supplementation in a dentate gyrus-derived neural precursor cell line promoted neuronal differentiation and resulted in lower cell motility and a reduced number of cells in the S phase of the cell cycle. This work suggests an additional function of the chemokine XCL1 in the brain and underpins the complexity of neuro-immune interactions that contribute to the regulation of adult hippocampal neurogenesis.
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Affiliation(s)
- Odette Leiter
- Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, 01307, Dresden, Germany
- German Center for Neurodegenerative Diseases (DZNE) Dresden, 01307, Dresden, Germany
- Queensland Brain Institute, The University of Queensland, Brisbane, 4072, Australia
| | - Stefanie N Bernas
- Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, 01307, Dresden, Germany
- German Center for Neurodegenerative Diseases (DZNE) Dresden, 01307, Dresden, Germany
| | - Suse Seidemann
- Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, 01307, Dresden, Germany
| | - Rupert W Overall
- Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, 01307, Dresden, Germany
- German Center for Neurodegenerative Diseases (DZNE) Dresden, 01307, Dresden, Germany
| | - Cindy Horenburg
- Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, 01307, Dresden, Germany
| | - Susann Kowal
- Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, 01307, Dresden, Germany
| | - Gerd Kempermann
- Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, 01307, Dresden, Germany
- German Center for Neurodegenerative Diseases (DZNE) Dresden, 01307, Dresden, Germany
| | - Tara L Walker
- Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, 01307, Dresden, Germany.
- German Center for Neurodegenerative Diseases (DZNE) Dresden, 01307, Dresden, Germany.
- Queensland Brain Institute, The University of Queensland, Brisbane, 4072, Australia.
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21
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de Lemos Muller CH, de Matos JR, Grigolo GB, Schroeder HT, Rodrigues-Krause J, Krause M. Exercise Training for the Elderly: Inflammaging and the Central Role for HSP70. ACTA ACUST UNITED AC 2019. [DOI: 10.1007/s42978-019-0015-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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22
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Oruç Z, Kaplan MA. Effect of exercise on colorectal cancer prevention and treatment. World J Gastrointest Oncol 2019; 11:348-366. [PMID: 31139306 PMCID: PMC6522766 DOI: 10.4251/wjgo.v11.i5.348] [Citation(s) in RCA: 62] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2019] [Revised: 04/17/2019] [Accepted: 05/06/2019] [Indexed: 02/05/2023] Open
Abstract
In recent years, because of improved cancer screening, detection and treatment modalities, a rapid increase in the population of colorectal and other cancer survivors has been observed. The increasing population has justified the requirement of preventive strategies such as lifestyle modifications with regard to obesity, physical activity, diet and smoking. Physical activity may prevent approximately 15% of the colon cancers. Furthermore, several observational studies have demonstrated the efficacy and dose-dependent and anti-cancer effects of exercise on decreasing the mortality and risk of recurrence before and after the colorectal cancer (CRC) diagnosis. However, the required exercise dose, type and intensity are yet unclear. The results of randomised prospective studies are expected to determine the optimal amount, type and intensity of exercise and formulate the most appropriate exercise plan and guidelines, according to the requirements and comorbidities of the patients. In addition, recent studies have focused on the molecular and genetic mechanisms underlying the effect of physical activity on disease outcomes and recurrence rates. This review aimed to investigate the effects of physical activity and the biological basis of these effects in preventing the risk and recurrence of CRC and decreasing the hazards of cancer and cancer treatment.
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Affiliation(s)
- Zeynep Oruç
- Department of Medical Oncology, Mersin City Hospital, Mersin 33000, Turkey
| | - Muhammed Ali Kaplan
- Department of Medical Oncology, Faculty of Medicine, Dicle University, Diyarbakır 21280, Turkey
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23
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Walker TL, Schallenberg S, Rund N, Grönnert L, Rust R, Kretschmer K, Kempermann G. T Lymphocytes Contribute to the Control of Baseline Neural Precursor Cell Proliferation but Not the Exercise-Induced Up-Regulation of Adult Hippocampal Neurogenesis. Front Immunol 2018; 9:2856. [PMID: 30619254 PMCID: PMC6297802 DOI: 10.3389/fimmu.2018.02856] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Accepted: 11/20/2018] [Indexed: 11/13/2022] Open
Abstract
Cross-talk between the peripheral immune system and the central nervous system is important for physiological brain health. T cells are required to maintain normal baseline levels of neural precursor proliferation in the hippocampus of adult mice. We show here that neither T cells, B cells, natural killer cells nor natural killer T cells are required for the increase in hippocampal precursor proliferation that occurs in response to physical exercise. In addition, we demonstrate that a subpopulation of T cells, regulatory T cells, is not involved in maintaining baseline levels of neural precursor proliferation. Even when applied at supraphysiological numbers, populations of both naive and stimulated lymphocytes had no effect on hippocampal precursor proliferation in vitro. In addition, physical activity had no effect on peripheral immune cells in terms of distribution in the bone marrow, lymph nodes or spleen, activation state or chemokine receptor (CXCR4 and CCR9) expression. Together these results suggest that lymphocytes are not involved in translating the peripheral effects of exercise to the neurogenic niche in the hippocampus and further support the idea that the exercise-induced regulation of adult neurogenesis is mechanistically distinct from its baseline control.
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Affiliation(s)
- Tara L Walker
- Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany.,German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany
| | - Sonja Schallenberg
- Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany
| | - Nicole Rund
- Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany.,German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany
| | - Lisa Grönnert
- Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany.,German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany
| | - Ruslan Rust
- Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany
| | - Karsten Kretschmer
- Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany
| | - Gerd Kempermann
- Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany.,German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany
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24
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Immunological Modulation in Long-Term Karate Practitioners. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 2018:1654148. [PMID: 30046332 PMCID: PMC6038592 DOI: 10.1155/2018/1654148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/23/2017] [Revised: 05/02/2018] [Accepted: 05/25/2018] [Indexed: 11/17/2022]
Abstract
Karate is a Japanese martial arts system with potential physical and psychological benefits. However, karate has been scarcely investigated from a psychobiological perspective, and its effects on the immune system remain virtually unknown. We designed the present study with the aim of analyzing the effects of karate practice on immunological parameters. 27 healthy male volunteer subjects participated in the study, 15 in the experimental group and 12 in the control. Experimental subjects were all karate players who had practiced this martial art for a minimum of three years attending regular lessons at a karate training center, in the evening, two to three days per week. Blood samples for the quantification of immunological parameters (total leukocytes, neutrophils, monocytes, eosinophils, basophils, lymphocytes, IgG, IgA, and IgM) were taken in both groups. A t-test for independent groups was performed in each dependent variable; a value of p<0.05 was considered to be significant. Karate practitioners exhibited a significantly higher number of total leukocytes (p<0.02), monocytes (p<0.01), and lymphocytes (p<0.01), a higher percentage of monocytes (p<0.01), and greater serum concentrations of IgG (p<0.02) and IgM (p<0.01). Our findings show that long-term karate practice is related to a broad modulation of immune parameters, including total and specific leukocyte counts, as well as immunoglobulin concentrations. This peculiar immunomodulatory profile, apart from its psychobiological relevance, may have noteworthy clinical implications.
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25
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Neutrophil and Monocyte Bactericidal Responses to 10 Weeks of Low-Volume High-Intensity Interval or Moderate-Intensity Continuous Training in Sedentary Adults. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2017; 2017:8148742. [PMID: 28656073 PMCID: PMC5471589 DOI: 10.1155/2017/8148742] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Accepted: 05/09/2017] [Indexed: 12/22/2022]
Abstract
Neutrophils and monocytes are key components of the innate immune system that undergo age-associated declines in function. This study compared the impact of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on immune function in sedentary adults. Twenty-seven (43 ± 11 years) healthy sedentary adults were randomized into ten weeks of either a HIIT (>90% maximum heart rate) or MICT (70% maximum heart rate) group training program. Aerobic capacity (VO2peak), neutrophil and monocyte bacterial phagocytosis and oxidative burst, cell surface receptor expression, and systemic inflammation were measured before and after the training. Total exercise time commitment was 57% less for HIIT compared to that for MICT while both significantly improved VO2peak similarly. Neutrophil phagocytosis and oxidative burst and monocyte phagocytosis and percentage of monocytes producing an oxidative burst were improved by training similarly in both groups. Expression of monocyte but not neutrophil CD16, TLR2, and TLR4 was reduced by training similarly in both groups. No differences in systemic inflammation were observed for training; however, leptin was reduced in the MICT group only. With similar immune-enhancing effects for HIIT compared to those for MICT at 50% of the time commitment, our results support HIIT as a time efficient exercise option to improve neutrophil and monocyte function.
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26
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Cao Dinh H, Beyer I, Mets T, Onyema OO, Njemini R, Renmans W, De Waele M, Jochmans K, Vander Meeren S, Bautmans I. Effects of Physical Exercise on Markers of Cellular Immunosenescence: A Systematic Review. Calcif Tissue Int 2017; 100:193-215. [PMID: 27866236 DOI: 10.1007/s00223-016-0212-9] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2016] [Accepted: 11/07/2016] [Indexed: 12/31/2022]
Abstract
Aging affects negatively the immune system, defined as immunosenescence, which increases the susceptibility of elderly persons to infection, autoimmune disease, and cancer. There are strong indications that physical exercise in elderly persons may prevent the age-related decline in immune response without significant side effects. Consequently, exercise is being considered as a safe mode of intervention to reduce immunosenescence. The aim of this review was to appraise the existing evidence regarding the impact of exercise on surface markers of cellular immunosenescence in either young and old humans or animals. PubMed and Web of Science were systematically screened, and 28 relevant articles in humans or animals were retrieved. Most of the intervention studies demonstrated that an acute bout of exercise induced increases in senescent, naïve, memory CD4+ and CD8+ T-lymphocytes and significantly elevated apoptotic lymphocytes in peripheral blood. As regards long-term effects, exercise induced increased levels of T-lymphocytes expressing CD28+ in both young and elderly subjects. Few studies found an increase in natural killer cell activity following a period of training. We can conclude that exercise has considerable effects on markers of cellular aspects of the immune system. However, very few studies have been conducted so far to investigate the effects of exercise on markers of cellular immunosenescence in elderly persons. Implications for immunosenescence need further investigation.
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Affiliation(s)
- H Cao Dinh
- Frailty in Ageing Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
- Gerontology Department, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
| | - I Beyer
- Frailty in Ageing Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
- Geriatrics Department, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium
| | - T Mets
- Frailty in Ageing Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
- Gerontology Department, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
- Geriatrics Department, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium
| | - O O Onyema
- Frailty in Ageing Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
- Gerontology Department, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
| | - R Njemini
- Frailty in Ageing Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
- Gerontology Department, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
| | - W Renmans
- Laboratory of Hematology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium
| | - M De Waele
- Laboratory of Hematology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium
| | - K Jochmans
- Laboratory of Hematology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium
| | - S Vander Meeren
- Laboratory of Hematology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium
| | - I Bautmans
- Frailty in Ageing Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium.
- Gerontology Department, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium.
- Geriatrics Department, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium.
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27
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Barry A, Cronin O, Ryan AM, Sweeney B, Yap SM, O'Toole O, Allen AP, Clarke G, O'Halloran KD, Downer EJ. Impact of Exercise on Innate Immunity in Multiple Sclerosis Progression and Symptomatology. Front Physiol 2016; 7:194. [PMID: 27313534 PMCID: PMC4889582 DOI: 10.3389/fphys.2016.00194] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2016] [Accepted: 05/16/2016] [Indexed: 12/21/2022] Open
Abstract
Multiple Sclerosis (MS), an idiopathic progressive immune-mediated neurological disorder of the central nervous system (CNS), is characterized by recurrent episodes of inflammatory demyelination and consequent axonal deterioration. It accounts for functional deterioration and lasting disability among young adults. A body of literature demonstrates that physical activity counteracts fatigue and depression and may improve overall quality of life in MS patients. Furthermore, much data indicates that exercise ameliorates chronic neuroinflammation and its related pathologies by tipping cytokine profiles toward an anti-inflammatory signature. Recent data has focused on the direct impact of exercise training on the innate immune system by targeting toll-like receptors (TLRs), signaling pattern recognition receptors that govern the innate immune response, shedding light on the physiological role of TLRs in health and disease. Indeed, TLRs continue to emerge as players in the neuroinflammatory processes underpinning MS. This review will highlight evidence that physical activity and exercise are potential immunomodulatory therapies, targeting innate signaling mechanism(s) to modulate MS symptom development and progression.
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Affiliation(s)
- Alison Barry
- Department of Physiology, School of Medicine, University College Cork Cork, Ireland
| | - Owen Cronin
- Department of Medicine, Cork University Hospital Cork, Ireland
| | - Aisling M Ryan
- Department of Neurology, Cork University Hospital Cork, Ireland
| | - Brian Sweeney
- Department of Neurology, Cork University Hospital Cork, Ireland
| | | | | | - Andrew P Allen
- Department of Psychiatry and Neurobehavioral Science, APC Microbiome Institute, University College Cork Cork, Ireland
| | - Gerard Clarke
- Department of Psychiatry and Neurobehavioral Science, APC Microbiome Institute, University College Cork Cork, Ireland
| | - Ken D O'Halloran
- Department of Physiology, School of Medicine, University College Cork Cork, Ireland
| | - Eric J Downer
- Department of Physiology, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin Dublin, Ireland
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28
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Shimizu K, Kon M, Tanimura Y, Hanaoka Y, Kimura F, Akama T, Kono I. Coenzyme Q10 supplementation downregulates the increase of monocytes expressing toll-like receptor 4 in response to 6-day intensive training in kendo athletes. Appl Physiol Nutr Metab 2015; 40:575-81. [PMID: 25941765 DOI: 10.1139/apnm-2014-0556] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
This study examined changes in toll-like receptor 4 (TLR-4)-expressing monocytes and lymphocyte subpopulations in response to continuous intensive exercise training in athletes, as well as the effect of coenzyme Q10 (CoQ10) supplementation on these changes. Eighteen male elite kendo athletes in Japan were randomly assigned to a CoQ10-supplementation group (n = 9) or a placebo-supplementation group (n = 9) using a double-blind method. Subjects in the CoQ10 group took 300 mg CoQ10 per day for 20 days. Subjects in the placebo group took the same dosage of placebo. All subjects practiced kendo 5.5 h per day for 6 consecutive days during the study period. Blood samples were collected 2 weeks before training, on the first day (day 1), third day (day 3), and fifth day of training (day 5), and 1 week after the training period (post-training) to ascertain TLR-4(+)/CD14(+) monocyte and lymphocyte subpopulations (CD3(+), CD4(+), CD8(+), CD28(+)/CD4(+), CD28(+)/CD8(+), and CD56(+)/CD3(-) cells) using flow cytometry analysis. The group × time interaction for TLR-4(+)/CD14(+) cells did not reach significance (p = 0.08). Within the CoQ10 group, the absolute number of TLR-4(+)/CD14(+) cells was significantly higher only at day 5. The placebo group showed a significant increase in the absolute number of TLR-4(+)/CD14(+) cells at day 3, day 5, and post-training (p < 0.05). There was no significant group × time interaction for any lymphocyte subpopulation. CD3(+), CD8(+), and CD56(+)/CD3(-) cells were significantly reduced at day 3 in both groups (p < 0.05). In conclusion, CoQ10 supplementation might downregulate the increase of TLR-4-expressing monocytes in response to continuous strenuous exercise training in kendo athletes.
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Affiliation(s)
- Kazuhiro Shimizu
- Department of Sport Science, Japan Institute of Sports Sciences, 3-15-1 Nishigaoka, Kita-ku, Tokyo, 115-0056 Japan
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29
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Effects of concurrent training on inflammatory markers and expression of CD4, CD8, and HLA-DR in overweight and obese adults. J Exerc Sci Fit 2014. [DOI: 10.1016/j.jesf.2014.06.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
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30
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TLR4-mediated blunting of inflammatory responses to eccentric exercise in young women. Mediators Inflamm 2014; 2014:479395. [PMID: 25294957 PMCID: PMC4175753 DOI: 10.1155/2014/479395] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2014] [Revised: 08/09/2014] [Accepted: 08/10/2014] [Indexed: 02/08/2023] Open
Abstract
This study assessed the inflammatory response mediated by the toll-like receptor 4 (TLR4) signaling pathway after acute eccentric exercise before and after an eccentric training program in women. Twenty women performed two acute eccentric bouts using a squat machine over a ~9 week interval. The training group (TG) carried out an eccentric training program during 6 weeks, while the control group (CG) did not follow any training. Protein content of markers involved in the TLR4-mediated activation of several nuclear transcription factors, such as nuclear factor κB (NF-κB), and interferon regulatory transcription factor 3 (IRF3), was analyzed. The inflammatory response after the first acute bout was similar between TG and CG, showing an upregulation of all the markers analyzed, with the exception of IRF3. After the second bout, the upregulation of TLR4 signaling pathway was blunted in TG, but not in CG, through both the myeloid differentiation factor 88- and toll/interleukin-1 receptor domain containing adapter inducing interferon-β-dependent pathways. These results highlight the role of the TLR4 in controlling the exercise-induced inflammatory response in young women. More importantly, these data suggest eccentric training may help to prevent TLR4 activation principally through NF-κB, and perhaps IRF3, downstream signaling in this population.
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31
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Euteneuer F, Schwarz MJ, Schmidmaier R, Hennings A, Riemer S, Stapf TM, Selberdinger VB, Süssenbach P, Dannehl K, Rief W. Blunted exercise-induced mobilization of monocytes in somatization syndromes and major depression. J Affect Disord 2014; 166:156-64. [PMID: 25012425 DOI: 10.1016/j.jad.2014.04.060] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2014] [Revised: 04/23/2014] [Accepted: 04/24/2014] [Indexed: 10/25/2022]
Abstract
BACKGROUND Previous research indicates that physical activity may alter the number of immune cells. We examined whether increasing or decreasing the level of physical activity affects circulating lymphocyte and monocyte counts in patients with somatization syndromes and patients with major depression. METHODS Thirty-eight participants with major depression, 26 participants with somatization syndromes and 47 healthy controls participated in the study. Using an experimental within-subject design, participants were involved in 1 week of increased physical activity (daily exercise sessions) and 1 week of reduced physical activity. Counts of total lymphocytes, lymphocyte subsets and monocytes were determined before and after each trial. Linear mixed models adjusted for sex, body mass index, age, fitness status and the order of trials were used for longitudinal data analysis. RESULTS One week of exercise increases the number of monocytes in healthy controls (p<.05), but not in patients with somatization syndromes or patients with major depression. In addition, after 1 week of exercise, depressive symptoms were reduced in patients with major depression (p<.05) while somatoform symptoms were reduced (p<.05) in both clinical groups. Baseline comparisons and mixed models indicated reduced T helper cell counts in patients with somatization syndromes. LIMITATIONS Relatively small sample size. The time of physical activity was relatively short and restricted to low-graded exercise. CONCLUSIONS This study demonstrates a blunted mobilization of monocytes by exercise in both patients with somatization syndromes and patients with major depression. In addition, even one week of exercise reduces somatoform and depressive symptoms.
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Affiliation(s)
- Frank Euteneuer
- Division of Clinical Psychology and Psychotherapy, Philipps Universität, Marburg, Germany.
| | - Markus J Schwarz
- Institute for Laboratory Medicine, Ludwig-Maximilian-Universität, Munich, Germany
| | - Ralf Schmidmaier
- Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig-Maximilian Universität, Munich, Germany
| | - Anika Hennings
- Division of Clinical Psychology and Psychotherapy, Philipps Universität, Marburg, Germany
| | - Sabine Riemer
- Division of Clinical Psychology and Psychotherapy, Philipps Universität, Marburg, Germany
| | - Theresa M Stapf
- Department of Psychiatry, Ludwig-Maximilian-Universität, Munich, Germany
| | | | - Philipp Süssenbach
- Division of Psychological Methods, Philipps Universität, Marburg, Germany
| | - Katharina Dannehl
- Division of Clinical Psychology and Psychotherapy, Philipps Universität, Marburg, Germany
| | - Winfried Rief
- Division of Clinical Psychology and Psychotherapy, Philipps Universität, Marburg, Germany
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32
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Müller L, Pawelec G. Aging and immunity - impact of behavioral intervention. Brain Behav Immun 2014; 39:8-22. [PMID: 24315935 DOI: 10.1016/j.bbi.2013.11.015] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Revised: 11/06/2013] [Accepted: 11/21/2013] [Indexed: 12/16/2022] Open
Abstract
Immune responses to pathogens to which they were not previously exposed are commonly less effective in elderly people than in young adults, whereas those to agents previously encountered and overcome in earlier life may be amplified. This is reflected in the robust finding in many studies that the proportions and numbers of naïve B and T cells are lower and memory cells higher in the elderly. In addition to the "extrinsic" effects of pathogen exposure, "intrinsic" events such as age-associated differences in haematopoeitic stem cells and their niches in the bone marrow associated with differences in cell maturation and output to the periphery are also observed. In the case of T cells, the "intrinsic" process of thymic involution, beginning before puberty, further contributes to reducing the production of naïve T cells. Like memory T cell populations, innate immune cells may be increased in number but decreased in efficacy on a per-cell basis. Thus, superimposed on chronological age alone, remodelling of immunity as a result of interactions with the environment over the life course is instrumental in shaping immune status in later life. In addition to interactions with pathogens, host microbiome and nutrition, exercise and stress, and many other extrinsic factors are crucial modulators of this "immunosenescence" process. In this review, we briefly outline the observed immune differences between younger and older people, and discuss the possible impacts of behavioral variations thereon.
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Affiliation(s)
- Ludmila Müller
- Max Planck Institute for Human Development, Lentzeallee 94, D-14195 Berlin, Germany.
| | - Graham Pawelec
- Center for Medical Research, University of Tübingen, Waldhörnlestr. 22, D-72072 Tübingen, Germany
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33
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Goh J, Ladiges WC. Exercise enhances wound healing and prevents cancer progression during aging by targeting macrophage polarity. Mech Ageing Dev 2014; 139:41-8. [PMID: 24932991 DOI: 10.1016/j.mad.2014.06.004] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Revised: 04/28/2014] [Accepted: 06/04/2014] [Indexed: 12/14/2022]
Abstract
Physical activity, which can include regular and repetitive exercise training, has been shown to decrease the incidence of age-related diseases. Aging is characterized by aberrant immune responses, including impaired wound healing and increased cancer risk. The behavior and polarized phenotype of tissue macrophages are distinct between young and old organisms. The balance of M1 and M2 macrophages is altered in the aged tissue microenvironment, with a tilt towards an M2-dominant macrophage population, as well as its associated signaling pathways. These M2-type responses may result in unresolved inflammation and create an environment that impairs wound healing and is favorable for cancer growth. We discuss the concept that exercise training can improve the regulation of macrophage polarization and normalize the inflammatory process, and thereby exert anticancer effects and enhance wound healing in older humans.
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Affiliation(s)
- Jorming Goh
- Interdisciplinary Program in Nutritional Sciences, University of Washington, Seattle, WA, USA; Department of Comparative Medicine, University of Washington, Seattle, WA, USA
| | - Warren C Ladiges
- Department of Comparative Medicine, University of Washington, Seattle, WA, USA.
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34
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Bigley AB, Spielmann G, LaVoy ECP, Simpson RJ. Can exercise-related improvements in immunity influence cancer prevention and prognosis in the elderly? Maturitas 2013; 76:51-6. [PMID: 23870832 DOI: 10.1016/j.maturitas.2013.06.010] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2013] [Accepted: 06/10/2013] [Indexed: 12/31/2022]
Abstract
Cancer incidence increases with advancing age. Over 60% of new cancers and 70% of cancer deaths occur in individuals aged 65 years or older. One factor that may contribute to this is immunosenescence - a canopy term that is used to describe age-related declines in the normal functioning of the immune system. There are multiple age-related deficits in both the innate and adaptive systems that may play a role in the increased incidence of cancer. These include decreased NK-cell function, impaired antigen uptake and presentation by monocytes and dendritic cells, an increase in 'inflammaging', a decline in the number of naïve T-cells able to respond to evolving tumor cells, and an increase in functionally exhausted senescent cells. There is consensus that habitual physical exercise can offer protection against certain types of cancer; however the evidence linking immunological mechanisms, exercise, and reduced cancer risk remain tentative. Multiple studies published over the last two decades suggest that exercise can mitigate the deleterious effects of age on immune function, thus increasing anti-cancer immunity. The potential ameliorative effect of exercise on these mechanisms include evidence that physical activity is able to stimulate greater NK-cell activity, enhance antigen-presentation, reduce inflammation, and prevent senescent cell accumulation in the elderly. Here we discuss the role played by the immune system in preventing and controlling cancer and how aging may retard these anti-cancer mechanisms. We also propose a pathway by which exercise-induced alterations in immunosenescence may decrease the incidence of cancer and help improve prognosis in cancer patients.
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Affiliation(s)
- Austin B Bigley
- Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, 3855 Holman Street, Houston, TX 77204, USA.
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35
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Simpson RJ, Lowder TW, Spielmann G, Bigley AB, LaVoy EC, Kunz H. Exercise and the aging immune system. Ageing Res Rev 2012; 11:404-20. [PMID: 22465452 DOI: 10.1016/j.arr.2012.03.003] [Citation(s) in RCA: 166] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2011] [Revised: 02/26/2012] [Accepted: 03/01/2012] [Indexed: 02/07/2023]
Abstract
Aging is associated with a decline in the normal functioning of the immune system that is described by the canopy term "immunosenescence". This contributes to poorer vaccine responses and the increased incidence of infection and malignancy seen in the elderly. Regular exercise has been associated with enhanced vaccination responses, lower numbers of exhausted/senescent T-cells, increased T-cell proliferative capacity, lower circulatory levels of inflammatory cytokines ("inflamm-aging"), increased neutrophil phagocytic activity, lowered inflammatory response to bacterial challenge, greater NK-cell cytotoxic activity and longer leukocyte telomere lengths in aging humans, all of which indicate that habitual exercise is capable of regulating the immune system and delaying the onset of immunosenescence. This contention is supported by the majority of animal studies that report improved immune responses and outcomes to viral infections and malignancies due to exercise training. However, whether or not exercise can reverse, as well as prevent, immunosenescence is a contentious issue, particularly because most longitudinal exercise training studies do not report the same positive effects of exercise on immunity that have been widely reported in studies with a cross-sectional design. In this review, we summarize some of the known effects of exercise on immunosenescence, discuss avenues for future research, and provide potential mechanisms by which exercise may help rejuvinate the aging immune system.
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