Respiratory and Metabolic Responses of CD4 + T Cells to Acute Exercise and their Association with Cardiorespiratory Fitness.

INTRODUCTION: The study aimed to investigate to what extent acute endurance exercise, especially eccentric exercise and cardiorespiratory fitness affect the metabolic profile of CD4 + cells. METHODS: 15 male, healthy adults aged between 20 and 33 years with a maximal oxygen uptake (VO 2max ) between 44 and 63 ml/kg/min performed a downhill run (DR) and a level run (LR) for 45 minutes at 70% of their VO 2max on a treadmill in a cross-over design. Blood samples were taken before (T0), directly after (T1), 3 hours after (T3), and 24 hours (T24) after each exercise for analyzing leukocyte numbers and cytokine levels. Isolated CD4 + cells were incubated for 4 hours in autologous resting versus 3 hours after exercise serum (T3 DR and T3 LR), and subsequently, cellular respiration, transcriptomic, and metabolomics profiles were measured. RESULTS: The systemic immune inflammation index increased significantly after DR and LR at T1 and T3 (p < .001). In contrast, the transcriptomic and metabolic profile of CD4 + cells showed no significant alterations after incubation in T3 exercise serum. However, cardiorespiratory fitness positively correlated with the maximal mitochondrial respiration in CD4 + cells after incubation with T3 LR serum (r = .617, p = .033) and with gene expression of oxidative phosphorylation and levels of different metabolites. Similarly, VO 2max was associated with an anti-inflammatory profile on RNA level. Lower lactate, methylmalonic acid, and D-gluconic acid levels were found in CD4 + cells of participants with a high VO 2max (p < .001). CONCLUSIONS: Acute exercise leads to a mild pro-inflammatory milieu with only small changes in the metabolic homeostasis of CD4 + cells. High cardiorespiratory fitness is associated with a metabolic shift to oxidative phosphorylation in CD4 + cells. Functional relevance of this metabolic shift needs to be further investigated.

Association of cardiorespiratory fitness level with vascular function and subclinical atherosclerosis in the elderly.

PURPOSE: Physical exercise is crucial for healthy aging and plays a decisive role in the prevention of atherosclerotic cardiovascular disease (ASCVD). A higher level of cardiorespiratory fitness (CRF) in the elderly is associated with lower cardiovascular and all-cause mortality. This study investigated the association of CRF level with vascular function and cardiovascular risk factors in the elderly. METHODS: We examined 79 apparently healthy and physically active subjects aged > 55 years (64 ± 4 years). Cardiovascular functional parameters assessed included brachial and central blood pressure (BP), pulse wave velocity (PWV), augmentation index (Aix), and ankle-brachial index. Sonography of the common carotid artery was performed. CRF level was determined by a cardiopulmonary exercise test, and everyday activity was quantified with an accelerometer. RESULTS: All participants had a higher CRF level than the reported age-specific normative values. Twenty-nine subjects had subclinical atherosclerosis of the common carotid artery. Compared with participants without atherosclerosis, they were older (p = 0.007), displayed higher brachial systolic BP (p = 0.006), and higher central systolic BP (p = 0.014). Lower brachial (p = 0.036) and central (p = 0.003) systolic BP, lower PWV (p = 0.004), lower Aix (p < 0.001), lower body fat percentage (< 0.001), and lower LDL cholesterol (p = 0.005) were associated with a higher CRF level. CONCLUSIONS: In this cohort of healthy and physically active individuals, subjects with subclinical atherosclerosis displayed higher systolic brachial and central BP. A higher CRF level was associated with enhanced vascular function, consistent with an influence of CRF on both BP and vascular function in the elderly.

Subpopulations of regulatory T cells are associated with subclinical atherosclerotic plaques, levels of LDL, and cardiorespiratory fitness in the elderly.

BACKGROUND: Atherosclerosis forms the pathological basis for the development of cardiovascular disease. Since pathological processes initially develop without clinically relevant symptoms, the identification of early markers in the subclinical stage plays an important role for initiating early interventions. There is evidence that regulatory T cells (Tregs) are involved in the development of atherosclerosis. Therefore, the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques (SAP). In addition, various lifestyle and risk factors, such as cardiorespiratory fitness, were investigated as associated signatures. METHODS: A cross-sectional study was performed in 79 participants (male: n = 50; age = 63.6 ± 3.7 years; body mass index = 24.9 ± 3.1 kg/m²; mean ± SD) who had no previous diagnosis of chronic disease and were not taking medication. Ultrasound of the carotids to identify SAP, cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were performed. Additionally, tests were conducted to assess blood lipids and determine glucose levels. Immunophenotyping of Tregs and their subtypes (resting (rTregs) and effector/memory (mTregs)) was performed by 8-chanel flow cytometry. Participants were categorized according to atherosclerotic plaque status. Linear and logistic regression models were used to analyze associations between parameters. RESULTS: SAP was detected in a total of 29 participants. The participants with plaque were older (64.5 ± 3.6 years vs. 62.9 ± 3.5 years) and had higher peripheral systolic blood pressure (133.8 ± 14.7 mmHg vs. 125.8 ± 10.9 mmHg). The participants with SAP were characterized by a lower percentage of rTregs (28.8% ± 10.7% vs. 34.6% ± 10.7%) and a higher percentage of mTregs (40.3% ± 14.7% vs. 30.0% ± 11.9%). Multiple logistic regression identified age (odds ratio (OR) = 1.20 (95% confidence interval (95%CI): 1.01-1.42)) and mTregs (OR = 1.05 (95%CI: 1.02-1.10)) as independent risk factors for SAP. Stepwise linear regression could reveal an association of peak oxygen uptake (ß = 0.441), low-density lipoprotein (LDL) (ß = -0.096), and SAP (ß = 6.733) with mTregs and LDL (ß = 0.104) with rTregs. CONCLUSION: While at an early stage of SAP, the total proportion of Tregs gives no indication of vascular changes, this is indicated by a shift in the Treg subgroups. Factors such as serum LDL or cardiopulmonary fitness may be associated with this shift and may also be additional diagnostic indicators. This could be used to initiate lifestyle-based preventive measures at an early stage, which may have a protective effect against disease progression.

12-week combined strength and endurance exercise attenuates CD8+ T-cell differentiation and affects the kynurenine pathway in the elderly: a randomized controlled trial.

BACKGROUND: Age-related accumulation of highly differentiated CD8+ effector memory re-expressing CD45RA (EMRA) T-cells and disruption of the kynurenine (KYN) pathway are associated with chronic inflammation and the development of insulin resistance. In this study the aim was to investigate the effects of 12-week combined strength and endurance exercise on CD8+ T-cell differentiation and KYN pathway metabolites. Ninety-six elderly subjects (f/m, aged 50-70) were randomized to a control (CON) or exercise (EX) group. The EX group completed combined strength and endurance training twice weekly for one hour each time at an intensity of 60% of the one-repetition maximum for strength exercises and a perceived exertion of 15/20 for endurance exercises. The EX group was also randomly subdivided into two groups with or without a concomitant balanced diet intervention in order to examine additional effects besides exercise alone. Before and after the intervention phase, the proportions of CD8+ T-cell subsets and levels of KYN pathway metabolites in peripheral blood were determined. RESULTS: The CD8+ EMRA T-cell subsets increased in the CON group but remained almost unchanged in the EX group (p = .02). Plasma levels of kynurenic acid (KA) increased in the EX group and decreased in the CON group (p = .03). Concomitant nutritional intervention resulted in lower levels of quinolinic acid (QA) compared with exercise alone (p = .03). Overall, there was a slight increase in the QA/KA ratio in the CON group, whereas it decreased in the EX group (p > .05). CONCLUSIONS: Combined strength and endurance training seems to be a suitable approach to attenuate CD8+ T-cell differentiation in the elderly and to redirect the KYN pathway towards KA. The clinical relevance of these effects needs further investigation.

Neurophysiological Markers for Monitoring Exercise and Recovery Cycles in Endurance Sports.

The current study analyzes the suitability and reliability of selected neurophysiological and vegetative nervous system markers as biomarkers for exercise and recovery in endurance sport. Sixty-two healthy men and women, endurance trained and moderately trained, performed two identical acute endurance tests (running trial 1 and running trial 2) followed by a washout period of four weeks. Exercise protocol consisted of an acute running trial lasting 60 minutes. An intensity corresponding to 95% of the heart rate at individual anaerobic threshold for 40 minutes was followed by 20 minutes at 110%. At pre-exercise, post-exercise, three hours post-exercise and 24 hours post-exercise, experimental diagnostics on Brain-derived neurotrophic factor (BDNF), heart rate variability (HRV), Stroop Color and Word Test (SCWT), and Short-Form McGill Pain Questionnaire (SF-MPQ) were performed. Significant changes over time were found for all parameters (p < .05). Furthermore, there was an approached statistical significance in the interaction between gender and training status in BDNF regulation (F(3) = 2.43; p = 0.06), while gender differences were found only for LF/HF-ratio (3hPoEx, F(3) = 3.40; p = 0.002). Regarding the reliability, poor ICC-values (< 0.5) were found for BDNF, Stroop sensitivity and pNN50, while all other parameters showed moderate ICC-values (0.5-0.75). Plasma-BDNF, SCWT performance, pain perception and all HRV parameters are suitable exercise-sensitive markers after an acute endurance exercise. Moreover, pain perception, SCWT reaction time and all HRV parameters show a moderate reliability, others rather poor. In summary, a selected neurophysiological and vegetative marker panel can be used to determine exercise load and recovery in endurance sports, but its repeatability is limited due to its vaguely reliability.

Immunological mechanisms of exercise therapy in dyslipidemia.

Numerous studies demonstrated the strong link between dyslipidemia and the cardiovascular risk. Physical activity and exercise represent effective prevention and therapy strategies for dyslipidemia and at the same time counteract numerous comorbidities that often accompany the disease. The physiological mechanisms are manifold, and primary mechanisms might be an increased energy consumption and associated adaptations of the substrate metabolism. Recent studies showed that there are bidirectional interactions between dyslipidemia and the immune system. Thus, abnormal blood lipids may favor pro-inflammatory processes, and at the same time inflammatory processes may also promote dyslipidemia. Physical activity has been shown to affect numerous immunological processes and has primarily anti-inflammatory effects. These are manifested by altered leukocyte subtypes, cytokine patterns, stress protein expression, and by reducing hallmarks of immunosenescence. The aim of this review is to describe the effects of exercise on the treatment dyslipidemia and to discuss possible immunological mechanisms against the background of the current literature.

The Role of Minerals in the Optimal Functioning of the Immune System.

Minerals fulfil a wide variety of functions in the optimal functioning of the immune system. This review reports on the minerals that are essential for the immune system's function and inflammation regulation. We also discuss nutritional aspects of optimized mineral supply. The supply of minerals is important for the optimal function of the innate immune system as well as for components of adaptive immune defense; this involves defense mechanisms against pathogens in addition to the long-term balance of pro- and anti-inflammatory regulation. Generally, a balanced diet is sufficient to supply the required balance of minerals to help support the immune system. Although a mineral deficiency is rare, there are nevertheless at-risk groups who should pay attention to ensure they are receiving a sufficient supply of minerals such as magnesium, zinc, copper, iron, and selenium. A deficiency in any of these minerals could temporarily reduce immune competence, or even disrupt systemic inflammation regulation in the long term. Therefore, knowledge of the mechanisms and supply of these minerals is important. In exceptional cases, a deficiency should be compensated by supplementation; however, supplement over-consumption may be negative to the immune system, and should be avoided. Accordingly, any supplementation should be medically clarified and should only be administered in prescribed concentrations.

An ergonomic welding torch reduces physical load response and improves welding quality in novices: a pilot study.

Objectives. This crossover pilot study aimed to compare the physical load response of an ergonomically improved welding torch versus a conventional torch. Methods. Ten inexperienced volunteers performed an experimental augmented virtual welding trial at chest height (ASME code 1G) and overhead (ASME code 4G) with both welding torches in random order. Skeletal muscle load and fatigue were assessed by surface electromyography and changes in isometric peak force. The sensation of pain, perceived exertion and welding execution quality were defined as further outcome parameters. Results. The muscle load response in three out of eight muscles was lower in favour of the ergonomic welding torch, which went along with a lower sensation of pain and a higher working accuracy. Conclusions. An ergonomically improved welding torch reduces the acute physical load response and sensation of pain, which ultimately allows performing better, and might contribute to prevention of musculoskeletal diseases in the long term.

Exercise and adrenergic regulation of immunity.

Exercise training has a profound impact on immunity, exerting a multitude of positive effects in indications such as immunosenescence, cancer, viral infections and inflammatory diseases. The immune, endocrine and central nervous systems work in a highly synergistic manner and it has become apparent that catecholamine signaling through leukocyte ß-adrenergic receptors (ß-ARs) is a key mechanism by which exercise mediates improvements in immune function to help mitigate numerous disease conditions. Central to this is the preferential mobilization and redistribution of effector lymphocytes with potent anti-viral and anti-tumor activity, their interaction with muscle-derived cytokines, and the effects of catecholamine signaling on mitochondrial biogenesis, immunometabolism and the resulting inflammatory response. Here, we review the impact of acute and chronic exercise on adrenergic regulation of immunity in the context of aging, cancer, viral infections and inflammatory disease. We also put forth our contention that exercise interventions designed to improve immunity, prevent disease and reduce inflammation should consider the catecholamine-AR signaling axis as a therapeutic target and ask whether or not the adrenergic signaling machinery can be 'trained' to improve immune responses to stress, disease or during the normal physiological process of aging. Finally, we discuss potential strategies to augment leukocyte catecholamine signaling to boost the effects of exercise on immunity in individuals with desensitized ß-ARs or limited exercise tolerance.

The Effects of Lifestyle and Diet on Gut Microbiota Composition, Inflammation and Muscle Performance in Our Aging Society.

Living longer is associated with an increased risk of chronic diseases, including impairments of the musculoskeletal and immune system as well as metabolic disorders and certain cancers, each of which can negatively affect the relationship between host and microbiota up to the occurrence of dysbiosis. On the other hand, lifestyle factors, including regular physical exercise and a healthy diet, can affect skeletal muscle and immune aging positively at all ages. Accordingly, health benefits could partly depend on the effect of such interventions that influence the biodiversity and functionality of intestinal microbiota. In the present review, we first discuss the physiological effects of aging on the gut microbiota, immune system, and skeletal muscle. Secondly, we describe human epidemiological evidence about the associations between physical activity and fitness and the gut microbiota composition in older adults. The third part highlights the relevance and restorative mechanisms of immune protection through physical activity and specific exercise interventions during aging. Fourth, we present important research findings on the effects of exercise and protein as well as other nutrients on skeletal muscle performance in older adults. Finally, we provide nutritional recommendations to prevent malnutrition and support healthy active aging with a focus on gut microbiota. Key nutrition-related concerns include the need for adequate energy and protein intake for preventing low muscle mass and a higher demand for specific nutrients (e.g., dietary fiber, polyphenols and polyunsaturated fatty acids) that can modify the composition, diversity, and metabolic capacity of the gut microbiota, and may thus provide a practical means of enhancing gut and systemic immune function.

Recovery-Stress Response of Blood-Based Biomarkers.

The purpose of this study was to investigate blood-based biomarkers and their regulation with regard to different recovery-stress states. A total of 35 male elite athletes (13 badminton, 22 soccer players) were recruited, and two venous blood samples were taken: one in a 'recovered' state (REC) after a minimum of one-day rest from exercise and another one in a 'non-recovered' state (NOR) after a habitual loading microcycle. Overall, 23 blood-based biomarkers of different physiologic domains, which address inflammation, muscle damage, and tissue repair, were analyzed by Luminex assays. Across all athletes, only creatine kinase (CK), interleukin (IL-) 6, and IL-17A showed higher concentrations at NOR compared to REC time points. In badminton players, higher levels of CK and IL-17A at NOR were found. In contrast, a higher value for S100 calcium-binding protein A8 (S100A8) at REC was found in badminton players. Similar differences were found for BDNF in soccer players. Soccer players also showed increased levels of CK, and IL-6 at NOR compared to REC state. Several molecular markers were shown to be responsive to differing recovery-stress states, but their suitability as biomarkers in training must be further validated.

Effects of a 6 Week Low-Dose Combined Resistance and Endurance Training on T Cells and Systemic Inflammation in the Elderly.

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.

Abdominal Obesity-Related Disturbance of Insulin Sensitivity Is Associated with CD8+ EMRA Cells in the Elderly.

Aging and overweight increase the risk of developing type 2 diabetes mellitus. In this cross-sectional study, we aimed to investigate the potential mediating role of T-EMRA cells and inflammatory markers in the development of a decreased insulin sensitivity. A total of 134 healthy older volunteers were recruited (age 59.2 (SD 5.6) years). T cell subpopulations were analyzed by flow cytometry. Furthermore, body composition, HOMA-IR, plasma tryptophan (Trp) metabolites, as well as cytokines and adipokines were determined. Using subgroup and covariance analyses, the influence of BMI on the parameters was evaluated. Moreover, correlation, multiple regression, and mediation analyses were performed. In the subgroup of participants with obesity, an increased proportion of CD8+EMRA cells and elevated concentrations of plasma kynurenine (KYN) were found compared to the lower-weight subgroups. Linear regression analysis revealed that an elevated HOMA-IR could be predicted by a higher proportion of CD8+EMRA cells and KYN levels. A mediation analysis showed a robust indirect effect of the Waist-to-hip ratio on HOMA-IR mediated by CD8+EMRA cells. Thus, the deleterious effects of abdominal obesity on glucose metabolism might be mediated by CD8+EMRA cells in the elderly. Longitudinal studies should validate this assumption and analyze the suitability of CD8+EMRA cells as early predictors of incipient prediabetes.

Physical Activity and Mental Health of Patients with Pulmonary Hypertension during the COVID-19 Pandemic.

The aim of the study was to analyze the effect of personal restrictions on physical activity, mental health, stress experience, resilience, and sleep quality in patients with pulmonary hypertension (PH) during the "lockdown" period of the COVID-19 pandemic. In total, 112 PH patients and 52 age-matched healthy control subjects completed a questionnaire on the topics of physical activity, mental health, resilience, and sleep quality. PH patients had significantly lower physical activity, mental health, and sleep quality compared to age-matched healthy controls. Physical activity positively correlated with mental health and sleep quality in the PH group. Mental wellbeing and life satisfaction could be predicted by total physical activity, sleep, stress level, and resilience. PH patients appeared as an especially vulnerable group, demanding interventions to promote an active lifestyle and protect mental health in these patients. This could be helpful in counseling on how to carry out physical activity while maintaining infection control.

Exercise training reduces workload, improves physical performance, and promotes overall health in welders.

OBJECTIVES: Welders demonstrate a significant prevalence of work-related musculoskeletal disorders as indicated by high rates of illness-related absenteeism. The aim of the study was to investigate the effects of a 24-week exercise program on workload, physical performance, and overall health in welders. METHODS: Seventy-seven professional welders were assigned to either a control group (CG), an endurance training group (ETG), or a strength training group (STG). Both groups conducted a 24-week, standardized and progressive endurance or resistance exercise training program. Before (TP1) and after training (TP2) all participants performed an experimental welding task (EWT) in order to test the hypothesis that training would reduce the relative load (%MVC) of eight skeletal muscles measured by surface electromyography. Secondary outcome measures included further EWT-induced stress parameters and a series of health-related outcome measures. RESULTS: Results revealed a lower muscle load in participants of the ETG and STG for trapezius muscle at TP2 compared to T1 (P < .05 vs CG). Rate of perceived exertion and visual analogue scale were decreased, while increase of maximum EWT duration was found in participants of the ETG and STG after training (P < .05 vs CG). At T2, body fat (%) decreased and physical performance (bicycle exercise test, isometric strength of core muscles) increased in ETG and STG (P < .05). CONCLUSION: Both regular endurance and strength training represent effective strategies for reducing workload and improving physical performance of welders. The results emphasize the importance of physical fitness for welders and might motivate health professionals in steel-industry to offer access to exercise training programs.

Physical Activity and Diet Shape the Immune System during Aging.

With increasing age, the immune system undergoes a remodeling process, termed immunosenescence, which is accompanied by considerable shifts in leukocyte subpopulations and a decline in various immune cell functions. Clinically, immunosenescence is characterized by increased susceptibility to infections, a more frequent reactivation of latent viruses, decreased vaccine efficacy, and an increased prevalence of autoimmunity and cancer. Physiologically, the immune system has some adaptive strategies to cope with aging, while in some settings, maladaptive responses aggravate the speed of aging and morbidity. While a lack of physical activity, decreased muscle mass, and poor nutritional status facilitate immunosenescence and inflammaging, lifestyle factors such as exercise and dietary habits affect immune aging positively. This review will discuss the relevance and mechanisms of immunoprotection through physical activity and specific exercise interventions. In the second part, we will focus on the effect of dietary interventions through the supplementation of the essential amino acid tryptophan, n-3 polyunsaturated fatty acids, and probiotics (with a special focus on the kynurenine pathway).