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Physical activity and sports play major roles in the overall health status of humans. It is well known that regular exercise helps to lower the risk for a broad variety of health problems, such as cardiovascular disease, type 2 diabetes, and cancer. Being physically active induces a wide variety of molecular adaptations, for example fiber type switches or other metabolic alterations, in skeletal muscle tissue. These adaptations are based on exercise-induced changes to the skeletal muscle transcriptome. Understanding their nature is crucial to improve the development of exercise-based therapeutic strategies. Recent research indicates that specifically epigenetic mechanisms, i.e., pathways that induce changes in gene expression patterns without altering the DNA base sequence, might play a major role in controlling skeletal muscle transcriptional patterns. Epigenetic mechanisms include DNA and histone modifications, as well as expression of specific microRNAs. They can be modulated by environmental factors or external stimuli, such as exercise, and eventually induce specific and fine-tuned changes to the transcriptional response. In this review, we highlight current knowledge on epigenetic changes induced in exercising skeletal muscle, their target genes, and resulting phenotypic changes. In addition, we raise the question of whether epigenetic modifications might serve as markers for the design and management of optimized and individualized training protocols, as prognostic tools to predict training adaptation, or even as targets for the design of “exercise mimics”.

PurposeWe investigated the cardiovascular individual response to 6 weeks (3×/week) of work-matched within the severe-intensity domain (high-intensity interval training, HIIT) or moderate-intensity domain (moderate-intensity continuous training, MICT). In addition, we analyzed the cardiovascular factors at baseline underlying the response variability.Methods42 healthy sedentary participants were randomly assigned to HIIT or MICT. We applied the region of practical equivalence-method for identifying the levels of responders to the maximal oxygen uptake (V̇O2max) response. For investigating the influence of cardiovascular markers, we trained a Bayesian machine learning model on cardiovascular markers.ResultsDespite that HIIT and MICT induced significant increases in V̇O2max, HIIT had greater improvements than MICT (p < 0.001). Greater variability was observed in MICT, with approximately 50% classified as “non-responder” and “undecided”. 20 “responders”, one “undecided” and no “non-responders” were observed in HIIT. The variability in the ∆V̇O2max was associated with initial cardiorespiratory fitness, arterial stiffness, and left-ventricular (LV) mass and LV end-diastolic diameter in HIIT; whereas, microvascular responsiveness and right-ventricular (RV) excursion velocity showed a significant association in MICT.ConclusionOur findings highlight the critical influence of exercise-intensity domains and biological variability on the individual V̇O2max response. The incidence of “non-responders” in MICT was one third of the group; whereas, no “non-responders” were observed in HIIT. The incidence of “responders” was 11 out of 21 participants in MICT, and 20 out of 21 participants in HIIT. The response in HIIT showed associations with baseline fitness, arterial stiffness, and LV-morphology; whereas, it was associated with RV systolic function in MICT.

microRNAs (miRs) have been proposed as a promising new class of biomarkers in the context of training adaptation. Using microarray analysis, we studied skeletal muscle miR patterns in sedentary young healthy females (n = 6) before and after a single submaximal bout of endurance exercise (‘reference training’). Subsequently, participants were subjected to a structured training program, consisting of six weeks of moderate-intensity continuous endurance training (MICT) and six weeks of high-intensity interval training (HIIT) in randomized order. In vastus lateralis muscle, we found significant downregulation of myomiRs, specifically miR-1, 133a-3p, and -5p, -133b, and -499a-5p. Similarly, exercise-associated miRs-23a-3p, -378a-5p, -128-3p, -21-5p, -107, -27a-3p, -126-3p, and -152-3p were significantly downregulated, whereas miR-23a-5p was upregulated. Furthermore, in an untargeted approach for differential expression in response to acute exercise, we identified n = 35 miRs that were downregulated and n = 20 miRs that were upregulated by factor 4.5 or more. Remarkably, KEGG pathway analysis indicated central involvement of this set of miRs in fatty acid metabolism. To reproduce these data in a larger cohort of all-female subjects (n = 29), qPCR analysis was carried out on n = 15 miRs selected from the microarray, which confirmed their differential expression. Furthermore, the acute response, i.e., the difference between miR concentrations before and after the reference training, was correlated with changes in maximum oxygen uptake (V̇O2max) in response to the training program. Here, we found that miRs-199a-3p and -19b-3p might be suitable acute-response candidates that correlate with individual degrees of training adaptation in females.

Objective: It is unclear whether and to what extent COVID-19 infection poses health risks and a chronic impairment of performance in athletes. Identification of individual health risk is an important decision-making basis for managing the pandemic risk of infection with SARS-CoV-2 in sports and return to play (RTP). Methods: This study aims 1) to analyze the longitudinal rate of seroprevalence of SARS-CoV-2 in German athletes, 2) to assess health-related consequences in athletes infected with SARS-CoV-2, and 3) to reveal effects of the COVID-19 pandemic in general and of a cleared SARS-CoV-2 infection on exercise performance. CoSmo-S is a prospective observational multicenter study establishing two cohorts: 1) athletes diagnosed positive for COVID-19 (cohort 1) and 2) federal squad athletes who perform their annual sports medical preparticipation screening (cohort 2). Comprehensive diagnostics including physical examination, laboratory blood analyses and blood biobanking, resting and exercise electrocardiogram (ECG), echocardiography, spirometry and exercise testing added by questionnaires are conducted at baseline and follow-up. Results and Conclusion: We expect that the results obtained, will allow us to formulate recommendations regarding RTP on a more evidence-based level.

The evaluation of the maximal oxygen uptake (V˙O2max) following exercise training is the classical assessment of training effectiveness. Research has lacked in investigating whether individuals that do not respond to the training intervention (V˙O2max), also do not improve in other health‐related parameters. We aimed to investigate the cardiovascular and metabolic adaptations (i.e., performance, body composition, blood pressure, vascular function, fasting blood markers, and resting cardiac function and morphology) to exercise training among participants who showed different levels of V˙O2max responsiveness. Healthy sedentary participants engaged in a 6‐week exercise training program, three times a week. Our results showed that responders had a greater increase in peak power output, second lactate threshold, and microvascular responsiveness, whereas non‐responders had a greater increase in cycling efficiency. No statistical differences were observed in body composition, blood pressure, fasting blood parameters, and resting cardiac adaptations. In conclusion, our study showed, for the first time, that in addition to the differences in the V˙O2max, a greater increase in microvascular responsiveness in responders compared to non‐responders was observed. Additionally, responders and non‐responders did not show differences in the adaptations on metabolic parameters. There is an increasing need for personalized training prescription, depending on the target clinical outcome. The evaluation of the maximal oxygen uptake (V˙O2max) following exercise training is the classical assessment of training effectiveness. Research has lacked in investigating whether individuals that do not respond to the training intervention (V˙O2max), also do not improve in other health‐related parameters. Our results showed that responders had a greater increase than non‐responders in peak power output, second lactate threshold, and microvascular responsiveness, whereas non‐responders had a greater increase in cycling efficiency than responders.

Background: Physical activity induces a range of physiological and molecular adaptations, particularly affecting skeletal muscle and the cardiovascular system, regulating both tissue architecture and metabolic pathways. Emerging evidence suggests that PIWI-interacting RNAs (piRNAs) may serve as potential biomarkers for these adaptations. Here, we analyzed piRNA patterns in the context of exercise. Methods: This study selected eight participants of the iReAct study (DRKS00017446) for piRNA analysis. Baseline assessments included demographic profiling and fitness evaluation, particularly maximal oxygen uptake (V̇O2max) assessment. In addition, blood samples were collected pre- and (for six of the eight participants) post- standard reference training sessions. Subsequently, subjects underwent 6-week training protocols, employing standardized high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) regimens. Next, RNA sequencing was conducted to identify differentially expressed piRNAs, and correlation analyses were performed between piRNA expression patterns and training-associated changes in V̇O2max. Finally, to identify piRNAs potentially of interest in the context of exercise, different screening procedures were applied. Results: There were unique and specific changes in individual piRNA expression levels in response to exercise. In addition, we could define correlations of piRNA expression patterns, namely of piR-32886, piR-33151, piR-12547, and piR-33074, with changes in V̇O2max. These correlations did not reach significance in the small sample size of this pilot study, but might be verified in larger, confirming studies. Conclusions: This hypothesis-generating study identifies characteristic piRNA patterns in the context of exercise. Their significance as biomarkers is yet to be determined.

Small, non‐coding RNAs (microRNAs) have been shown to regulate gene expression in response to exercise in various tissues and organs, thus possibly coordinating their adaptive response. Thus, it is likely that differential microRNA expression might be one of the factors that are responsible for different training responses of different individuals. Consequently, determining microRNA patterns might be a promising approach toward the development of individualized training strategies. However, little is known on (1) microRNA patterns and their regulation by different exercise regimens and (2) possible correlations between these patterns and individual training adaptation. Here, we present microarray data on skeletal muscle microRNA patterns in six young, female subjects before and after six weeks of either moderate‐intensity continuous or high‐intensity interval training on a bicycle ergometer. Our data show that n = 36 different microRNA species were regulated more than twofold in this cohort (n = 28 upregulated and n = 8 downregulated). In addition, we correlated baseline microRNA patterns with individual changes in VO2max and identified some specific microRNAs that might be promising candidates for further testing and evaluation in the future, which might eventually lead to the establishment of microRNA marker panels that will allow individual recommendations for specific exercise regimens. Using microarrays and qPCR analysis, we studied microRNA patterns in skeletal muscle in healthy subjects undergoing two different six‐week exercise programs. We identified several miRNAs that had not been implicated in exercise adaptation before. In addition, our data suggest that exercise‐induced changes in microRNA patterns are dependent on exercise type and also on individual background, a finding that suggests that microRNAs might serve as biomarkers for the development of individualized training regimens in the future.

Background An infection with SARS-CoV-2 can lead to a variety of symptoms and complications, which can impair athletic activity. Objective We aimed to assess the clinical symptom patterns, diagnostic findings, and the extent of impairment in sport practice in a large cohort of athletes infected with SARS-CoV-2, both initially after infection and at follow-up. Additionally, we investigated whether baseline factors that may contribute to reduced exercise tolerance at follow-up can be identified. Methods In this prospective, observational, multicenter study, we recruited German COVID elite-athletes (cEAs, n  = 444) and COVID non-elite athletes (cNEAs, n  = 481) who tested positive for SARS-CoV-2 by PCR (polymerase chain reaction test). Athletes from the federal squad with no evidence of SARS-CoV-2 infection served as healthy controls (EAcon, n  = 501). Questionnaires were used to assess load and duration of infectious symptoms, other complaints, exercise tolerance, and duration of training interruption at baseline and at follow-up 6 months after baseline. Diagnostic tests conducted at baseline included resting and exercise electrocardiogram (ECG), echocardiography, spirometry, and blood analyses. Results Most acute and infection-related symptoms and other complaints were more prevalent in cNEA than in cEAs. Compared to cEAs, EAcon had a low symptom load. In cNEAs, female athletes had a higher prevalence of complaints such as palpitations, dizziness, chest pain, myalgia, sleeping disturbances, mood swings, and concentration problems compared to male athletes ( p  < 0.05). Until follow-up, leading symptoms were drop in performance, concentration problems, and dyspnea on exertion. Female athletes had significantly higher prevalence for symptoms until follow-up compared to male. Pathological findings in ECG, echocardiography, and spirometry, attributed to SARS-CoV-2 infection, were rare in infected athletes. Most athletes reported a training interruption between 2 and 4 weeks (cNEAs: 52.9%, cEAs: 52.4%), while more cNEAs (27.1%) compared to cEAs (5.1%) had a training interruption lasting more than 4 weeks ( p  < 0.001). At follow-up, 13.8% of cNEAs and 9.9% of cEAs ( p  = 0.24) reported their current exercise tolerance to be under 70% compared to pre-infection state. A persistent loss of exercise tolerance at follow-up was associated with persistent complaints at baseline, female sex, a longer break in training, and age > 38 years. Periodical dichotomization of the data set showed a higher prevalence of infectious symptoms such as cough, sore throat, and coryza in the second phase of the pandemic, while a number of neuropsychiatric symptoms as well as dyspnea on exertion were less frequent in this period. Conclusions Compared to recreational athletes, elite athletes seem to be at lower risk of being or remaining symptomatic after SARS-CoV-2 infection. It remains to be determined whether persistent complaints after SARS-CoV-2 infection without evidence of accompanying organ damage may have a negative impact on further health and career in athletes. Identifying risk factors for an extended recovery period such as female sex and ongoing neuropsychological symptoms could help to identify athletes, who may require a more cautious approach to rebuilding their training regimen. Trial Registration Number DRKS00023717; 06.15.2021—retrospectively registered.

Background. Physical exercise exerts a positive effect on many chronic conditions, specifically lifestyle-related diseases such as overweight and obesity, type 2 diabetes mellitus (T2DM), cardiovascular conditions and osteoarthritis (OA). As a result of common risk factors, most of these patients present with multiple conditions. Exercise- and disease-related biomarkers, such as adipokines, are emerging tools in training supervision and regulation; however, their significance in subjects with multimorbidities is unknown. Subjects and Methods. To address this issue, adipokines leptin, adiponectin and resistin were assessed in a cohort of subjects with multimorbidities (n = 39) presenting with at least two of the abovementioned conditions or relevant risk factors before and after a six-month exercise and lifestyle intervention program (‘MultiPill-Exercise’), and correlated with training adaptation, namely changes in relative maximum oxygen uptake (V·O2max). Results. There was a significant negative correlation between baseline leptin concentrations and training effect for relative V·O2max (after three months: rho = −0.54, p = 0.020 *; after six months: rho = −0.45, p = 0.013 *), with baseline leptin explaining 35% of the variance in delta relative V·O2max after three months and 23% after six months. Conclusions. Leptin might be a suitable surrogate biomarker in the context of exercise-based lifestyle intervention programs in subjects with multimorbidity.