Cardiovascular, muscular, and skeletal adaptations to recreational team handball training: a randomized controlled trial with young adult untrained men.

PURPOSE: The prevalence of lifestyle diseases has escalated, and effective exercise training programmes are warranted. This study tested the hypothesis that regular participation in small-sided team handball training could provide beneficial health effects on cardiovascular, skeletal, and muscular parameters in young adult untrained men. METHOD: Twenty-six untrained 20-30-year-old men were randomly allocated to either a team handball training group (HG; n = 14), which completed 1.9 ± 0.3 training sessions per week over 12 weeks, or an inactive control group (CG; n = 12). Physiological training adaptations were assessed pre- and post interventions by DXA scans, blood samples, muscle biopsies, and physical tests. RESULTS: The average heart rate during training was equivalent to 84 ± 4% of maximal heart rate. Compared to CG, HG displayed significant increases in VO2max (11 ± 6%), proximal femur bone mineral density (2 ± 1%), whole-body bone mineral content (2 ± 1%), intermittent endurance performance (32 ± 16%), incremental treadmill test performance (16 ± 7%) and muscle citrate synthase activity (22 ± 28%) as well as decreases in total fat mass (7 ± 7%) and total fat percentage (6 ± 7%) (all p < 0.05). There were no significant changes in muscle mass, blood pressure, resting heart rate, muscle hydroxyl-acyl-dehydrogenase activity, or blood lipids (all p > 0.05). CONCLUSION: Participation in regular recreational team handball training was associated with positive cardiovascular, skeletal, and muscular adaptations, including increased maximal oxygen uptake, increased muscle enzymatic activity, and improved bone mineralization as well as lower fat percentage. These findings suggest that recreational team handball training may be an effective health-promoting activity for young adult men.

Correction to: Cardiovascular, muscular, and skeletal adaptations to recreational team handball training: a randomized controlled trial with young adult untrained men.

The author would like to correct the errors in the publication of the original article. The corrected details are given below for your reading.

Rapid switch-off of the human myosin heavy chain IIX gene after heavy load muscle contractions is sustained for at least four days.

Long-term heavy load contractions decrease the relative amount of the myosin heavy chain (MHC) IIX isoform in human skeletal muscle, but the timing of the down-regulation in the short term is unknown. Untrained subjects performed two resistance bouts, in two consecutive days, with one leg, the other leg serving as a control (age 24±1, n=5). Muscle biopsies were obtained in both legs before, immediately after, and 24, 54, and 96 hours after exercise. Serial cryosection analysis combined immunohistochemistry and ATPase histochemistry with In Situ hybridization to identify the distribution of MHC isoforms and their corresponding transcripts, enabling identification of transitional fibers. Fibers positive solely for MHC IIX mRNA decreased in the exercised leg throughout the study period. At 96 hours post-exercise, no fibers solely expressed MHC IIX mRNA. In contrast, the number of fibers expressing MHC IIA mRNA increased throughout the study period. The percentage of fibers expressing mRNA for MHC I was unchanged in both legs at all time points. Pronounced depletion of glycogen in the MHC IIX fibers of the exercised leg verifies that the type IIX fibers were active during the heavy load contractions. Major mismatch between MHC at the mRNA and protein levels was only found in the fibers of the exercised leg. These data provide unequivocal in situ evidence of an immediate shutdown of the MHC IIX gene after resistance exercise. A further novel finding was that the silencing of the MHC IIX gene is sustained at least 4 days after removal of the stimulus.

Alpine Skiing With total knee ArthroPlasty (ASWAP): metabolism, inflammation, and skeletal muscle fiber characteristics.

We investigated the effect of alpine skiing for 12 weeks on skeletal muscle characteristics and biomarkers of glucose homeostasis and cardiovascular risk factors. Twenty-three patients with a total knee arthroplasty (TKA) were studied 2.9 ± 0.9 years (mean ± SD) after the operation. Fourteen patients participated in the intervention group (IG) and nine in the control group (CG). Blood samples and muscle biopsies were obtained before (PRE) and 7.3 ± 0.8 days after (POST) the intervention, and blood samples again after a retention (RET) phase of 8 weeks. With skiing, glucose homeostasis improved in IG (decrease in fasting insulin, increase in muscle glycogen) but not in CG. Fiber type distribution and size, as well as capillary density and number of capillaries around the fibers (CAF), were not different between the operated and the non-operated leg in either group. The relative number of type I fibers increased with skiing in IG with no change in CG. Inflammatory biomarkers, plasma lipids, and mitochondrial proteins and activity did not change. Alpine skiing is metabolically beneficial and can be used as a training modality by elderly people with TKA.

Safety and efficacy of resistance training in germ cell cancer patients undergoing chemotherapy: a randomized controlled trial.

BACKGROUND: Bleomycin-etoposid-cisplatin (BEP) chemotherapy is curative in most patients with disseminated germ cell cancer (GCC) but also associated with toxic actions and dysfunction in non-targeted tissues. We investigated changes in muscle function during BEP and the safety and efficacy of resistance training to modulate these changes. METHODS: Thirty GCC patients were randomly assigned to resistance training (resistance training group (INT), n=15) or usual care (CON, n=15) during 9 weeks of BEP therapy. Resistance training consisted of thrice weekly sessions of four exercises, 3-4 sets/exercise of 10-15 repetitions at 12-15 repetition maximum load. The primary endpoint was muscle fibre size, assessed in muscle biopsies from musculus vastus lateralis. Secondary endpoints were fibre phenotype composition, body composition, strength, blood biochemistry and patient-reported endpoints. Healthy age-matched subjects (REF, n=19) performed the same RT-programme for comparison purposes. RESULTS: Muscle fibre size decreased by -322 µm(2) (95% confidence interval (CI): -899 to 255; P=0.473) in the CON-group and increased by +206 µm(2) (95% CI: -384 to 796; P=0.257) in the INT-group (adjusted mean difference (AMD), +625 µm(2), 95% CI: -253 to 1503, P=0.149). Mean differences in type II fibre size (AMD, +823 µm(2), P=0.09) and lean mass (AMD, +1.49 kg, P=0.07) in favour of the INT-group approached significance. The REF-group improved all muscular endpoints and had significantly superior changes compared with the INT-group (P<0.05). CONCLUSIONS: BEP was associated with significant reduction in lean mass and strength and trends toward unfavourable changes in muscle fibre size and phenotype composition. Resistance training was safe and attenuated dysfunction in selected endpoints, but BEP blunted several positive adaptations observed in healthy controls. Thus, our study does not support the general application of resistance training in this setting but larger-scaled trials are required to confirm this finding.

Muscle dysfunction in cancer patients.

BACKGROUND: Muscle dysfunction is a prevalent phenomenon in the oncology setting where patients across a wide range of diagnoses are subject to impaired muscle function regardless of tumor stage and nutritional state. Here, we review the current evidence describing the degree, causes and clinical implications of muscle dysfunction in cancer patients. The efficacy of exercise training to prevent and/or mitigate cancer-related muscle dysfunction is also discussed. DESIGN: We identified 194 studies examining muscular outcomes in cancer patients by searching PubMed and EMBASE databases. RESULTS: Muscle dysfunction is evident across all stages of the cancer trajectory. The causes of cancer-related muscle dysfunction are complex, but may involve a wide range of tumor-, therapy- and/or lifestyle-related factors, depending on the clinical setting of the individual patient. The main importance of muscle dysfunction in cancer patients lies in the correlation to vital clinical end points such as cancer-specific and all-cause mortality, therapy complications and quality of life (QoL). Such associations strongly emphasize the need for effective therapeutic countermeasures to be developed and implemented in oncology practice. Significant progress has been made over the last decade in the field of exercise oncology, indicating that exercise training constitutes a potent modulator of skeletal muscle function in patients with cancer. CONCLUSION: There are clear associations between muscle dysfunction and critical clinical end points. Yet there is a discrepancy between timing of exercise intervention trials, which can improve muscle function, and study populations in whom muscle function are proven prognostic important for clinical end points. Thus, future exercise trials should in early-stage patients, be powered to evaluate clinical outcomes associated with improvements in muscle function, or be promoted in advanced stage settings, aiming to reverse cancer-related muscle dysfunction, and thus potentially improve time-to-progression, treatment toxicity and survival.

Ageing is associated with diminished muscle re-growth and myogenic precursor cell expansion early after immobility-induced atrophy in human skeletal muscle.

Recovery of skeletal muscle mass from immobilisation-induced atrophy is faster in young than older individuals, yet the cellular mechanisms remain unknown. We examined the cellular and molecular regulation of muscle recovery in young and older human subjects subsequent to 2 weeks of immobility-induced muscle atrophy. Retraining consisted of 4 weeks of supervised resistive exercise in 9 older (OM: mean age) 67.3, range 61-74 yrs) and 11 young (YM: mean age 24.4, range 21-30 yrs) males. Measures of myofibre area (MFA), Pax7-positive satellite cells (SCs) associated with type I and type II muscle fibres, as well as gene expression analysis of key growth and transcription factors associated with local skeletal muscle milieu, were performed after 2 weeks immobility (Imm) and following 3 days (+3d) and 4 weeks (+4wks) of retraining. OM demonstrated no detectable gains in MFA (vastus lateralis muscle) and no increases in number of Pax7-positive SCs following 4wks retraining, whereas YM increased their MFA (P < 0.05), number of Pax7-positive cells, and had more Pax7-positive cells per type II fibre than OM at +3d and +4wks (P < 0.05). No age-related differences were observed in mRNA expression of IGF-1Ea, MGF, MyoD1 and HGF with retraining, whereas myostatin expression levels were more down-regulated in YM compared to OM at +3d (P < 0.05). In conclusion, the diminished muscle re-growth after immobilisation in elderly humans was associated with a lesser response in satellite cell proliferation in combination with an age-specific regulation of myostatin. In contrast, expression of local growth factors did not seem to explain the age-related difference in muscle mass recovery.

The formation of ubiquitin rich condensates triggers recruitment of the ATG9A lipid transfer complex to initiate basal autophagy.

Autophagy is an essential cellular recycling process that maintains protein and organelle homeostasis. ATG9A vesicle recruitment is a critical early step in autophagy to initiate autophagosome biogenesis. The mechanisms of ATG9A vesicle recruitment are best understood in the context of starvation-induced non-selective autophagy, whereas less is known about the signals driving ATG9A vesicle recruitment to autophagy initiation sites in the absence of nutrient stress. Here we demonstrate that loss of ATG9A or the lipid transfer protein ATG2 leads to the accumulation of phosphorylated p62 aggregates in the context of basal autophagy. Furthermore, we show that p62 degradation requires the lipid scramblase activity of ATG9A. Lastly, we present evidence that poly-ubiquitin is an essential signal that recruits ATG9A and mediates autophagy foci assembly in nutrient replete cells. Together, our data support a ubiquitin-driven model of ATG9A recruitment and autophagosome formation during basal autophagy.

The Integration of Proteome-Wide PTM Data with Protein Structural and Sequence Features Identifies Phosphorylations that Mediate 14-3-3 Interactions.

14-3-3s are abundant proteins that regulate essentially all aspects of cell biology, including cell cycle, motility, metabolism, and cell death. 14-3-3s work by docking to phosphorylated Ser/Thr residues on a large network of client proteins and modulating client protein function in a variety of ways. In recent years, aided by improvements in proteomics, the discovery of 14-3-3 client proteins has far outpaced our ability to understand the biological impact of individual 14-3-3 interactions. The rate-limiting step in this process is often the identification of the individual phospho-serines/threonines that mediate 14-3-3 binding, which are difficult to distinguish from other phospho-sites by sequence alone. Furthermore, trial-and-error molecular approaches to identify these phosphorylations are costly and can take months or years to identify even a single 14-3-3 docking site phosphorylation. To help overcome this challenge, we used machine learning to analyze predictive features of 14-3-3 binding sites. We found that accounting for intrinsic protein disorder and the unbiased mass spectrometry identification rate of a given phosphorylation significantly improves the identification of 14-3-3 docking site phosphorylations across the proteome. We incorporated these features, coupled with consensus sequence prediction, into a publicly available web app, called "14-3-3 site-finder". We demonstrate the strength of this approach through its ability to identify 14-3-3 binding sites that do not conform to the loose consensus sequence of 14-3-3 docking phosphorylations, which we validate with 14-3-3 client proteins, including TNK1, CHEK1, MAPK7, and others. In addition, by using this approach, we identify a phosphorylation on A-kinase anchor protein-13 (AKAP13) at Ser2467 that dominantly controls its interaction with 14-3-3.

Increased mitochondrial substrate sensitivity in skeletal muscle of patients with type 2 diabetes.

AIMS/HYPOTHESIS: Mitochondrial respiration has been linked to insulin resistance. We studied mitochondrial respiratory capacity and substrate sensitivity in patients with type 2 diabetes (patients), and obese and lean control participants. METHODS: Mitochondrial respiration was measured in permeabilised muscle fibres by respirometry. Protocols for respirometry included titration of substrates for complex I (glutamate), complex II (succinate) and both (octanoyl-carnitine). Myosin heavy chain (MHC) composition, antioxidant capacity (manganese superoxide dismutase [MnSOD]), citrate synthase activity and maximal oxygen uptake (VO2) were also determined. Insulin sensitivity was determined with the isoglycaemic-hyperinsulinaemic clamp technique. RESULTS: Insulin sensitivity was different (p < 0.05) between the groups (patients

Normal mitochondrial function and increased fat oxidation capacity in leg and arm muscles in obese humans.

AIM/HYPOTHESIS: The aim of this study was to investigate mitochondrial function, fibre-type distribution and substrate oxidation during exercise in arm and leg muscles in male postobese (PO), obese (O) and age- and body mass index (BMI)-matched control (C) subjects. The hypothesis of the study was that fat oxidation during exercise might be differentially preserved in leg and arm muscles after weight loss. METHODS: Indirect calorimetry was used to calculate fat and carbohydrate oxidation during both progressive arm-cranking and leg-cycling exercises. Muscle biopsy samples were obtained from musculus deltoideus (m. deltoideus) and m. vastus lateralis muscles. Fibre-type composition, enzyme activity and O(2) flux capacity of saponin-permeabilized muscle fibres were measured, the latter by high-resolution respirometry. RESULTS: During the graded exercise tests, peak fat oxidation during leg cycling and the relative workload at which it occurred (FatMax) were higher in PO and O than in C. During arm cranking, peak fat oxidation was higher in O than in C, and FatMax was higher in O than in PO and C. Similar fibre-type composition was found between groups. Plasma adiponectin was higher in PO than in C and O, and plasma leptin was higher in O than in PO and C. CONCLUSIONS: In O subjects, maximal fat oxidation during exercise and the eliciting relative exercise intensity are increased. This is associated with higher intramuscular triglyceride levels and higher resting non esterified fatty acid (NEFA) concentrations, but not with differences in fibre-type composition, mitochondrial function or muscle enzyme levels compared with Cs. In PO subjects, the changes in fat oxidation are preserved during leg, but not during arm, exercise.

Myostatin expression during human muscle hypertrophy and subsequent atrophy: increased myostatin with detraining.

Myostatin is a potent negative regulator of skeletal muscle mass, but its role in human skeletal muscle hypertrophy and atrophy is sparsely described. Muscle biopsies were obtained from young male subjects before and after 30 and 90 days of resistance training as well as after 3, 10, 30, 60 and 90 days of subsequent detraining. Myostatin mRNA increased significantly with detraining. We observed a 28 kDa myostatin immunoreactive protein, which, however, was also present in myostatin knock out mice skeletal muscle. As a novel finding we consistently detected a 10 kDa band, which may represent a mature myostatin monomer under reducing conditions or a novel, unknown myostatin form. Further, we observed a significant increase in this 10 kDa band after 3 days of detraining preceding the rapid type II fiber atrophy, in which almost half of the acquired fiber area was lost after only 10 days of detraining. Accordingly, an increase in the level of the 10 kDa protein is associated with rapid type II fiber atrophy, suggesting myostatin-mediated specific type II fiber atrophy, which in combination with our mRNA data support a role for myostatin in the negative regulation of adult human skeletal muscle mass.

Changes in muscle strength and morphology after muscle unloading in Special Forces missions.

The purpose of the present study was to determine the changes in maximal muscle strength, rapid force capacity, jumping performance and muscle morphology following a Special Forces military operation involving 8 days of muscle unloading. Nine male Special Forces soldiers were tested before (pre) and immediately after (post1) an 8-day simulated special support and reconnaissance (SSR) mission and after 3 h of active recovery (post2). Maximal muscle strength (MVC) and rate of force development (RFD) were measured along with maximal counter movement jump height (JH). Muscle biopsies were obtained from the vastus lateralis at pre and post1. Acute reductions were found in MVC (11%), JH (10%) and RFD (17-22%) after 8 days of muscle unloading (post1) (P≤0.05). Type IIX fiber type area% increased (P≤0.05) at post1 together with a tendency toward increased type IIX fiber type % (P=0.09) and decreased type I fiber type % (P=0.06), suggesting a transition toward a less fatigue-resistant fiber-type profile. In conclusion, short-term unloading during SSR missions led to marked reductions in mechanical muscle function and functional performance, which may be partly explained by the changes in muscle morphology. Future studies should identify intervention strategies to counter-act the observed impairments.

Effects of resistance training on endurance capacity and muscle fiber composition in young top-level cyclists.

Equivocal findings exist on the effect of concurrent strength (S) and endurance (E) training on endurance performance and muscle morphology. Further, the influence of concurrent SE training on muscle fiber-type composition, vascularization and endurance capacity remains unknown in top-level endurance athletes. The present study examined the effect of 16 weeks of concurrent SE training on maximal muscle strength (MVC), contractile rate of force development (RFD), muscle fiber morphology and composition, capillarization, aerobic power (VO2max), cycling economy (CE) and long/short-term endurance capacity in young elite competitive cyclists (n=14). MVC and RFD increased 12-20% with SE (P<0.01) but not E. VO2max remained unchanged. CE improved in E to reach values seen in SE. Short-term (5-min) endurance performance increased (3-4%) after SE and E (P<0.05), whereas 45-min endurance capacity increased (8%) with SE only (P<0.05). Type IIA fiber proportions increased and type IIX proportions decreased after SE training (P<0.05) with no change in E. Muscle fiber area and capillarization remained unchanged. In conclusion, concurrent strength/endurance training in young elite competitive cyclists led to an improved 45-min time-trial endurance capacity that was accompanied by an increased proportion of type IIA muscle fibers and gains in MVC and RFD, while capillarization remained unaffected.

Effects of strength training on endurance capacity in top-level endurance athletes.

The effect of concurrent strength (S) and endurance (E) training on adaptive changes in aerobic capacity, endurance performance, maximal muscle strength and muscle morphology is equivocal. Some data suggest an attenuated cardiovascular and musculoskeletal response to combined E and S training, while other data show unimpaired or even superior adaptation compared with either training regime alone. However, the effect of concurrent S and E training only rarely has been examined in top-level endurance athletes. This review describes the effect of concurrent SE training on short-term and long-term endurance performance in endurance-trained subjects, ranging from moderately trained individuals to elite top-level athletes. It is concluded that strength training can lead to enhanced long-term (>30 min) and short-term (<15 min) endurance capacity both in well-trained individuals and highly trained top-level endurance athletes, especially with the use of high-volume, heavy-resistance strength training protocols. The enhancement in endurance capacity appears to involve training-induced increases in the proportion of type IIA muscle fibers as well as gains in maximal muscle strength (MVC) and rapid force characteristics (rate of force development), while likely also involving enhancements in neuromuscular function.

Effects of strength training on muscle fiber types and size; consequences for athletes training for high-intensity sport.

Training toward improving performance in sports involving high intense exercise can and is done in many different ways based on a mixture of tradition in the specific sport, coaches' experience and scientific recommendations. Strength training is a form of training that now-a-days have found its way into almost all sports in which high intense work is conducted. In this review we will focus on a few selected aspects and consequences of strength training; namely what effects do strength training have of muscle fiber type composition, and how may these effects change the contractile properties of the muscle and finally how will this affect the performance of the athlete. In addition, the review will deal with muscle hypertrophy and how it develops with strength training. Overall, it is not the purpose of this review to give a comprehensive up-date of the area, but to pin-point a few issues from which functional training advises can be made. Thus, more than a review in the traditional context this review should be viewed upon as an attempt to bring sports-physiologists and coaches or others working directly with the athletes together for a mutual discussion on how recently acquired physiological knowledge are put into practise.

Early and late rate of force development: differential adaptive responses to resistance training?

The objective of this study is to investigate the potentially opposing influence of qualitative and quantitative muscular adaptations in response to high-intensity resistance training on contractile rate of force development (RFD) in the early (<100 ms) and later phases (>200 ms) of rising muscle force. Fifteen healthy young males participated in a 14-week resistance training intervention for the lower body and 10 matched subjects participated as controls. Maximal muscle strength (MVC) and RFD were measured during maximal voluntary isometric contraction of the quadriceps femoris muscle. Muscle biopsies were obtained from the vastus lateralis. The main findings were that RFD in the late phase of rising muscle force increased in response to resistance training whereas early RFD remained unchanged and early relative RFD (i.e., RFD/MVC) decreased. Quantitatively, muscle fiber cross-sectional area and MVC increased whereas, qualitatively, the relative proportion of type IIX muscle fibers decreased. Multiple regression analysis showed that while increased MVC positively influenced both early and late RFD, decreased-type IIX negatively influenced early RFD only. In conclusion, early and late RFD responded differently to high-intensity resistance training due to differential influences of qualitative and quantitative muscular adaptations on early and later phases of rising muscle force.

Muscle function and postural balance in lifelong trained male footballers compared with sedentary elderly men and youngsters.

The present study investigated whether elderly subjects exposed to lifelong football training have better rapid muscle force characteristics, body composition and postural stability in comparison with untrained elderly. Ten elderly men exposed to lifelong football training (FTE; 69.6 +/- 1.4 years) and eight age-matched untrained elderly men (UE; 70.5 +/- 1.0 years) were studied and 49 untrained young men (UY; 32.4 +/- 0.9 years) served as a reference group. FTE showed an elevated rate of force development (RFD) and impulse at 0-30, 100 and 200 ms (relative RFD at 1/6 MVC: 567 +/- 39 vs 353 +/- 42% MVC/s), higher total lean body mass (56.9 +/- 0.8 vs 52.7 +/- 2.2 kg) and better postural stability (Flamingo test: 15 +/- 1 vs 33 +/- 2 falls) compared with UE (P<0.05), with no difference between FTE and UY. The proportion of type IIA fibers was higher and the area percentage of type IIX fibers was lower in FTE than in UE (P<0.05). Rapid muscle force characteristics and postural stability were consistently higher in elderly subjects exposed to lifelong football training, providing an enhanced ability to counteract unexpected perturbations in postural balance. The superior RFD and balance in elderly footballers were of such a magnitude that no deficit could be observed when compared with young untrained individuals.