To Örebro University

High-load resistance exercise (>60% of 1-repetition maximum) is a well-known stimulus to enhance skeletal muscle hypertrophy with chronic training. However, studies have intriguingly shown that low-load resistance exercise training (RET) (≤60% of 1-repetition maximum) can lead to similar increases in skeletal muscle hypertrophy as compared to high-load RET. This has raised questions about the underlying mechanisms for eliciting the hypertrophic response with low-load RET. A key characteristic of low-load RET is performing resistance exercise to, or close to, task failure, thereby inducing muscle fatigue. The primary aim of this evidence-based narrative review is to explore whether muscle fatigue may act as an indirect or direct mechanism contributing to skeletal muscle hypertrophy during low-load RET. It has been proposed that muscle fatigue could indirectly stimulate muscle hypertrophy through increased muscle fibre recruitment, mechanical tension, ultrastructural muscle damage, the secretion of anabolic hormones, and/or alterations in the expression of specific proteins involved in muscle mass regulation (e.g., myostatin). Alternatively, it has been proposed that fatigue could directly stimulate muscle hypertrophy through the accumulation of metabolic by-products (e.g., lactate), and/or inflammation and oxidative stress. This review summarizes the existing literature eluding to the role of muscle fatigue as a stimulus for low-load RET-induced muscle hypertrophy and provides suggested avenues for future research to elucidate how muscle fatigue could mediate skeletal muscle hypertrophy.

Background: We investigated the impact of 1) passive heating (PH) induced by single and intermittent/prolonged hot-water immersion (HWI) and 2) the duration of PH, on muscle contractile function under the unfatigued state, and during the development of muscle fatigue.

Methods: Twelve young males volunteered for this study consisting of two phases: single phase (SP) followed by intermittent/prolonged phase (IPP), with both phases including two conditions (i.e., four trials in total) performed randomly: control passive sitting (CON) and HWI (44-45°C; water up to the waist level). SP-HWI included one continuous 45-min bath (from 15 to 60 min). IPP-HWI included an initial 45-min bath (from 15 to 60 min) followed by eight additional 15-min baths interspaced with 15-min breaks at room temperature between 75 and 300 min. Intramuscular (Tmu; measured in the vastus lateralis muscle) and rectal (Trec) temperatures were determined. Neuromuscular testing (performed in the knee extensors and flexors) was performed at baseline and 60 min later during SP, and at baseline, 60, 90, 150 and 300 min after baseline during IPP. A fatiguing protocol (100 electrical stimulations of the knee extensors) was performed after the last neuromuscular testing of each trial.

Results: HWI increased Tmu and Trec to 38°C-38.5°C (p < 0.05) during both SP and IPP. Under the unfatigued state, HWI did not affect electrically induced torques at 20 Hz (P20) and 100 Hz (P100). However, it induced a shift towards a faster contractile profile during both SP and IPP, as evidenced by a decreased P20/P100 ratio (p < 0.05) and an improved muscle relaxation (i.e., reduced half-relaxation time and increased rate of torque relaxation; p < 0.05). Despite a reduced voluntary activation (i.e., -2.63% ± 4.19% after SP-HWI and -5.73% ± 4.31% after IPP-HWI; condition effect: p < 0.001), HWI did not impair maximal isokinetic and isometric contraction torques. During the fatiguing protocol, fatigue index and the changes in muscle contractile properties were larger after HWI than CON conditions (p < 0.05). Finally, none of these parameters were significantly affected by the heating duration.

Conclusion: PH induces changes in muscle contractile function which are not augmented by prolonged exposure when thermal stress is moderate.

Age-related loss of skeletal muscle mass leads to a reduction of strength. It is likely due to an inadequate stimulation of muscle protein synthesis (MPS) in response to anabolic stimuli, such as mechanical load. Ribosome biogenesis is a major determinant of translational capacity and is essential for the control of muscle mass. This mini-review aims to put forth the hypothesis that ribosome biogenesis is impaired by aging in response to mechanical load, which could contribute to the age-related anabolic resistance and progressive muscle atrophy. Recent animal studies indicate that aging impedes muscle hypertrophic response to mechanical overload. This is associated with an impaired transcription of ribosomal DNA (rDNA) by RNA polymerase I (Pol I), a limited increase in total RNA concentration, a blunted activation of AKT/mTOR pathway, and an increased phosphorylation of AMPK. In contrast, an age-mediated impairment of ribosome biogenesis is unlikely in response to electrical stimulations. In human, the hypertrophic response to resistance exercise training is diminished with age. This is accompanied by a deficit in long-term MPS and an absence of increased total RNA concentration. The results addressing the acute response to resistance exercise suggest an impaired Pol I-mediated rDNA transcription and attenuated activation/expression of several upstream regulators of ribosome biogenesis in muscles from aged individuals. Altogether, emerging evidence indicates that impaired ribosome biogenesis could partly explain age-related anabolic resistance to mechanical load, which may ultimately contribute to progressive muscle atrophy. Future research should develop more advanced molecular tools to provide in-depth analysis of muscle ribosome biogenesis.

Background: We investigated the impact of moderate muscle cooling induced by single and intermittent/prolonged cold-water immersions (CWI) on muscle force and contractility in unfatigued state and during the development of fatigue resulting from electrically induced contractions.

Methods: Twelve young males participated in this study consisting of two phases [single phase (SP) followed by intermittent/prolonged phase (IPP)], with both phases including two conditions (i.e., four trials in total) performed randomly: control passive sitting (CON) and cold-water immersions (10°C). SP-CWI included one 45 min-bath (from 15 to 60 min). IPP-CWI included three baths (45 min-bath from 15 to 60 min, and 15 min-baths from 165 to 180 min and from 255 to 270 min), with participants sitting at room temperature the rest of the time until 300 min. Blood pressure and intramuscular (Tmu) temperature were assessed, and neuromuscular testing was performed at baseline and 60 min after baseline during SP, and at baseline, 60, 90, 150 and 300 min after baseline during IPP. A fatiguing protocol (100 electrical stimulations) was performed after the last neuromuscular testing of each trial.

Results: In unfatigued state, SP-CWI and IPP-CWI reduced electrically induced torque at 100 Hz (P100) but not at 20 Hz (P20), and increased P20/P100 ratio. The changes from baseline for P100 and P20/P100 ratio were lower in IPP-CWI than SP-CWI. Both cold-water immersion conditions slowed down muscle contraction and relaxation, and reduced maximal isokinetic contraction torque, but the changes from baseline were lower after IPP-CWI than SP-CWI. cold-water immersions did not impair maximal voluntary isometric contraction. During the fatiguing protocol, torque fatigue index and the changes in muscle contractile properties were larger after IPP-CWI than SP-CWI, but were in the same range as after CON conditions. The differences of muscle contractile function between SP-CWI and IPP-CWI were accompanied by a lower reduction of superficial Tmu and a smaller increase in systolic blood pressure after IPP-CWI than SP-CWI.

Conclusion: IPP-CWI induces a less pronounced fast-to-slow contractile transition compared to SP-CWI, and this may result from the reduced vasoconstriction response and enhanced blood perfusion of the superficial muscle vessels, which could ultimately limit the reduction of superficial Tmu.

Cells rapidly lose their physiological phenotype upon disruption of their extracellular matrix (ECM)-intracellular cytoskeleton interactions. By comparing adult mouse skeletal muscle fibers, isolated either by mechanical dissection or by collagenase-induced ECM digestion, we investigated acute effects of ECM disruption on cellular and mitochondrial morphology, transcriptomic signatures, and Ca2+ handling. RNA-sequencing showed striking differences in gene expression patterns between the two isolation methods with enzymatically dissociated fibers resembling myopathic phenotypes. Mitochondrial appearance was grossly similar in the two groups, but 3D electron microscopy revealed shorter and less branched mitochondria following enzymatic dissociation. Repeated contractions resulted in a prolonged mitochondrial Ca2+ accumulation in enzymatically dissociated fibers, which was partially prevented by cyclophilin inhibitors. Of importance, muscle fibers of mice with severe mitochondrial myopathy show pathognomonic mitochondrial Ca2+ accumulation during repeated contractions and this accumulation was concealed with enzymatic dissociation, making this an ambiguous method in studies of native intracellular Ca2+ fluxes.

BACKGROUND: Patients with breast cancer exhibit muscle weakness, which is associated with increased mortality risk and reduced quality of life. Muscle weakness is experienced even in the absence of loss of muscle mass in breast cancer patients, indicating intrinsic muscle dysfunction. Physical activity is correlated with reduced cancer mortality and disease recurrence. However, the molecular processes underlying breast cancer-induced muscle weakness and the beneficial effect of exercise are largely unknown.

METHODS: Eight-week-old breast cancer (MMTV-PyMT, PyMT) and control (WT) mice had access to active or inactive in-cage voluntary running wheels for 4 weeks. Mice were also subjected to a treadmill test. Muscle force was measured ex vivo. Tumour markers were determined with immunohistochemistry. Mitochondrial biogenesis and function were assessed with transcriptional analyses of PGC-1α, the electron transport chain (ETC) and antioxidants superoxide dismutase (Sod) and catalase (Cat), combined with activity measurements of SOD, citrate synthase (CS) and β-hydroxyacyl-CoA-dehydrogenase (βHAD). Serum and intramuscular stress levels were evaluated by enzymatic assays, immunoblotting, and transcriptional analyses of, for example, tumour necrosis factor-α (TNF-α) and p38 mitogen-activated protein kinase (MAPK) signalling.

RESULTS: PyMT mice endured shorter time and distance during the treadmill test (~30%, P < 0.05) and ex vivo force measurements revealed ~25% weaker slow-twitch soleus muscle (P < 0.001). This was independent of cancer-induced alteration of muscle size or fibre type. Inflammatory stressors in serum and muscle, including TNF-α and p38 MAPK, were higher in PyMT than in WT mice (P < 0.05). Cancer-induced decreases in ETC (P < 0.05, P < 0.01) and antioxidant gene expression were observed (P < 0.05). The exercise intervention counteracted the cancer-induced muscle weakness and was accompanied by a less aggressive, differentiated tumour phenotype, determined by increased CK8 and reduced CK14 expression (P < 0.05). In PyMT mice, the exercise intervention led to higher CS activity (P = 0.23), enhanced β-HAD and SOD activities (P < 0.05), and reduced levels of intramuscular stressors together with a normalization of the expression signature of TNFα-targets and ETC genes (P < 0.05, P < 0.01). At the same time, the exercise-induced PGC-1α expression, and CS and β-HAD activity was blunted in muscle from the PyMT mice as compared with WT mice, indicative that breast cancer interfere with transcriptional programming of mitochondria and that the molecular adaptation to exercise differs between healthy mice and those afflicted by disease.

CONCLUSIONS: Four-week voluntary wheel running counteracted muscle weakness in PyMT mice which was accompanied by reduced intrinsic stress and improved mitochondrial and antioxidant profiles and activities that aligned with muscles of healthy mice.

The application of post-exercise cooling (e.g., cold water immersion) and post-exercise heating has become a popular intervention which is assumed to increase functional recovery and may improve chronic training adaptations. However, the effectiveness of such post-exercise temperature manipulations remains uncertain. The aim of this comprehensive review was to analyze the effects of post-exercise cooling and post-exercise heating on neuromuscular function (maximal strength and power), fatigue resistance, exercise performance, and training adaptations. We focused on three exercise types (resistance, endurance and sprint exercises) and included studies investigating (1) the early recovery phase, (2) the late recovery phase, and (3) repeated application of the treatment. We identified that the primary benefit of cooling was in the early recovery phase (< 1 h post-exercise) in improving fatigue resistance in hot ambient conditions following endurance exercise and possibly enhancing the recovery of maximal strength following resistance exercise. The primary negative impact of cooling was with chronic exposure which impaired strength adaptations and decreased fatigue resistance following resistance training intervention (12 weeks and 4-12 weeks, respectively). In the early recovery phase, cooling could also impair sprint performance following sprint exercise and could possibly reduce neuromuscular function immediately after endurance exercise. Generally, no benefits of acute cooling were observed during the 24-72-h recovery period following resistance and endurance exercises, while it could have some benefits on the recovery of neuromuscular function during the 24-48-h recovery period following sprint exercise. Most studies indicated that chronic cooling does not affect endurance training adaptations following 4-6 week training intervention. We identified limited data employing heating as a recovery intervention, but some indications suggest promise in its application to endurance and sprint exercise.

PURPOSE: Traditional high-intensity interval exercise (HIIE) highly stimulates the cardiorespiratory system and increases energy expenditure (EE) during exercise. High-intensity resistance exercise (HIRE) has become more popular in recreationally active subjects. The physiological responses to HIRE performed with light or moderate load is currently largely unknown. Here, we examined the effect of the type of interval exercise [HIRE at 40% (HIRE40) and 60% (HIRE60) 1-RM vs. traditional HIIE] on the cardiorespiratory response and EE during and after exercise.

METHODS: Fifteen recreationally active adults randomly completed traditional HIIE on an ergocyle, HIRE40 and HIRE60. The sessions consisted of two sets of ten 30-s intervals (power at 100% VO_2max during HIIE; maximal number of repetitions for 10 different free-weight exercises during HIRE40 and HIRE60) separated by 30-s active recovery periods. Gas exchange, heart rate (HR) and EE were assessed during and after exercise.

RESULTS: VO_2mean, VO_2peak, HR_mean, the time spent above 90% VO_2max and HR_max, and aerobic EE were lower in both HIRE sessions compared with HIIE (P < 0.05). Anaerobic glycolytic contribution to total exercise EE was higher in HIRE40 and HIRE60 compared with HIIE (P < 0.001). EE from excess post-exercise oxygen consumption (EPOC) was similar after the three sessions. Overall, similar cardiorespiratory responses and EE were found in HIRE40 and HIRE60.

CONCLUSIONS: HIRE is not as effective as HIIE for increasing the cardiorespiratory response and EE during exercise, while EPOC remains similar in HIRE and HIIE. These parameters are not substantially different between HIRE40 and HIRE60.

Introduction

In athletes, exposure to cold during winter sports may impair physical performance. Severe muscle cooling appears to reduce maximal force and induces a shift towards a slower contractile profile. However, whether moderate muscle cooling and the duration of cooling affect muscle contractile profile (assessed from electrically evoked torque at low and high frequencies) and maximal voluntary force (isometric and isokinetic contractions) remains to be clarified. Therefore, the aim of this study was to investigate the impact of acute and prolonged cooling on electrically evoked torque and maximal voluntary contraction torque in young males. 

Methods

Twelve active males (27.2 ± 6.6 years old) were recruited for this study, consisting of 2 phases: acute and prolonged exposures. During each phase, participants were randomly exposed to cold water immersion (CWI, 10°C, up to the iliac crest) or passive resting (PR). Exposure to CWI was either continuous during 45min (acute CWI, A-CWI) or intermittent during a period of 300min [prolonged CWI (P-CWI) including immersions between baseline to 45min, 165 to 180min, and 255 to 270min]. Muscle (Tmu, average across 1, 2 and 3cm depth) and rectal (Trec) temperatures were assessed using thermo-sensors. Transcutaneous electrical stimulation of the quadriceps muscle was performed to determine torques at low (20 Hz: P20) and high (100 Hz: P100) frequencies, and P20/P100 ratio was calculated. Maximal voluntary isometric torque of the knee extensors (MVIC), as well as peak isokinetic torques (90°/s) of knee extensors (KE-IsoC) and flexors (KF-isoC) were determined. Neuromuscular tests were performed at baseline (BL) and 60min after BL during acute exposure, and at BL, 60, 90, 150 and 300min after BL during prolonged exposure.

Results

Trec did not change after A-CWI while it was reduced (0.8 ± 0.4°C, p<0.001) after P-CWI compared to BL. Tmu decreased during A-CWI and P-CWI compared to BL (6.1 ± 2.2°C and 4.6 ± 1.1°C, respectively, p<0.001), with larger reduction of Tmu after A-CWI than P-CWI (p<0.05). P20 was not affected by the conditions. P100 was lower after 60min in A-CWI and P-CWI compared to PR (p<0.05). After the last bath (60min in A-CWI and 300min in P-CWI), P100 was nearly significantly higher in A-CWI than P-CWI (p=0.05). P20/P100 was higher after 60min in A-CWI and P-CWI compared to PR (p<0.001), but this ratio was lower in P-CWI than A-CWI after the last bath (p<0.05). MVIC torque remained unchanged during A-CWI and P-CWI, while KE-IsoC and KF-IsoC torques were similarly reduced after A-CWI and P-CWI compared to PR (p<0.05).

Conclusion

Moderate muscle cooling preferentially impairs maximal force production of dynamic contractions, but not isometric contractions, regardless of exposure duration. A shift towards a slower contractile profile (i.e., increased P20/P100) is more evident after A-CWI than P-CWI, which may be partially explained by a larger reduction of Tmu rather than the exposure duration or reduced Trec.

PURPOSE: Unaccustomed eccentric contractions generally result in a long-lasting contractile impairment, referred to as prolonged low-frequency force depression (PLFFD), and delayed-onset muscle soreness (DOMS). We here used repeated drop jumps (DJs) as an eccentric contraction model and studied the effects of increasing the time between DJs from 20 s to 5 min. We hypothesized that both PLFFD and DOMS would be less marked at the longer DJ interval due to the longer time to restore structural elements between DJs.

METHODS: Young men (n = 12) randomly performed 50 DJs with either 20-s (DJ-20 s) or 5-min (DJ-5 min) rest between DJs. Voluntary, 20 Hz and 100 Hz electrically stimulated isometric knee extension torques and muscle soreness were monitored before and for 7 days after DJs; serum CK activity was measured to assess muscle fibre protein leakage. In additional experiments, changes in mRNA levels were assessed in muscle biopsies collected before and 1 h after exercise.

RESULTS: A marked PLFFD was observed with both protocols and the extent of 20 Hz torque depression was smaller immediately and 1 day after DJ-5 min than after DJ-20 s (p < 0.05), whereas the MVC and 100 Hz torques were similarly decreased with the two protocols. Markedly larger differences between the two protocols were observed for the muscle soreness score, which 1-4 days after exercise was about two times larger with DJ-20 s than with DJ-5 min (p < 0.01).

CONCLUSIONS: The larger protective effect of the longer DJ interval against DOMS than against PLFFD indicates that their underlying mechanisms involve different structural elements.