The relationship between single muscle fibre and voluntary rate of force development in young and old males.

PURPOSE: It is suggested that the early phase (< 50 ms) of force development during a muscle contraction is associated with intrinsic contractile properties, while the late phase (> 50 ms) is associated with maximal force. There are no direct investigations of single muscle fibre rate of force development (RFD) as related to joint-level RFD METHODS: Sixteen healthy, young (n = 8; 26.4 ± 1.5 yrs) and old (n = 8; 70.1 ± 2.8 yrs) males performed maximal voluntary isometric contractions (MVC) and electrically evoked twitches of the knee extensors to assess RFD. Then, percutaneous muscle biopsies were taken from the vastus lateralis and chemically permeabilized, to assess single fibre function. RESULTS: At the joint level, older males were ~ 30% weaker and had ~ 43% and ~ 40% lower voluntary RFD values at 0-100 and 0-200 ms, respectively, than the younger ones (p ≤ 0.05). MVC torque was related to every voluntary RFD epoch in the young (p ≤ 0.001), but only the 0-200 ms epoch in the old (p ≤ 0.005). Twitch RFD was ~ 32% lower in the old compared to young (p < 0.05). There was a strong positive relationship between twitch RFD and voluntary RFD during the earliest time epochs in the young (≤ 100 ms; p ≤ 0.01). While single fibre RFD was unrelated to joint-level RFD in the young, older adults trended (p = 0.052-0.055) towards significant relationships between joint-level RTD and Type I single fibre RFD at the 0-30 ms (r2 = 0.48) and 0-50 ms (r2 = 0.49) time epochs. CONCLUSION: Electrically evoked twitches are good predictors of early voluntary RFD in young, but not older adults. Only the older adults showed a potential relationship between single fibre (Type I) and joint-level rate of force development.

Titin force in muscle cells alters lattice order, thick and thin filament protein formation.

Skeletal muscle force production is increased at longer compared to shorter muscle lengths because of length-dependent priming of thick filament proteins in the contractile unit before contraction. Using small-angle X-ray diffraction in combination with a mouse model that specifically cleaves the stretch-sensitive titin protein, we found that titin cleavage diminished the length-dependent priming of the thick filament. Strikingly, a titin-sensitive, length-dependent priming was also present in thin filaments, which seems only possible via bridge proteins between thick and thin filaments in resting muscle, potentially myosin-binding protein C. We further show that these bridges can be forcibly ruptured via high-speed stretches. Our results advance a paradigm shift to the fundamental regulation of length-dependent priming, with titin as the key driver.

COVID-19 Pandemic and Exercise (COPE) trial: a multigroup pragmatic randomised controlled trial examining effects of app-based at-home exercise programs on depressive symptoms.

BACKGROUND: The number of adults across the globe with significant depressive symptoms has grown substantially during the COVID-19 pandemic. The extant literature supports exercise as a potent behaviour that can significantly reduce depressive symptoms in clinical and non-clinical populations. OBJECTIVE: Using a suite of mobile applications, at-home exercise, including high intensity interval training (HIIT) and/or yoga, was completed to reduce depressive symptoms in the general population in the early months of the pandemic. METHODS: A 6-week, parallel, multiarm, pragmatic randomised controlled trial was completed with four groups: (1) HIIT, (2) Yoga, (3) HIIT+yoga, and (4) waitlist control (WLC). Low active, English-speaking, non-retired Canadians aged 18-64 years were included. Depressive symptoms were measured at baseline and weekly following randomisation. RESULTS: A total of 334 participants were randomised to one of four groups. No differences in depressive symptoms were evident at baseline. The results of latent growth modelling showed significant treatment effects in depressive symptoms for each active group compared with the WLC, with small effect sizes (ESs) in the community-based sample of participants. Treatment groups were not significantly different from each other. Effect sizes were very large (eg, week 6 ES range=-2.34 to -2.52) when restricting the analysis only to participants with high depressive symptoms at baseline. CONCLUSIONS: At-home exercise is a potent behaviour to improve mental health in adults during the pandemic, especially in those with increased levels of depressive symptoms. Promotion of at-home exercise may be a global public health target with important personal, social and economic implications as the world emerges scathed by the pandemic. TRIAL REGISTRATION NUMBER: NCT04400279.

Rate of force development is Ca2+-dependent and influenced by Ca2+-sensitivity in human single muscle fibres from older adults.

Natural adult aging is associated with declines in skeletal muscle performance, including impaired Ca2+ sensitivity and a slowing of rapid force production (rate of force redevelopment; ktr). The purpose of this study was to investigate the relationship between impaired Ca2+ sensitivity and ktr of single muscle fibres from young and older adults. Participants included 8 young (22-35 yrs) and 8 older (60-81 yrs) males who were living independently. A percutaneous muscle biopsy of the vastus lateralis of each participant was performed. Single muscle fibre mechanical tests included maximal Ca2+-activated force (Po), force-pCa curves, and ktr. We showed a decrease in pCa50 in old type II fibres compared to young, indicating impaired Ca2+ sensitivity in older adults. The ktr behaved in a Ca2+-dependent manner such that with increasing [Ca2+], ktr increases, to a plateau. Interestingly, ktr was not different between young and old muscle fibres. Furthermore, we found strong associations between pCa50 and ktr in both old type I and type II fibres, such that those fibres with lower Ca2+ sensitivity had a slowed ktr. This Ca2+ association, combined with impaired Ca2+ handling in older adults suggests a potential Ca2+-dependent mechanism affecting the transition from weakly- to strongly-bound cross-bridge states, leading to a decline in skeletal muscle performance. Future research is needed to explore the role alterations to Ca2+ sensitivity/handling could be playing in age-related whole muscle performance declines.

The torque-frequency relationship is impaired similarly following two bouts of eccentric exercise: No evidence of a protective repeated bout effect.

High-intensity eccentric exercise can lead to muscle damage and weakness. The 'repeated bout effect' (RBE) can attenuate these impairments when performing a subsequent bout. The influence of eccentric exercise-induced muscle damage on low-frequency force production is well-characterized; however, it is unclear how eccentric exercise and the RBE affect torque production across a range of stimulation frequencies (i.e., the torque-frequency relationship). We investigated the influence of an initial (Bout 1) and repeated bout (Bout 2) of eccentric exercise on the elbow flexor torque-frequency relationship. Eleven males completed two bouts of high-intensity eccentric elbow flexions, 4 weeks apart. Torque-frequency relationships were constructed at baseline and 0.5, 24, 48, 72, 96, and 168 h following both bouts via percutaneous stimulation at 1, 6, 10, 20, 30, 40, 50, and 100 Hz. Serum creatine kinase activity, self-reported muscle soreness, and isometric maximum voluntary contraction torque indirectly inferred the presence of muscle damage following Bout 1, and attenuation of muscle damage following Bout 2. Torque amplitude at all stimulation frequencies was impaired 30 min following eccentric exercise, however, torque at lower (1-10 Hz) and higher frequencies (40-100 Hz) recovered within 24 h while torque across the middle frequency range (20-30 Hz) recovered by 48 h. No between-bout differences were detected in absolute or normalized torque at any stimulation frequency, indicating no protective RBE on the elbow flexor torque-frequency relationship.

Power loss is attenuated following a second bout of high-intensity eccentric contractions due to the repeated bout effect's protection of rate of torque and velocity development.

High-intensity unaccustomed eccentric contractions result in weakness and power loss because of fatigue and muscle damage. Through the repeated bout effect (RBE), adaptations occur, then damage and weakness are attenuated following a subsequent bout. However, it is unclear whether the RBE protects peak power output. We investigated the influence of the RBE on power production and estimated fatigue- and damage-induced neuromuscular impairments following repeated high-intensity eccentric contractions. Twelve healthy adult males performed 5 sets of 30 maximal eccentric elbow flexions and repeated an identical bout 4 weeks later. Recovery was tracked over 7 days following both bouts. Reduced maximum voluntary isometric contraction torque, and increased serum creatine kinase and self-reported soreness indirectly inferred muscle damage. Peak isotonic power, time-dependent measures - rate of velocity development (RVD) and rate of torque development (RTD) - and several electrophysiological indices of neuromuscular function were assessed. The RBE protected peak power, with a protective index of 66% 24 h after the second eccentric exercise bout. The protection of power also related to preserved RVD (R2 = 0.61, P < 0.01) and RTD (R2 = 0.39, P < 0.01). Furthermore, the RBE's protection against muscle damage permitted the estimation of fatigue-associated neuromuscular performance decrements following eccentric exercise. Novelty: The repeated bout effect protects peak isotonic power. Protection of peak power relates to preserved rates of torque and velocity development, but more so rate of velocity development. The repeated bout effect has little influence on indices of neuromuscular fatigue.

Fiber Type and Size as Sources of Variation in Human Single Muscle Fiber Passive Elasticity.

Studies on single muscle fiber passive material properties often report relatively large variation in elastic modulus (or normalized stiffness), and it is not clear where this variation arises. This study was designed to determine if the stiffness, normalized to both fiber cross-sectional area and length, is inherently different between types 1 and 2 muscle fibers. Vastus lateralis fibers (n = 93), from ten young men, were mechanically tested using a cumulative stretch-relaxation protocol. SDS-PAGE classified fibers as types 1 or 2. While there was a difference in normalized stiffness between fiber types (p = 0.0019), an unexpected inverse relationship was found between fiber diameter and normalized stiffness (r = -0.64; p < 0.001). As fiber type and diameter are not independent, a one-way analysis of covariance (ANCOVA) including fiber diameter as a covariate was run; this eliminated the effect of fiber type on normalized stiffness (p = 0.1935). To further explore the relationship between fiber size and elastic properties, we tested whether stiffness was linearly related to fiber cross-sectional area, as would be expected for a homogenous material. Passive stiffness was not linearly related to fiber area (p < 0.001), which can occur if single muscle fibers are better represented as composite materials. The rule of mixtures for composite materials was used to explore whether the presence of a stiff perimeter-based fiber component could explain the observed results. The model (R2 = 0.38) predicted a perimeter-based normalized stiffness of 8800 ± 2600 kPa/µm, which is within the range of basement membrane moduli reported in the literature.

Age-related changes in human single muscle fibre passive elastic properties are sarcomere length dependent.

PURPOSE: Studies have revealed an age-related decrease in the ability to produce force as well as an increase in the contractile stiffness and passive stress of single muscle fibres. However, further insight into age-related changes to the passive properties of human skeletal muscles is needed. The aim of this study was to characterize single muscle fibre passive properties from young and old males across a physiologic range of sarcomere lengths (SLs). METHODS: Ten young ([YM]: mean age: 25.4 years) and ten old ([OM]: mean age: 68.9 years) males participated. Vastus lateralis muscles were biopsied and 182 fibres were tested and analyzed (90 YM and 92 OM) using a cumulative stretch-relaxation protocol. Passive mechanical characteristics of each fibre were obtained by fitting the integral of the logistic function to experimental stress-SL data. RESULTS: Muscle fibres from older individuals had significantly greater passive elastic moduli at short SL (1.9-2.65 µm) compared with young (p < 0.05). This resulted in a significantly larger passive stress for SLs between 2.1 µm and 3.55 µm for older individuals when compared with young (p < 0.05). CONCLUSION: These results provide novel insight into the length dependency of changes in single muscle fibre passive mechanical properties with age.

Residual force enhancement and force depression in human single muscle fibres.

Residual force depression (rFD) and residual force enhancement (rFE) are intrinsic contractile properties of muscle. rFD is characterized as a decrease in steady-state isometric force following active shortening compared with a purely isometric contraction at the same muscle length and level of activation. By contrast, isometric force is increased following active lengthening compared to a reference isometric contraction at the same muscle length and level of activation; this is termed rFE. To date, there have been no investigations of rFD and rFE in human muscle fibres, therefore the purpose of this study was to determine whether rFD and rFE occur at the single muscle fibre level in humans. rFD and rFE were investigated in maximally activated single muscle fibres biopsied from the vastus lateralis of healthy adults. To induce rFD, fibres were activated and shortened from an average sarcomere length (SL) of 3.2-2.6 µm. Reference isometric contractions were performed at an average SL of 2.6 µm. To induce rFE, fibres were actively lengthened from an average SL of 2.6-3.2 µm and a reference isometric contraction was performed at an average SL of 3.2 µm. Isometric steady-state force was lower following active shortening (p < 0.05), and higher following active lengthening (p < 0.05), as compared to the reference isometric contractions. We demonstrated rFD and rFE in human single fibres which is consistent with previous animal models. The non-responder phenomenon often reported in rFE studies involving voluntary contractions at the whole human level was not observed at the single fibre level.

Prolonged exercise training improves the acute type II muscle fibre satellite cell response in healthy older men.

KEY POINTS: Skeletal muscle stem cells, termed satellite cells, play a crucial role in repair and remodelling of muscle in response to exercise An age-related decline in satellite cell number and/or function has been hypothesized to be a key factor in the development of sarcopenia and/or the blunted muscle fibre adaptive response to prolonged exercise training in older persons We report that performing prolonged exercise training improves the acute type II muscle fibre satellite cell response following a single bout of resistance exercise in older men. The observed improvement in muscle satellite function is associated with an increase in muscle fibre capillarization following exercise training suggesting a possible functional link between capillarization and satellite cell function. ABSTRACT: Age-related type II muscle fibre atrophy is accompanied by a fibre type-specific decline in satellite cell number and function. Exercise training restores satellite cell quantity in older adults; however, whether it can restore the impaired satellite cell response to exercise in older adults remains unknown. Therefore we assessed the acute satellite cell response to a single exercise session before and after prolonged exercise training in older men. Fourteen older men (74 ± 8 years) participated in a 12-week exercise training programme (resistance exercise performed twice per week, high intensity interval training once per week). Before and after training, percutaneous biopsies from the vastus lateralis muscle were taken prior to and following 24 and 48 h of post-exercise recovery. Muscle fibre characteristics were evaluated by immunohistochemistry and mRNA expression by RT-PCR. Whereas no changes were observed in type II muscle fibres, type I muscle fibre satellite cell content increased significantly at 24 and 48 h after a single bout of resistance exercise before the exercise training programme (P < 0.01). Following the exercise training programme, both type I and type II muscle fibre satellite cell content increased significantly at 24 and 48 h after a single bout of resistance exercise (P < 0.05). The greater acute increase in type II muscle fibre satellite cell content at 24 h post-exercise recovery after training was correlated with an increase in type II muscle fibre capillarization (r = 0.671, P = 0.012). We show that the acute muscle satellite cell response following exercise can be improved by prolonged exercise training in older men.

Activation reduction following an eccentric contraction impairs torque steadiness in the isometric steady-state.

BACKGROUND: The isometric steady-state following active lengthening is associated with greater torque production and lower activation, as measured by electromyographic activity (EMG), in comparison with a purely isometric contraction (ISO) at the same joint angle. This phenomenon is termed residual force enhancement (RFE). While there has been a great deal of research investigating the basic mechanisms of RFE, little work has been performed to understand the everyday relevance of RFE. The purpose of this study was to investigate whether neuromuscular control strategies differ between ISO and RFE by measuring torque steadiness of the human ankle plantar flexors. METHODS: Following ISO maximal voluntary contractions in 12 males (25 ± 4 years), an active lengthening contraction was performed at 15°/s over a 30° ankle excursion, ending at the same joint angle as ISO (5° dorsiflexion; RFE). Surface EMG of the tibialis anterior and soleus muscles was recorded during all tasks. Torque steadiness was determined as the standard deviation (SD) and coefficient of variation (CV) of the torque trace in the ISO and RFE condition during activation-matching (20% and 60% integrated EMG) and torque-matching (20% and 60% maximal voluntary contraction) experiments. Two-tailed, paired t tests were used, within subjects, to determine the presence of RFE/activation reduction (AR) and whether there was a difference in torque steadiness between ISO and RFE conditions. RESULTS: During the maximal and submaximal conditions, there was 5%-9% RFE with a 9%-11% AR (p < 0.05), respectively, with no difference in antagonist coactivation between RFE and ISO (p > 0.05). There were no differences in SD and CV of the torque trace for the 20% and 60% activation-matching or the 60% and maximal torque-matching trials in either the RFE or ISO condition (p > 0.05). During the 20% torque-matching trial, there were ∼37% higher values for SD and CV in the RFE as compared with the ISO condition (p < 0.05). A significant moderate-to-strong negative relationship was identified between the reduction in torque steadiness following active lengthening and the accompanying AR (p < 0.05). CONCLUSION: It appears that while the RFE-associated AR provides some improved neuromuscular economy, this comes at the cost of increased torque fluctuations in the isometric steady-state following active lengthening during submaximal contractions.

Mitigating the bilateral deficit: reducing neural deficits through residual force enhancement and activation reduction.

PURPOSE: The bilateral deficit (BLD) is characterized by a reduction in maximal voluntary torque during a bilateral contraction relative to the sum of left and right unilateral contractions. The BLD has been attributed to interhemispheric inhibition as a result of unilateral torque differences between limbs. If the BLD is the result of interhemispheric inhibition, lowering activation for a torque matching task, as shown in residual force enhancement (RFE), may help overcome the decrease in neural drive during bilateral contractions. Therefore, the purpose of the present study was to determine whether RFE could reduce the BLD. METHODS: Participants (n = 12) performed both isometric and RFE MVCs of the elbow flexors under three conditions: (1) unilateral-left; (2) unilateral-right; and (3) bilateral. To directly address the purpose of the study, a sub-group of participants that displayed both RFE and a BLD ("Responders", n = 6) were selected from the participant pool. RESULTS: "Responders" displayed RFE (7.1 ± 5.3%) and an isometric BLD (BI: - 9.9 ± 3.2%). In the RFE state, the BLD was no longer significant (- 5.8 ± 7.9%), accompanied by the elimination of differences in biceps brachii EMG between arms (left: - 11.7 ± 10.3%; right: - 11.5 ± 13.2%), as seen during isometric contractions (left: - 12.0 ± 23.2%; right: - 21.1 ± 16.6%). CONCLUSION: Residual force enhancement appears to mitigate the BLD, alleviating the effects of a decrease in neural drive by allowing more force for a given level of muscle activation when compared to a purely isometric contraction.

Ingestion of a Multi-Ingredient Supplement Does Not Alter Exercise-Induced Satellite Cell Responses in Older Men.

Background: Nutritional supplementation can have beneficial effects on body composition, strength, and function in older adults. However, whether the response of satellite cells can be altered by nutritional supplementation in older adults remains unknown. Objective: We assessed whether a multi-ingredient protein-based supplement taken over a prolonged period of time could alter the muscle satellite cell response after exercise in older men. Methods: Twenty-seven older men [mean ± SD age: 73 ± 1 y; mean ± SD body mass index (kg/m2): 28 ± 1] participated in a randomized double-blind experiment. Participants were randomly divided into an experimental (EXP) group (n = 13) who consumed a multi-ingredient protein-based supplement [30 g whey protein, 2.5 g creatine, 500 IU vitamin D, 400 mg Ca, and 1500 mg n-3 (ω-3) polyunsaturated fatty acids] 2 times/d for 7 wk or a control (CON; 22 g maltodextrin) group (n = 14). After 7 wk of supplementation, all participants performed a single resistance exercise session, and muscle biopsy samples were taken from the vastus lateralis before and 24 and 48 h after exercise. Immunohistochemistry was used to assess the change in type I and II muscle fiber satellite cell content and activation status of the cells. In addition, mRNA expression of the myogenic regulatory factors was determined by using reverse transcriptase-polymerase chain reaction. Results: In response to the single bout of exercise, type I muscle fiber satellite cell content was significantly increased at 24 h (0.132 ± 0.015 and 0.131 ± 0.011 satellite cells/fiber in CON and EXP groups, respectively) and 48 h (0.126 ± 0.010 and 0.120 ± 0.012 satellite cells/fiber in CON and EXP groups, respectively) compared with pre-exercise (0.092 ± 0.007 and 0.118 ± 0.017 satellite cells/fiber in CON and EXP groups, respectively) muscle biopsy samples (P < 0.01), with no difference between the 2 groups. In both groups, we observed no significant changes in type II muscle fiber satellite cell content after exercise. Conclusion: Ingesting a multi-ingredient protein-based supplement for 7 wk did not alter the type I or II muscle fiber satellite cell response during postexercise recovery in older men. This trial was registered at www.clinicaltrials.gov as NCT02281331.

Pronounced energy restriction with elevated protein intake results in no change in proteolysis and reductions in skeletal muscle protein synthesis that are mitigated by resistance exercise.

Preservation of lean body mass (LBM) may be important during dietary energy restriction (ER) and requires equal rates of muscle protein synthesis (MPS) and muscle protein breakdown (MPB). Currently, the relative contribution of MPS and MPB to the loss of LBM during ER in humans is unknown. We aimed to determine the impact of dietary protein intake and resistance exercise on MPS and MPB during a controlled short-term energy deficit. Adult men (body mass index, 28.6 ± 0.6 kg/m2; age 22 ± 1 yr) underwent 10 d of 40%-reduced energy intake while performing unilateral resistance exercise and consuming lower protein (1.2 g/kg/d, n = 12) or higher protein (2.4 g/kg/d, n = 12). Pre- and postintervention testing included dual-energy X-ray absorptiometry, primed constant infusion of ring-[13C6]phenylalanine, and 15[N]phenylalanine to measure acute postabsorptive MPS and MPB; D2O to measure integrated MPS; and gene and protein expression. There was a decrease in acute MPS after ER (higher protein, 0.059 ± 0.006 to 0.051 ± 0.009%/h; lower protein, 0.061 ± 0.005 to 0.045 ± 0.006%/h; P < 0.05) that was attenuated with resistance exercise (higher protein, 0.067 ± 0.01%/h; lower protein, 0.061 ± 0.006%/h), and integrated MPS followed a similar pattern. There was no change in MPB (energy balance, 0.080 ± 0.01%/hr; ER rested legs, 0.078 ± 0.008%/hr; ER exercised legs, 0.079 ± 0.006%/hr). We conclude that a reduction in MPS is the main mechanism that underpins LBM loss early in ER in adult men.-Hector, A. J., McGlory, C., Damas, F., Mazara, N., Baker, S. K., Phillips, S. M. Pronounced energy restriction with elevated protein intake results in no change in proteolysis and reductions in skeletal muscle protein synthesis that are mitigated by resistance exercise.

Neither load nor systemic hormones determine resistance training-mediated hypertrophy or strength gains in resistance-trained young men.

We reported, using a unilateral resistance training (RT) model, that training with high or low loads (mass per repetition) resulted in similar muscle hypertrophy and strength improvements in RT-naïve subjects. Here we aimed to determine whether the same was true in men with previous RT experience using a whole-body RT program and whether postexercise systemic hormone concentrations were related to changes in hypertrophy and strength. Forty-nine resistance-trained men (23 ± 1 yr, mean ± SE) performed 12 wk of whole-body RT. Subjects were randomly allocated into a higher-repetition (HR) group who lifted loads of ∼30-50% of their maximal strength (1RM) for 20-25 repetitions/set (n = 24) or a lower-repetition (LR) group (∼75-90% 1RM, 8-12 repetitions/set, n = 25), with all sets being performed to volitional failure. Skeletal muscle biopsies, strength testing, dual-energy X-ray absorptiometry scans, and acute changes in systemic hormone concentrations were examined pretraining and posttraining. In response to RT, 1RM strength increased for all exercises in both groups (P < 0.01), with only the change in bench press being significantly different between groups (HR, 9 ± 1, vs. LR, 14 ± 1 kg, P = 0.012). Fat- and bone-free (lean) body mass and type I and type II muscle fiber cross-sectional area increased following training (P < 0.01) with no significant differences between groups. No significant correlations between the acute postexercise rise in any purported anabolic hormone and the change in strength or hypertrophy were found. In congruence with our previous work, acute postexercise systemic hormonal rises are not related to or in any way indicative of RT-mediated gains in muscle mass or strength. Our data show that in resistance-trained individuals, load, when exercises are performed to volitional failure, does not dictate hypertrophy or, for the most part, strength gains.