Muscle Force Generation Research Articles

Design and Applications of High Force Generation in 3D-Printed Pneumatic Artificial Muscles

Increasing the force generation and scalability of soft pneumatic actuators poses significant challenges in robotics applications, especially where high load capacities and precise control are required. This paper presents UniBPAM, a novel, scalable soft pneumatic actuator optimized through 3D printing to enhance force generation. By analyzing design parameters, such as the number of sides, height, and origami factor, UniBPAM achieved a 21.48% increase in force generation. Scalable across diameters from 36 to 144 mm, the actuator demonstrated the ability to lift up to 57 kg with 84.9% strain at larger scales. Additionally, the BiBPAM variant enables bidirectional actuation in robotic joints via motion control, which is realized through PID systems, making it suitable for various robotic applications.

Hindlimb kinematics, kinetics, and muscle dynamics during sit-to-stand and sit-to-walk transitions in emus (Dromaius novaehollandiae).

Terrestrial animals not only need to walk and run but also lie prone to rest and then stand up. Sit-to-stand (STS) and sit-to-walk (STW) transitions are vital behaviours little studied in species other than humans so far, but likely impose biomechanical constraints on limb design because they involve near-maximal excursions of limb joints that should require large length changes and force production from muscles. By integrating data from experiments into musculoskeletal simulations, we analysed joint motions, ground reaction forces, and muscle dynamics during STS and STW in a large terrestrial, bipedal, and cursorial bird: the emu (Dromaius novaehollandiae, ∼30 kg). Simulation results suggest that in both STS and STW, emus operate near the functional limits (∼50 % of shortening/lengthening) of some of their hindlimb muscles, particularly in distal muscles with limited capacity for length change and leverage. Both movements involved high muscle activations (> 50 %) and force generation of the major joint extensor muscles early in the transition. STW required larger net joint moments and non-sagittal motions than STS, entailing greater demands for muscle capacity. Whilst our study involves multiple assumptions, our findings lay the groundwork for future studies to understand, for example, how tendon contributions may reduce excessive muscle demands, especially in the distal hindlimb. As the first investigation into how an avian species stands up, this study provides a foundational framework for future comparative studies investigating organismal morphofunctional specialisations and evolution, offering potential robotics and animal welfare applications.

Rate of Force Development During a Handgrip Task Is Correlated with the Post-Impact Ball Speed of the Flat Serve

The aim of the present research was to test the hypothesis that rate of force development (RFD) during a handgrip task of the dominant arm in three different positions is associated with maximal post-impact ball speed of flat serve (PIBS). Altogether 23 elite junior boys (aged 14.84 ± 2.47 years; weight 59.51 ± 13.83 kg; height 170.47 ± 16.34 cm) tennis players participated in the study. To assess the maximal voluntary contraction (MVC) and RFD during the task, four handgrip tests and a serve test were applied to estimate PIBS. Spearman’s rank correlation showed a significant positive correlation between RFD of dominant arm in each three position and PIBS (r = 0.82–0.86; p < 0.001). A very large, significantly positive correlation was also found between MVC of the dominant arm and PIBS (r = 0.88; p < 0.01). The result of the present study indicated that rapid force generation of muscles in the forearm and wrist may probably play a role in the formation of a stable contact point, and it is in connection with PIBS. It is in contrast to the slow maximal force exertion that much rather characterizes the general strength state of players. Therefore, measurement of the RFD during a handgrip task is suggested in the testing session of the flat serve of junior tennis players.

Myosin Isoform-Dependent Effect of Omecamtiv Mecarbil on the Regulation of Force Generation in Human Cardiac Muscle.

Omecamtiv mecarbil (OM) is a small molecule that has been shown to improve the function of the slow human ventricular myosin (MyHC) motor through a complex perturbation of the thin/thick filament regulatory state of the sarcomere mediated by binding to myosin allosteric sites coupled to inorganic phosphate (Pi) release. Here, myofibrils from samples of human left ventricle (β-slow MyHC-7) and left atrium (α-fast MyHC-6) from healthy donors were used to study the differential effects of μmolar [OM] on isometric force in relaxing conditions (pCa 9.0) and at maximal (pCa 4.5) or half-maximal (pCa 5.75) calcium activation, both under control conditions (15 °C; equimolar DMSO; contaminant inorganic phosphate [Pi] ~170 μM) and in the presence of 5 mM [Pi]. The activation state and OM concentration within the contractile lattice were rapidly altered by fast solution switching, demonstrating that the effect of OM was rapid and fully reversible with dose-dependent and myosin isoform-dependent features. In MyHC-7 ventricular myofibrils, OM increased submaximal and maximal Ca2+-activated isometric force with a complex dose-dependent effect peaking (40% increase) at 0.5 μM, whereas in MyHC-6 atrial myofibrils, it had no effect or-at concentrations above 5 µM-decreased the maximum Ca2+-activated force. In both ventricular and atrial myofibrils, OM strongly depressed the kinetics of force development and relaxation up to 90% at 10 μM [OM] and reduced the inhibition of force by inorganic phosphate. Interestingly, in the ventricle, but not in the atrium, OM induced a large dose-dependent Ca2+-independent force development and an increase in basal ATPase that were abolished by the presence of millimolar inorganic phosphate, consistent with the hypothesis that the widely reported Ca2+-sensitising effect of OM may be coupled to a change in the state of the thick filaments that resembles the on-off regulation of thin filaments by Ca2+. The complexity of this scenario may help to understand the disappointing results of clinical trials testing OM as inotropic support in systolic heart failure compared with currently available inotropic drugs that alter the calcium signalling cascade.

Effects of Short-Term Treatment of Rabbit Extraocular Muscle With Ciliary Neurotrophic Factor.

Little is known about the effect of ciliary neurotrophic factor (CNTF) on extraocular muscles, but microarray studies suggested CNTF might play a role in the development and/or maintenance of strabismus. The effect of short-term treatment of adult rabbit extraocular muscle with injected CNTF was examined for its ability to alter muscle characteristics. Eight adult New Zealand white rabbits received an injection into one superior rectus muscle of 2 µg/100 µL CNTF on 3 consecutive days. One week after the first injection, the rabbits were euthanized, and the treated and contralateral superior rectus muscles were assessed for force generation capacity and contraction characteristics using an in vitro stimulation protocol and compared to naïve control superior rectus muscles. All muscles were analyzed to determine mean cross-sectional areas and expression of slow twitch myosin heavy chain isoform. Short-term treatment of rabbit superior rectus muscles with CNTF resulted in a significant decrease in muscle force generation, but only at the higher stimulation frequencies. Significantly decreased myofiber cross-sectional areas of the treated muscles correlated with the decreased generated force. In addition, there were significant changes to contractile properties of the treated muscles, as well as a decrease in the number of myofibers expressing slow twitch myosin heavy chain. We show that short-term treatment of a single rabbit superior rectus muscle results in decreased myofiber size, decreased force, and altered contractile characteristics. Further studies are needed to determine if it can play a role in improving alignment in animal models of strabismus.

Macrophages modulate skeletal muscle wasting and recovery in acute lung injury in mice.

Skeletal muscle dysfunction in critical illnesses leaves survivors weak and functionally impaired. Macrophages infiltrate muscles; however, their functional role is unclear. We aim to examine muscle leukocyte composition and the effect of macrophages on muscle mass and function in the murine acute lung injury (ALI)-associated skeletal muscle wasting model. We performed flow cytometry of hindlimb muscle to identify myeloid cells pre-injury and time points up to 29 days after intratracheal lipopolysaccharide ALI. We evaluated muscle force and morphometrics after systemic and intramuscular clodronate-induced macrophage depletions between peak lung injury and recovery (day 5-6) versus vehicle control. Our results show muscle leukocytes changed over ALI course with day 3 neutrophil infiltration (130.5 ± 95.6cells/mg control to 236.3 ± 70.6cells/mg day 3) and increased day 10 monocyte abundance (5.0 ± 3.4%CD45+CD11b+ day 3 to 14.0 ± 2.6%CD45+CD11b+ day 10, p = 0.005). Although macrophage count did not significantly change, pro-inflammatory (27.0 ± 7.2% day 3 to 7.2 ± 3.8% day 10, p = 0.02) and anti-inflammatory (30.5 ± 11.1% day 3 to 52.7 ± 9.7% day 10, p = 0.09) surface marker expression changed over the course of ALI. Macrophage depletion following peak lung injury increased muscle mass and force generation. These data suggest muscle macrophages beyond peak lung injury limit or delay muscle recovery. Targeting macrophages could augment muscle recovery following lung injury.

The impacts of muscle-specific force-velocity properties on predictions of mouse muscle function during locomotion.

Introduction: The accuracy of musculoskeletal models and simulations as methods for predicting muscle functional outputs is always improving. However, even the most complex models contain various assumptions and simplifications in how muscle force generation is simulated. One common example is the application of a generalised ("generic") force-velocity relationship, derived from a limited data set to each muscle within a model, uniformly across all muscles irrespective of whether those muscles have "fast" or "slow" contractile properties. Methods: Using a previously built and validated musculoskeletal model and simulation of trotting in the mouse hindlimb, this work examines the predicted functional impact of applying muscle-specific force-velocity properties to typically fast (extensor digitorum longus; EDL) and slow-contracting (soleus; SOL) muscles. Results: Using "real" data led to EDL producing more positive work and acting significantly more spring-like, and soleus producing more negative work and acting more brake-like in function compared to muscles modelled using "generic" force-velocity data. Extrapolating these force-velocity properties to other muscles considered "fast" or "slow" also substantially impacted their predicted function. Importantly, this also further impacted EDL and SOL function beyond that seen when changing only their properties alone, to a point where they show an improved match to ex vivo experimental data. Discussion: These data suggest that further improvements to how musculoskeletal models and simulations predict muscle function should include the use of different values defining their force-velocity relationship depending on their fibre-type composition.

Four phases of a force transient emerge from a binary mechanical system.

Accurate models of muscle contraction are important for understanding both muscle performance and the therapeutics that enhance physiological function. However, models are only accurate and meaningful if they are consistent with physical laws. A single muscle fiber contains billions of randomly fluctuating atoms that on the spatial scale of a muscle fiber generate unidirectional force and power output. This thermal system is formally constrained by the laws of thermodynamics, and a recently developed thermodynamic model of muscle force generation provides qualitative descriptions of the muscle force-velocity relationship, muscle force generation, muscle force transients, and the thermodynamic work loop of muscle with a thermodynamic (not molecular) power stroke mechanism. To demonstrate the accuracy of this model requires that its outputs be quantitatively compared with experimentally observed muscle function. Here I show that a two-state thermodynamic model accurately describes the experimentally observed four-phase force transient response to both mechanical and chemical perturbations. This is the simplest possible model of one of the most complex characteristic signatures of muscle mechanics.

Neuroprotective treatment with the nitrone compound OKN-007 mitigates age-related muscle weakness in aging mice.

Despite the universal impact of sarcopenia on compromised health and quality of life in the elderly, promising pharmaceutical approaches that can effectively mitigate loss of muscle and function during aging have been limited. Our group and others have reported impairments in peripheral motor neurons and loss of muscle innervation as initiating factors in sarcopenia, contributing to mitochondrial dysfunction and elevated oxidative stress in muscle. We recently reported a reduction in α motor neuron loss in aging mice in response to the compound OKN-007, a proposed antioxidant and anti-inflammatory agent. In the current study, we asked whether OKN-007 treatment in wildtype male mice for 8-9months beginning at 16months of age can also protect muscle mass and function. At 25months of age, we observed a reduction in the loss of whole-body lean mass, a reduced loss of innervation at the neuromuscular junction and well-preserved neuromuscular junction morphology in OKN-007 treated mice versus age matched wildtype untreated mice. The loss in muscle force generation in aging mice (~ 25%) is significantly improved with OKN-007 treatment. In contrast, OKN-007 treatment provided no protection in loss of muscle mass in aging mice. Mitochondrial function was improved by OKN-007 treatment, consistent with its potential antioxidative properties. Together, these exciting findings are the first to demonstrate that interventions through neuroprotection can be an effective therapy to counter aging-related muscle dysfunction.

Reduction and recovery of self-sustained muscle activity after fatiguing plantar flexor contractions.

Persistent inward calcium and sodium currents (PICs) are crucial for initiation and maintenance of motoneuron firing, and thus muscular force. However, there is a lack of data describing the effects of fatiguing exercise on PIC activity in humans. We simultaneously applied tendon vibration and neuromuscular electrical stimulation (VibStim) before and after fatiguing exercise. VibStim induces self-sustained muscle activity that is proposed to result from PIC activation. Twelve men performed 5-s maximal isometric plantar flexor contractions (MVC) with 5-s rests until joint torque was reduced to 70%MVC. VibStim trials consisted of five 2-s trains of neuromuscular electrical stimulation (20 Hz, evoking 10% MVC) of triceps surae with simultaneous Achilles tendon vibration (115 Hz) without voluntary muscle activation. VibStim was applied before (PRE), immediately (POST), 5-min (POST-5), and 10-min (POST-10) after exercise completion. Sustained torque (Tsust) and soleus electromyogram amplitudes (EMG) measured 3 s after VibStim were reduced (Tsust: -59.0%, p<0.001; soleus EMG: -38.4%, p<0.001) but largely recovered by POST-5, and changes in MVC and Tsust were correlated across the four time points (r=0.69; p<0.001). After normalisation to values obtained at the end of the vibration phase to control for changes in fibre-specific force and EMG signal characteristics, decreases in Tsust (-42.9%) and soleus EMG (-22.6%) remained significant and were each correlated with loss and recovery of MVC (r=0.41 and 0.46, respectively). The parallel changes observed in evoked self-sustained muscle activity and force generation capacity provide motivation for future examinations on the potential influence of fatigue-induced PIC changes on motoneuron output.

Senolytic treatment does not mitigate oxidative stress-induced muscle atrophy but improves muscle force generation in CuZn superoxide dismutase knockout mice.

Oxidative stress is associated with tissue dysfunctions that can lead to reduced health. Prior work has shown that oxidative stress contributes to both muscle atrophy and cellular senescence, which is a hallmark of aging that may drive in muscle atrophy and muscle contractile dysfunction. The purpose of the study was to test the hypothesis that cellular senescence contributes to muscle atrophy or weakness. To increase potential senescence in skeletal muscle, we used a model of oxidative stress-induced muscle frailty, the CuZn superoxide dismutase knockout (Sod1KO) mouse. We treated 6-month-old wildtype (WT) and Sod1KO mice with either vehicle or a senolytic treatment of combined dasatinib (5 mg/kg) + quercetin (50 mg/kg) (D + Q) for 3 consecutive days every 15 days. We continued treatment for 7 months and sacrificed the mice at 13 months of age. Treatment with D + Q did not preserve muscle mass, reduce NMJ fragmentation, or alter muscle protein synthesis in Sod1KO mice when compared to the vehicle-treated group. However, we observed an improvement in muscle-specific force generation in Sod1KO mice treated with D + Q when compared to Sod1KO-vehicle mice. Overall, these data suggest that reducing cellular senescence via D + Q is not sufficient to mitigate loss of muscle mass in a mouse model of oxidative stress-induced muscle frailty but may mitigate some aspects of oxidative stress-induced muscle dysfunction.

The assessment of paraspinal muscle epimuscular fat in participants with and without low back pain: A case-control study

It remains unclear whether paraspinal muscle fatty infiltration in low back pain (LBP) is i) solely intramuscular, ii) is lying outside the epimysium between the muscle and fascial plane (epimuscular) or iii) or combination of both, as imaging studies often use different segmentation protocols that are not thoroughly described. Epimuscular fat possibly disturbs force generation of paraspinal muscles, but is seldomly explored. This project aimed to 1) compare epimuscular fat in participants with and without chronic LBP, and 2) determine whether epimuscular fat is different across lumbar spinal levels and associated with BMI, age, sex and LBP status, duration or intensity. Fat and water lumbosacral MRIs of 50 chronic LBP participants and 41 healthy controls were used. The presence and extent of epimuscular fat for the paraspinal muscle group (erector spinae and multifidus) was assessed using a qualitative score (0–5 scale; 0 = no epimuscular fat and 5 = epimuscular fat present along the entire muscle) and quantitative manual segmentation method. Chi-squared tests evaluated associations between qualitative epimuscular fat ratings and LBP status at each lumbar level. Bivariate and partial spearman’s rho correlation assessed relationships between quantitative and qualitative epimuscular fat with participants’ characteristics. Epimuscular fat was more frequent at the L4-L5 (X2 = 13.781, p = 0.017) and L5-S1 level (X2 = 27.825, p < 0.001) in participants with LBP compared to controls, which was not found for the higher lumbar levels. The total qualitative score (combined from all levels) showed a significant positive correlation with BMI, age, sex (female) and LBP status (r = 0.23–0.55; p < 0.05). Similarly, the total area of epimuscular fat (quantitative measure) was significantly correlated with BMI, age and LBP status (r = 0.26–0.57; p < 0.05). No correlations were found between epimuscular fat and LBP duration or intensity. Paraspinal muscle epimuscular fat is more common in chronic LBP patients. The functional implications of epimuscular fat should be further explored.

Pushing forward: exploring the impact of the sitting position on muscle activation patterns and force generation during paralympic sit-cross-country skiing.

Paralympic cross-country sit-skiing is a discipline of the Paralympic Winter Games where athletes use a specialized sledge. Athletes are classified into different groups according to their functional abilities. The double poling technique is used to push the sledge forward and generate speed. Different sitting positions in the sledge are used based on the individual impairment. To date there is no data available on the effects of these different positions on muscle activation patterns. The aim of this study was to analyze the muscle activation patterns of the trunk and upper body muscles in relation to the poling force. Nine Able-bodied athletes were tested on a treadmill at submaximal speed in three sitting positions for 4 min in a flat and uphill condition. Sitting positions included a "knee-high" position, a "knee-low" position, and a "neutral" position with the sitting platform parallel to the ground. Unilateral pole forces and surface EMG from three trunk muscles, two upper limb muscles, and one lower limb muscle were recorded simultaneously on the dominate side. Data were segmented into individual cycles and mean values and standard deviations calculated for each subject and condition. Statistical analyses, including a Friedman test and Bonferroni correction, were applied to examine significant differences across different sitting positions. Our findings demonstrate that while certain muscle groups such as the erector spinae and triceps show consistent patterns of activation across different sitting positions, there is considerable variability among individual athletes, suggesting individualized strategies for task execution. Overall, force application was most efficient in the "knee low" position with 691.33 ± 148.83 N and least efficient in the "knee high" position with 582.81 ± 115.11 N. Testing impaired athletes will be the next step in understanding the neurophysiological aspects of the poling movement. This experimental protocol provides a basis for understanding the movement of paralympic cross-country sit-skiing in greater depth.

Novel characteristics of the temporal transition to maximum tongue pressure in Parkinson’s disease: A pilot study

IntroductionThe reason why maximum tongue pressure (MTP) decreases in patients with Parkinson’s disease (PD) remains unclear. Repeated measurements of isometric force and MTP may be useful for analyzing muscle wasting and force generation. The purpose of this pilot study was to evaluate the clinical characteristics and temporal transition of MTP in PD and normal control (NC) groups. MethodsThere were 18 participants in this study: 10 with PD and 8 NCs. The MTP was measured 20 times at regular intervals. The area under the curve of MTP temporal transitions, time to reach MTP, and total transition time of the tongue pressure (time to return to baseline) were compared between the groups. ResultsMTP decreased from baseline in PD subjects. Unlike NCs, PD subjects showed diverse and inconsistent temporal transitions. The decrease in MTP and delays in time to reach MTP and time to return to baseline were significantly greater in PD subjects (p < 0.05), while there was no group difference in area under the curve values. According to repeated-measures ANOVA, MTP was not different over time between PD subjects and NCs. ConclusionIn this study, muscle fatigue did not affect the decrease in MTP seen in PD subjects, or the diversity and inconsistency of the temporal transition in MTP in that group. These findings indicate that the motor control needed for the repeated, identical movements associated with MTP generation may be impaired in PD patients.

Tapping Into Skeletal Muscle Biomechanics for Design and Control of Lower Limb Exoskeletons: A Narrative Review.

Lower limb exoskeletons and exosuits ("exos") are traditionally designed with a strong focus on mechatronics and actuation, whereas the "human side" is often disregarded or minimally modeled. Muscle biomechanics principles and skeletal muscle response to robot-delivered loads should be incorporated in design/control of exos. In this narrative review, we summarize the advances in literature with respect to the fusion of muscle biomechanics and lower limb exoskeletons. We report methods to measure muscle biomechanics directly and indirectly and summarize the studies that have incorporated muscle measures for improved design and control of intuitive lower limb exos. Finally, we delve into articles that have studied how the human-exo interaction influences muscle biomechanics during locomotion. To support neurorehabilitation and facilitate everyday use of wearable assistive technologies, we believe that future studies should investigate and predict how exoskeleton assistance strategies would structurally remodel skeletal muscle over time. Real-time mapping of the neuromechanical origin and generation of muscle force resulting in joint torques should be combined with musculoskeletal models to address time-varying parameters such as adaptation to exos and fatigue. Development of smarter predictive controllers that steer rather than assist biological components could result in a synchronized human-machine system that optimizes the biological and electromechanical performance of the combined system.

The Effect of Skeletal Fixation on Nerve Healing in a Rat

Objective To investigate the effect of rigid internal skeletal fixation of a rat femoral shaft fracture on the healing of an induced sciatic nerve crush injury as assessed by functional outcomes. Methods Thirty-six male Lewis rats were divided into two groups. A unilateral sciatic nerve crush injury and a same-level transverse femur fracture were created in all animals. Animals in the first group underwent immediate open reduction internal fixation (ORIF) with a stainless steel plate and screws. Animals in the second group were treated non-operatively (NON) without internal or external fixation or bracing. At each of the six-time points relevant to different nerve degeneration and regeneration stages, three animals in each group underwent bilateral limb assessments of electrophysiology, muscle mass, and nerve histomorphometry. Results Outcome measurements of the ORIF group (n=17) and NON group (n=16) showed the ORIF group to have both significantly greater tibialis anterior muscle force generation and sciatic nerve conduction velocity across the zone of injury for the overall groups. Force and conduction velocity measurements were greater for the ORIF group at selective time points in the subgroup analysis. Histologic analysis confirmed a greater cross-sectional area of the sciatic nerve in the ORIF group. Conclusion This study provides information about the influence of the stability of the skeletal and soft tissue environment on the nerve healing process. The significantly greater maximum force generation and conduction velocity and the increased cross-sectional areas with greater axon counts observed in our ORIF group support our hypothesis that rigid internal skeletal fixation of a fracture promotes superior recovery of a concomitant peripheral nerve injury. The findings of this study suggest that superior healing of the peripheral nerve injury may occur with stable skeletal fixation.

Creatine Kinase Equilibration and ΔGATP over an Extended Range of Physiological Conditions: Implications for Cellular Energetics, Signaling, and Muscle Performance.

In this report, we establish a straightforward method for estimating the equilibrium constant for the creatine kinase reaction (CK Keq″) over wide but physiologically and experimentally relevant ranges of pH, Mg2+ and temperature. Our empirical formula for CK Keq″ is based on experimental measurements. It can be used to estimate [ADP] when [ADP] is below the resolution of experimental measurements, a typical situation because [ADP] is on the order of micromolar concentrations in living cells and may be much lower in many in vitro experiments. Accurate prediction of [ADP] is essential for in vivo studies of cellular energetics and metabolism and for in vitro studies of ATP-dependent enzyme function under near-physiological conditions. With [ADP], we were able to obtain improved estimates of ΔGATP, necessitating the reinvestigation of previously reported ADP- and ΔGATP-dependent processes. Application to actomyosin force generation in muscle provides support for the hypothesis that, when [Pi] varies and pH is not altered, the maximum Ca2+-activated isometric force depends on ΔGATP in both living and permeabilized muscle preparations. Further analysis of the pH studies introduces a novel hypothesis around the role of submicromolar ADP in force generation.

The Developmental Implications of Muscle-Targeted Magnetic Mitohormesis: A Human Health and Longevity Perspective.

Muscle function reflects muscular mitochondrial status, which, in turn, is an adaptive response to physical activity, representing improvements in energy production for de novo biosynthesis or metabolic efficiency. Differences in muscle performance are manifestations of the expression of distinct contractile-protein isoforms and of mitochondrial-energy substrate utilization. Powerful contractures require immediate energy production from carbohydrates outside the mitochondria that exhaust rapidly. Sustained muscle contractions require aerobic energy production from fatty acids by the mitochondria that is slower and produces less force. These two patterns of muscle force generation are broadly classified as glycolytic or oxidative, respectively, and require disparate levels of increased contractile or mitochondrial protein production, respectively, to be effectively executed. Glycolytic muscle, hence, tends towards fibre hypertrophy, whereas oxidative fibres are more disposed towards increased mitochondrial content and efficiency, rather than hypertrophy. Although developmentally predetermined muscle classes exist, a degree of functional plasticity persists across all muscles post-birth that can be modulated by exercise and generally results in an increase in the oxidative character of muscle. Oxidative muscle is most strongly correlated with organismal metabolic balance and longevity because of the propensity of oxidative muscle for fatty-acid oxidation and associated anti-inflammatory ramifications which occur at the expense of glycolytic-muscle development and hypertrophy. This muscle-class size disparity is often at odds with common expectations that muscle mass should scale positively with improved health and longevity. Brief magnetic-field activation of the muscle mitochondrial pool has been shown to recapitulate key aspects of the oxidative-muscle phenotype with similar metabolic hallmarks. This review discusses the common genetic cascades invoked by endurance exercise and magnetic-field therapy and the potential physiological differences with regards to human health and longevity. Future human studies examining the physiological consequences of magnetic-field therapy are warranted.

Neuromuscular junction transmission failure in aging and sarcopenia: The nexus of the neurological and muscular systems.

Sarcopenia, or age-related decline in muscle form and function, exerts high personal, societal, and economic burdens when untreated. Integrity and function of the neuromuscular junction (NMJ), as the nexus between the nervous and muscular systems, is critical for input and dependable neural control of muscle force generation. As such, the NMJ has long been a site of keen interest in the context of skeletal muscle function deficits during aging and in the context of sarcopenia. Historically, changes of NMJ morphology during aging have been investigated extensively but primarily in aged rodent models. Aged rodents have consistently shown features of NMJ endplate fragmentation and denervation. Yet, the presence of NMJ changes in older humans remains controversial, and conflicting findings have been reported. This review article describes the physiological processes involved in NMJ transmission, discusses the evidence that supports NMJ transmission failure as a possible contributor to sarcopenia, and speculates on the potential of targeting these defects for therapeutic development. The technical approaches that are available for assessment of NMJ transmission, whether each approach has been applied in the context of aging and sarcopenia, and the associated findings are summarized. Like morphological studies, age-related NMJ transmission deficits have primarily been studied in rodents. In preclinical studies, isolated synaptic electrophysiology recordings of endplate currentsor potentials have been mostly used, and paradoxically, have shown enhancement, rather than failure, with aging. Yet, in vivo assessment of single muscle fiber action potential generation using single fiber electromyography and nerve-stimulated muscle force measurements show evidence of NMJ failure in aged mice and rats. Together these findings suggest that endplate response enhancement may be a compensatory response to post-synaptic mechanisms of NMJ transmission failure in aged rodents. Possible, but underexplored, mechanisms of this failure are discussed including the simplification of post-synaptic folding and altered voltage-gated sodium channel clustering or function. In humans, there is limited clinical data that has selectively investigated single synaptic function in the context of aging. If sarcopenic older adults turn out to exhibit notable impairments in NMJ transmission (this has yet to be examined but based on available evidence appears to be plausible) then these NMJ transmission defects present a well-defined biological mechanism and offer a well-defined pathway for clinical implementation. Investigation of small molecules that are currently available clinically or being testing clinically in other disorders may provide a rapid route for development of interventions for older adults impacted by sarcopenia.

Non-invasive Analysis of Fiber Type Composition in Lower Limb Skeletal Muscles Using Reduced Interference Rihaczek Distribution.

Fiber composition is an important factor influencing force generation and endurance of different skeletal muscles. The analysis of the heterogeneous composition of muscles has gained importance in the field of sports biomechanics and biomedicine. In this work, an attempt is made to analyze the fiber composition of Rectus femoris (type II dominant) and Soleus (type I dominant) muscles using surface electromyography. Isometric signals are acquired from the muscles of 15 participants using a well-defined protocol and are further processed using reduced interference Rihaczek distribution. Instantaneous median frequency (IMDF) is extracted from the non-fatigue (NF) and fatigue (F) segments of the signals and is analyzed. From the distributions, it is found that the spectral power increases in the lower frequencies of the signal recorded from the rectus femoris and in the higher frequencies of signals recorded from the soleus during fatigue. The soleus is showing higher IMDF values than the rectus femoris in both segments. A reduction of 14% and an increase of 10% is observed in the IMDF during fatigue for rectus femoris and soleus, respectively. Thus, the extracted feature is found to be sensitive and statistically significant (p<0.05) to differentiate fiber types as well as the NF and F states of the two muscles.Clinical Relevance- This study may be extended to non-invasively analyze the fiber type shifts in muscles due to athletic training and pathological conditions.