Sex, gender and the pulmonary physiology of exercise

In this review, we detail how the pulmonary system's response to exercise is impacted by both sex and gender in healthy humans across the lifespan. First, the rationale for why sex and gender differences should be considered is explored, and then anatomical differences are highlighted, namely that females typically have smaller lungs and airways than males. Thereafter, we describe how these anatomical differences can impact functional aspects such as respiratory muscle energetics and activation, mechanical ventilatory constraints, diaphragm fatigue, and pulmonary gas exchange in healthy adults and children. Finally, we detail how gender can impact the pulmonary response to exercise.

Assessing Mitochondrial Energetics of Skeletal Muscle in the Study of Muscle Mobility and Aging (SOMMA)

Mitochondria produce energy as ATP that essential for muscle contraction and movement. We hypothesize that age-related decreases in the capacity to generate ATP in muscle plays a major role in loss of mobility with aging. In SOMMA, we use high-resolution respirometry to measure the activity of electron transport system (ETS) in permeabilized muscle fibers from muscle biopsies. This allows us to assay ETS function in a highly controlled ex vivo experiment at the myocellular level, removed from other potentially limiting physiological factors including supplies of substrates and oxygen. We are also measuring the maximal capacity to generate ATP (ATPmax) in vivo by 31PMRS. ATPmax reflects the rate of phosphocreatine replenishment via oxidative phosphorylation. Analysis from the first 113 participants indicates that ATPmax correlates with Maximal OXPHOS (r=0.27, P=0.005), and Maximal ETS capacity (r=0.17, P=0.08). This suggests that these approaches provide complementary information on skeletal muscle energetics.

Predictive Simulations of Gait with Exoskeletons that Alter Energetics

Robotic exoskeletons, designed to augment human locomotion, have the potential to restore function in those with mobility impairments and enhance it in able-bodied individuals. However, optimally controlling these devices, to work in concert with complex and diverse human users, is a challenge. Accurate model simulations of the interaction between exoskeletons and walking humans may expedite the design process and improve control. Here, we use predictive gait simulations to investigate the effect of an exoskeleton that alters the energetic consequences of walking. To validate our approach, we re-created an past experimental paradigm where robotic exoskeletons were used to shift people’s energetically optimal step frequency to frequencies higher and lower than normally preferred. To match the experimental controller, we modelled a knee-worn exoskeleton that applied resistive torques that were either proportional or inversely proportional to step frequency—decreasing or increasing the energy optimal step frequency, respectively. We were able to replicate the experiment, finding higher and lower optimal step frequencies than in natural walking under each respective condition. Our simulated resistive torques and objective landscapes resembled the measured experimental resistive torque and energy landscapes. Individual muscle energetics revealed distinct coordination strategies consistent with each exoskeleton controller condition. Predicted step frequency and energetic outcomes were best achieved by increasing the number of virtual participants (varying whole-body anthropometrics), rather than number of muscle parameter sets (varying muscle anthropometrics). In future, our approach can be used to design controllers in advance of human testing, to help identify reasonable solution spaces or tailor design to individual users.

The Synergic Role of Actomyosin Architecture and Biased Detachment in Muscle Energetics: Insights in Cross Bridge Mechanism Beyond the Lever-Arm Swing

Muscle energetics reflects the ability of myosin motors to convert chemical energy into mechanical energy. How this process takes place remains one of the most elusive questions in the field. Here, we combined experimental measurements of in vitro sliding velocity based on DNA-origami built filaments carrying myosins with different lever arm length and Monte Carlo simulations based on a model which accounts for three basic components: (i) the geometrical hindrance, (ii) the mechano-sensing mechanism, and (iii) the biased kinetics for stretched or compressed motors. The model simulations showed that the geometrical hindrance due to acto-myosin spatial mismatching and the preferential detachment of compressed motors are synergic in generating the rapid increase in the ATP-ase rate from isometric to moderate velocities of contraction, thus acting as an energy-conservation strategy in muscle contraction. The velocity measurements on a DNA-origami filament that preserves the motors’ distribution showed that geometrical hindrance and biased detachment generate a non-zero sliding velocity even without rotation of the myosin lever-arm, which is widely recognized as the basic event in muscle contraction. Because biased detachment is a mechanism for the rectification of thermal fluctuations, in the Brownian-ratchet framework, we predict that it requires a non-negligible amount of energy to preserve the second law of thermodynamics. Taken together, our theoretical and experimental results elucidate less considered components in the chemo-mechanical energy transduction in muscle.

Measures of excess $$ \dot{\mathrm{V}} $$CO2 and recovery $$ \dot{\mathrm{V}} $$CO2 as indices of performance fatigability during exercise: a pilot study

Background The severity of performance fatigability and the capacity to recover from activity are profoundly influenced by skeletal muscle energetics, specifically the ability to buffer fatigue-inducing ions produced from anaerobic metabolism. Mechanisms responsible for buffering these ions result in the production of excess carbon dioxide (CO2) that can be measured as expired CO2 ($$ \dot{\mathrm{V}} $$ V ̇ CO2) during cardiopulmonary exercise testing (CPET). The primary objective of this study was to assess the feasibility of select assessment procedures for use in planning and carrying out interventional studies, which are larger interventional studies investigating the relationships between CO2 expiration, measured during and after both CPET and submaximal exercise testing, and performance fatigability. Methods Cross-sectional, pilot study design. Seven healthy subjects (30.7±5.1 years; 5 females) completed a peak CPET and constant work-rate test (CWRT) on separate days, each followed by a 10-min recovery then 10-min walk test. Oxygen consumption ($$ \dot{\mathrm{V}} $$ V ̇ O2) and $$ \dot{\mathrm{V}} $$ V ̇ CO2 on- and off-kinetics (transition constant and oxidative response index), excess-$$ \dot{\mathrm{V}} $$ V ̇ CO2, and performance fatigability severity scores (PFSS) were measured. Data were analyzed using regression analyses. Results All subjects that met the inclusion/exclusion criteria and consented to participate in the study completed all exercise testing sessions with no adverse events. All testing procedures were carried out successfully and outcome measures were obtained, as intended, without adverse events. Excess-$$ \dot{\mathrm{V}} $$ V ̇ CO2 accounted for 61% of the variability in performance fatigability as measured by $$ \dot{\mathrm{V}} $$ V ̇ O2 on-kinetic ORI (ml/s) (R2=0.614; y = 8.474x − 4.379, 95% CI [0.748, 16.200]) and 62% of the variability as measured by PFSS (R2=0.619; y = − 0.096x + 1.267, 95% CI [−0.183, −0.009]). During CPET, $$ \dot{\mathrm{V}} $$ V ̇ CO2 -off ORI accounted for 70% (R2=0.695; y = 1.390x − 11.984, 95% CI [0.331, 2.449]) and $$ \dot{\mathrm{V}} $$ V ̇ CO2 -off Kt for 73% of the variability in performance fatigability measured by $$ \dot{\mathrm{V}} $$ V ̇ O2 on-kinetic ORI (ml/s) (R2=0.730; y = 1.818x − 13.639, 95% CI [0.548, 3.087]). Conclusion The findings of this study suggest that utilizing $$ \dot{\mathrm{V}} $$ V ̇ CO2 measures may be a viable and useful addition or alternative to $$ \dot{\mathrm{V}} $$ V ̇ O2 measures, warranting further study. While the current protocol appeared to be satisfactory, for obtaining select cardiopulmonary and performance fatigability measures as intended, modifications to the current protocol to consider in subsequent, larger studies may include use of an alternate mode or measure to enable control of work rate constancy during performance fatigability testing following initial CPET.

The synergic role of actomyosin architecture and biased detachment in muscle energetics: insights in cross bridge mechanism beyond the lever-arm swing

Muscle energetics reflects the ability of myosin motors to convert chemical energy into mechanical energy. How this process takes place remains one of the most elusive questions in the field. Here we combined experimental measurements of in vitro sliding velocity based on DNA-origami built filaments carrying myosins with different lever arm length and simulations based on a Monte-Carlo model which accounts for three basic components: (i) the geometrical hindrance, (ii) the mechano-sensing mechanism, and (iii) the biased kinetics for stretched or compressed motors. The model simulations showed that the geometrical hindrance due to acto-myosin spatial mismatching and the preferential detachment of compressed motors are synergic in generating the rapid increase in the ATP-ase rate from isometric to moderate velocities of contraction, thus acting as an energy-conservation strategy in muscle contraction. The velocity measurements on a DNA-origami filament that preserves the motors’ distribution showed that geometrical hindrance and biased detachment generate a non-zero sliding velocity even without rotation of the myosin lever-arm, which is widely recognized as the basic event in muscle contraction. Because biased detachment is a mechanism for the rectification of thermal fluctuations, in the Brownian-ratchet framework, we predict that it requires a non-negligible amount of energy to preserve the second law of thermodynamics. Taken together, our theoretical and experimental results elucidate non-conventional components in the chemo-mechanical energy transduction in muscle.

Magnetic Resonance-Compatible Arm-Crank Ergometry: A New Platform Linking Whole-Body Calorimetry to Upper-Extremity Biomechanics and Arm Muscle Metabolism

IntroductionEvaluation of the effect of human upper-body training regimens may benefit from knowledge of local energy expenditure in arm muscles. To that end, we developed a novel arm-crank ergometry platform for use in a clinical magnetic resonance (MR) scanner with 31P spectroscopy capability to study arm muscle energetics. Complementary datasets on heart-rate, whole-body oxygen consumption, proximal arm-muscle electrical activity and power output, were obtained in a mock-up scanner. The utility of the platform was tested by a preliminary study over 4 weeks of skill practice on the efficiency of execution of a dynamic arm-cranking task in healthy subjects.ResultsThe new platform successfully recorded the first ever in vivo31P MR spectra from the human biceps brachii (BB) muscle during dynamic exercise in five healthy subjects. Changes in BB energy- and pH balance varied considerably between individuals. Surface electromyography and mechanical force recordings revealed that individuals employed different arm muscle recruitment strategies, using either predominantly elbow flexor muscles (pull strategy; two subjects), elbow extensor muscles (push strategy; one subject) or a combination of both (two subjects). The magnitude of observed changes in BB energy- and pH balance during ACT execution correlated closely with each strategy. Skill practice improved muscle coordination but did not alter individual strategies. Mechanical efficiency on group level seemed to increase as a result of practice, but the outcomes generated by the new platform showed the additional caution necessary for the interpretation that total energy cost was actually reduced at the same workload.ConclusionThe presented platform integrates dynamic in vivo31P MRS recordings from proximal arm muscles with whole-body calorimetry, surface electromyography and biomechanical measurements. This new methodology enables evaluation of cyclic motor performance and outcomes of upper-body training regimens in healthy novices. It may be equally useful for investigations of exercise physiology in lower-limb impaired athletes and wheelchair users as well as frail patients including patients with debilitating muscle disease and the elderly.

Force and Boldness: Cumulative Assets of a Successful Crayfish Invader

Multiple causes can determine the disturbance of natural equilibrium in a population of a species, with a common one being the presence of invasive competitors. Invasives can drive native species to the resettlement of the trophic position, changing reproduction strategies or even daily normal behaviours. Here, we investigated the hypothesis that more effective anatomical features of an intruder (Faxonius limosus) come with increased boldness behaviour, contributing to their invasion success in competition against the native species (Pontastacus leptodactylus). We tested the boldness of specimens representing the two species by video-based assessment of crayfish individuals’ attempts to leave their settlement microenvironment. The experiment was followed by a series of measurements concerning chelae biometry, force and muscle energetics. The native species was less expressive in terms of boldness even if it had larger chelae and better muscular tissue performance. In contrast, because of better biomechanical construction of the chelae, the invasive species was capable of twice superior force achievements, which expectedly explained its bolder behaviour. These findings suggest that, in interspecific agonistic interactions, the behaviour strategy of the invasive crayfish species is based on sheer physical superiority, whereas the native crayfish relies on intimidation display.

Deficits in the Skeletal Muscle Transcriptome and Mitochondrial Coupling in Progressive Diabetes-Induced CKD Relate to Functional Decline

Two-thirds of those with type-2 diabetes (T2DM) have or will develop chronic kidney disease (CKD), characterized by rapid renal decline that, together with superimposed T2DM-related metabolic sequelae, synergistically promote early frailty and mobility-deficits that increases risk of mortality. Distinguishing the mechanisms linking renal decline to mobility deficits in CKD progression and/or increasing severity in T2DM is instrumental in both identifying those at high-risk for functional decline, and in formulating effective treatment strategies to prevent renal failure. While evidence suggests that skeletal muscle energetics may relate to the development of these comorbidities in advanced-CKD, this has never been assessed across the spectrum of CKD progression, especially in T2DM-induced CKD. Here, using next-gen sequencing, we first report significant downregulation in transcriptional networks governing oxidative phosphorylation, coupled electron-transport, electron-transport-chain(ETC)-complex assembly, and mitochondrial organization in both middle- and late-stage CKD in T2DM. Furthermore, muscle mitochondrial coupling is impaired as early as stage 3-CKD, with additional deficits in ETC-respiration, enzymatic activity, and increased redox-leak. Moreover, mitochondrial ETC function and coupling strongly related to muscle performance, and physical function. Our results indicate that T2DM-induced CKD progression impairs physical function, with implications for altered metabolic transcriptional networks and mitochondrial functional deficits, as primary mechanistic factors early in CKD-progression in T2DM.