Muscle Energetics Research Articles

Lower muscle mitochondrial energetics is associated with greater phenotypic frailty in older women and men: the Study of Muscle, Mobility and Aging.

Phenotypic frailty syndrome identifies older adults at greater risk for adverse health outcomes. Despite the critical role of mitochondria in maintaining cellular function, including energy production, the associations between muscle mitochondrial energetics and frailty have not been widely explored in a large, well-phenotyped, older population. The Study of Muscle, Mobility and Aging (SOMMA) assessed muscle energetics in older adults (N = 879, mean age = 76.3 years, 59.2% women). 31Phosporous magnetic resonance spectroscopy measured maximal production of adenosine triphosphate (ATPmax) in vivo, while ex vivo high-resolution respirometry of permeabilized muscle fibers from the vastus lateralis measured maximal oxygen consumption supported by fatty acids and complex I- and II-linked carbohydrates (e.g., Max OXPHOSCI+CII). Five frailty criteria, shrinking, weakness, exhaustion, slowness, and low activity, were used to classify participants as robust (0, N = 397), intermediate (1-2, N = 410), or frail (≥ 3, N = 66). We estimated the proportional odds ratio (POR) for greater frailty, adjusted for multiple potential confounders. One-SD decrements of most respirometry measures (e.g., Max OXPHOSCI+CII, adjusted POR = 1.5, 95%CI [1.2,1.8], p = 0.0001) were significantly associated with greater frailty classification. The associations of ATPmax with frailty were weaker than those between Max OXPHOSCI+CII and frailty. Muscle energetics was most strongly associated with slowness and low physical activity components. Our data suggest that deficits in muscle mitochondrial energetics may be a biological driver of frailty in older adults. On the other hand, we did observe differential relationships between measures of muscle mitochondrial energetics and the individual components of frailty.

Abstract 16878: Exercise Intolerance in Heart Failure With Preserved Ejection Fraction is More Closely Related to Energetic Decline During Exercise Than to Mitochondrial Oxidative Capacity in Recovery

Introduction: Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with severe exercise intolerance (EI) and exertional fatigue. Impaired skeletal muscle high-energy phosphate metabolism has been reported in HFpEF patients and postulated as a potential contributor to EI. However, whether EI is more closely related to rapid energetic decline during exercise, or reduced mitochondrial oxidative capacity remains unknown. Hypothesis: We hypothesized that six-minute walk distance (6MWD) is more closely related to the rate of skeletal muscle energetic decline during exercise than mitochondrial oxidative capacity in HFpEF. Methods: Calf muscle energetics were measured by phosphorus magnetic resonance spectroscopy ( 31 PMRS). The rate of phosphocreatine (PCr) decline normalized to work performed during graded plantar flexion exercise to volitional fatigue and the time for PCr post-exercise recovery, an established metric inversely related to mitochondrial oxidative capacity, were measured in 64 HFpEF patients (age: 65 ± 11 years; 53% women). Results: The mean rate of PCr decline, PCr recovery time, and 6MWD were 52 ± 108 μmol/g wet weight/KJ, 80 ± 45 seconds, and 296 ± 109 meters, respectively. The 6MWD was inversely related to the rate of PCr decline (r = -0.46; P = 0.0002; Figure, A ) but not significantly related to the PCr recovery time (r = -0.06; P = 0.66; Figure, B ), as determined by Pearson’s correlation coefficients. Conclusions: EI, as measured by 6MWD, in HFpEF patients is closely associated with impaired skeletal muscle metabolism, specifically rapid skeletal muscle PCr decline during exercise rather than mitochondrial oxidative capacity. This suggests that impaired glycolytic metabolism and substrate delivery may contribute metabolically to EI in HFpEF patients.

Isolated cardiac muscle contracting against a real-time model of systemic and pulmonary cardiovascular loads.

Isolated cardiac tissues allow a direct assessment of cardiac muscle function and enable precise control of experimental loading conditions. However, current experimental methods do not expose isolated tissues to the same contraction pattern and cardiovascular loads naturally experienced by the heart. In this study, we implement a computational model of systemic-pulmonary impedance that is solved in real time and imposed on contracting isolated rat muscle tissues. This systemic-pulmonary model represents the cardiovascular system as a lumped-parameter, closed-loop circuit. The tissues performed force-length work-loop contractions where the model output informed both the shortening and restretch phases of each work-loop. We compared the muscle mechanics and energetics associated with work-loops driven by the systemic-pulmonary model with that of a model-based loading method that only accounts for shortening. We obtained results that show simultaneous changes of afterload and preload or end-diastolic length of the muscle, as compared with the static, user-defined preload as in the conventional loading method. This feature allows assessment of muscle work output, heat output, and efficiency of contraction as functions of end-diastolic length. The results reveal the behavior of cardiac muscle as a pump source to achieve load-dependent work and efficiency outputs over a wider range of loads. This study offers potential applications of the model to investigate cardiac muscle response to hemodynamic coupling between systemic and pulmonary circulations in an in vitro setting.NEW & NOTEWORTHY We present the use of a "closed-loop" model of systemic and pulmonary circulations to apply, for the first time, real-time model-calculated preload and afterload to isolated cardiac muscle preparations. This method extends current experimental protocols where only afterload has been considered. The extension to include preload provides the opportunity to investigate ventricular muscle response to hemodynamic coupling and as a pump source across a wider range of cardiovascular loads.

Acetate and succinate benefit host muscle energetics as exercise-associated post-biotics.

Recently, the gut microbiome has emerged as a potent modulator of exercise-induced systemic adaptation and appears to be crucial for mediating some of the benefits of exercise. This study builds upon previous evidence establishing a gut microbiome-skeletal muscle axis, identifying exercise-induced changes in microbiome composition. Metagenomics sequencing of fecal samples from non-exercise-trained controls or exercise-trained mice was conducted. Biodiversity indices indicated exercise training did not change alpha diversity. However, there were notable differences in beta-diversity between trained and untrained microbiomes. Exercise significantly increased the level of the bacterial species Muribaculaceae bacterium DSM 103720. Computation simulation of bacterial growth was used to predict metabolites that accumulate under in silico culture of exercise-responsive bacteria. We identified acetate and succinate as potential gut microbial metabolites that are produced by Muribaculaceae bacterium, which were then administered to mice during a period of mechanical overload-induced muscle hypertrophy. Although no differences were observed for the overall muscle growth response to succinate or acetate administration during the first 5 days of mechanical overload-induced hypertrophy, acetate and succinate increased skeletal muscle mitochondrial respiration. When given as post-biotics, succinate or acetate treatment may improve oxidative metabolism during muscle hypertrophy.

Associations between skeletal muscle energetics and accelerometry-based performance fatigability: Study of Muscle, Mobility and Aging.

Performance fatigability is typically experienced as insufficient energy to complete daily physical tasks, particularly with advancing age, often progressing toward dependency. Thus, understanding the etiology of performance fatigability, especially cellular-level biological mechanisms, may help to delay the onset of mobility disability. We hypothesized that skeletal muscle energetics may be important contributors to performance fatigability. Participants in the Study of Muscle, Mobility and Aging completed a usual-paced 400-m walk wearing a wrist-worn ActiGraph GT9X to derive the Pittsburgh Performance Fatigability Index (PPFI, higher scores = more severe fatigability) that quantifies percent decline in individual cadence-versus-time trajectory from their maximal cadence. Complex I&II-supported maximal oxidative phosphorylation (max OXPHOS) and complex I&II-supported electron transfer system (max ETS) were quantified exvivo using high-resolution respirometry in permeabilized fiber bundles from vastus lateralis muscle biopsies. Maximal adenosine triphosphate production (ATPmax) was assessed invivo by 31P magnetic resonance spectroscopy. We conducted tobit regressions to examine associations of max OXPHOS, max ETS, and ATPmax with PPFI, adjusting for technician/site, demographic characteristics, and total activity count over 7-day free-living among older adults (N = 795, 70-94 years, 58% women) with complete PPFI scores and ≥1 energetics measure. Median PPFI score was 1.4% [25th-75th percentile: 0%-2.9%]. After full adjustment, each 1 standard deviation lower max OXPHOS, max ETS, and ATPmax were associated with 0.55 (95% CI: 0.26-0.84), 0.39 (95% CI: 0.09-0.70), and 0.54 (95% CI: 0.27-0.81) higher PPFI score, respectively. Our findings suggested that therapeutics targeting muscle energetics may potentially mitigate fatigability and lessen susceptibility to disability among older adults.

Validation of a musculoskeletal model for simulating muscle mechanics and energetics during diverse human hopping tasks.

Computational musculoskeletal modelling has emerged as an alternative, less-constrained technique to indirect calorimetry for estimating energy expenditure. However, predictions from modelling tools depend on many assumptions around muscle architecture and function and motor control. Therefore, these tools need to continue to be validated if we are to eventually develop subject-specific simulations that can accurately and reliably model rates of energy consumption for any given task. In this study, we used OpenSim software and experimental motion capture data to simulate muscle activations, muscle fascicle dynamics and whole-body metabolic power across mechanically and energetically disparate hopping tasks, and then evaluated these outputs at a group- and individual-level against experimental electromyography, ultrasound and indirect calorimetry data. Comparing simulated and experimental outcomes, we found weak to strong correlations for peak muscle activations, moderate to strong correlations for absolute fascicle shortening and mean shortening velocity, and strong correlations for gross metabolic power. These correlations tended to be stronger on a group-level rather than individual-level. We encourage the community to use our publicly available dataset from SimTK.org to experiment with different musculoskeletal models, muscle models, metabolic cost models, optimal control policies, modelling tools and algorithms, data filtering etc. with subject-specific simulations being a focal goal.

Impaired Cardiac and Skeletal Muscle Energetics Following Anthracycline Therapy for Breast Cancer.

Anthracycline-related cardiac toxicity is a recognized consequence of cancer therapies. We assess resting cardiac and skeletal muscle energetics and myocyte, sarcomere, and mitochondrial integrity in patients with breast cancer receiving epirubicin. In a prospective, mechanistic, observational, longitudinal study, we investigated chemotherapy-naive patients with breast cancer receiving epirubicin versus sex- and age-matched healthy controls. Resting energetic status of cardiac and skeletal muscle (phosphocreatine/gamma ATP and inorganic phosphate [Pi]/phosphocreatine, respectively) was assessed with 31P-magnetic resonance spectroscopy. Cardiac function and tissue characterization (magnetic resonance imaging and 2D-echocardiography), cardiac biomarkers (serum NT-pro-BNP and high-sensitivity troponin I), and structural assessments of skeletal muscle biopsies were obtained. All study assessments were performed before and after chemotherapy. Twenty-five female patients with breast cancer (median age, 53 years) received a mean epirubicin dose of 304 mg/m2, and 25 age/sex-matched controls were recruited. Despite comparable baseline cardiac and skeletal muscle energetics with the healthy controls, after chemotherapy, patients with breast cancer showed a reduction in cardiac phosphocreatine/gamma ATP ratio (2.0±0.7 versus 1.1±0.5; P=0.001) and an increase in skeletal muscle Pi/phosphocreatine ratio (0.1±0.1 versus 0.2±0.1; P=0.022). This occurred in the context of increases in left ventricular end-systolic and end-diastolic volumes (P=0.009 and P=0.008, respectively), T1 and T2 mapping (P=0.001 and P=0.028, respectively) but with preserved left ventricular ejection fraction, mass and global longitudinal strain, and no change in cardiac biomarkers. There was preservation of the mitochondrial copy number in skeletal muscle biopsies but a significant increase in areas of skeletal muscle degradation (P=0.001) in patients with breast cancer following chemotherapy. Patients with breast cancer demonstrated a reduction in skeletal muscle sarcomere number from the prechemotherapy stage compared with healthy controls (P=0.013). Contemporary doses of epirubicin for breast cancer treatment result in a significant reduction of cardiac and skeletal muscle high-energy 31P-metabolism alongside structural skeletal muscle changes. URL: https://www. gov; Unique identifier: NCT04467411.

Reduced Muscle Energetics And Fitness In Older Adults With Diabetes Independent Of Adiposity And Activity

Reduced Muscle Energetics And Fitness In Older Adults With Diabetes Independent Of Adiposity And Activity

Evidence for inefficient contraction and abnormal mitochondrial activity in sarcopenia using magnetic resonance spectroscopy.

Mitochondrial dysfunction has been implicated in sarcopenia. 31 P magnetic resonance spectroscopy (MRS) enables non-invasive measurement of adenosine triphosphate (ATP) synthesis rates to probe mitochondrial function. Here, we assessed muscle energetics in older sarcopenic and non-sarcopenic men and compared with muscle biopsy-derived markers of mitochondrial function. Twenty Chinese men with sarcopenia (SARC, age=73.1±4.1years) and 19 healthy aged and sex-matched controls (CON, age=70.3±4.2years) underwent assessment of strength, physical performance, and magnetic resonance imaging. Concentrations of phosphocreatine (PCr), ATP and inorganic phosphate (Pi) as well as muscle pH were measured at rest and during an interleaved rest-exercise protocol to probe muscle mitochondrial function. Results were compared to biopsy-derived mitochondrial complex activity and expression to understand underlying metabolic perturbations. Despite matched muscle contractile power (strength/cross-sectional area), the ATP contractile cost was higher in SARC compared with CON (low-intensity exercise: 1.06±0.59 vs. 0.57±0.22, moderate: 0.93±0.43 vs. 0.58±0.68, high: 0.70±0.57 vs. 0.43±0.51mmolL-1 min-1 bar-1 cm-2 , P=0.003, <0.0001 and <0.0001, respectively). Post-exercise mitochondrial oxidative synthesis rates (a marker of mitochondrial function) tended to be longer in SARC but did not reach significance (17.3±6.4 vs. 14.6±6.5mmolL-1 min-1 , P=0.2). However, relative increases in end-exercise ADP in SARC (31.8±9.9 vs. 24.0±7.3mmolL-1 , P=0.008) may have been a compensatory mechanism. Mitochondrial complex activity was found to be associated with exercise-induced drops in PCr [citrate synthetase activity (CS), Spearman correlation rho=-0.42, P=0.03] and end-exercise ADP (complex III, rho=-0.52, P=0.01; CS rho=-0.45, P=0.02; SDH rho=-0.45, P=0.03), with CS also being strongly associated with the PCr recovery rate following low intensity exercise (rho=-0.47, P=0.02), and the cost of contraction at high intensity (rho=-0.54, P=0.02). Interestingly, at high intensity, the fractional contribution of oxidative phosphorylation to exercise was correlated with activity in complex II (rho=0.5, P=0.03), CS (rho=0.47, P=0.02) and SDH (rho=0.46, P=0.03), linking increased mitochondrial complex activity with increased ability to generate energy through oxidative pathways. This study used 31 P MRS to assess ATP utilization and resynthesis in sarcopenic muscle and demonstrated abnormal increases in the energy cost during exercise and perturbed mitochondrial energetics in recovery. Associations between mitochondrial complex activity and the fractional contribution to energy requirement during exercise indicate increased ability to generate energy oxidatively in those with better mitochondrial complex activity.

Nutritional State and COPD: Effects on Dyspnoea and Exercise Tolerance

Chronic Obstructive Pulmonary Disease (COPD) is a disease that is spreading worldwide and is responsible for a huge number of deaths annually. It is characterized by progressive and often irreversible airflow obstruction, with a heterogeneous clinical manifestation based on disease severity. Along with pulmonary impairment, COPD patients display different grades of malnutrition that can be linked to a worsening of respiratory function and to a negative prognosis. Nutritional impairment seems to be related to a reduced exercise tolerance and to dyspnoea becoming a major determinant in patient-perceived quality of life. Many strategies have been proposed to limit the effects of malnutrition on disease progression, but there are still limited data available to determine which of them is the best option to manage COPD patients. The purpose of this review is to highlight the main aspects of COPD-related malnutrition and to underline the importance of poor nutritional state on muscle energetics, exercise tolerance and dyspnoea.

Time course of muscle activation, energetics and mechanics of running in minimalist and traditional cushioned shoes during level running

The study aimed to compare the ankle muscles activation, biomechanics and energetics of running in male runners during submaximal level run using minimalist (MinRS) and traditional cushioned (TrdRS) running shoes. During 45-min running in MinRS and TrdRS, the ankle muscles pre- and co-activation, biomechanics, and energetics of running of 16 male endurance runners (25.5 ± 3.5 yr) were assessed using surface electromyography (tibialis anterior and gastrocnemius lateralis), instrumented treadmill and indirect calorimetry, respectively. The net energy cost of running (Cr) was similar for both conditions (P = 0.25) with a significant increase over time (P < 0.0001). Step frequency (P < 0.001), and total mechanical work (P = 0.001) were significantly higher in MinRS than in TrdRS with no evolution over time (P = 0.28 and P = 0.85, respectively). The ankle muscles pre- and co-activation during the contact phase did not differ between the two shoe conditions (P ≥ 0.33) or over time (P ≥ 0.15). In conclusion, during 45-min running, Cr and muscle pre- and co-activation were not significantly different between MinRS and TrdRS with significantly higher step frequency and total mechanical work noted in the former than in the latter. Moreover, Cr significantly increased during the 45-min trial in both shoe conditions along with no significant change over time in muscle activation and biomechanical variables.

Increased adiposity is associated with altered skeletal muscle energetics.

The objective of this pilot study was to characterize relationships between skeletal muscle energy metabolism and body composition in healthy adults with varied amounts and distribution of adipose tissue. In vivo muscle energetics were quantified using dynamic 31P magnetic resonance spectroscopy with knee extension exercise standardized to subject lean body mass. Spearman's correlation analysis examined relationships between muscle metabolism indices and measures of adiposity including body mass index (BMI), total body fat, and quadriceps intermuscular adipose tissue (IMAT). Post hoc partial correlations were examined controlling for additional body composition measures. Kruskal-Wallis tests with Dunn-Sidak post hoc comparisons evaluated group differences in energy metabolism based on body composition profiles (i.e., lean, normal-weight obese, and overweight-obese) and IMAT tertiles. BMI negatively correlated with end-exercise muscle pH after correcting for IMAT and total body fat (r = -0.46, P = 0.034). Total adiposity negatively correlated with maximum oxidative capacity after correcting for IMAT (r = -0.54, P = 0.013). IMAT positively correlated with muscle proton buffering capacity after correcting for total body fat (r = 0.53, P = 0.023). Body composition groups showed differences in end-exercise fall in [PCr] with normalized workload (P = 0.036; post hoc: overweight-obese < lean, P = 0.029) and maximum oxidative capacity (P = 0.021; post hoc: normal-weight obese < lean, P = 0.016). IMAT tertiles showed differences in end-exercise fall in [PCr] with normalized workload (P = 0.035; post hoc: 3rd < 1st, P = 0.047). Taken together, these results support increased adiposity is associated with reduced muscle energetic efficiency with more reliance on glycolysis, and when accompanied with reduced lean mass, is associated with reduced maximum oxidative capacity.NEW & NOTEWORTHY Skeletal muscle energy production is influenced by both lean body mass and adipose tissue but the effect of their distribution on energy metabolism is unclear. This study examined variations in quadriceps muscle energy metabolism in healthy adults with varied relative amounts of lean and adipose tissue. Results suggest increased adiposity is associated with reduced muscle energetic efficiency with more reliance on glycolysis, and when accompanied with reduced lean mass, is associated with reduced maximum oxidative capacity.

Effects of hydroxyurea on skeletal muscle energetics and force production in a sickle cell disease murine model.

Hydroxyurea (HU) is commonly used as a treatment for patients with sickle cell disease (SCD) to enhance fetal hemoglobin production. This increased production is expected to reduce anemia (which depresses oxygen transport) and abnormal Hb content alleviating clinical symptoms such as vaso-occlusive crisis and acute chest syndrome. The effects of HU on skeletal muscle bioenergetics in vivo are still unknown. Due to the beneficial effects of HU upon oxygen delivery, improved skeletal muscle energetics and function in response to a HU treatment have been hypothesized. Muscle energetics and function were analyzed during a standardized rest-exercise-recovery protocol, using 31P-magnetic resonance spectroscopy in Townes SCD mice. Measurements were performed in three groups of mice: one group of 2-mo-old mice (SCD2m, n = 8), another one of 4-mo-old mice (SCD4m, n = 8), and a last group of 4-mo-old mice that have been treated from 2 mo of age with HU at 50 mg/kg/day (SCD4m-HU, n = 8). As compared with SCD2m mice, SCD4m mice were heavier and displayed a lower acidosis. As lower specific forces were developed by SCD4m compared with SCD2m, greater force-normalized phosphocreatine consumption and oxidative and nonoxidative costs of contraction were also reported. HU-treated mice (SCD4m-HU) displayed a significantly higher specific force production as compared with untreated mice (SCD4m), whereas muscle energetics was unchanged. Overall, our results support a beneficial effect of HU on muscle function.NEW & NOTEWORTHY Our results highlighted that force production decreases between 2 and 4 mo of age in SCD mice thereby indicating a decrease of muscle function during this period. Of interest, HU treatment seemed to blunt the observed age effect given that SCD4m-HU mice displayed a higher specific force production as compared with SCD4m mice. In that respect, HU treatment would help to maintain a higher capacity of force production during aging in SCD.

SEX DIFFERENCES IN SKELETAL MUSCLE ENERGETICS AMONG OLDER ADULTS

Abstract Mobility impairment is the most common disability among older adults, with an earlier presentation, higher prevalence, and greater severity in women compared to men. A decline in skeletal muscle metabolism contributes to the loss of mobility with age. However, it is unknown if sex-specific differences in muscle energetics can explain the disparity in mobility impairment among men and women. In the Study of Muscle, Mobility, and Aging (SOMMA), muscle energetics was characterized using in vivo Phosphorus Magnetic Resonance Spectroscopy and High-Resolution Respirometry of permeabilized fiber bundles from muscle biopsies. In this analysis of 773 participants aged 70–94 years, 519 were women, of which 16% were deemed lower extremity mobility impaired based on a Short Physical Performance Battery (SPPB) score

INTRODUCTION TO SOMMA: CONCEPTUAL CONSTRUCT AND PARTICIPANT CHARACTERISTICS

Abstract SOMMA aims to characterize key muscle characteristics and their longitudinal association with declines in mobility. To assess mitochondrial energetics in muscle, respiration assays were performed on biopsies of the vastus lateralis and the capacity to generate ATP (ATPmax) was determined by 31P MR spectroscopy. Other properties examined in biopsies include denervation, fiber type and size, capillary density and oxidative damage. We archive ~150mg for ancillary science. In a subset, we obtained biopsies of subcutaneous adipose for measurements including cell senescence and for archiving. To assess body composition, SOMMA used whole body MR for quadriceps volume and D3 Creatine dilution for total skeletal muscle mass. We measured fitness by cardiopulmonary exercise testing. Participants also had many other assessments of physical and cognitive performance including chair stands, balance, gait speed, leg power, stair climbing, Trails B, MOCA, and patterns of physical activity by actigraphy.

NEB mutations disrupt the super-relaxed state of myosin and remodel the muscle metabolic proteome in nemaline myopathy

Nemaline myopathy (NM) is one of the most common non-dystrophic genetic muscle disorders. NM is often associated with mutations in the NEB gene. Even though the exact NEB-NM pathophysiological mechanisms remain unclear, histological analyses of patients’ muscle biopsies often reveal unexplained accumulation of glycogen and abnormally shaped mitochondria. Hence, the aim of the present study was to define the exact molecular and cellular cascade of events that would lead to potential changes in muscle energetics in NEB-NM. For that, we applied a wide range of biophysical and cell biology assays on skeletal muscle fibres from NM patients as well as untargeted proteomics analyses on isolated myofibres from a muscle-specific nebulin‐deficient mouse model. Unexpectedly, we found that the myosin stabilizing conformational state, known as super-relaxed state, was significantly impaired, inducing an increase in the energy (ATP) consumption of resting muscle fibres from NEB-NM patients when compared with controls or with other forms of genetic/rare, acquired NM. This destabilization of the myosin super-relaxed state had dynamic consequences as we observed a remodeling of the metabolic proteome in muscle fibres from nebulin‐deficient mice. Altogether, our findings explain some of the hitherto obscure hallmarks of NM, including the appearance of abnormal energy proteins and suggest potential beneficial effects of drugs targeting myosin activity/conformations for NEB-NM.

Mitochondrial Energetics in Skeletal Muscle Are Associated With Leg Power and Cardiorespiratory Fitness in the Study of Muscle, Mobility and Aging.

Mitochondrial energetics are an important property of aging muscle, as generation of energy is pivotal to the execution of muscle contraction. However, its association with functional outcomes, including leg power and cardiorespiratory fitness, is largely understudied. In the Study of Muscle, Mobility, and Aging, we collected vastus lateralis biopsies from older adults (n = 879, 70-94 years, 59.2% women). Maximal State 3 respiration (Max OXPHOS) was assessed in permeabilized fiber bundles by high-resolution respirometry. Capacity for maximal adenosine triphosphate production (ATPmax) was measured in vivo by 31P magnetic resonance spectroscopy. Leg extension power was measured with a Keiser press system, and VO2 peak was determined using a standardized cardiopulmonary exercise test. Gender-stratified multivariate linear regression models were adjusted for age, race, technician/site, adiposity, and physical activity with beta coefficients expressed per 1-SD increment in the independent variable. Max OXPHOS was associated with leg power for both women (β = 0.12 Watts/kg, p < .001) and men (β = 0.11 Watts/kg, p < .050). ATPmax was associated with leg power for men (β = 0.09 Watts/kg, p < .05) but was not significant for women (β = 0.03 Watts/kg, p = .11). Max OXPHOS and ATPmax were associated with VO2 peak in women and men (Max OXPHOS, β women = 1.03 mL/kg/min, β men = 1.32 mL/kg/min; ATPmax β women = 0.87 mL/kg/min, β men = 1.50 mL/kg/min; all p < .001). Higher muscle mitochondrial energetics measures were associated with both better cardiorespiratory fitness and greater leg power in older adults. Muscle mitochondrial energetics explained a greater degree of variance in VO2 peak compared to leg power.

Muscle endurance: Is bipedalism the cause?

One may ask if the transition to bipedalism from the condition of quadrupedalism, which occurred about 7 million years ago, has been the cause or consequence of a series of fundamental physiological muscular aspects including the cost of locomotion, a crucial determinant of endurance, which has been found to be significantly lower in humans than in apes. This issue strictly links to unsolved issues regarding the significance of several muscular structural and functional adaptations, classically attributed to bipedalism and its associated locomotions, which we cannot simply attribute to the acquisition of the upright position and which may directly or indirectly contribute to the observed changes in muscle energetics that make the modern human an exceptional endurance walker and runner compared to quadrupedals.

P.03 Myosin dysregulation in nemaline myopathy

Nemaline myopathy (NM) is one of the most common congenital myopathies. NM is often related to pathogenic variants in the <i>NEB, ACTA1, TPM2</i> and <i>TPM3</i> genes. Even though the exact disease mechanisms remain to be elucidated, histological analyses of NM patients' muscle biopsies may reveal unexplained accumulation of glycogen and abnormal mitochondria. Thus, the aim of the present work was to identify what could cause such change in muscle energetics. For that, we applied mant-ATP chase experiments on skeletal muscle fibres from patients diagnosed with NM. We observed that the myosin-stabilising conformational state, known as the super-relaxed state, was significantly impaired, inducing an increase in the energy (ATP) consumption of resting patient muscle fibres expressing NEB and ACTA1 mutations. Such alteration was linked to hyper-phosphorylation of myosin-binding protein C, a protein linking myosin molecules to the thin filaments. Hence, our results may indicate a contribution of myosin to some of the histopathological aberrations related to NM.

PSIII-A-12 Longissimus Thoracis Mitochondrial Capacities and Temperament of Stocker Calves are Related to Meat Quality at Harvest in Brahman but not in Angus Cattle

Abstract Brahman cattle reportedly have decreased meat quality compared to Angus but little is known about the cellular mechanisms driving this difference. We hypothesized that live animal skeletal muscle mitochondria would be related to meat quality. Trapezius and longissimus thoracis (LT) samples were collected from 10-mo-old Angus and Brahman steers designated as calm, intermediate, or temperamental (n=12/group/breed) based on pen score and exit velocity at weaning. Samples were analyzed for citrate synthase (CS) and cytochrome c oxidase (CCO) activities as markers of mitochondrial volume density and function. Calm and temperamental LT samples were also analyzed for oxidative phosphorylation (P) and electron transfer (E) capacities via high-resolution respirometry. At approximately 14.5-mo-old, steers were placed in pens and fed ad libitum. After at least 120 d on feed, animals were harvested and 13th rib LT samples were collected, vacuum packaged, aged 14d, frozen, then subjected to Warner-Bratzler Shear Force (WBSF). Impacts of temperament and breed on WBSF were determined using mixed linear models with breed, temperament, and breed × temperament as fixed effects. Relationships between mitochondrial variables and WBSF were determined using Pearson’s Correlations. Regardless of temperament, WBSF was greater in Brahman than Angus steers (P&amp;lt; 0.0001). Temperament did not impact WBSF in Angus but temperamental Brahman had greater WBSF than both calm and intermediate Brahman (P≤0.01). CS and CCO activities at 10 mo of age were not correlated with WBSF. However, Brahman LT intrinsic (relative to CS) P with complex I (PCI), maximal P with complexes I and II (PCI+II), maximal E with complexes I and II (ECI+II), and E with complex II only (ECII) were positively correlated with WBSF (P≤0.05) while no LT mitochondrial capacity measures correlated with WBSF in Angus. These data may shed light on differences in skeletal muscle energetics leading to decreased meat quality in temperamental Brahman steers.