Repeated sprint training in hypoxia induces specific skeletal muscle adaptations through S100A protein signaling.

Athletes increasingly engage in repeated sprint training consisting in repeated short all-out efforts interspersed by short recoveries. When performed in hypoxia (RSH), it may lead to greater training effects than in normoxia (RSN); however, the underlying molecular mechanisms remain unclear. This study aimed at elucidating the effects of RSH on skeletal muscle metabolic adaptations as compared to RSN. Sixteen healthy young men performed nine repeated sprint training sessions in either normoxia (FIO2 = 0.209, RSN, n = 7) or normobaric hypoxia (FIO2 = 0.136, RSH, n = 9). Before and after the training period, exercise performance was assessed by using repeated sprint ability (RSA) and Wingate tests. Vastus lateralis muscle biopsies were performed to investigate muscle metabolic adaptations using proteomics combined with western blot analysis. Similar improvements were observed in RSA and Wingate tests in both RSN and RSH groups. At the muscle level, RSN and RSH reduced oxidative phosphorylation protein content but triggered an increase in mitochondrial biogenesis proteins. Proteomics showed an increase in several S100A family proteins in the RSH group, among which S100A13 most strongly. We confirmed a significant increase in S100A13 protein by western blot in RSH, which was associated with increased Akt phosphorylation and its downstream targets regulating protein synthesis. Altogether our data indicate that RSH may activate an S100A/Akt pathway to trigger specific adaptations as compared to RSN.

Alterations to neuromuscular properties of skeletal muscle are temporally dissociated from the oxygen uptake slow component.

To assess if the alteration of neuromuscular properties of knee extensors muscles during heavy exercise co-vary with the SCV ([Formula: see text] slow component), eleven healthy male participants completed an incremental ramp test to exhaustion and five constant heavy intensity cycling bouts of 2, 6, 10, 20 and 30 minutes. Neuromuscular testing of the knee extensor muscles were completed before and after exercise. Results showed a significant decline in maximal voluntary contraction (MVC) torque only after 30 minutes of exercise (-17.01% ± 13.09%; p < 0.05) while single twitch (PT), 10 Hz (P10), and 100 Hz (P100) doublet peak torque amplitudes were reduced after 20 and 30 minutes (p < 0.05). Voluntary activation (VA) and M-wave were not affected by exercise, but significant correlation was found between the SCV and PT, MVC, VA, P10, P100, and P10/P100 ratio, respectively (p < 0.015). Therefore, because the development of the SCV occurred mainly between 2-10 minutes, during which neuromuscular properties were relatively stable, and because PT, P10 and P100 were significantly reduced only after 20-30 minutes of exercise while SCV is stable, a temporal relationship between them does not appear to exist. These results suggest that the development of fatigue due to alterations of neuromuscular properties is not an essential requirement to elicit the SCV.

The metabolic profiles of different fiber type populations under the emergence of the slow component of oxygen uptake.

To investigate the influence of different metabolic muscle fiber profiles on the emergence of the slow component of oxygen uptake ([Formula: see text]SC), 12 habitually active males completed four sessions of different combinations of work-to-work transition exercises up to severe intensity. Each transition was modeled to analyze the different kinetic parameters. Using a new approach, combining Henneman's principle and superposition principle, a reconstructed kinetics was built by temporally aligning the start of each new transition and summing them. The primary phase time constant significantly slowed and the gain at the end (GainEnd) significantly increased when transitions started from a higher intensity (p < 0.001). Kinetic parameters from the reconstructed curve ([Formula: see text], time delay of primary phase, [Formula: see text]End and GainEnd) were not significantly different from one transition to severe exercise. These results suggest that the appearance of the [Formula: see text]SC is at least related to, if not the result of, the different metabolic properties of muscle fibers.

Hybrid fiber alterations in exercising seniors suggest contribution to fast-to-slow muscle fiber shift.

BACKGROUND: Human skeletal muscle is composed of a functional and metabolic continuum of slow (Type I) and fast fibers (IIa and IIx). Hybrid fibers co-expressing different myosin heavy chains are also present and seem to be more prominent in aging muscle. Their role is debated; hybrid fibers were reported either in a transitional state, between slow and fast fibers, or as fixed individual entities. This study examined the fate of hybrid fibers with an endurance exercise intervention in an elderly sedentary population. METHODS: Twenty-two sedentary healthy elderly men and women underwent a 16-week supervised endurance exercise intervention. Eighteen endurance-trained age- and gender-matched volunteers served as controls. Fiber type distribution was determined by immunohistochemistry on vastus lateralis muscle biopsies pre-intervention and post-intervention. RESULTS: A total of 13840 fibers were analyzed. At baseline, a Type II dominant fiber profile was observed compared with the control group, with more Type IIa (P = 0.0301) and Type IIx fibers (P = 0.0328). Hybrid fibers represented almost 5% of total muscle fibers in both groups. There was no significant difference between groups (I-IIa, P = 0.6719 and IIa-IIx, P = 0.0998). Intervention triggered qualitative dynamics towards an increase in Type I, and decrease in Type II fibers, paralleled by an increase in I-IIa hybrids (P = 0.0301). CONCLUSIONS: The present study is, to our knowledge, the first to examine hybrid muscle fiber type adaptations to an endurance exercise intervention in the elderly. Hybrid fiber proportions did not differ between chronic sedentary state and chronic endurance-trained state. Exercise intervention increased Type I-IIa hybrid fibers along with shift dynamics in other fiber types suggesting the contribution of hybrid fiber to a fast-to-slow fiber type transition, eventually serving as intermediate reservoir from one monomorphic myosin heavy chain expressing fiber type to another. This finding favours the transitional theory regarding hybrid muscle fibers and exercise, crucial to understanding reversible mechanisms of sarcopenia and development of prevention measures.

Distinct patterns of skeletal muscle mitochondria fusion, fission and mitophagy upon duration of exercise training.

AIM: Healthy ageing interventions encompass regular exercise to prevent mitochondrial dysfunction, key player in sarcopenia pathogenesis. Mitochondrial biogenesis has been well documented, but mitochondrial remodelling in response to exercise training is poorly understood. Here we investigated fusion, fission and mitophagy before and after an exercise intervention in older adults. METHODS: Skeletal muscle biopsies were collected from 22 healthy sedentary men and women before and after 4 months of supervised training. Eight lifelong trained age- and gender-matched volunteers served as positive controls. Transmission electron microscopy was used to estimate mitochondrial content. Western blotting and qRT-PCR were used to detect changes in specific proteins and transcripts. RESULTS: After intervention, mitochondrial content increased to levels of controls. While enhancement of fusion was prevalent after intervention, inhibition of fission and increased mitophagy were dominant in controls. Similarly to PARKIN, BCL2L13 content was higher in controls. The observed molecular adaptations paralleled long-term effects of training on physical fitness, exercise efficiency and oxidative capacity. CONCLUSIONS: This study describes distinct patterns of molecular adaptations in human skeletal muscle under chronic exercise training. After 16 weeks of exercise, the pattern was dominated by fusion to increase mitochondrial content to the metabolic demands of exercise. In lifelong exercise, the pattern was dominated by mitophagy synchronized with increased fusion and decreased fission, indicating an increased mitochondrial turnover. In addition to these temporally distinct adaptive mechanisms, this study suggests for the first time a specific role of BCL2L13 in chronic exercise that requires constant maintenance of mitochondrial quality.

Thigh and abdominal adipose tissue depot associations with testosterone levels in postmenopausal females.

OBJECTIVE: Research findings on the relationship between serum androgens and adipose tissue in older females are inconsistent. We aimed to clarify the relationship using state-of-the-art techniques to evaluate associations between body fat distribution and plasma testosterone (T) levels in older postmenopausal women. DESIGN: Observational, cross-sectional study of healthy, community dwelling postmenopausal women. PATIENTS AND MEASUREMENTS: Postmenopausal women (60-80 years old) were included in this study. Overall body composition was evaluated by dual-energy X-ray absorptiometry. Abdominal and thigh fat depots were measured by magnetic resonance imaging. Circulating T concentrations were analysed by liquid chromatography-tandem mass spectrometry. RESULTS: Thirty-five women (66.6 ± 0.8 years) participated in this study. T levels were positively associated with clinical proxy measures of adiposity including weight (ρ = 0.39), BMI (ρ = 0.43) and waist circumference (ρ = 0.39) (all P < 0.05). Fat mass and % body fat were correlated with T levels (ρ = 0.42 and 0.38 respectively, both P < 0.05). T correlated with overall and superficial abdominal fat (ρ = 0.34 and 0.37 respectively, both P < 0.05) but not with visceral adipose tissue. T increased with greater thigh fat (ρ = 0.49, P < 0.05) in both superficial and deep depots (ρ = 0.50 and 0.35 respectively, both P < 0.05). CONCLUSION: Our results suggest that postmenopausal women with higher circulating T levels have both higher regional and overall body adiposity. These findings underscore the sexual dimorphism in the relationship between serum androgen levels and adiposity.

Enhanced Respiratory Chain Supercomplex Formation in Response to Exercise in Human Skeletal Muscle.

Mitochondrial dysfunction is a hallmark of multiple metabolic complications. Physical activity is known to increase mitochondrial content in skeletal muscle, counteracting age-related decline in muscle function and protecting against metabolic and cardiovascular complications. Here, we investigated the effect of 4 months of exercise training on skeletal muscle mitochondria electron transport chain complexes and supercomplexes in 26 healthy, sedentary older adults. Exercise differentially modulated respiratory complexes. Complex I was the most upregulated complex and not stoichiometrically associated to the other complexes. In contrast to the other complexes, complex I was almost exclusively found assembled in supercomplexes in muscle mitochondria. Overall, supercomplex content was increased after exercise. In particular, complexes I, III, and IV were redistributed to supercomplexes in the form of I+III2+IV. Taken together, our results provide the first evidence that exercise affects the stoichiometry of supercomplex formation in humans and thus reveal a novel adaptive mechanism for increased energy demand.