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+III+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.

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.

Background: Podocalyxin (podxl) is a heavily glycosylated transmembrane protein mainly found on the apical membrane of rat podocytes and also in endothelial, hematopoietic, and tumor cells. Despite of its interest no much is known about the transcriptional regulation of podxl in different cells. Thus, we aimed at studying the functional features of the 5'-regulatory region of the human Podxl gene.

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.

To assess if the alteration of neuromuscular properties of knee extensors muscles during heavy exercise co-vary with the SCV ($${\dot{{\rm{V}}}{\rm{O}}}_{2}$$V̇O2 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.