Significance: High-intensity interval training (HIIT) has become popular because it is a time-efficient way to increase endurance. An intriguing and so-far-unanswered question is how a few minutes of HIIT can be that effective. We exposed recreationally active men to one session of three to six sets of 30-s high-intensity cycling exercise. Muscle biopsies taken 24 h later showed an extensive fragmentation of the sarcoplasmic reticulum (SR) Ca ²⁺ channels, the ryanodine receptor 1 (RyR1). In isolated mouse muscle fibers, this fragmentation was accompanied by increased SR Ca ²⁺ leak, which can trigger mitochondrial biogenesis. The HIIT-induced RyR1 fragmentation did not occur in muscles exposed to antioxidant, which offers an explanation for why antioxidants blunt effects of endurance training.

Non‐technical summary  Wasting and severely impaired function of skeletal muscle is frequently observed in critically ill intensive care unit (ICU) patients, with negative consequences for recovery and quality of life. An experimental rat ICU model has been used to study the mechanisms underlying this unique wasting condition in neuromuscularly blocked and mechanically ventilated animals at durations varying between 6 h and 2 weeks. The complete ‘mechanical silencing’ of skeletal muscle (removal of both weight bearing and activation) resulted in a specific myopathy frequently observed in ICU patients and characterized by a preferential loss of the motor protein myosin. A highly complex and coordinated protein synthesis and degradation system was observed in the time‐resolved analyses. It is suggested the ‘mechanical silencing’ of skeletal muscle is a dominating factor triggering the specific myopathy associated with the ICU intervention, and strongly supporting the importance of interventions counteracting the complete unloading in ICU patients.

The current investigation was designed to: (a) assess the impact of aging on elastic characteristics of single skeletal muscle fibers from young (N = 6) and older men (N = 6); and (b) correlate the potential changes, with the fiber contractile properties. Chemically skinned single muscle fibers (n = 235) from vastus lateralis muscle were maximally activated. Maximal force and cross-sectional area were measured, and specific force calculated. The slack test was used to measure maximal unloaded shortening velocity. A quick release of 0.15% of fiber length was applied to determine instantaneous stiffness. The myosin heavy chain isoform composition of each single fiber was determined by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE). Aging induces changes in both fiber elasticity (i.e., increased instantaneous stiffness) and contractility (i.e., reduced specific force and unloaded shortening velocity) in type I and IIa fibers. However, the changes in fiber stiffness may not directly influence contractile characteristics alterations.

Mammalian cells exhibit remarkable diversity in cell size, but the factors that regulate establishment and maintenance of these sizes remain poorly understood. This is especially true for skeletal muscle, comprised of syncytial myofibers that each accrue hundreds of nuclei during development. Here, we directly explore the assumed causal relationship between multinucleation and establishment of normal size through titration of myonuclear numbers during mouse neonatal development. Three independent mouse models, where myonuclear numbers were reduced by 75, 55, or 25%, led to the discovery that myonuclei possess a reserve capacity to support larger functional cytoplasmic volumes in developing myofibers. Surprisingly, the results revealed an inverse relationship between nuclei numbers and reserve capacity. We propose that as myonuclear numbers increase, the range of transcriptional return on a per nuclear basis in myofibers diminishes, which accounts for both the absolute reliance developing myofibers have on nuclear accrual to establish size, and the limits of adaptability in adult skeletal muscle.