Skeletal muscle atrophy and strength loss induced by short-term simulated spaceflight are offset or attenuated by resistance exercise (RE). This study compared the effects of plantar flexor and knee extensor RE on muscle size and function in 17 healthy men (aged 26-41years) subjected to 90 days 6 degrees head-down-tilt bed rest with (BRE; n = 8) or without (BR; n = 9) RE. The RE program consisted of coupled maximal concentric and eccentric actions in the supine squat (4 sets of 7 repetitions) and calf press (4 x 14) every third day employing a gravity-independent flywheel ergometer (FW). Prior to, and following bed rest, muscle volume was assessed using magnetic resonance imaging. Similarly, muscle strength and power and surface electromyographic (EMG) activity were determined during maximal actions using FW or isokinetic dynamometry. In BR, knee extensor and plantar flexor muscle volume decreased (P < 0.05) 18% and 29%, respectively. Torque or force and power decreased (P < 0.05) 31 60% (knee extension) and 37-56% (plantar flexion) while knee extensor and plantar flexor EMG activity decreased 31-38% and 28-35%, respectively following BR. Muscle atrophy in BRE was prevented (P > 0.05; knee extensors) or attenuated (-15%; plantar flexors). BRE maintained task-specific force, power and EMG activity. The decrease in non-task-specific torque was less (P < 0.05) than in BR. The present data imply that the triceps surae and quadriceps muscles show different responsiveness to long-term bed rest with or without resistance exercise. The results also suggest that designing in-flight resistance exercise protocols for space travellers is complex and must extend beyond preserving muscle only.

Muscle biopsies were obtained from the vastus lateralis before and after 84 days of bed-rest from six control (BR) and six resistance-exercised (BRE) men to examine slow-and fast-twitch muscle fibre contractile function. BR did not exercise during bed-rest and had a 17 and 40% decrease in whole muscle size and function, respectively. The BRE group performed four sets of seven maximal concentric and eccentric supine squats 2-3 days per week (every third day) that maintained whole muscle strength and size. Slow (MHC I) and fast (MHC IIa) muscle fibres were studied at 15• C for diameter, peak force (P o ), contractile velocity (V o ) and force-power parameters. SDS-PAGE was performed on each single fibre after the functional experiments to determine MHC isoform composition. MHC I and IIa BR fibres were, respectively, 15 and 8% smaller, 46 and 25% weaker (P o ), 21 and 6% slower (V o ), and 54 and 24% less powerful after bed-rest (P < 0.05). BR MHC I and IIa P o and power normalized to cell size were lower (P < 0.05). BRE MHC I fibres showed no change in size or V o after bed-rest; however, P o was 19% lower (P < 0.05), resulting in 20 and 30% declines (P < 0.05) in normalized P o and power, respectively. BRE MHC IIa fibres showed no change in size, P o and power after bed-rest, while V o was elevated 13% (P < 0.05). BRE MHC IIa normalized P o and power were 10 and 15% lower (P < 0.05), respectively. MHC isoform composition shifted away from MHC I fibres, resulting in an increase (P < 0.05) in MHC I/IIa (BR and BRE) and MHC IIa/IIx (BR only) fibres. These data show that the contractile function of the MHC I fibres was more affected by bed-rest and less influenced by the resistance exercise protocol than the MHC IIa fibres. Considering the large differences in power of human MHC I and IIa muscle fibres (5-to 6-fold), the maintenance of whole muscle function with the resistance exercise programme is probably explained by (1) the maintenance of MHC IIa power and (2) the shift from slow to fast (MHC I → MHC I/IIa) in single fibre MHC isoform composition.

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The present data suggest that this resistance exercise paradigm counteracts quadriceps and abates the more substantial triceps surae muscle atrophy in bedridden subjects, and therefore should be an important asset to space travellers.

Adaptive changes of major body systems in astronauts during spaceflight can be simulated by strict anti-orthostatic head-down tilt (HDT) bed rest (BR), a ground-based microgravity (microG) model that provides a meaningful opportunity to study atrophy mechanisms and possible countermeasures under controlled experimental conditions. As nitric oxide (NO) signaling is linked to muscle activity, we investigated altered expression of the three major isoforms of nitric oxide synthase (NOS 1-3) at cellular compartments during prolonged HDT BR without (control group) and with resistance exercise interventions (exercise group) using a flywheel ergometer (FWE). Atrophy detected in mixed (fast-slow) m. vastus lateralis (VL) and slow-type m. soleus (SOL) myofiber Types I and II (minus 35-40% of myofiber cross-sectional area) was prevented by FWE training. Concomitant to muscle atrophy, reduced NOS 1 protein and immunostaining was found in VL not in SOL biopsies. In trained VL, NOS 1 protein and immunostaining at myofibers II were significantly increased at the end of BR. Exercise altered NOS 2/caveolin 3 co-immunostaining patterns of subsarcolemmal focal accumulations in VL or SOL myofibers, which suggests reorganization of sarcolemmal microdomains. In trained VL, increased capillary-to-fiber (C/F) ratio and NOS 3 protein content were documented. Activity-linked NO signaling may be widespread in skeletal muscle cellular compartments that may be directly or indirectly impacted by adequate exercise countermeasure protocols to offset the negative effects induced by disuse, immobilization, or extended exposure to microgravity.

These data suggest that the exercise countermeasures programme prevented MHC shifts in the SOL and mitigated MHC shifts in the VL. Furthermore, in the VL it appears that the resistance training programme employed in this investigation during bedrest, emphasized the use of MHC IIa phenotype muscle fibres.

Ribosome biogenesis and MYC transcription are associated with acute resistance exercise (RE) and are distinct from endurance exercise in human skeletal muscle throughout a 24 h time course of recovery.r A PCR-based method for relative ribosomal DNA (rDNA) copy number estimation was validated by whole genome sequencing and revealed that rDNA dosage is positively correlated with ribosome biogenesis in response to RE.r Acute RE modifies rDNA methylation patterns in enhancer, intergenic spacer and non-canonical MYC-associated regions, but not the promoter.r Myonuclear-specific rDNA methylation patterns with acute mechanical overload in mice corroborate and expand on rDNA findings with RE in humans. r A genetic predisposition for hypertrophic responsiveness may exist based on rDNA gene dosage.Vandré C. Figueiredo completed his PhD in Biomedical Sciences at the Liggins Institute, The University of Auckland, under the supervision of Dr David Cameron-Smith before joining the laboratory of Dr John McCarthy at the University of Kentucky for his postdoctoral training in 2016. His research is focused on the role of ribosome biogenesis and the cellular signalling regulating skeletal muscle size. He seeks to understand the mechanism of muscle size determination hoping to apply this knowledge to ameliorate muscle atrophy conditions, with particular interest in ageing, cachexia and muscle disuse.

How regular physical activity is able to improve health remains poorly understood.The release of factors from skeletal muscle following exercise has been proposed as a possible mechanism mediating such systemic benefits. We describe a mechanism wherein skeletal muscle, in response to a hypertrophic stimulus induced by mechanical overload (MOV), released extracellular vesicles (EVs) containing musclespecific miR-1 that were preferentially taken up by epidydimal white adipose tissue (eWAT). In eWAT, miR-1 promoted adrenergic signaling and lipolysis by targeting Tfap2α, a known repressor of Adrβ3 expression. Inhibiting EV release prevented the MOV-induced increase in eWAT miR-1 abundance and expression of lipolytic genes. Resistance exercise decreased skeletal muscle miR-1 expression with a concomitant increase in plasma EV miR-1 abundance, suggesting a similar mechanism may be operative in humans. Altogether, these findings demonstrate that skeletal muscle promotes metabolic adaptations in adipose tissue in response to MOV via EV-mediated delivery of miR-1.