Muscle unloading: A comparison between spaceflight and ground‐based models

Abstract

Prolonged unloading of skeletal muscle, a common outcome of events such as spaceflight, bed rest and hindlimb unloading, can result in extensive metabolic, structural and functional changes in muscle fibres. With advancement in investigations of cellular and molecular mechanisms, understanding of disuse muscle atrophy has significantly increased. However, substantial gaps exist in our understanding of the processes dictating muscle plasticity during unloading, which prevent us from developing effective interventions to combat muscle loss. This review aims to update the status of knowledge and underlying mechanisms leading to cellular and molecular changes in skeletal muscle during unloading. We have also discussed advances in the understanding of contractile dysfunction during spaceflights and in ground‐based models of muscle unloading. Additionally, we have elaborated on potential therapeutic interventions that show promising results in boosting muscle mass and strength during mechanical unloading. Finally, we have identified key gaps in our knowledge as well as possible research direction for the future.

Effects of Spaceflight on Musculoskeletal Health: A Systematic Review and Meta-analysis, Considerations for Interplanetary Travel

“…Research articles were included and eligible within this review provided that (1) group means and standard deviations for pre-and post-spaceflight measures of strength, muscle mass or BMD were reported (or provided by the corresponding author when requested via e-mail), ( 2) exercise-based countermeasures to mitigate the detrimental effect of µG on muscle force production, muscle mass or BMD were included, (3) the population of the studies were human, (4) muscle function (e.g., strength or power) assessments were included, and finally (5) spaceflight rather than simulated spaceflight / µG was used. Studies which included actual spaceflight were selected as immobilization and bed rest have been reported to be a poor analogue for the study of changes in muscle mass associated with spaceflight, due to differences in activity and energy balance, along with environmental and methodological differences [2,5,46,47]. Studies were excluded if: they were written in a language other than English, were published abstracts (from conference proceedings), did not include means and standard deviations for both pre-and post-spaceflight, if simulated spaceflight/simulated µG were used, if they used animal models (observation of animals in orbit are not ideal models of the effects of spaceflight on human bone [2,48]), or assessed muscle changes from muscle biopsies, along with any systematic or narrative reviews.…”

“…Such flywheel devices have been used in studies where bedrest is used as an analogue for µG, with the results of such studies highlighting that such countermeasures can negate the detrimental effects of simulated µG in, terms of force production, muscle mass and fiber type shifts [74,75,103,104] and may offset the interference effects of concurrent training [105]. It is not clear whether these beneficial effects of such countermeasures are a result of the higher loads and lower repetitions used, when compared to actual exercise reported by ISS crewmembers, or due to the differences in simulated and actual µG [2,5,46,47].…”

Mammalian circadian systems: Organization and modern life challenges

“…During space flight, astronauts are exposed to changes in basically all environmental Zeitgebers experienced on earth. Sunrise and sunset occur approximately every 45 minutes, instead of every 24‐hours, diets and potentially feeding‐fasting cycles are altered, and microgravity entails prolonged muscle unloading and induces a fluid shift in the human body, impacting the metabolic, mechano‐skeletal and cardiovascular systems 256,257 . Interestingly, however, circadian rhythms in blood pressure have been shown persist in space with lower pressure during sleep 258‐260 .…”

Plantar Stimulations during 3-Day Hindlimb Unloading Prevent Loss of Neural Progenitors and Maintain ERK1/2 Activity in the Rat Hippocampus

“…There are no data about the functional state of adult neurogenesis during or after space flight, but a few papers demonstrated negative effects of long-term hindlimb unloading (HU) on the hippocampal neurogenesis of rodents [8,9]. HU is a widely used model of simulated microgravity that reproduces such changes as reduced motor activity, atrophy of hindlimb muscles, and cephalic fluid shift [10,11]. To prevent muscle atrophy, dynamic foot stimulation (DFS) of the plantar Life 2021, 11, 449 2 of 8 surface was invented firstly for astronauts [12] and then for rodents [13].…”