Prolonged periods in microgravity (μG) environments result in deconditioning of numerous physiological systems, particularly muscle at molecular, single fiber, and whole muscle levels. This deconditioning leads to loss of strength and cardiorespiratory fitness. Loading muscle produces mechanical tension with resultant mechanotransduction initiating molecular signaling that stimulates adaptations in muscle. Exercise can reverse deconditioning resultant from phases of detraining, de-loading, or immobilization. On Earth, applications of loading using exercise models are common, as well as in μG settings as countermeasures to deconditioning. The primary modalities include, but are not limited to, aerobic training (or “cardio”) and resistance training, and have historically been dichotomized; the former primarily thought to improve cardiorespiratory fitness, and the latter primarily improving strength and muscle size. However, recent work questions this dichotomy, suggesting adaptations to loading through exercise are affected by intensity of effort independent of modality. Furthermore, similar adaptations may occur where sufficient intensity of effort is used. Traditional countermeasures for μG-induced deconditioning have focused upon engineering-based solutions to enable application of traditional models of exercise. Yet, contemporary developments in understanding of the applications, and subsequent adaptations, to exercise induced muscular loading in terrestrial settings have advanced such in recent years that it may be appropriate to revisit the evidence to inform how exercise can used in μG. With the planned decommissioning of the International Space Station as early as 2024 and future goals of manned moon and Mars missions, efficiency of resources must be prioritized. Engineering-based solutions to apply exercise modalities inevitably present issues relating to devices mass, size, energy use, heat production, and ultimately cost. It is necessary to identify exercise countermeasures to combat deconditioning while limiting these issues. As such, this brief narrative review considers recent developments in our understanding of skeletal muscle adaptation to loading through exercise from studies conducted in terrestrial settings, and their applications in μG environments. We consider the role of intensity of effort, comparisons of exercise modalities, the need for concurrent exercise approaches, and other issues often not considered in terrestrial exercise studies but are of concern in μG environments (i.e., O2 consumption, CO2 production, and energy costs of exercise).

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