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Prolonged exposure to microgravity during spaceflights leads to severe deterioration in the physical performance of astronauts. To understand the effectiveness of existing in-flight daily countermeasures and to plan exercise onboard the International Space Station, we compared supine treadmill running to traditional upright treadmill running on earth. Specifically, we assessed the cardiorespiratory responses to conventional upright running to the responses to supine treadmill running under 0.3 g, 0.6 g, and 1 g of body weight in younger