Physical exercise protects cardiovascular fitness in long-term spaceflight: what have we learned?

As space exploration advances into the era of deep space exploration, humanity faces unprecedented challenges in maintaining astronaut health, not only during prolonged space travel but also in adapting to low-gravity environments, such as those on the Moon or Mars. Extended exposure to the space environment accelerates the physiological aging process, triggering changes that impact multiple systems. These effects highlight the urgent need for effective countermeasures. Exercise has been shown to mitigate the detrimental impacts of microgravity on cardiovascular and musculoskeletal systems, including reduced cardiac reserve, arterial stiffening, venous thrombosis, metabolic dysfunction, and frailty. In addition, exercise offers potential benefits in reducing aging-related declines in mental health and immune function during extended space missions. This review synthesizes evidence on physical exercise as a critical countermeasure, analyzing its role across the mission lifecycle: pre-flight conditioning, in-flight mitigation, and post-flight rehabilitation, as well as the underlying mechanisms involved. We also evaluate strategies for optimizing exercise regimens and key metrics for assessing astronaut health outcomes. Developing scientifically rigorous, individualized exercise protocols supported by emerging technologies such as artificial intelligence promises to enhance astronaut cardiovascular health, optimize mission performance, and minimize the risks associated with long-duration space travel and gravity variations.