Physical Activity Guidelines for Astronauts: An Immunological Perspective

Spaceflight imposes unique physiological stressors that profoundly disrupt immune regulation, including impaired lymphocyte activation, latent viral reactivation, and chronic low-grade inflammation. While structured exercise is the cornerstone countermeasure for musculoskeletal and cardiovascular health, current protocols rarely integrate immune endpoints into their design. This review aims to synthesize current evidence on the immunological effects of exercise in spaceflight and propose a novel framework for immune-focused physical activity guidelines tailored to long-duration missions. Evidence indicates that exercise intensity and modality critically determine immune outcomes. Acute strenuous exercise may transiently suppress immunity via cortisol and reactive oxygen species pathways, whereas chronic moderate-to-vigorous training enhances immune surveillance, reduces systemic inflammation, and supports T-cell and NK-cell function. Exerkines such as IL-15, IL-7, and irisin emerge as central mediators of exercise-induced immunomodulation, with potential applications for spaceflight countermeasures. Incorporating immune health into exercise guidelines represents a necessary paradigm shift for astronaut care. A structured framework-emphasizing aerobic, resistance, and HIIT modalities; moderate-to-vigorous intensity; daily training; immune biomarker monitoring; and integration with nutrition and sleep-can enhance resilience against infection, viral reactivation, and cancer risk. Immune-focused countermeasures will be essential to safeguard astronaut health and ensure mission success on future deep-space expeditions.