Abstract
The central biomedical challenge for human exploration is not simply how far spacecraft can travel but whether human physiology can adapt safely to prolonged life beyond Earth.Spaceflight provides a unique testbed for defining the limits of physiological adaptation and resilience.The human body, adapted to Earth's gravitational environment, must respond simultaneously to microgravity or partial gravity, ionising radiation, altered atmospheric composition, circadian disruption and confinement.Determining when these responses progress from adaptation to deconditioning, disease and impaired operational performance is essential for crew health and mission success.The resulting insights also inform ageing, physical inactivity, critical illness, musculoskeletal and cardiovascular disease, and healthcare delivery in remote or resource-limited environments.This is a particularly timely period for space physiology.On 6 April 2026, Artemis II conducted the first crewed lunar flyby in >50 years, with subsequent Artemis missions intended to support sustained human activity on and around the Moon and prepare for future missions to Mars (National Aeronautics & Space Administration, 2026).Beyond low Earth orbit, longer mission durations, delayed communications, the absence of rapid evacuation, and sustained exposure to interacting environmental stressors fundamentally alter the biomedical context.Crew members will consequently require greater autonomy in monitoring and managing their health.Together, these environmental and operational hazards comprise the space exposome, i.e., the cumulative mission exposures and their interactions with individual susceptibility.The space integrome describes the corresponding integrated, multiscale biological response across genes, molecules, cells, tissues, organs, physiological systems and behaviour, which collectively determines adaptation, resilience or maladaptation (Bailey, 2025; Bailey et al., 2025).Deeper longitudinal phenotyping of the exposome-integrome interaction is therefore needed to determine how combined stressors modify individual risk and to guide personalised countermeasure selection.Although >30 health risks have been associated with exploration-class missions, the additive, antagonistic and non-linear effects of combined exposures remain poorly characterised (Bailey, 2025; Bailey et al., 2025).