Monitoring and modulating interconnected physiological systems in space using portable closed-loop technologies.

Human spaceflight exposes individuals to prolonged, multifactorial stressors, including microgravity, radiation, isolation, confinement, altered light-dark cycles, and operational demands, that affect biological, cognitive, psychological, behavioral, and social domains. These stressors may contribute to body deconditioning, dysregulated stress responses, sleep disruption, increased pain vulnerability, impaired cognition, mood disturbances, and interpersonal conflict. As human space exploration moves toward longer missions beyond low Earth orbit, effective countermeasures will require small, portable, autonomous, low-power technologies capable of continuously monitoring interconnected systems and delivering personalized interventions in real-time. In this perspective, we propose that the consequences of spaceflight are best understood through a network physiology framework, in which stress regulation, sleep, pain, cognition, mood, social interaction, and other physiological functions are viewed as dynamically coupled components of an integrated system. Within this framework, disturbances in one domain may propagate to other domains, reducing resilience and increasing vulnerability to multisystem dysfunction. We discuss how advances in multimodal wearable and habitat-integrated sensing, combined with AI-based analysis, enable continuous monitoring in space-relevant environments. Body-worn and ambient sensors can capture neural, autonomic, cardiovascular, thermal, and behavioral signals, enabling longitudinal assessment of system-level adaptation. Integrating these signals with AI-based analysis may help identify deviations from adaptive network states, derive markers of multisystem resilience, and guide personalized countermeasures. We further discuss the potential of AI-guided, closed-loop, non-pharmacological interventions to restore physiological balance and maintain performance during long-duration missions. Beyond spaceflight, this framework may also inform precision health approaches to multisystem dysfunction on Earth.