Review and outlook of space human research programs

Human space exploration is entering a new era of deep space missions to the Moon, Mars, and beyond, where the combined effects of microgravity, complex radiation, confinement, and circadian disruption pose critical challenges to human health and performance. This paper systematically reviews the evolution of space human research, highlighting key milestones from early missions—such as Yuri Gagarin’s inaugural flight and Valeri Polyakov’s 437-day space endurance record—to the International Space Station era, which enabled systematic studies on physiological adaptations. These efforts have identified multisystem risks, including bone loss (1%–2% monthly), muscle atrophy, cardiovascular deconditioning, and neuro-ocular syndromes, prompting the development of countermeasures like advanced resistive exercise devices (ARED). Ground-based analogues, particularly head-down tilt bed rest (HDBR) and dry immersion, have been critical in replicating the physiological effects of weightlessness, revealing detailed mechanistic insights into fluid shift dynamics, musculoskeletal unloading, and sensory-motor conflict.Major research initiatives, such as NASA’s Human Research Program (HRP), have transitioned from addressing near-Earth orbit risks to a systematic, risk-driven framework for deep space exploration. The landmark Twins Study revealed intricate molecular-level adaptations—including telomere elongation, chromatin instability, and immune gene reprogramming—during Scott Kelly’s 340-day mission, underscoring the body’s remarkable resilience and the largely reversible nature of most changes post-flight. Concurrently, the Space Omics and Medical Atlas (SOMA) project integrated multi-omics data from missions like Inspiration4, building a multidimensional map of short-duration flight impacts on immune function, skin biology, and metabolic pathways.Research aboard China’s Tiangong Space Station constitutes a major pillar of contemporary space life science. It has enabled the acquisition of large-scale, longitudinal datasets on astronaut physiology, including cardiovascular, musculoskeletal, visual, and neuroendocrine system dynamics throughout extended missions. Chinese investigations have pioneered distinctive countermeasures, such as bone-fluid flow vibration technology for osteoporosis prevention and acupoint stimulation regimens informed by traditional medicine principles, demonstrating efficacy in mitigating specific pathologies like optic disc edema. Breakthroughs in fundamental biology include the first successful differentiation of human renal epithelial cell-derived induced pluripotent stem cells into cardiomyocytes in microgravity, revealing calcium signaling anomalies and identifying thiamine as a potential corrective agent. The development of sophisticated organ-on-chip platforms, notably a vascular tissue chip, has permitted detailed analysis of arterial remodeling and oxidative stress, validating protective compounds like flavanols. Technological innovations encompass portable detection systems integrating microfluidics and Raman spectroscopy, multi-modal cognitive performance assessment models, and the establishment of a substantial space medicine experimental database (V1.0) to support risk prediction and theoretical advancement for future lunar and deep space expeditions.Isolation studies, such as Mars-500 and SIRIUS, have further elucidated the psychosocial, sleep-circadian, and cardiovascular-metabolic interplay under confined, resource-limited conditions, highlighting the criticality of team cohesion and personalized behavioral support. Extreme environment analogs like NASA’s NEEMO and ESA’s CAVES/PANGAEA programs provide unique insights into team performance and scientific operations under isolated, high-fidelity conditions. Despite these advances, significant challenges persist in quantifying cumulative radiation risks, understanding the nonlinear, coupled effects of multiple stressors, predicting individual variability in adaptation trajectories, and validating long-duration countermeasures such as artificial gravity. Future research must leverage artificial intelligence for predictive modeling from small sample sizes, multi-omics integration for mechanistic discovery, and cross-species comparative biology (e.g., extremophile models like tardigrades) to uncover universal stress tolerance mechanisms. The development of individualized, real-time health monitoring and intervention systems will be essential. By synergizing real-flight data with ground-based simulations, space human research will not only safeguard astronauts on extended missions but also illuminate fundamental principles of life’s adaptability, ultimately supporting humanity’s transition to a sustainable, multi-planetary species.