Molecular and physiologic changes in the SpaceX Inspiration4 civilian crew.

Human spaceflight has historically been managed by government agencies, such as the NASA Twins Study1, but new commercial spaceflight opportunities have opened spaceflight to a broader population. In 2021, the SpaceX Inspiration4 mission launched the first-ever all civilian crew to low Earth orbit, which included the youngest American astronaut (age 29), novel in-flight experimental technologies (handheld ultrasound imaging, smartwatch wearables, and immune profiling), ocular alignment measurements, and new protocols for in-depth, multi-omic molecular and cellular profiling. Here we report the primary findings from the 3-day spaceflight mission, which induced a broad range of physiological and stress responses, neurovestibular changes indexed by ocular misalignment, and altered neurocognitive functioning, some of which match long-term spaceflight2, but almost all of which did not differ from baseline (pre-flight) after return to Earth. Overall, these preliminary civilian spaceflight data suggest that short-duration missions do not pose a significant health risk, and moreover present a rich opportunity to measure the earliest phases of adaptation to spaceflight in the human body at anatomical, cellular, physiologic, and cognitive levels. Finally, these methods and results lay the foundation for an open, rapidly expanding biomedical database for astronauts3, which can inform countermeasure development for both private and government-sponsored space missions.

Paving the way to better understand the effects of prolonged spaceflight on operational performance and its neural bases.

Space exploration objectives will soon move from low Earth orbit to distant destinations like Moon and Mars. The present work provides an up-to-date roadmap that identifies critical research gaps related to human behavior and performance in altered gravity and space. The roadmap summarizes (1) key neurobehavioral challenges associated with spaceflight, (2) the need to consider sex as a biological variable, (3) the use of integrative omics technologies to elucidate mechanisms underlying changes in the brain and behavior, and (4) the importance of understanding the neural representation of gravity throughout the brain and its multisensory processing. We then highlight the need for a variety of target-specific countermeasures, and a personalized administration schedule as two critical strategies for mitigating potentially adverse effects of spaceflight on the central nervous system and performance. We conclude with a summary of key priorities for the roadmaps of current and future space programs and stress the importance of new collaborative strategies across agencies and researchers for fostering an integrative cross- and transdisciplinary approach from cells, molecules to neural circuits and cognitive performance. Finally, we highlight that space research in neurocognitive science goes beyond monitoring and mitigating risks in astronauts but could also have significant benefits for the population on Earth.