The spaceflight environment is characterized by temperature extremes, microgravity, solar and galactic cosmic radiation, lack of atmospheric pressure, and high-speed micrometeorites. While these factors induce a host of physiological, biomedical, and environmental stressors to flight crews, long duration spaceflight has revealed an additional group of stressors that impact crew performance and health. This paper will provide members of the medical community with a basic understanding of human-related stressors in the spaceflight environment, the effects of these stressors, and the role that the behavioral sciences (e.g., psychology, human factors, sociology, habitability) play in supporting crew health in space. Some of the current tools and methodologies used by behavioral scientists for countering spaceflight stressors and promoting crew health, productivity, and mission success will also be discussed. These countermeasures allow us to sustain human presence in flight for increasing periods, as well as to participate in increasingly complex and lengthy missions. We now, however, stand on the forefront of a new challenge. Our experience in long-duration spaceflight has revealed that it is often the human element * To whom correspondence should be addressed: Senior Human Systems Engineer/SPACEHAB, NASA Johnson Space Center, 2101 Nasa Rd. 1, Houston, TX 77058, USA Supporting Human Performance in Spaceflight 75Vol. 6 No. While experience in long duration spaceflight has demonstrated how extremely capable crews are, it has also demonstrated that if designers and mission executors do not support the human factor through good design, environmental habitability, and mission support, crew productivity, health, and mission success will suffer. “I think [psychological issues] is going to be one of the major findings of this mission [Mir 18 (Norm Thagard)]. If we expect to send people on missions of two or three years, we darn well better deal Regarding the physical effects of adaptation to spaceflight, about 40-50% of flight crews during their first few days of microgravity experience a condition called Space Adaptation Sickness (SAS), which causes symptoms such as nausea, disorientation, headache, and a sea-sick or flu-like feeling. Some of the above named factors can be alleviated by exercise and pharmacological interventions, but others remain a significant obstacle to maintaining the health of astronauts during long duration missions. Similarly, crews must undergo the stress associated with re-adapting to the 1-g environment upon return to Earth. These physiological factors are a significant concern for a human mission to Mars. These and other adaptive physiological and physical processes represent change from a normal state of functioning for the astronauts and can thus contribute to increased psychological stress levels. Psychological and Interpersonal Stressors Russian and American experience has revealed the importance of the psychosocial or interpersonal stressors associated with long-duration spaceflight (9,12-14). THE EFFECTS OF STRESSORS ON FLIGHT CREWS The psychological and performance aspects of spaceflight are of particular importance at this point in time because of the deployment of ISS operations. While few performance decrements have been noted to occur during short missions (7-12 days), longer duration flights (4+ months) have revealed a tendency for astronauts to develop symptoms of cumulative fatigue and asthenia (16). Asthenia is generally characterized by abnormal fatigue, weakness, emotional lability, irritability, and minor disorders of attention and memory (16). Albert Holland, Chief of Psychological Support at NASA JSC in Houston, Texas, has been supporting crews and their families for over 15 years (see reference 14). The experience of Russia and the US in long duration spaceflight has revealed the need for psychological countermeasures to support human crews in space and facilitate their resistance to the stressors of spaceflight. Accordingly, countermeasures are being developed, validated, and implemented, which aim to lessen the impact of these stressors on crews and subsequently increase mission safety and success while lowering risk. Psychological countermeasures involve astronaut selection, training, and in-flight support. SPACE HABITABILITY Operational habitability refers to the design, integration and support of human, machine, mission, and environmental elements that promote optimal performance, physical and psychological health, and safety in long duration spaceflight. Habitability pertains to the qualities of a mission that enable people to live and work in a safe and productive manner. The characteristics of the operational mission environment can include periods of exceptionally high workload, fatigue, chronic noise, stress, temperature changes, lack of privacy, and isolation. These factors can and often have produced performance changes. Given the realization of these factors as characterizing the mission environment at times, space psychologists work to design support systems and countermeasures that will aid crewmembers when these effects are experienced. CONCLUSION Long duration spaceflight has revealed a multitude of psychological, physiological, psychosocial and environmental-interface challenges to crews operating within them. 9th International Man in Space Symposium, Cologne, Germany, International Academy of Astronautics, 1991; 37. 18. Shaposhnikov YeA, Malinkina YuA, Rudometkin NM, Gerasimovich AA. Selected conclusions from psychoneurological monitoring of the status of cosmonauts on space station Mir. 24th Meeting of the Working Group on Space Biology and Medicine, Moscow, 1991; 49-50. 19. Galarza L, Holland AW, Arvey RD, et al. Identifying psychological predictors of astronaut adaptation to long duration space missions. Proceedings of the Aerospace Medical Association Annual Meeting, Detroit, MI; 1999. 20. Whitmore M, McQuilkin M.

As humanity advances into deep space exploration, astronauts on long-duration missions face significant challenges posed by circadian rhythm disruptions and sleep disorders, which arise from extreme environmental stressors such as microgravity, ionizing radiation, and operational workload. These disruptions not only compromise physiological and psychological health but also impair cognitive function and mission-critical performance. In this review, we summarized established countermeasures encompassing pharmacological interventions, light-based circadian regulation, and work–rest schedule optimization alongside innovative approaches such as gut microbiota modulation and traditional Chinese medicine. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/ ). Abstract As humanity advances into deep space exploration, astronauts on long-duration missions face significant challenges posed by circadian rhythm disruptions and sleep disorders, which arise from extreme environmental stressors such as microgravity, ionizing radiation, and operational workload. These disruptions not only compromise physiological and psychological health but also impair cognitive function and mission-critical performance. Introduction The circadian rhythm is an internal timing mechanism that organisms have evolved to adapt to the Earth’s 24 h rotation, important for maintaining physiological health, cognitive function, and work performance [ 1 ]. Human sleep–wake cycles represent a core component of this regulatory system, governed by periodic fluctuations aligned with diurnal light–dark cycles. As global space exploration progresses toward long-duration missions, astronauts encounter extreme environments lacking the natural 24 h light–dark periodicity essential for circadian stability. While adequate sleep and alertness maintenance are essential for executing mission-critical tasks, increasing evidence indicates that circadian misalignment and sleep dysfunction are common among astronauts. The combined effects of sleep deprivation, circadian disruption, prolonged wakefulness, and high workload elevate the risk of operational errors, a paramount safety concern for current and future space missions [ 9 ]. Notably, NASA classifies sleep deficiency and circadian rhythm disorders as Category 1 risks for long-duration spaceflight [ 3 ], underscoring the urgent need for strategies to stabilize circadian function and optimize sleep for crew health and mission safety. Astronauts must frequently adjust schedules under communication delays to adapt to evolving mission priorities, making enhanced crew autonomy critical. Future schedules will likely prioritize astronaut self-management to balance task-rest time, ensuring sufficient sleep while achieving mission objectives, especially for long-duration autonomous missions like deep space and Mars exploration. Therefore, decision-support tools are essential. The Fatigue Avoidance Scheduling Tool (FAST™), originally developed for aircrew scheduling optimization, could be adapted with mission-specific constraints to improve prediction accuracy and utility for astronaut self-scheduling. Biomathematical models to predict fatigue [ 57 ] could further assist in optimizing rest periods, particularly for long-duration autonomous missions to Mars and beyond. Studies indicate non-professional schedulers struggle with complex constraints [ 58 ], making such tools critical for maintaining performance under demanding conditions. 5. Human Flora Therapy Existing circadian interventions for astronauts (pharmacotherapy, phototherapy, schedule adjustments) face limitations including side-effects and limited long-term efficacy. Emerging research highlights the gut microbiota’s critical role in sleep regulation through multiple biological pathways. In summary, gut microbiota interventions offer innovative solutions for astronaut sleep disorders, but translation to space requires addressing environmental stability, individualization, and operational feasibility. Integrating these approaches with existing countermeasures may enhance circadian resilience for long-duration missions. 6. Traditional Chinese Medicine Treatment In recent years, Traditional Chinese medicine (TCM) has emerged as a Further research is needed to establish safety, efficacy, and compatibility with existing aerospace medical protocols, ensuring its integration as a complementary strategy for managing astronaut sleep health during long-duration missions. 7. Discussion As human space exploration advances, an increasing number of astronauts are undertaking long-duration missions, during which circadian rhythm disruption and sleep disturbances are frequently reported among crew members. Inadequate sleep duration and quality pose risks to astronauts’ physical and mental health, as well as mission success. Zhang Yang’s team established PBPK models for rats under simulated weightlessness to extrapolate human PK for folic acid and Zolpidem tartrate [ 130 ]. To further advance research in space pharmacokinetics, Microphysiological systems (MPSs), also known as organ-on-a-chip systems, already deployed on the ISS, provide more physiologically relevant platforms for space PK research [ 131 ]. Enhancing international collaboration and data sharing will facilitate systematic, controlled in-space PK experiments to optimize dosing and develop astronaut-tailored therapeutics. Drug stability is critical for long-duration missions (≥2 years). In conclusion, addressing astronaut sleep disorders requires integrating diverse countermeasures, prioritizing space-adaptive PK/PD research, and advancing diagnostics. Ground-based models and in-space trials must be complemented by international collaboration to ensure evidence-based, safe, and effective solutions for long-duration missions.

During future long-duration space exploration missions, humans will be exposed to combinations of extreme physical, psychological, and interpersonal demands. These demands create risks for the safety, performance, health, and well-being of both individuals and crew. The communication latency in deep space means that explorers will increasingly have to operate independently and take responsibility for their own self-care and self-management. At present, several research programs are focused on developing and testing digital technologies and countermeasures that support the effective functioning of deep space crews. Although promising, these initiatives have been stimulated mostly by technological opportunity rather than cogent theory. In this perspective, we argue that digital technologies developed for spaceflight should be informed by well-being-supportive design principles and be cognizant of broader conversations around the development and use of digital health applications, especially pertaining to issues of autonomy, privacy, and trust. These issues are important for designing potentially mission-critical health technologies and may be determining factors in the safe and successful completion of future off-world endeavors.

<h4>Background</h4>Space exploration, especially long-duration missions such as those to Mars, presents unique and significant challenges to astronaut health. Space medicine, which focuses on maintaining health in extreme environments without access to definitive medical care, emphasizes preventive measures. Lifestyle medicine (LM), grounded in six pillars such as healthy nutrition, regular physical activity, restorative sleep, stress management, positive social connections, and avoidance of risky substances, has proven effective for disease prevention on Earth. However, its application to spaceflight and remote Earth environments remains underexplored. This raises the question of how LM framework can sustain astronaut health and inform preventive and primary care strategies for remote Earth populations.<h4>Objective</h4>This narrative review examines how LM can support astronaut health during long-duration missions and draws parallels with healthcare needs in remote Earth populations. It establishes principles for integrating lifestyle and space medicine and provides recommendations for their application in both contexts.<h4>Results</h4>Each LM pillar is uniquely challenged in space. Nutritional constraints arise from limited food variety and storage capacity; microgravity and workload restrictions limit physical activity; circadian disruption and environmental noise affect sleep; isolation, confinement, and mission stress compromise stress regulation and social connections; restricted crew size and communication delays limit social connection; and strict medication policies highlight the dual role of substance use as both risks and necessity. While individual countermeasures have been tested in space, no integrated framework addressing all pillars simultaneously has yet been implemented. Technological innovations, such as wearable devices for continuous monitoring, telehealth modules for remote support, and virtual reality platforms for mental health and social en Objective This narrative review examines how LM can support astronaut health during long-duration missions and draws parallels with healthcare needs in remote Earth populations. It establishes principles for integrating lifestyle and space medicine and provides recommendations for their application in both contexts. Results Each LM pillar is uniquely challenged in space. Space medicine and astronaut healthcare is an area where health management autonomy will become increasingly important, especially in the context of longer exploration missions to the Moon and Mars ( Patel et al., 2020 ; Komorowski et al., 2021 ). Mission durations vary significantly, with short missions lasting less than 30 days, mid-term missions lasting up to 6 months on stations like Mir or ISS, and long-duration interplanetary missions presenting complex health challenges ( Cinelli et al., 2020 ). Long-duration interplanetary and deep space exploration missions, like lunar bases and Mars colonization, present unique and extended health challenges ( NASA, 2020 ; Air and Space, 2017 ; Kahn et al., 2014 ). These missions amplify the hostile space environment, requiring astronauts to adapt and to maintain physical health, cognitive function, and psychological resilience over prolonged periods. Recent studies have identified key physiological and clinical challenges associated with long-duration space missions and outlined directions for future research ( Nguyen and Urquieta, 2023 ; Tomsia et al., 2024 ). For example, mindfulness and relaxation practices have emerged as key tools for managing stress in space for long-duration missions ( Pagnini, 2024 ). These practices may help astronauts stay As mission durations have shifted from short-term flights during the shuttle era to long-duration stays aboard the ISS, and now towards even longer deep space missions to Mars, astronauts are increasingly exposed to the cumulative effects of psychosocial stressors. Mission length is hypothesized to be a key factor influencing social dynamics, as several indicators of crew functioning have been reported to decline over time ( Kanas et al., 2009 ). This suggests that spaceflight impacts short-duration crews differently than long-duration crews. Reintegration after space flight represents a critical moment as many challenges can be experienced for both astronauts and their families. Indeed, reunion after long term separation requires reshaping family dynamics and re-establishing interpersonal roles. Research on how absent astronauts experience these challenges is scarce ( Johnson et al., 2012 ). However, studies have shown this period may involve reduced mood and performance, and in some cases, major depressive disorders, anxiety, or substance use requiring medical and psychological support ( Le Roy et al., 2023 ). However, while many substances are prohibited, the extreme psychological stressors of long-duration and deep-space missions could increase the theoretical risk of misuse if any substances were available, underscoring the importance of prioritizing psychological rather than pharmacological coping strategies. As missions extend beyond low Earth orbit, new challenges emerge. Isolation, disrupted circadian rhythms, and mission-related stress are known to affect mental wellbeing ( Kanas, 1998 ; Flynn, 2005 ; Kalb and Solomon, 2007 ; Kandarpa et al., 2019 ; Marazziti et al., 2022 ). While these experiences occurred post-mission rather than in-flight, they highlight the importance of destigmatizing mental healthcare and substance use disorders in astronaut population. Doing so will not only allow astronauts to receive appropriate support but also foster an environment where prevention and early intervention are possible. Before the mission, astronauts already undergo rigorous psychological evaluations, but future long-duration expeditions may require more comprehensive screening using validated tools adapted for spaceflight to better detect vulnerabilities.

UNSTRUCTURED The psychological well-being of astronauts is becoming just as vital as their physical and technical readiness as space missions extend into deep space. Long-duration missions pose unique challenges, such as isolation, confinement, communication delays, and microgravity, which can significantly affect mental health and cognitive performance. This commentary discusses the need for innovative mental health support systems, including automated psychotherapy, as well as Earth-based training methods like mindfulness and relaxation techniques, to address the psychological demands of space travel. By integrating these approaches into pre-mission preparation and in-flight routines, astronauts can develop self-regulation strategies to manage stress, improve focus, and enhance emotional resilience. Automated psychotherapy available 24-7 provides real-time confidential support when communication with Earth is delayed. As space exploration moves forward, the success of missions will depend not only on technological advancements but also on the development of psychological countermeasures that prioritize mental health alongside physical well-being. This paper emphasizes the importance of continued research and collaboration to refine and test these tools in analog environments, ensuring astronauts are mentally and emotionally prepared for the challenges of space.

Microgravity, confinement, isolation, and immobilization are just some of the features astronauts have to cope with during space missions. Consequently, long-duration space travel can have detrimental effects on human physiology. Although research has focused on the cardiovascular and musculoskeletal system in particular, the exact impact of spaceflight on the human central nervous system remains to be determined. Previous studies have reported psychological problems, cephalic fluid shifts, neurovestibular problems, and cognitive alterations, but there is paucity in the knowledge of the underl

Long duration missions present numerous risks to crew health and performance. The international space community is actively studying these effects and possible mitigation techniques, but much work remains to be done. As such the space community and space agencies are increasingly cooperating to enable timely answers in support of exploration mission needs. Crew health and performance are critical to successful human exploration. Long-duration missions bring numerous risks that must be understood and mitigated in order to keep astronauts healthy, rather than treat a diagnosed health disorder. C

"Since its inception, the U.S. human spaceflight program has grown from launching a single man into orbit to an ongoing space presence involving numerous crewmembers. As the U.S. space program evolves, propelled in part by increasing international and commercial collaborations, long duration or exploration spaceflights - such as extended stays on the International Space Station or missions to Mars - become more realistic. These types of missions will likely expose crews to levels of known risk that are beyond those allowed by current health standards, as well as to a range of risks that are po

The medical care of space crews is the primary limiting factor in the achievement of long-duration space missions. (Nicogossian 2003) The goal of this thesis was to develop a model of long-duration human space flight astronaut health and a medical supply demand model in support of such missions. This model will be integrated into an existing comprehensive interplanetary supply chain management and logistics architecture simulation and optimization tool, SpaceNet. The model provides two outputs, Alphah and Mass, for each set of input variables. Alphah is an estimate of crew health and is displa

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