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MINI REVIEW article

Front. Physiol., 03 October 2025

Sec. Environmental, Aviation and Space Physiology

Volume 16 - 2025 | https://doi.org/10.3389/fphys.2025.1663701

This article is part of the Research TopicInnovations in Tools and Methods for Life Sciences Research in SpaceView all 5 articles

Beyond the lab coat: methodological challenges in space life sciences

Martine Van Puyvelde,,
Martine Van Puyvelde1,2,3*Nicholas H. van den Berg,Nicholas H. van den Berg1,4Lara StasLara Stas5Perseverence Savieri,Perseverence Savieri5,6Hortense Corly,Hortense Corlùy1,7Jeroen Van Cutsem,Jeroen Van Cutsem1,7Xavier NeytXavier Neyt1Guido Simonelli,,Guido Simonelli4,8,9Nathalie Pattyn,,Nathalie Pattyn1,4,8
  • 1VIPER Research Unit, LIFE department, Royal Military Academy, Brussels, Belgium
  • 2Brain, Body and Cognition, Faculty of Psychology and Educational Sciences, Vrije Universiteit Brussel, Brussels, Belgium
  • 3School of Natural Sciences and Psychology, Faculty of Science, Liverpool John Moores University, Liverpool, United Kingdom
  • 4Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Coeur de Montréal, CIUSSS du Nord de l’Île-de-Montréal, Montreal, QC, Canada
  • 5Core Facility-Support for Quantitative and Qualitative Research, Vrije Universiteit, Brussels, Belgium
  • 6Faculty of Medicine, Research Center for Digital Medicine Research Group, Vrije Universiteit, Brussels, Belgium
  • 7Human Physiology and Sports Physiotherapy Research Group, Vrije Universiteit Brussel, Brussels, Belgium
  • 8Department of Medicine, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada
  • 9Department of Neuroscience, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada

As plans for deep space and long-duration missions advance, research in space and space-analog environments is becoming an urgent scientific priority. However, this type of fieldwork poses a unique set of challenges. The development of research methodologies and designs cannot rely on broad evidence base and thus requires scientific judgment and multidisciplinary psychophysiological expertise. Most studies comprise small samples, often lack control groups, sex differences have seldom been directly tested in this area and inter-individual variability is prevalent in this population. Moreover, this research domain is characterized by several exceptional factors that must be addressed. The target population is highly trained and not representative of the general population, demanding adapted study designs and highly sensitive and operationally relevant research tools. To avoid overburdening the already heavy operational schedules of this population, a careful and feasible balance must be established between scientific data quality and acceptable monitoring load. Furthermore, several issues of location, timing, and type of baseline measures must be explicitly considered, while long-term follow-up designs are necessary to assess both recovery and persistent post-mission effects. Major space agencies have indeed identified methodological issues as a knowledge gap in this area. In this review, we provide an overview of these methodological challenges unique to space life sciences and offer solutions where possible. We argue that space research remains feasible despite these constraints, but only when it is approached with the understanding that such fieldwork often requires fundamentally different methods than traditional laboratory science.

Introduction

Humanity is increasingly aiming for a long-term presence in space. To support this goal, space life sciences encompass multiple research domains, each contributing to our understanding of human adaptation. As recently summarized (Berliner et al., 2024), three major areas intersect here. First, technological innovations to support space travel; second, environmental research on potentially sustaining future life; and third, studies on the physiological and psychological effects of spaceflight—covering the so-called “human factor”. In the context of the current article, the human factor refers to the adaptability of the atypical, highly trained operator who typically performs above average across all performance domains (Strangman et al., 2014).

The major space agencies have each defined research roadmaps providing a comprehensive overview of knowledge gaps (e.g., European Space Agency, 2016). The current review aims at identifying the unique methodological challenges posed by the space environment which need to be addressed to close those knowledge gaps. These challenges may affect every phase of research—from design over field data collection to final statistical analysis and interpretation. This methodological perspective thus identifies recurring pitfalls and highlights proposed solutions. Hence, this is not an exhaustive review, but a summary of key methodological patterns and constraints observed in space (-analog) studies.

Sampling challenges in space research: small samples, sex differences, inter-individual variability and the absence of control groups

Small sample sizes

The NASA Apollo Biomedical Results Report (1974) stated: ‘… because of the small number of individuals who flew in space and because of the variability of their responses, it was impossible to distinguish between space-related physiological changes and individual physiological variations (Johnston and Dietlein, 1974, p.43)’.

To date, little has changed. The literature on space-related research remains saturated with concerns regarding small sample sizes that are statistically underpowered, inter-individual variability that hinders distinction between environmental- and individual-related factors and the absence of control groups (e.g., Clément, 2025; Desai et al., 2022; Mairesse et al., 2019; Pattyn et al., 2009; Stavnichuk et al., 2020; Strangman et al., 2014). This raises the question as to how to address the problem.

A possible solution is to promote international cooperation by standardizing protocols across space agencies, facilitating data sharing, and enabling joint analyses across missions (Desai et al., 2022; Roberts et al., 2020; Stavnichuk et al., 2020; Van Ombergen et al., 2022). Similarly, some authors pooled blood sample data (e.g., Bisserier et al., 2021; Brojakowska et al., 2022) or densitometry results (Sibonga et al., 2015) across ISS and MIR missions.

Molecular biology seemed like a way around the small number of individuals. This includes cross-species cell analyses, development of predictive models, real-time monitoring, and standardization of crew dose and risk metrics related to cosmic radiation (Slaba et al., 2025; Willis et al., 2024). For instance, Galčenko et al. (2025) used transcriptomic data from human cell lines exposed to microgravity and Michaletti et al. (2017) examined osteoblasts from three healthy hip-replacement donors. However, even here, Stavnichuk et al. (2020) reported high variability in bone formation markers and emphasized that more data are needed to determine to what extent individual covariates (e.g., age, physical activity, nutrition) may influence outcomes.

Sex differences

Regarding sex-differences, space research data are even scarcer. Earth-based evidence shows differences in sleep, activity, and cognition—domains critical for mission success. Women generally sleep longer but experience more wake after sleep onset (WASO) and insomnia (Jonasdottir et al., 2021). In a hypoxic bedrest space analog, the return of WASO-deviations to baseline was absent in females (Van Cutsem et al., 2022). During Antarctic overwintering, only men showed activity decline, but women reported more sleep and psychosocial disturbances (Steinach et al., 2016). Cognitively, women prioritize accuracy over speed and men vice versa—indicating complementary strengths (Hughes-Fulford et al., 2024; Mark et al., 2014). Though more prone to motion sickness, women may outperform men in vestibular tasks, albeit with higher variability (Zhang et al., 2024).

In space, female astronauts showed higher rates of immediate post-flight orthostatic intolerance—the inability to remain upright without fainting—and greater plasma volume loss (Mark et al., 2014). Some authors suggest that radiation exposure limits are lower for women (e.g., Mark et al., 2014; Parihar et al., 2020). Likewise, rodent studies indicated that radiation may threaten cognition through neuroinflammation and hippocampal damage (Krukowski et al., 2018). On the other hand, Hughes-Fulford, 2023a emphasized that there is no clear evidence that women are at higher risk of radiation-related effects during the mission, only that postflight cancer risk may reduce their lifespan by 3%. Nevertheless, one fundamental difference between men and women is that women “carry” all their gametes at all times, potentially increasing the risk of radiation-related effects on future offspring.

To address these problems, researchers propose to increase female participation in spaceflights, in order to improve our understanding and move beyond the default male model (D’souza et al., 2022; Mark et al., 2014). For instance, when it concerns countermeasures, an increased sex-disaggregated approach could lead to more adjusted female space health and security measures for women in space.

Statistical and methodological considerations

When studying small populations, researchers face profound statistical challenges that demand tailored approaches different from conventional inferential methods. In such contexts, classical hypothesis testing becomes underpowered, p-values unstable, and models may fail to converge, while the power and generalizability of findings remain limited (Pattyn et al., 2009). Moreover, traditional techniques such as repeated-measures ANOVA can exacerbate the problem by applying listwise deletion, thereby further reducing statistical power. Corrections for multiple comparisons, such as Bonferroni adjustments, are also overly conservative in this context, increasing the risk of Type II errors (i.e., not finding a true effect).

Therefore, tailored analytical approaches are needed. A key distinction must be made between studies that describe the entire astronaut population and those that collect a sample from a wider reference population. In the first case, when all individuals in the target group are observed (e.g., all active astronauts on a certain mission), statistical inference is unnecessary—here, descriptive statistics, individual-level analyses, and visualizations suffice. However, if the goal is to generalize to a broader population (e.g., astronauts across agencies or future crews) statistical inference becomes necessary and must be adapted to small-sample limitations.

In this context, researchers are encouraged to focus on effect sizes, and the uncertainty of parameter estimates via confidence intervals. Effect sizes quantify the magnitude of observed effects. For example, effect sizes can reflect the strength of physiological changes in response to spaceflight. Confidence intervals indicate estimate precision with wider intervals signalizing greater uncertainty.

A helpful analytical approach in small sample studies might be using Bayesian methods. They allow the incorporation of prior knowledge (e.g., from analog populations or historical missions) to stabilize estimates and improve inference (Gelman and Shalizi, 2013; McElreath, 2020). Also, hierarchical (multilevel) models can be considered useful, as they can borrow strength across repeated measures or related individuals (e.g., astronauts in the same space shuttle) to enhance power and account for nested data structures. These models naturally accommodate missing data under more realistic assumptions (e.g., missing at random), making them more appropriate than techniques like repeated-measures ANOVA. They also allow researchers to model individual differences explicitly. This is particularly useful because intra-individual variability often exceeds between-group differences (e.g., sex-differences) in astronaut research (Robin et al., 2023).

Lastly, to eliminate the effect of confounding variables in the context of limited power, Pattyn et al. (2009) suggested comparing data from individual astronauts to carefully matched control groups (matching based on gender, background variables and other relevant features).

Absence of control groups

Control groups have only become common in recent studies. Yet, without control groups, distinguishing environmental from individual factors remains difficult. Matching for the multiple stressors faced in space is not evident (Desai et al., 2022), but some innovative approaches have been suggested. Pattyn et al. (2009) matched astronauts with similar control groups to apply neuropsychological analyses of cognition in flight. To study radiation effects, Boice (2019) proposed examining cognitive performance in nuclear workers with high radionuclide exposure with astronaut-standardized tasks. The NASA Twins Study (Garrett-Bakelman et al., 2019) compared an astronaut in space with his identical twin on Earth and Moore et al. (2019) used a matched ground-control group and a sleep-restricted cohort. Bosch-Bruguera et al. (2021) also used a matched control-group in a longitudinal design to account for maturation effects of their investigation of skill decay over time during an Antarctic overwintering. Moreover, as will be discussed below, the use of control groups has already yielded new insights into cognitive impairment in space that were previously not available (e.g., Kuldavletova et al., 2023; Moore et al., 2019; Pattyn et al., 2009; Stahn et al., 2019). Therefore, authors are encouraged to invest time and resources in research designs implementing control groups.

Measurement validity under operational constraints: from test batteries to wearables under controlled conditions

Sensitivity and accuracy of a standardized cognitive test battery adapted to space operationality: how to measure a rigorously trained population

Given the exceptional cognitive profile of astronauts, current test batteries may lack the sensitivity to detect subtle impairments (Fowler and Manzey, 2000; Pattyn et al., 2009; Strangman et al., 2014; Van Puyvelde et al., 2022a) as well as tasks capturing the operational relevance critical for mission success (Moore et al., 2019; Petit et al., 2019; Wenzel, 2021). Although many studies reported no cognitive decline or even improvement during missions (e.g., Dev et al., 2024; Garrett-Bakelman et al., 2019; Slack et al., 2016; Paul et al., 2010), other findings—including both anecdotal descriptions such as self-reports and interviews (e.g., Bluth, 1984; Johnston and Dietlein, 1974; Burgess, 2000; Manzey et al., 1995; Van Puyvelde et al., 2022b) and studies using operational tasks, control groups and brain references—found impairments that persisted, even after return to Earth (e.g., Clement, 2025; Kuldavletova et al., 2023; Moore et al., 2019; Pattyn et al., 2009; Jones et al., 2022; Petit et al., 2019; Stahn et al., 2019). Therefore, the observed improvements in certain studies might reflect learning or observer effects (e.g., Clément, 2025; Desai et al., 2022; Strangman et al., 2014) rather than true enhancement. Indeed, Benke et al. (1993) used 30 habituation sessions over 8 months pre-flight to avoid learning effects in-flight. However, aiming for maximal stabilization of performance also means losing sensitivity to environmental or situation influences, trade-off performance scientists are well aware of (Pattyn et al., 2024). Accordingly, Wenzel (2021) emphasized the need to define clear thresholds for acceptable versus unacceptable performance. This implies that both baselines and normative criteria must be tailored to specific tasks to determine when performance has significantly declined.

Sensitivity and accuracy of wearables: how to balance monitoring load and scientific data quality

Survey fatigue and monitoring burden remain key challenges in every type of fieldwork including space (-analog) research (Ghafourifard, 2024; Andreassi, 2007; Kelly et al., 2005), especially when workload, sleep loss, and frustration start to accumulate (Pattyn et al., 2018; Van Puyvelde et al., 2022a). Therefore, finding a balance between data-collection quality and practical feasibility in terms of crew’s preference and environmental constraints is critical. Wearables are gaining popularity as practical, user-friendly alternatives (Fonseca et al., 2017) despite the lack of a robust multistage validation (Doherty et al., 2024; Giurgiu et al., 2023); hence, blurring lines between commercial and scientific use (Baron et al., 2018; Lee and Finkelstein, 2015).

This search for balance between the scientific ideal and environmental realities may explain why Jones et al. (2024) used the Apple Watch Series 6 to assess heart rate variability—despite previous studies showing its limited accuracy even in resting position (e.g., Bonneval et al., 2025; O’Grady et al., 2024), let alone in dynamic operational settings. Similarly, the choice to use 1-h HRV windows rather than the 3–5 min guidelines (non-stationarity, Berntson et al., 1997) and omitting raw signal quality checks draws the attention to the importance of ensuring that practicality does not come at the expense of scientific and physiological expertise.

Baseline? the importance of longitudinal investigations

Multiple stressors may elicit distinct physiological or cognitive responses (Wenzel, 2021). The timing, location, and type of baseline measures must therefore be chosen carefully. Longitudinal time-points can robustly build a reference framework for each participant. For instance, physiological stress research distinguishes between phasic (acute) and tonic (anticipatory) stress responses—such as pre-mission logistical or personal concerns—which can confound both baseline and subsequent in-flight measures (Pattyn et al., 2009; Van Puyvelde et al., 2020). Such baseline distortions may help explain reported in-flight cognitive improvements. Indeed, a closer look at the TWIN Study (Garrett-Bakelman et al., 2019) results reveals conspicuously low baseline levels compared to the early in-flight performance. Besides timing, baseline locations must also be consistent or contextually meaningful (Bialeschki et al., 2012). Overall, based on psychophysiological research, three types of baselines are recommended: (1) a resting baseline to compare with resting in-flight measures, (2) a “vanilla” baseline (i.e., a neutral task matched in sensory/motor load to the experimental task), to isolate metabolic effects inherent to the imposed task (Tininenko et al., 2012), and (3) a task-specific physiological baseline to compare with in-flight measures across conditions.

Careful timing is also crucial for in-flight measures, as most adaptation timelines for basic physiological processes still need to be defined. Entering space was described as a “traumatic experience of habituative adaptation,” sometimes reducing workload capacity (Johnston and Dietlein, 1974, p. 850). Despite decades of technological evolution, this description from the heroic age still stands. Similar habituation periods have since been observed in space (-analog) research (Pattyn et al., 2018; Clément et al., 2020). For instance, polar studies suggest a three-week adaptation period—challenging Jones et al. (2024) assumption that cognitive space-induced effects are fully observable on day 1 rather than day 4.

Finally, post-flight measures are important for assessing recovery and long-term effects. Several studies have documented persistent post-flight impairments (e.g., Garrett-Bakelman et al., 2019; Manzey et al., 1995; Moore et al., 2019), including altered gene expression, DNA damage, telomere shortening, and cognitive deficits. Autonomic regulation changes are even shown to last longer in the post-flight recording than the actual in-flight exposure (Migeotte et al., 2003). At the skeletal level, bone density recovery often remained incomplete, even 2 years postflight (Sibonga et al., 2020; Vico et al., 2017). These findings—along with interviews from analog environments (Van Puyvelde et al., 2022b)—highlight the need for protective strategies; not only during but also after missions. One proposed solution is to continuously measure until recovery has occurred (Roberts et al., 2020; Wenzel, 2021).

Time-in-space or time-on-station

Long-duration space research remains limited, despite its growing relevance. The scarcity of such missions blurs the definition of what is “long-duration”, which may lead to the classification of relatively short flights as “long-duration. To illustrate, in a space context, Strangman et al. (2014) considered space missions over 21 days as “long-duration,” reflecting this lack of longer flights. In contrast, in a space-analog context, Van Puyvelde et al. (2022b) defined missions over 12 months as “long-duration”. Today, aside from the Apollo notebooks, only two major long-duration studies have been published: the 340-day ISS Twin Study (Garrett-Bakelman et al., 2019) and the 438-day MIR mission (Manzey et al., 1998).

Anyhow, prolonged missions expose astronauts to sustained cumulative stressors—gravity shifts, radiation, sleep loss, fatigue and workload variations—all of which may, at some point, override psychophysiological compensation mechanisms. Several effects are time-dependent. For instance, bone resorption markers (bone loss) peaked within 11 days, while formation markers responded too slowly and weakly to reverse damage. After longer stays, breakdown decelerated faster, but the damage was greater and recovery remained incomplete after 3–5 months (Stavnichuk et al., 2020). Sibonga et al. (2024) similarly reported greater bone loss after longer missions, with models estimating that 62% of astronauts would return from a Mars mission with osteoporosis-level T-scores (Axpe et al., 2020).

Long-duration space (-analog) missions also affect hippocampal regions involved in memory, emotion, and spatial cognition (Stahn et al., 2019; Stahn and Kühn, 2021). Brain imaging shows structural changes, including brain shift, cerebrospinal fluid redistribution, ventricular expansion, and gray matter loss (e.g., McGregor et al., 2023; Van Ombergen et al., 2018; 2019). Ventricle expansion also increases with mission length, with the greatest changes in the first 6 months and up to 3 years before full recovery (McGregor et al., 2023). Petit et al. (2019) observed attention lapses, reflected in theta oscillations during electroencephalographic recordings, along with impaired visuomotor performance during docking tasks in an ISS crew after 2 months in space.

According to Clement (2025), the accumulation of stressors over time may underlie the often reported “space fog”. Jones et al. (2022) supported this view, noting, however, that sleep quantity was a defining factor in the multi-stressor dynamics of neurobehavioral responses and perceived workload over time. Moreover, radiation-induced cognitive deficits are shown to worsen under high workload—even at low exposure levels (Hanbury et al., 2016). Hence, the combined burden of time-in-space and workload variations may deplete cognitive reserves and/or increase the risk of relying on pharmacological support (Johnston and Dietlein, 1974; Strangman et al., 2014; Van Puyvelde et al., 2022a; Van Puyvelde et al., 2022b).

Overall, time-in-space must be systematically included in multi-stressor research, as its cumulative burden on cognitive, skeletal, and neural health is critical for future long-duration missions. This means that gathering meta-data about the multiple dynamics of the context and their stressors (unexpected events and logbooks included) is essential in order to better understand and interpret study results.

Anonymization

In qualitative research, the trade-off between providing sufficient detail to address research questions and protecting participant anonymity has long been acknowledged (e.g., Kaiser, 2009). Similar ethical and methodological challenges arise in space (-analog) research. Due to the small number of crew members and the public and media attention generated by such missions, full anonymization is often unfeasible. As a result, logbook reports describing impactful events that are—as described above—potentially critical for interpreting unexpected outcomes, may be excluded from analysis. This limitation has already been cited as a reason why certain data remained inaccessible or unavailable for desired long-term follow-up analyses (e.g., Bisserier et al., 2021; Jones et al., 2024).

Low earth orbit (LEO) and beyond LEO missions: location-specific variation in the impact of gravity and ionizing radiation (IR)

Except for the Apollo notebooks, most of the studies are limited to low Earth orbit (LEO) missions. Yet, both gravitational and radiation exposure effects vary with the trajectory and destination. For instance, a Mars mission involves a transition from Earth’s gravity (9.807 m/s2), through microgravity in transit, to Mars’ reduced gravity (3.711 m/s2), illustrating location-specific gravitational shifts (Bettiol et al., 2018).

Similarly, Moon IR-levels can double those on the ISS and reach 200–1000 times Earth-levels (Asrar, 2025; Zhang et al., 2020). ESA estimated that a Mars mission could expose astronauts in 1 day to the equivalent of a full year’s radiation on Earth—and this repeatedly for months (Asrar, 2025). Astronauts face both acute bursts (e.g., EVAs or solar storms) and prolonged exposure (Tavakol et al., 2024). IR thus remains a key risk, and both journey and destination must be included in estimation models (Willis et al., 2024).

Discussion

Space (-analog) research faces several unique methodological challenges including small and heterogeneous samples, inconsistent baselines and lack of tools tailored to highly trained astronauts (Desai et al., 2022; Strangman et al., 2014). These limitations worsen when sex differences are ignored (Hughes-Fulford, 2023a). Although advances like omics modeling, biosample analyses, and cross-agency data harmonization (Abdelfattah et al., 2024; Galčenko et al., 2025; Roberts et al., 2020) are promising, their ecological validity remains limited. Nonetheless, limited data is already guiding policy. For instance, a recent model indicated an 85.2% chance for female vs 22.8% for male astronauts to meet anxiety criteria during Mars missions (Desai et al., 2022)—an aspect that the authors indicated as a comorbidity factor in sleep problems. Such interpretations, while well-intended, risk overgeneralization.

Earth-based matched control groups remain underused, likely due to logistical and financial constraints (e.g., Boice, 2019; Kuldavletova et al., 2023). Yet funding should account for these essential but costly designs. Data repositories of major space agencies have been in the making for decades but are still not enforced. Moreover, inconsistent baselines, follow-up, and recovery measurements risk distorting data (Migeotte et al., 2003; Sibonga et al., 2020; Vico et al., 2017). Long-duration missions are particularly hazardous due to cumulative stressors like microgravity, radiation, sleep loss and workload variations (Hanbury et al., 2016; Moore et al., 2019; Van den Berg et al., 2023). Therefore, extended follow-up studies to monitor post-mission recovery and long-term health outcomes are warranted (Roberts et al., 2020; Sibonga et al., 2020; Vico et al., 2017).

Fieldwork is demanding, time-consuming, and often requires methodological deviations from traditional lab-based research. To gather statistically powered field samples remains difficult—especially for sex-specific comparisons. For instance, our team needed 14 years and seven Antarctic overwintering data collection campaigns to collect an acceptable database of 30 female winter-over sojourners in sleep studies using polysomnography. Such timelines are unsustainable for most research units considering the pace of research funding and required publishing.

Hence, more resources and innovative statistical approaches are needed. Considering the methodological realities discussed, relying solely on traditional statistical metrics such as p-values remains insufficient, especially given the small sample sizes and pronounced individual variability characteristic of space (-analog) research. Enhanced reporting practices, including effect sizes, comprehensive visualizations, and precise parameter estimations via confidence intervals, should thus be prioritized. Advanced statistical methods, notably multilevel and mixed-effects models, further align methodological rigor with the inherent complexity of space-based research.

We therefore strongly encourage authors to explicitly state in their publications that fieldwork—especially in extreme environments—demands a fundamentally different methodological approach than traditional laboratory studies. Only by acknowledging these realities, can we ensure that field studies are evaluated fairly, appreciating their unique contextual, logistical, and scientific contributions rather than penalizing inherent constraints. This would avoid the “dormant data” that currently plagues the field of space life sciences, where relevant measurements are sometimes never published due to their anecdotal nature, which is not familiar to reviewers not specialized in this area of expertise.

Author contributions

MV: Conceptualization, Writing – original draft, Writing – review and editing. Nv: Writing – review and editing. LS: Methodology, Writing – review and editing. PS: Methodology, Writing – review and editing. HC: Writing – review and editing. JV: Writing – review and editing. XN: Writing – review and editing. GS: Writing – review and editing. NP: Conceptualization, Funding acquisition, Methodology, Supervision, Writing – review and editing.

Funding

The author(s) declare that financial support was received for the research and/or publication of this article. The current project was funded by Belgian Defence Royal Higher Institute for Defence (RHID) grant HFM/22-04.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Generative AI statement

The author(s) declare that no Generative AI was used in the creation of this manuscript.

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References

Abdelfattah F., Schulz H., Wehland M., Corydon T. J., Sahana J., Kraus A., et al. (2024). Omics studies of specialized cells and stem cells under microgravity conditions. Int. J. Mol. Sci. 25 (18), 10014. doi:10.3390/ijms251810014

PubMed Abstract | CrossRef Full Text | Google Scholar

Andreassi J. L. (2007). Psychophysiology. Human behavior and physiological response. New York: Psychology Press. doi:10.4324/9780203880340

CrossRef Full Text | Google Scholar

Asrar F. M. (2025). How to keep astronauts healthy in deep space. Nature, 642(8066), 31–33. doi:10.1038/d41586-025-01691-y

PubMed Abstract | CrossRef Full Text | Google Scholar

Axpe E., Chan D., Abegaz M. F., Schreurs A. S., Alwood J. S., Globus R. K., et al. (2020). A human mission to Mars: predicting the bone mineral density loss of astronauts. PLoS One 15 (1), e0226434. doi:10.1371/journal.pone.0226434

PubMed Abstract | CrossRef Full Text | Google Scholar

Baron K. G., Duffecy J., Berendsen M. A., Mason I. C., Lattie E. G., Manalo N. C. (2018). Feeling validated yet? A scoping review of the use of consumer-targeted wearable and Mobile technology to measure and improve sleep. Sleep. Med. Rev. 40, 151–159. doi:10.1016/j.smrv.2017.12.002

PubMed Abstract | CrossRef Full Text | Google Scholar

Benke T., Koserenko O., Watson N. V., Gerstenbrand F. (1993). Space and cognition: the measurement of behavioral functions during a 6-day space mission. Aviat. space, Environ. Med. 64 (5), 376–379.

PubMed Abstract | Google Scholar

Berliner A. J., Zezulka S., Hutchinson G. A., Bertoldo S., Cockell C. S., Arkin A. P. (2024). Domains of life sciences in spacefaring: what, where, and how to get involved. Nat. Res. 10 (Issue 1), 12. doi:10.1038/s41526-024-00354-y

PubMed Abstract | CrossRef Full Text | Google Scholar

Berntson G. G., Bigger J. T., Jr., Eckberg D. L., Grossman P., Kaufmann P. G., Malik M., et al. (1997). Heart rate variability: origins, methods, and interpretive caveats. Psychophysiol. 34, 623–648. doi:10.1111/j.1469-8986.1997.tb02140.x

PubMed Abstract | CrossRef Full Text | Google Scholar

Bettiol L., De La Torre A., Patel D., Oluwafemi F., Kamaletdinova G., Kumar Singh R., et al. (2018). Manned mars mission risks evaluation. In 69th international astronautical congress (IAC 2018) (pp. 1–10).

Google Scholar

Bialeschki M. D., Henderson K. A., Hickerson B. D., Browne L. (2012). Challenges to field-based outdoor research: pitfalls and possibilities. J. Outdoor Recreat. Educ. Leadersh. 4 (1), 74. doi:10.7768/1948-5123.1094

CrossRef Full Text | Google Scholar

Bisserier M., Shanmughapriya S., Rai A. K., Gonzalez C., Brojakowska A., Garikipati V. N. S., et al. (2021). Cell-free mitochondrial DNA as a potential biomarker for astronauts’ health. J. Am. Heart Assoc. 10 (21), e022055. doi:10.1161/JAHA.121.022055

PubMed Abstract | CrossRef Full Text | Google Scholar

Bluth B. J. (1984). The benefits and dilemmas of an international space station. Acta Astronaut. 11 (2), 149–153. doi:10.1016/0094-5765(84)90006-7

PubMed Abstract | CrossRef Full Text | Google Scholar

Boice J. D. (2019). “The million person Study relevance to space exploration and Mars,”Int. J. Radiat. Biol., 98 4. 551–559. doi:10.1080/09553002.2019.1589020

PubMed Abstract | CrossRef Full Text | Google Scholar

Bonneval L., Wing D., Sharp S., Tristao Parra M., Moran R., LaCroix A., et al. (2025). Validity of heart rate variability measured with apple watch series 6 compared to laboratory measures. Sensors 25 (8), 2380. doi:10.3390/s25082380

PubMed Abstract | CrossRef Full Text | Google Scholar

Bosch Bruguera M., Fink A., Schröder V., López Bermúdez S., Dessy E., van den Berg F. P., et al. (2021). Assessment of the effects of isolation, confinement and hypoxia on spaceflight piloting performance for future space missions - the SIMSKILL experiment in Antarctica. Acta Astronaut. 179 (2021), 471–483. doi:10.1016/j.actaastro.2020.11.019

CrossRef Full Text | Google Scholar

Brojakowska A., Kour A., Thel M. C., Park E., Bisserier M., Garikipati V. N. S., et al. (2022). Retrospective analysis of somatic mutations and clonal hematopoiesis in astronauts. Commun. Biol. 5 (1), 828. doi:10.1038/s42003-022-03777-z

PubMed Abstract | CrossRef Full Text | Google Scholar

Burgess P. W. (2000). “Real-world multitasking from a cognitive neuroscience perspective,” in Control of Cognitive Processes: attention and performance XVIII. Editors S. Monsell, and J. Driver (Cambridge, United States: MIT Press), 465–472.

Google Scholar

Clément G. (2025). The brain in space 245–276. doi:10.1007/978-1-0716-4422-5_6

CrossRef Full Text | Google Scholar

Clément G. R., Boyle R. D., George K. A., Nelson G. A., Reschke M. F., Williams T. J., et al. (2020). Challenges to the central nervous system during human spaceflight missions to Mars. J. neurophysiology 123 (5), 2037–2063. doi:10.1152/jn.00476.2019

PubMed Abstract | CrossRef Full Text | Google Scholar

D'souza S., Haghgoo N., Mankame K., Mummigatti S., Saadi A. (2022). Safe spaceflight for women: examining the data gap and improving design considerations. J. Space Saf. Eng. 9 (2), 154–159. doi:10.1016/j.jsse.2022.02.010

CrossRef Full Text | Google Scholar

Desai R. I., Limoli C. L., Stark C. E. L., Stark S. M. (2022). Impact of spaceflight stressors on behavior and cognition: a molecular, neurochemical, and neurobiological perspective. Neurosci. Biobehav. Rev. 138, 104676. doi:10.1016/j.neubiorev.2022.104676

PubMed Abstract | CrossRef Full Text | Google Scholar

Dev S. I., Khader A. M., Begerowski S. R., Anderson S. R., Clément G., Bell S. T. (2024). Cognitive performance in ISS astronauts on 6-month low Earth orbit missions. Front. Physiology 15, 1451269. doi:10.3389/fphys.2024.1451269

PubMed Abstract | CrossRef Full Text | Google Scholar

Doherty C., Baldwin M., Keogh A., Caulfield B., Argent R. (2024). Keeping pace with wearables: a living umbrella review of systematic reviews evaluating the accuracy of consumer wearable technologies in health measurement. Sports Med. 54 (11), 2907–2926. doi:10.1007/s40279-024-02077-2

PubMed Abstract | CrossRef Full Text | Google Scholar

European Space Agency (2016). Roadmaps for future research (roadmap v6). European Space Agency. Available online at: https://indico.gsi.de/event/6401/images/751-Roadmap_v6.pdf.

Google Scholar

Fonseca P., Weysen T., Goelema M. S., Møst E. I., Radha M., Lunsingh Scheurleer C., et al. (2017). Validation of photoplethysmography-based sleep staging compared with polysomnography in healthy middle-aged adults. Sleep 40 (7), zsx097. doi:10.1093/sleep/zsx097

PubMed Abstract | CrossRef Full Text | Google Scholar

Fowler B., Manzey D. (2000). Summary of research issues in monitoring of mental and perceptual-motor performance and stress in space. Aviat. Space, Environ. Med. 71 (9), A76–A77.

PubMed Abstract | Google Scholar

Galčenko K., Bourdakou M. M., Spyrou G. M. (2025). Academic editors: caterina morabito exploring the impact of microgravity on gene expression: dysregulated pathways and candidate repurposed drugs. Int. J. Mol. Sci. 2025, 1287. doi:10.3390/ijms

CrossRef Full Text | Google Scholar

Garrett-Bakelman F. E., Darshi M., Green S. J., Gur R. C., Lin L., Macias B. R., et al. (2019). The NASA twins study: a multidimensional analysis of a year-long human spaceflight. Science 364 (6436), eaau8650. doi:10.1126/science.aau8650

PubMed Abstract | CrossRef Full Text | Google Scholar

Gelman A., Shalizi C. R. (2013). Philosophy and the practice of Bayesian statistics. Br. J. Math. Stat. Psychol. 66 (1), 8–38. doi:10.1111/j.2044-8317.2011.02037.x

PubMed Abstract | CrossRef Full Text | Google Scholar

Ghafourifard M. (2024). Survey fatigue in questionnaire based research: the issues and solutions. J. caring Sci. 13 (4), 214–215. doi:10.34172/jcs.33287

PubMed Abstract | CrossRef Full Text | Google Scholar

Giurgiu M., Ketelhut S., Kubica C., Nissen R., Doster A. K., Thron M., et al. (2023). Assessment of 24-hour physical behaviour in adults via wearables: a systematic review of validation studies under laboratory conditions. Int. J. Behav. Nutr. Phys. activity 20 (1), 68. doi:10.1186/s12966-023-01473-7

PubMed Abstract | CrossRef Full Text | Google Scholar

Hanbury D. B., Peiffer A. M., Dugan G., Andrews R. N., Cline J. M. (2016). Long-term cognitive functioning in single-dose total-body gamma-irradiated rhesus monkeys (Macaca mulatta). Radiat. Res. 186 (5), 447–454. doi:10.1667/RR14430.1

PubMed Abstract | CrossRef Full Text | Google Scholar

Hughes-Fulford (2023a). “This is a mistake in the text. Hughes-Fulford et al., 2023 should be Hughes-Fulford et al,” in 2024 in the text of which the reference is in the list.

Google Scholar

Hughes-Fulford (2023b). See above, should be Hughes-Fulford et al.

Google Scholar

Hughes-Fulford M., Carroll D. J., Allaway H. C. M., Dunbar B. J., Sawyer A. J. (2024). “Women in space: a review of known physiological adaptations and health perspectives,” in Experimental physiology (John Wiley and Sons Inc). doi:10.1113/EP091527

CrossRef Full Text | Google Scholar

Johnston R. S., Dietlein L. F. (1974). The proceeding of the skylab life sciences symposium, II. Available online at: https://ntrs.nasa.gov/search.jsp?R=19750006309.

Google Scholar

Jonasdottir S. S., Minor K., Lehmann S. (2021). Gender differences in nighttime sleep patterns and variability across the adult lifespan: a global-scale wearables study. Sleep 44 (2), zsaa169. doi:10.1093/sleep/zsaa169

PubMed Abstract | CrossRef Full Text | Google Scholar

Jones C. W., Basner M., Mollicone D. J., Mott C. M., Dinges D. F. (2022). Sleep deficiency in spaceflight is associated with degraded neurobehavioral functions and elevated stress in astronauts on six-month missions aboard the international space station. Sleep 45 (3), zsac006. doi:10.1093/sleep/zsac006

PubMed Abstract | CrossRef Full Text | Google Scholar

Jones C. W., Overbey E. G., Lacombe J., Ecker A. J., Meydan C., Ryon K., et al. (2024). Molecular and physiological changes in the SpaceX Inspiration4 civilian crew. Nature 632 (8027), 1155–1164. doi:10.1038/s41586-024-07648-x

PubMed Abstract | CrossRef Full Text | Google Scholar

Kaiser K. (2009). Protecting respondent confidentiality in qualitative research. Qual. health Res. 19 (11), 1632–1641. doi:10.1177/1049732309350879

PubMed Abstract | CrossRef Full Text | Google Scholar

Kelly T. H., Hienz R. D., Zarcone T. J., Wurster R. M., Brady J. V. (2005). Crewmember performance before, during, and after spaceflight. J. Exp. analysis Behav. 84 (2), 227–241. doi:10.1901/jeab.2005.77-04

PubMed Abstract | CrossRef Full Text | Google Scholar

Krukowski K., Grue K., Frias E. S., Pietrykowski J., Jones T., Nelson G., et al. (2018). Female mice are protected from space radiation-induced maladaptive responses. Brain, Behav. Immun. 74, 106–120. doi:10.1016/j.bbi.2018.08.008

PubMed Abstract | CrossRef Full Text | Google Scholar

Kuldavletova O., Navarro Morales D. C., Quarck G., Denise P., Clément G. (2023). Spaceflight alters reaction time and duration judgment of astronauts. Front. Physiology 14, 1141078. doi:10.3389/fphys.2023.1141078

PubMed Abstract | CrossRef Full Text | Google Scholar

Lee J., Finkelstein J. (2015). Consumer sleep tracking devices: a critical review. Digit. Healthc. Empower. Eur. 210, 458–460. doi:10.3233/978-1-61499-512-8-458

PubMed Abstract | CrossRef Full Text | Google Scholar

Mairesse O., MacDonald-Nethercott E., Neu D., Tellez H. F., Dessy E., Neyt X., et al. (2019). Preparing for Mars: human sleep and performance during a 13 month stay in Antarctica. Sleep 42 (1), 1–12. doi:10.1093/sleep/zsy206

PubMed Abstract | CrossRef Full Text | Google Scholar

Manzey D., Lorenz B., Schiewe A., Finell G., Thiele G. (1995). Dual-task performance in space: results from a single-case study during a short-term space mission. Hum. Factors 37, 667–681. doi:10.1518/001872095778995599

PubMed Abstract | CrossRef Full Text | Google Scholar

Manzey D., Lorenz B., Poljakov V. (1998). Mental performance in extreme environments: results from a performance monitoring study during a 438-day spaceflight. Ergonomics 41 (4), 537–559. doi:10.1080/001401398186991

PubMed Abstract | CrossRef Full Text | Google Scholar

Mark S., Scott G. B. I., Donoviel D. B., Leveton L. B., Mahoney E., Charles J. B., et al. (2014). The impact of sex and gender on adaptation to space: executive summary. J. Women’s Health 23 (11), 941–947. doi:10.1089/jwh.2014.4914

PubMed Abstract | CrossRef Full Text | Google Scholar

McElreath R. (2020). Statistical rethinking. A bayesian course with examples in R and STAN. New York: Chapman and Hall/CRC. doi:10.1201/9780429029608

CrossRef Full Text | Google Scholar

McGregor H. R., Hupfeld K. E., Pasternak O., Beltran N. E., De Dios Y. E., Bloomberg J. J., et al. (2023). Impacts of spaceflight experience on human brain structure. Sci. Rep. 13 (1), 7878. doi:10.1038/s41598-023-33331-8

PubMed Abstract | CrossRef Full Text | Google Scholar

Michaletti A., Gioia M., Tarantino U., Zolla L. (2017). Effects of microgravity on osteoblast mitochondria: a proteomic and metabolomics profile. Sci. Rep. 7 (1), 15376. doi:10.1038/s41598-017-15612-1

PubMed Abstract | CrossRef Full Text | Google Scholar

Migeotte P. F., Prisk G. K., Paiva M. (2003). Microgravity alters respiratory sinus arrhythmia and short-term heart rate variability in humans. Am. J. Physiology-Heart Circulatory Physiology 284 (6), H1995–H2006. doi:10.1152/ajpheart.00409.2002

PubMed Abstract | CrossRef Full Text | Google Scholar

Moore S. T., Dilda V., Morris T. R., Yungher D. A., MacDougall H. G., Wood S. J. (2019). Long-duration spaceflight adversely affects post-landing operator proficiency. Sci. Rep. 9 (1), 2677. doi:10.1038/s41598-019-39058-9

PubMed Abstract | CrossRef Full Text | Google Scholar

O’Grady B., Lambe R., Baldwin M., Acheson T., Doherty C. (2024). The validity of apple watch series 9 and ultra 2 for serial measurements of heart rate variability and resting heart rate. Sensors 24 (19), 6220. doi:10.3390/s24196220

PubMed Abstract | CrossRef Full Text | Google Scholar

Parihar V. K., Angulo M. C., Allen B. D., Syage A., Usmani M. T., Passerat de la Chapelle E., et al. (2020). Sex-specific cognitive deficits following space radiation exposure. Front. Behav. Neurosci. 14, 535885. doi:10.3389/fnbeh.2020.535885

PubMed Abstract | CrossRef Full Text | Google Scholar

Pattyn N., Migeotte P. F., Morais J., Soetens E., Cluydts R., Kolinsky R. (2009). Crew performance monitoring: putting some feeling into it. Acta Astronaut. 65 (3–4), 325–329. doi:10.1016/j.actaastro.2009.01.063

CrossRef Full Text | Google Scholar

Pattyn N., Van Puyvelde M., Fernandez-Tellez H., Roelands B., Mairesse O. (2018). From the midnight sun to the longest night: sleep in Antarctica. Sleep. Med. Rev. 37, 159–172. doi:10.1016/j.smrv.2017.03.001

PubMed Abstract | CrossRef Full Text | Google Scholar

N. Pattyn, J. Van Cutsem, A. Martin, R. Hauffa, J. S. F. Ungerer, N. Pattynet al. (2024). Handbook of mental performance: lessons from high performance domains (Milton Park, UK: Routledge).

Google Scholar

Paul F. J., Mandal M. K., Ramachandran K., Panwar M. R. (2010). Cognitive performance during long-term residence in a polar environment. J. Environ. Psychol. 30 (1), 129–132. doi:10.1016/j.jenvp.2009.09.007

CrossRef Full Text | Google Scholar

Petit G., Cebolla A. M., Fattinger S., Petieau M., Summerer L., Cheron G., et al. (2019). Local sleep-like events during wakefulness and their relationship to decreased alertness in astronauts on ISS. NPJ Microgravity 5 (1), 10. doi:10.1038/s41526-019-0069-0

PubMed Abstract | CrossRef Full Text | Google Scholar

Roberts D. D., Stahn A. C., Seidler R. D., Wuyts F. L. (2020). Towards understanding the effects of spaceflight on the brain. Lancet Neurology 10 (19), 808. doi:10.1016/S1474-4422(20)30304-5

PubMed Abstract | CrossRef Full Text | Google Scholar

Robin A., Van Ombergen A., Laurens C., Bergouignan A., Vico L., Linossier M. T., et al. (2023). Comprehensive assessment of physiological responses in women during the ESA dry immersion VIVALDI microgravity simulation. Nat. Commun. 14 (1), 6311. doi:10.1038/s41467-023-41990-4

PubMed Abstract | CrossRef Full Text | Google Scholar

Sibonga J. D., Spector E. R., Johnston S. L., Tarver W. J., Reeves J. M. (2015). Evaluating bone loss in ISS astronauts. Aerosp. Med. Hum. Perform. 86, A38–A44. doi:10.3357/AMHP.EC06.2015

PubMed Abstract | CrossRef Full Text | Google Scholar

Sibonga J. D., Spector E. R., Keyak J. H., Zwart S. R., Smith S. M., Lang T. F. (2020). Use of quantitative computed tomography to assess for clinically-relevant skeletal effects of prolonged spaceflight on astronaut hips. J. Clin. Densitom. 23 (2), 155–164. doi:10.1016/j.jocd.2019.08.005

PubMed Abstract | CrossRef Full Text | Google Scholar

Sibonga J. D., Spector E. R., Yardley G., Alwood J. S., Myers J., Evans H. J., et al. (2024). Risk of bone fracture due to spaceflight-induced changes to bone. Human health countermeasures element, Johnson Space Center (JSC), Evidence Report. Available online at: https://ntrs.nasa.gov/citations/20240005190.

Google Scholar

Slaba T. C., Rahmanian S., George S., Laramore D., Norbury J. W., Werneth C. M., et al. (2025). Validated space radiation exposure predictions from Earth to Mars during Artemis-I. Npj Microgravity 11 (1), 6. doi:10.1038/s41526-025-00459-y

PubMed Abstract | CrossRef Full Text | Google Scholar

Slack K. J., Williams T. J., Schneiderman J. S., Whitmire A. M., Picano J. J., Leveton L. B., et al. (2016). Risk of adverse cognitive or behavioral conditions and psychiatric disorders: evidence report.

Google Scholar

Stahn A. C., Kühn S. (2021). Brains in space: the importance of understanding the impact of long-duration spaceflight on spatial cognition and its neural circuitry. Cogn. Process. 22 (Suppl. 1), 105–114. doi:10.1007/s10339-021-01050-5

PubMed Abstract | CrossRef Full Text | Google Scholar

Stahn A. C., Gunga H. C., Kohlberg E., Gallinat J., Dinges D. F., Kühn S. (2019). Brain changes in response to long antarctic expeditions. N. Engl. J. Med. 381 (23), 2273–2275. doi:10.1056/NEJMc190490

PubMed Abstract | CrossRef Full Text | Google Scholar

Stavnichuk M., Mikolajewicz N., Corlett T., Morris M., Komarova S. V. (2020). A systematic review and meta-analysis of bone loss in space travelers. Npj Microgravity 6 (1), 13. doi:10.1038/s41526-020-0103-2

PubMed Abstract | CrossRef Full Text | Google Scholar

Steinach M., Kohlberg E., Maggioni M. A., Mendt S., Opatz O., Stahn A., et al. (2016). Sleep quality changes during overwintering at the German antarctic stations neumayer II and III: the gender factor. PLoS ONE 11 (2), e0150099–32. doi:10.1371/journal.pone.0150099

PubMed Abstract | CrossRef Full Text | Google Scholar

Strangman G. E., Sipes W., Beven G. (2014). Human cognitive performance in spaceflight and analogue environments. Aviat. Space Environ. Med. 85 (10), 1033–1048. doi:10.3357/ASEM.3961.2014

PubMed Abstract | CrossRef Full Text | Google Scholar

Tavakol D. N., Nash T. R., Kim Y., Graney P. L., Liberman M., Fleischer S., et al. (2024). Modeling the effects of protracted cosmic radiation in a human organ-on-chip platform. Adv. Sci. 11 (42), 2401415. doi:10.1002/advs.202401415

PubMed Abstract | CrossRef Full Text | Google Scholar

Tininenko J. R., Measelle J. R., Ablow J. C., High R. (2012). Respiratory control when measuring respiratory sinus arrhythmia during a talking task. Biol. Psychol. 89 (3), 562–569. doi:10.1016/j.biopsycho.2011.12.022

PubMed Abstract | CrossRef Full Text | Google Scholar

Van Cutsem J., Pattyn N., Mairesse O., Delwiche B., Fernandez Tellez H., Van Puyvelde M., et al. (2022). Adult female sleep during hypoxic bed rest. Front. Neurosci. 16 (May), 852741–16. doi:10.3389/fnins.2022.852741

PubMed Abstract | CrossRef Full Text | Google Scholar

Van den Berg N. H., Michaud X., Pattyn N., Simonelli G. (2023). How sleep research in extreme environments can inform the military: advocating for a transactional model of sleep adaptation. Curr. Psychiatry Rep. 25 (2), 73–91. doi:10.1007/s11920-022-01407-3

PubMed Abstract | CrossRef Full Text | Google Scholar

Van Ombergen A., Jillings S., Jeurissen B., Tomilovskaya E., Rühl R. M., Rumshiskaya A., et al. (2018). Brain tissue–volume changes in cosmonauts. N. Engl. J. Med. 379 (17), 1678–1680. doi:10.1056/NEJMc1809011

PubMed Abstract | CrossRef Full Text | Google Scholar

Van Ombergen A., Jillings S., Jeurissen B., Tomilovskaya E., Rumshiskaya A., Litvinova L., et al. (2019). Brain ventricular volume changes induced by long-duration spaceflight. Proc. Natl. Acad. Sci. 116 (21), 10531–10536. doi:10.1073/pnas.1820354116

PubMed Abstract | CrossRef Full Text | Google Scholar

Van Ombergen A., Chaput D., Fomina E., Gil V., Girgenrath M., Hirsch N., et al. (2022). Isolation standard measures: a set of validated and feasible measurements ensuring comparability across isolation and confinement studies. 73rd Int. Astronaut. Congr. (IAC). No.IAC-22-A1-1-3-x69152, 1–10. Available online at: https://ntrs.nasa.gov/citations/20220013722.

Google Scholar

Van Puyvelde M., Neyt X., Vanderlinden W., Van den Bossche M., Bucovaz T., De Winne T., et al. (2020). Voice reactivity as a response to acute hypobaric hypoxia at high altitude. Aerosp. Med. Hum. Perform. 91 (6), 471–478. doi:10.3357/amhp.5390.2020

PubMed Abstract | CrossRef Full Text | Google Scholar

Van Puyvelde M., Gijbels D., Van Caelenberg T., Smith N., Bessone L., Buckle-Charlesworth S., et al. (2022a). Living on the edge: how to prepare for it? Front. Neuroergonomics 3, 1007774. doi:10.3389/fnrgo.2022.1007774

PubMed Abstract | CrossRef Full Text | Google Scholar

Van Puyvelde M., Van Cutsem J., Lacroix E., Pattyn N. (2022b). A state-of-the-art review on the use of modafinil as A performance-enhancing drug in the context of military operationality. Mil. Med. 187 (11-12), 52–64. doi:10.1093/milmed/usab398

PubMed Abstract | CrossRef Full Text | Google Scholar

Vico L., Van Rietbergen B., Vilayphiou N., Linossier M. T., Locrelle H., Normand M., et al. (2017). Cortical and trabecular bone microstructure did not recover at weight-bearing skeletal sites and progressively deteriorated at non-weight-bearing sites during the year following international space station missions. J. Bone Mineral Res. 32 (10), 2010–2021. doi:10.1002/jbmr.3188

PubMed Abstract | CrossRef Full Text | Google Scholar

Wenzel E. M. (2021). Standard measures for use in analog studies, ISS, and research for long-duration exploration missions. Available online at: http://www.sti.nasa.gov.

Google Scholar

Willis C. R. G., Calvaruso M., Angeloni D., Baatout S., Benchoua A., Bereiter-Hahn J., et al. (2024). How to obtain an integrated picture of the molecular networks involved in adaptation to microgravity in different biological systems? Npj Microgravity 10 (1), 50. doi:10.1038/s41526-024-00395-3

PubMed Abstract | CrossRef Full Text | Google Scholar

Zhang L., Qin C., Chien J. H. (2024). The sex effect on balance control while standing on vestibular-demanding tasks with/without vestibular simulations: implication for sensorimotor training for future space missions. Front. Physiology 14, 1298672. doi:10.3389/fphys.2023.1298672

PubMed Abstract | CrossRef Full Text | Google Scholar

Zhang S., Wimmer-Schweingruber R. F., Yu J., Wang C., Fu Q., Zou Y., et al. (2020). First measurements of the radiation dose on the lunar surface. Sci. Adv. 6 (39), eaaz1334. doi:10.1126/sciadv.aaz133

PubMed Abstract | CrossRef Full Text | Google Scholar

Keywords: space life sciences, space analogs, field research, research methodologies, space, space methodology

Citation: Van Puyvelde M, van den Berg NH, Stas L, Savieri P, Corlùy H, Van Cutsem J, Neyt X, Simonelli G and Pattyn N (2025) Beyond the lab coat: methodological challenges in space life sciences. Front. Physiol. 16:1663701. doi: 10.3389/fphys.2025.1663701

Received: 10 July 2025; Accepted: 25 August 2025;
Published: 03 October 2025.

Edited by:

Guy Trudel, Ottawa Hospital Research Institute (OHRI), Canada

Reviewed by:

Alexandra Whitmire, National Aeronautics and Space Administration, United States

Copyright © 2025 Van Puyvelde, van den Berg, Stas, Savieri, Corlùy, Van Cutsem, Neyt, Simonelli and Pattyn. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Martine Van Puyvelde, bWFydGluZS52YW4ucHV5dmVsZGVAdnViLmJl

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