We present a theoretical framework modeling early colorectal carcinogenesis under extraterrestrial conditions. The intestinal crypt is represented as a stochastic compartment governed by APC, KRAS, and TP53 oncogenic axes, combining clonal competition, mutation, and environmental modulation into a nonlinear deterministic drift coupled with radiation-induced jump perturbations. Using Freidlin–Wentzell theory, malignant commitment is formulated as a rare escape event from a metastable homeostatic basin. The resulting transition landscape, verified via geometric minimum action and Monte Carlo statistics, demonstrates how environmental stochasticity and mission duration nonlinearly amplify risk through exponential barrier crossing, providing a quantitative framework for future experimental calibration.
Spaceflight induces stress that damages tissues and promotes disease. The brain may be particularly vulnerable due to its high bioenergetic demand and to microgravity-induced headward fluid shifts that impose mechanical and vascular stress. Prior work has shown that spaceflight can alter the structure and function of the brain and reshape its transcriptome in ways that implicate disease-relevant gene pathways. Here, we used single-nucleus transcriptomic analyses to test whether spaceflight engages neurodegeneration-associated transcriptional programs and activates disease-associated microglia. Young (3 months) or older (7 months) female mice were flown to the International Space Station or retained as terrestrial controls for 55–58 days before euthanasia. Brain nuclei were processed for single-nucleus RNA sequencing, annotated, and grouped into seven primary cell types. All cell types exhibited large numbers of differentially expressed genes as a function of spaceflight, whereas few genes were affected by age. Pathway analysis showed that these genes were enriched for processes upstream of neurodegenerative pathology, including mitochondrial and oxidative stress, proteostasis, and cell death, rather than for brain-specific outcomes such as synaptic and neuroplasticity pathways. Spaceflight further drove an increase in microglial gene signatures associated with activated states, including disease-associated, MHC-II, interferon-responsive, and inflammatory microglia. Together, these findings indicate that spaceflight induces a transcriptional landscape consistent with elevated risk for neurodegenerative disease, likely reflecting cellular sensitization rather than established pathology at this exposure duration. These results underscore the need for further studies to define relative risk and to identify countermeasures as human missions venture farther and longer into space.
The study aimed to compute the interactions between cardiac, blood pressure and respiratory signals during a 6-degree head-down tilt (HDT). Twenty-eight healthy male participants, aged 26.41 ± 5.7 years (mean ± S.D.), performed the HDT. The protocol included five minutes in each of three positions: baseline (supine), HDT and recovery (supine). The study found that HDT had a greater impact on the cardiac and vascular systems compared to the respiratory system. Cardiovascular interactions predominantly influenced the directional flow of information, while no significant changes were observed in cardio-respiratory and vasculo-respiratory signal coupling. The findings further demonstrated that the parasympathetic nervous system became more active during HDT, strengthening the coupling between the vascular and cardiac systems. The responses were attributed to the activation of the baroreflex, a critical homeostatic corrective mechanism in humans that helps maintain stable arterial blood pressure. The coherence coupling analysis approach presented in this study detects the information flow between the systems, which helps in the identification of changes in system coupling during the HDT.
Human spaceflight exposes the central nervous system (CNS) to microgravity and related stressors that may induce structural, functional, and molecular brain alterations; however, heterogeneity across studies limits a unified understanding. This systematic review evaluated the effects of real and simulated microgravity on CNS structure, function, cerebrovascular physiology, and biomarkers in humans. A PRISMA-guided search up to April 08, 2026 was conducted. A total of 33 human studies were included, covering real spaceflight, simulated microgravity, acute microgravity, and intracranial pressure–focused investigations. Across heterogeneous human studies, microgravity-related exposures were associated with multi-level CNS changes. Structurally, findings included ventricular enlargement, upward brain displacement, inferior CSF redistribution, and increased aqueductal flow, often with incomplete recovery. Diffusion imaging showed widespread white-matter alterations (decreased fractional anisotropy, increased radial diffusivity, free-water shifts) with tract-specific remodeling. Gray matter exhibited regional decreases (frontal/temporal) and increases (sensorimotor/parietal), reflecting redistribution rather than atrophy. Functional MRI revealed alterations in large-scale functional connectivity, with reduced posterior cingulate and visuospatial connectivity and increased supramarginal and insular connectivity, partly reversible. Physiological and biomarker findings included altered cerebrovascular regulation, optic nerve sheath enlargement, pituitary deformation, SANS-related features, increased NfL, GFAP, and Aβ40/42, and a reduced Aβ42/Aβ40 ratio. In short, microgravity-related exposure is associated with CNS adaptations reflecting neuroplasticity and early neural stress. However, these findings should not be viewed as definitive evidence of irreversible neural injury or neurodegeneration, given the small cohorts, heterogeneous protocols, variable follow-up timing, and methodological differences across studies; longitudinal multimodal research and targeted countermeasure trials are therefore needed.
Deconditioning of the cardiovascular system is caused by the effects of microgravity through reduced mechanical loading, which results in a reduction in baroreflex function, plasma volume, stroke volume, and orthostatic tolerance. Countermeasures for deconditioning include physical activity, but the nature and effectiveness of this countermeasure are inconsistent. Therefore, the purpose of the review is to provide an overview of the evidence base related to physical activity interventions to prevent or reduce the effects of cardiorespiratory deconditioning resulting from real or simulated microgravity environments. The review employed the Arksey and O’Malley methodology for conducting a scoping review and followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) reporting guideline. Literature searches using databases (PubMed, Scopus, CINAHL, EMBASE, and Web of Science) were conducted comprehensively to identify relevant studies. Only those studies involving individuals exposed to microgravity (astronauts or human microgravity analogues such as head-down bed rest, parabolic flights), who had been provided with exercise-based countermeasures, and measured their effects on the cardiovascular system, were selected for inclusion. Twelve studies met the inclusion criteria. For the most part, multimodal exercise (both aerobic and resistance training) interventions demonstrated better preservation of cardiovascular function than single modality exercise, especially if they involved mechanical loading. Other countermeasures, such as LBNP (Lower Body Negative Pressure) and AG (Artificial Gravity) were found to improve both hemodynamics and orthostatic tolerance. Significant variability existed among the studies in terms of exercise duration, intensity, and population characteristics, making it difficult to determine the best dose of exercise. Exercise training appears to be the most effective countermeasure for microgravity induced cardio-respiratory deconditioning. However, additional studies are required to establish the most effective training parameters and to evaluate the feasibility of these interventions for long-duration spaceflight as well as terrestrial unloading conditions.
Astrobiological analog environments comprise Earth-based environments that share similarities with a target setting (another planetary body or Precambrian Earth conditions) and whose defining features influence extant or fossil biological components, enabling astrobiological interpretation. Although not synonymous with extreme environments, they often impose selective pressures that favor extremophiles and extremotolerant organisms, making them suitable for exploring habitability, the limits of life, and its evolutionary history. Global cataloging initiatives have identified such sites worldwide; however, Brazil is often absent despite its growing research effort in astrobiology. Here, we developed a comprehensive database compiling Brazilian environments proposed as astrobiological analogs. Publications in English and Portuguese up to 2025 were reviewed using keywords such as "extremophile*", "brazil", and "analog*". Selected studies either explicitly described analog environments or investigated extremophiles and their habitats in Brazil. Each query included environment type, microenvironment, abiotic factors, putative extraterrestrial analog, life forms, terrestrial biome, conservation status, research area, and astrobiological recognition. Our analysis revealed a wide diversity of analog environments across terrestrial, subterranean, and aquatic settings. We argue that Brazil, despite being traditionally considered "mesophilic", harbors a valuable array of astrobiologically relevant analog sites, reinforcing the need to expand global analog studies beyond traditionally recognized regions.
Understanding how plants regulate growth and structural form under controlled modulation of gravity-vector persistence is essential for both space agriculture and terrestrial crop biomechanics. While clinostats are widely used as ground-based tools to study gravity-regulated responses, they alter the temporal structure of the gravitational stimulus rather than reproducing true microgravity, with most studies focused primarily on qualitative suppression of gravitropic curvature. Therefore, this study established a quantitative, morphology-based framework to evaluate shoot responses to controlled gravity-vector perturbation using a 2-D clinostat. Pea seedlings (Pisum sativum L.) were subjected to five graded gravity-vector perturbation treatments, spanning static horizontal exposure and continuous clinostat rotation at multiple speeds. Stem morphology was monitored over 10 days using time-resolved image analysis and final destructive measurements. Temporal analyses showed that stem straightness reflects an integrated postural response governed by the balance between gravity-induced bending and intrinsic straightening mechanisms. Continuous rotation suppressed cumulative curvature compared with the static horizontal condition, whereas the non-rotating vertical control maintained near-constant straightness. Increased inter-individual variability at 1 rpm indicated a transitional perturbation regime, whereas higher rotation speeds produced more consistent postural stabilization. Straightness and slenderness were not correlated at the final stage, demonstrating that posture regulation and growth allocation represent functionally independent axes of shoot adaptation under gravity perturbation.
Pharmaceutical stability is a critical determinant of crew health and mission success in long-duration spaceflight. Current regulatory frameworks governing drug stability are primarily based on terrestrial testing paradigms, including International Council for Harmonisation (ICH) guidelines, which assume controlled environmental conditions. However, spaceflight introduces unique stressors such as microgravity, ionizing radiation, exposure to the vacuum of space,and operational constraints that are not accounted for in existing models. This study systematically evaluates the limitations of current regulatory systems through a structured review of experimental evidence, space agency reports, and regulatory documents. Findings indicate that pharmaceutical degradation in space deviates significantly from Earth-based predictions due to multi-factorial interactions and highly formulation-dependent vulnerabilities. Additionally, fragmentation across regulatory and operational bodies results in inconsistent handling of pharmaceuticals across missions. The efficacy of physiological countermeasures against spaceflight-induced adaptations heavily relies on the integrity of these medications. Based on these findings, this study proposes a biomedical and health-centric regulatory science framework incorporating environment-specific testing, standardized packaging, dynamic shelf-life management, and international data integration. The proposed framework aims to enhance predictive reliability, mitigate clinical risks, and safeguard astronaut health and physiological resilience in future deep space missions.
Ethylene is a gaseous plant hormone that influences diverse phases of plant growth and development. The influence of gravitational conditions on ethylene production in plants is a crucial issue for the cultivation of plants under altered gravity conditions, such as in space. The primary objective of this study was to ascertain the impact of gravitational conditions on ethylene production in plants. To this end, rice seedlings were cultivated under hypergravity conditions at 300 g. The ethylene content released in hypergravity-treated samples was three times higher than that in 1 g-grown samples. This is the first evidence that the hypergravity conditions affect the ethylene production in plants. The expression level of the OsACS1 gene for 1-aminocyclopropane-1-carboxylic acid (ACC) synthase, which is a pivotal enzyme in ethylene biosynthesis in plants, was twofold higher in hypergravity-treated shoots compared to 1 g-grown shoots. These results suggest that the upregulation of OsACS1 gene may be associated with the stimulation of ethylene production in rice seedlings grown under hypergravity conditions. In contrast, our previous space experiments have demonstrated that the expression level of OsACS1 in rice shoots substantially decreased under microgravity conditions. The contrasting change in the expression level under hypergravity and microgravity conditions suggests that OsACS1 may be a gravity-responsive gene in rice shoots with a broad spectrum of responsiveness to gravitational forces. Moreover, the present results support the hypothesis that the ethylene production in rice seedlings may be reduced under microgravity conditions.
Standard issue track etch neutron personal dosemeters have been used for measurements on board the International Space Station (ISS), but routine dose reporting is not possible because the radiation environment in the ISS is complex: additional methods are required beyond those used normally, to help identify and discard the signal that is due to charged particles that were not produced by neutron interactions. A different calibration is also required for the neutron-induced component of the signal because the neutron field extends to much higher energies than those encountered routinely in terrestrial workplaces. The analytical methods applied to make the necessary corrections are described in detail in this paper and some of the limitations are discussed. Use of these methods allows an estimate to be made of the neutron component of dose within the ISS environment. Specifically, measurements made during the ESA MATROSHKA contract and its subsequent scientific exploitation during the EC HAMLET project, are presented. Assessed neutron effective dose rates were in the range 58 µSv d−1 to 151 µSv d−1. Original dose estimates from model calculations performed during HAMLET are compared to that obtained by using recent environmental and radiation transport models, but the effect on the dose estimate is shown to be negligible.
Altered gravity is known to modulate cellular gene expression, leading to physiological adaptations accompanied by changes in circulating biomarkers, including microRNAs (miRNAs). During long-duration space missions, exposure to microgravity contributes to musculoskeletal degeneration, including muscle atrophy and bone loss, which represent major health risks for astronauts. MiRNAs play key regulatory roles in gene expression and biological pathways associated with diseases and microgravity- induced conditions. It is well known that food-derived bioactive compounds (BCs) can directly or indirectly influence miRNA expression and related genes, thereby affecting cellular pathways involved in bone and muscle regeneration.In this study, we employed an integrated bioinformatics approach to investigate the molecular mechanism underlying microgravity-associated musculoskeletal alterations. Specifically, we identified differentially expressed miRNAs shared among osteoporosis, muscle atrophy, and simulated microgravity conditions. Using MIENTURNET and Reactome tools, we characterised their target genes and pathways and explored food-derived BCs capable of modulating these miRNAs, genes, and pathways.Our analysis identified a set of 13 miRNAs shared among the three conditions (miR-21, miR-24–3p, miR-23b, miR-29a-3p, miR-23a, miR-155–5p, miR-223, miR-98, miR-25, let-7g-5p, miR-27a, miR-148a, miR-206) which revealed significant overlaps in genes and pathways, suggesting conserved molecular mechanisms linking bone and muscle degeneration to microgravity-induced changes.Notably, we identified interactions between BCs and key miRNAs including ursolic acid with let-7g-5p and quercetin with miR-206. Tocotrienol and epicatechin were associated with upregulation of miR-206, potentially supporting myoblast differentiation and muscle regeneration. Additional compounds identified through the STITCH database, such as curcumin, carotene, quercetin, and myricetin, target genes implicated in metabolic regulation and tissue remodelling (ccnd1, scarb1, pim1), indicating a broad modulatory potential.Overall, these results provide novel insights into the molecular mechanisms underlying microgravity-induced musculoskeletal and metabolic alterations. They also highlight food-derived BCs as promising nutritional countermeasures to mitigate health risks during long-duration space missions. These results have translational relevance for terrestrial disease-related conditions and are also potentially correlated with pathological condition such as osteoporosis and muscle atrophy, which are also associated with ageing.
Breast cancer is one of the most common types of cancer in women, and its treatment depends on the type and severity of the disease. Traditional treatments lead to side effects that require searching for alternative treatment methods. Microgravity is one such method that is currently being studied. In summary, exposure of cancer cells to microgravity dramatically changes morphological, biological, and genetic functions and increases the apoptosis rate. In this manuscript, a comprehensive study is conducted on the effects of microgravity on the breast cancer cell line (AMJ13) in terms of external appearance characteristics, growth behavior, biological properties, cell effectiveness, and DNA damage by exposing the cells to simulated microgravity for 24 h. The results showed a significant change in the morphology and growth behavior of the cells due to being subjected to simulated microgravity conditions compared with the control cells. The cytotoxicity test (MTT) showed an increase in cell inhibition rate under the influence of microgravity. The effect of the microgravity environment extended beyond the morphology level of the cells to the genetic level, as the comet examination showed apparent damage to the DNA compared with the control cells. This comprehensive study opens up possibilities for microgravity as an essential tool in studying cell behavior and conducting cancer treatment research in the future.
Space biology investigates how living organisms respond to microgravity, cosmic radiation, confinement, and other spaceflight-associated stressors. With the rapid expansion of high-throughput omics technologies, space missions now generate vast multi-layered datasets spanning genomics, transcriptomics, proteomics, metabolomics, and epigenomics. The integration, curation, and analysis of these datasets rely heavily on specialized bioinformatics databases and platforms. This review provides a comprehensive overview of the major databases supporting space biology research, including NASA’s GeneLab and Life Sciences Data Archive, the European Space Agency’s space omics initiatives, Japan Aerospace Exploration Agency resources, and emerging global platforms. We compare their scope, accessibility, metadata standards, and analytical capabilities, highlight case studies such as the NASA Twins Study, and discuss challenges in data standardization, interoperability, and AI-driven integration. Finally, we propose a vision for a unified global space biology database ecosystem aligned with FAIR data principles.
Human spaceflight exposes astronauts to a unique combination of environmental stressors, which can induce significant physiological and molecular changes to several organ systems with a profound effect on physiological homeostasis. Among these systems, the gut microbiome represents a highly dynamic and environmentally sensitive ecosystem whose perturbation during space missions may have significant consequences for host health. Here, we review evidence from astronaut cohorts, as well as ground-based and in-flight animal studies, demonstrating that spaceflight conditions, with a specific emphasis on microgravity and space radiation, can drive gut dysbiosis and functional microbial shifts. These changes are associated with compromised epithelial integrity, elevation of pro-inflammatory cytokines and impairment of immune surveillance, collectively creating conditions that may favor pro-oncogenic signaling and tumorigenesis. We further examine promising microbiome-targeted countermeasures as potential strategies to preserve gut microbiome homeostasis during space missions. These findings highlight the importance of managing gut health to mitigate carcinogenic risks in astronauts, providing strategies for safer and long-duration manned space exploration.
This systematic review aimed to characterize the landscape of cardiovascular research in the context of spaceflight and its Earth-based analogs. In collaboration with subject matter experts from the Ames Life Science Data Archive Analysis Working Group, we developed targeted search terms for spaceflight-related exposures and specific cardiovascular outcomes. A team of librarians translated these terms into structured search strategies across Ovid Medline, Embase, and CINAHL, yielding 18,837 records after deduplication. Screening was completed in collaboration with citizen scientists from the Space Open Life Sciences Team for International Collaborative Exploration (SOLSTICE). Title and abstract screening identified 3512 relevant articles. Articles were labelled based on population (human, rodent, primate, other), exposure type (actual spaceflight, simulated microgravity, other), and primary outcome focus (cardiovascular, hematopoietic, or other). Humans comprised 69.1% of the study populations. Actual spaceflight was studied in 28.1% of articles, and Earth-based models of microgravity were used in 43.3%. Cardiovascular outcomes were the most frequently reported (60.1%). For full-text screening, the primary focus was on 855 studies reporting cardiovascular outcomes in humans exposed to actual microgravity. Within this group, the most common outcomes were heart rate (70 studies), cardiac measurements (47 studies), and blood pressure (45 studies), while vasculature outcomes were reported in 27 studies. This curated and annotated dataset provides a foundation for future quantitative synthesis to support the mechanistic understanding of spaceflight-induced cardiovascular changes. The findings are directly relevant to upcoming human missions to the Moon and Mars, helping inform health risk mitigation strategies for long-duration space travel.
The return of humanity to the Moon necessitates an accurate assessment of the radiation risks posed by energetic particles in space, including omnipresent Galactic Cosmic Rays (GCRs) and sporadic Solar Energetic Particles (SEPs). The former has been recognized as the main source of radiation during solar quiet periods to deep space explorers and is a critical factor for mission risk assessment. Monte Carlo simulation is a useful method for investigating space radiation risks under specific conditions. This method generally requires considerable computational resources. Meanwhile uncertainties in the GCR dose estimates may arise from various factors that are not yet agreed within the community and have precluded a consensus on mission risk evaluation. This study presents a systematic deconstruction of effective dose uncertainties for astronauts on the lunar surface using a full-chain Geant4-based Monte Carlo simulation framework. This framework integrates the state-of-the-art description of GCR sources, the REDMoon (Radiation Environment and Dose at the Moon) lunar environment model, and energy deposition within ICRP (International Commission on Radiological Protection) Adult Male (AM) and Adult Female (AF) reference computational phantoms. Using the response function method, we avoid the repeated execution of the Monte Carlo program and are able to calculate GCR dose on the lunar surface under specific conditions solely through simple matrix computations. We also quantify the deviations arising from physics lists, anatomical differences in gender, and two radiobiology models: ICRP-60 and NSCR-2012 (NASA Space Cancer Risk). The obtained effective dose under the broad GCR spectrum is strongly anti-correlated with the solar activity, while our results also show a small but visible solar-cycle dependent difference between dose quantities in AM and AF phantoms. Our study further reveals that the choice of physics lists and Linear Energy Transfer (LET) calculation methods can introduce a variation range of approximately 8%-15%, while the selection of the radiobiology model introduces a variation range of approximately 2%-10%. This study assists in quick assessment of lunar mission risks and emphasizes the priority for developing more validated and unified standards to reach a consensus on mission risk evaluation across different agencies.
Spaceflight is known to alter immune function and has been associated with reactivation of latent viruses, such as herpesviruses, in astronauts. The human and rodent genomes also contain thousands of endogenous retroviral sequences (ERVs) which are remnants of ancient germline retroviral infections that have been epigenetically silenced over evolutionary time. Although transcriptionally repressed under baseline conditions, ERV-associated molecular signatures such as double-stranded RNA and reverse transcriptase activity can re-emerge in response to environmental stress. Expression of these has been implicated in a wide range of human disorders, including neurological, autoimmune, and carcinogenic conditions. As exploration missions extend into deep space, astronauts will be chronically exposed to a unique combination of stressors, including microgravity and high-energy ionizing radiation, raising the question of whether these exposures could perturb ERV regulation. In this pilot study, we investigated ERV-associated surrogate markers in both cell and rodent models following simulated spaceflight stressors. We observed early induction of ERV-linked molecular signatures shortly after exposure, as well as persistent evidence of these signatures that remained detectable over a year after space radiation challenge in vivo. Together these findings indicate that spaceflight related stressors can elicit both acute and long-lasting epigenetic perturbations leading to transcriptional activation of ERV-related genetic loci. Given the cumulative and repeated exposure to both space radiation and microgravity that astronauts will experience during long duration missions, these results highlight the need for deeper investigation into ERV biology in the space environment and its potential implications for astronaut health.
Spaceflight-Associated Neuro-Ocular Syndrome (SANS) has remained poorly understood throughout the history of human spaceflight despite being classified as the largest physiologic barrier that astronauts face. Existing mechanistic explanations of SANS are limited in accounting for its tissue specificity, interindividual heterogeneity, and persistence beyond return to Earth, which has left countermeasure development without a coherent biological target. Through integration of tissue-resolved murine spaceflight transcriptomic datasets with human retinal ganglion cell models of Leber Hereditary Optic Neuropathy (LHON), we define a share pattern of injury underlying SANS. Across all datasets, suppression of mitochondrial oxidative phosphorylation (OXPHOS) consistently preceded innate immune, interferon, and PANoptotic activation, establishing metabolic collapse as the initiating event rather than a downstream consequence. Strain-dependent divergence in mitochondrial resilience between BALB/c and C57BL/6 J mice onboard the International Space Station (ISS) supports a threshold-dependent susceptibility model, and cross-species convergence with LHON-derived retinal ganglion cells identifies shared molecular signatures linking spaceflight neurodegeneration with terrestrial mitochondrial optic neuropathies. These findings support reclassification of SANS as a mitochondrial-inflammatory optic neuropathy, spaceflight-associated optic neuropathy (SAON), providing the first mechanistically complete basis for countermeasure development, risk stratification, and an evolution from syndromic classification towards a defined disease framework.
