Automated Psychotherapy in a Spaceflight Environment: Advantages, Drawbacks, and Unknowns.

Various behavioral and mental health issues have been reported by space crews for decades, with the overall number of mental health complications expected to be higher than is publicly known. The broad range of mental health complications encountered in space is expected to grow as people venture deeper into space. Issues with privacy, dual relationships, and delayed communications make rendering effective psychological therapy difficult in a spaceflight environment and nearly impossible in deep space. Automated psychotherapy offers a way to provide psychotherapy to astronauts both in deep space and low Earth orbit. Although automated psychotherapy is growing in popularity on Earth, little is known about its efficacy in space. This viewpoint serves to highlight the knowns and unknowns regarding this treatment modality for future deep space missions, and places an emphasis on the need for further research into the applicability and practicality of automated psychotherapy for the spaceflight environment, especially as it relates to long-duration, deep space missions.

Food systems for long-term spaceflight: Understanding the role of non-nutrient polyphenols in astronauts' health.

Background: Manned space exploration missions have developed at a rapid pace, with missions to Mars likely to be in excess of 1000 days being planned for the next 20 years. As such, it is important to understand and address the challenges that astronauts face, such as higher radiation exposure, altered gravity, and isolation. Meanwhile, until now the formulation of space food systems has not focused on non-nutrients, and has not considered issues arising from their absence during space missions or the possibility of them to solve the challenges caused by space hazards. Aims: This study investigates, by systematic review, current space food systems and the potential for non-nutrients, such as flavonoids and polyphenols, to counteract radiation- and low gravity-induced degeneration of bone, vision, muscle strength, immune function and cognition. Results and discussion: A systematic approach found 39 related animal model studies, and that polyphenol dietary interventions have been shown to mitigate radiation-related physiological problems and cognitive decline, as well as reduce the implications of radiotherapy. From the results of these studies, it appears that berry extracts have a significant effect on preventing cognitive problems through attenuating the expression of NADPH-oxidoreductase-2 (NOX2) and cycloocygenase-2 (COX2) in both frontal cortex and hippocampus and immune system problems caused by radiation similar to that experienced in space. For physiological problems like alteration of blood-testicular barrier permeability and oxidative stress in kidney and liver caused by gamma rays and X-rays, various polyphenol compounds including resveratrol and tea polyphenols have a certain degree of protective effect like enhancing metabolism of heart and decreasing DNA damage respectively. Due to the lack of quantitative studies and the limited number of relevant studies, it is impossible to compare which polyphenol compounds are more effective. Only one study showed no difference in the performances of a blueberry extract-fed group and a control group exposed to Fe irradiation after 12 months. Conclusion: In conclusion, current animal studies have shown that polyphenols can mitigate radiation damage to some extent, but more research is needed to enable the application of a polyphenol diet to actual space flights.

Cardiovascular adaptations and pathological changes induced by spaceflight: from cellular mechanisms to organ-level impacts.

The advancement in extraterrestrial exploration has highlighted the crucial need for studying how the human cardiovascular system adapts to space conditions. Human development occurs under the influence of gravity, shielded from space radiation by Earth's magnetic field, and within an environment characterized by 24-hour day-night cycles resulting from Earth's rotation, thus deviating from these conditions necessitates adaptive responses for survival. With upcoming manned lunar and Martian missions approaching rapidly, it is essential to understand the impact of various stressors induced by outer-space environments on cardiovascular health. This comprehensive review integrates insights from both actual space missions and simulated experiments on Earth, to analyze how microgravity, space radiation, and disrupted circadian affect cardiovascular well-being. Prolonged exposure to microgravity induces myocardial atrophy and endothelial dysfunction, which may be exacerbated by space radiation. Mitochondrial dysfunction and oxidative stress emerge as key underlying mechanisms along with disturbances in ion channel perturbations, cytoskeletal damage, and myofibril changes. Disruptions in circadian rhythms caused by factors such as microgravity, light exposure, and irregular work schedules, could further exacerbate cardiovascular issues. However, current research tends to predominantly focus on disruptions in the core clock gene, overlooking the multifactorial nature of circadian rhythm disturbances in space. Future space missions should prioritize targeted prevention strategies and early detection methods for identifying cardiovascular risks, to preserve astronaut health and ensure mission success.

Omics Studies of Specialized Cells and Stem Cells under Microgravity Conditions.

The primary objective of omics in space with focus on the human organism is to characterize and quantify biological factors that alter structure, morphology, function, and dynamics of human cells exposed to microgravity. This review discusses exciting data regarding genomics, transcriptomics, epigenomics, metabolomics, and proteomics of human cells and individuals in space, as well as cells cultured under simulated microgravity. The NASA Twins Study significantly heightened interest in applying omics technologies and bioinformatics in space and terrestrial environments. Here, we present the available publications in this field with a focus on specialized cells and stem cells exposed to real and simulated microgravity conditions. We summarize current knowledge of the following topics: (i) omics studies on stem cells, (ii) omics studies on benign specialized different cell types of the human organism, (iii) discussing the advantages of this knowledge for space commercialization and exploration, and (iv) summarizing the emerging opportunities for translational regenerative medicine for space travelers and human patients on Earth.

Effects of intermittent seating upright, lower body negative pressure, and exercise on functional tasks performance after head-down tilt bed rest.

Introduction: Bed rest can be used as a ground-based analog of the body unloading associated with spaceflight. In this study, we determined how strict head-down tilt bed rest affects subjects' performance of functional tests (sit-to-stand, tandem walk, walk-and-turn, dynamic posturography) that challenge astronauts' balance control systems immediately after they return from space. Methods: Forty-seven participants were assessed before and a few hours after 30 days of 6° head down tilt bed rest at the DLR:envihab facility. During this bed rest study, called SANS-CM, the participants were divided into 4 groups that either a) were positioned in head-down tilt continuously throughout the 30 days; b) sat upright for 6 h a day; c) were exposed to lower body negative pressure (LBNP) for 6 h a day; or d) exercised for 60 min and then wore venous-occlusive cuffs for 6 h a day. Results: Results showed that strict head-down tilt bed rest caused deficits in performance of functional tasks that were similar to those observed in astronauts after spaceflight. Seated upright posture mitigated these deficits, whereas exercise or LBNP and cuffs partly mitigated them. Discussion: These data suggest that more direct, active sensorimotor-based countermeasures may be necessary to maintain preflight levels of functional performance after a long period of body unloading.

Artificial Gravity: An Effective Countermeasure for Microgravity-Induced Headward Fluid Shift?

Long-duration spaceflight is associated with pathophysiological changes in the intracranial compartment hypothetically linked to microgravity-induced headward fluid shift. This study aimed to determine if daily artificial gravity (AG) sessions can mitigate these effects, supporting its application as a countermeasure to spaceflight. Twenty-four healthy adult volunteers (16 men) were exposed to 60 days of six-degree head-down tilt bed rest (HDTBR) as a ground-based analog of chronic headward fluid shift. Subjects were divided equally into three groups: No AG (control), daily 30-minute intermittent AG (iAG), and daily 30-minute continuous (cAG). Internal carotid artery (ICA) stroke volume (ICASV), ICA resistive index (ICARI), ICA flow rate (ICAFR), aqueductal cerebral spinal fluid flow velocity (CSFV), and intracranial volumetrics were quantified at 3T. MRI was performed at baseline, 14 and 52 days into HDTBR, and three days after HDTBR(recovery). A mixed model approach was used with intervention and time as the fixed effect factors and the subject as the random effect factor. Compared to baseline, HDTBR was characterized by expansion of lateral ventricular, white matter, gray matter, and brain + total intracranial cerebral spinal fluid volumes, increased CSFv, decreased ICASV, and decreased ICAFR by 52 days into HBTBR (All Ps <0.05). ICARI was only increased 14 days into HDTBR (P <0.05). Neither iAG nor cAG significantly affected measurements compared to HDTBR alone, indicating that thirty minutes of daily exposure was insufficient to mitigate the intracranial effects of headward fluid shift. Greater AG session exposure time, gravitational force or both are suggested for future countermeasure research.

Differential Functional Changes in Visual Performance during Acute Exposure to Microgravity Analogue and Their Potential Links with Spaceflight-Associated Neuro-Ocular Syndrome.

BACKGROUND: Spaceflight-Associated Neuro-Ocular Syndrome (SANS) is a complex pathology threatening the health of astronauts, with incompletely understood causes and no current specific functional diagnostic or screening test. We investigated the use of the differential performance of the visual system (central vs. perimacular visual function) as a candidate marker of SANS-related pathology in a ground-based microgravity analogue. METHODS: We used a simple reaction time (SRT) task to visual stimuli, presented in the central and perimacular field of view, as a measure of the overall performance of the visual function, during acute settings (first 10 min) of vertical, bed rest (BR), -6°, and -15° head-down tilt (HDT) presentations in healthy participants (n = 8). We built dose-response models linking the gravitational component to SRT distribution parameters in the central vs. perimacular areas. RESULTS: Acute exposure to microgravity induces detectable changes between SRT distributions in the perimacular vs. central retina (increased mean, standard deviation, and tau component of the ex-Gaussian function) in HDT compared with vertical presentation. CONCLUSIONS: Functional testing of the perimacular retina might be beneficial for the earlier detection of SANS-related ailments in addition to regular testing of the central vision. Future diagnostic tests should consider the investigation of the extra-macular areas, particularly towards the optic disc.

Safety protocols, precautions, and countermeasures aboard the International Space Station (ISS) to prevent ocular injury.

The International Space Station (ISS) is a $100 billion epicenter of human activity in the vacuum of space, displaying mankind's collective endeavor to explore the cosmic frontier. Even within the marvels of technological sophistication aboard the ISS, the human eye remains a highly vulnerable structure. In the absence of multiple layers of protection and risk assessments, crewmembers would face a substantial increase in vulnerability to ocular injury. Aside from stringent preflight screening criteria for astronauts, the ISS is equipped with ophthalmic medications, environmental control and life support systems (e.g., humidity regulation, carbon dioxide removal, pressurized device regulators), and radiation protection to reduce ocular injury. Moreover, additional countermeasures are currently being developed to mitigate the effects of spaceflight-associated neuro-ocular syndrome (SANS) and lunar dust toxicity for the Artemis Program missions. The success of future endeavors hinges not only on continued technological innovation, but also respecting the intricate interplay between human physiology and the extraterrestrial environments. Establishing habitations on the Moon and Mars, as well as NASA's Gateway Program (humanity's first space station around the Moon), will introduce a new set of challenges, underscoring the necessity for continuous insights into ocular health in space. We discuss the safety protocols, precautions, and countermeasures implemented on the ISS to prevent ocular injury - an aspect often overshadowed by the grandeur of space exploration.

Spaceflight-induced contractile and mitochondrial dysfunction in an automated heart-on-a-chip platform.

With current plans for manned missions to Mars and beyond, the need to better understand, prevent, and counteract the harmful effects of long-duration spaceflight on the body is becoming increasingly important. In this study, an automated heart-on-a-chip platform was flown to the International Space Station on a 1-mo mission during which contractile cardiac function was monitored in real-time. Upon return to Earth, engineered human heart tissues (EHTs) were further analyzed with ultrastructural imaging and RNA sequencing to investigate the impact of prolonged microgravity on cardiomyocyte function and health. Spaceflight EHTs exhibited significantly reduced twitch forces, increased incidences of arrhythmias, and increased signs of sarcomere disruption and mitochondrial damage. Transcriptomic analyses showed an up-regulation of genes and pathways associated with metabolic disorders, heart failure, oxidative stress, and inflammation, while genes related to contractility and calcium signaling showed significant down-regulation. Finally, in silico modeling revealed a potential link between oxidative stress and mitochondrial dysfunction that corresponded with RNA sequencing results. This represents an in vitro model to faithfully reproduce the adverse effects of spaceflight on three-dimensional (3D)-engineered heart tissue.

The human microbiome in space: parallels between Earth-based dysbiosis, implications for long-duration spaceflight, and possible mitigation strategies.

SUMMARYThe human microbiota encompasses the diverse communities of microorganisms that reside in, on, and around various parts of the human body, such as the skin, nasal passages, and gastrointestinal tract. Although research is ongoing, it is well established that the microbiota exert a substantial influence on the body through the production and modification of metabolites and small molecules. Disruptions in the composition of the microbiota-dysbiosis-have also been linked to various negative health outcomes. As humans embark upon longer-duration space missions, it is important to understand how the conditions of space travel impact the microbiota and, consequently, astronaut health. This article will first characterize the main taxa of the human gut microbiota and their associated metabolites, before discussing potential dysbiosis and negative health consequences. It will also detail the microbial changes observed in astronauts during spaceflight, focusing on gut microbiota composition and pathogenic virulence and survival. Analysis will then turn to how astronaut health may be protected from adverse microbial changes via diet, exercise, and antibiotics before concluding with a discussion of the microbiota of spacecraft and microbial culturing methods in space. The implications of this review are critical, particularly with NASA's ongoing implementation of the Moon to Mars Architecture, which will include weeks or months of living in space and new habitats.

Microbiology of human spaceflight: microbial responses to mechanical forces that impact health and habitat sustainability.

SUMMARYUnderstanding the dynamic adaptive plasticity of microorganisms has been advanced by studying their responses to extreme environments. Spaceflight research platforms provide a unique opportunity to study microbial characteristics in new extreme adaptational modes, including sustained exposure to reduced forces of gravity and associated low fluid shear force conditions. Under these conditions, unexpected microbial responses occur, including alterations in virulence, antibiotic and stress resistance, biofilm formation, metabolism, motility, and gene expression, which are not observed using conventional experimental approaches. Here, we review biological and physical mechanisms that regulate microbial responses to spaceflight and spaceflight analog environments from both the microbe and host-microbe perspective that are relevant to human health and habitat sustainability. We highlight instrumentation and technology used in spaceflight microbiology experiments, their limitations, and advances necessary to enable next-generation research. As spaceflight experiments are relatively rare, we discuss ground-based analogs that mimic aspects of microbial responses to reduced gravity in spaceflight, including those that reduce mechanical forces of fluid flow over cell surfaces which also simulate conditions encountered by microorganisms during their terrestrial lifecycles. As spaceflight mission durations increase with traditional astronauts and commercial space programs send civilian crews with underlying health conditions, microorganisms will continue to play increasingly critical roles in health and habitat sustainability, thus defining a new dimension of occupational health. The ability of microorganisms to adapt, survive, and evolve in the spaceflight environment is important for future human space endeavors and provides opportunities for innovative biological and technological advances to benefit life on Earth.

Cardiovascular effects of long-duration space flight.

Introduction: Early studies exploring the physiological effects of space travel have indicated the body's capacity for reversible adaptation. However, the impact of long-duration spaceflight, exceeding 6 months, presents more intricate challenges. Effects on the Cardiovascular CV System: Extended exposure to microgravity and radiation profoundly affects the CV system. Notable phenomena include fluid shifts toward the head and modified arterial pressure. These changes disrupt blood pressure regulation and elevate cardiac output. Additionally, the loss of venous compression leads to a reduction in central venous pressure. Fluid and Plasma Volume Changes: The displacement of fluid from the vascular system to the interstitium, driven by baroreceptor stimulation, results in a 10%-15% decline in plasma volume. Cardiac Muscle and Hematocrit Variations: Intriguingly, despite potential increases in cardiac workload, cardiac muscle atrophy and perplexing variations in hematocrit levels have been observed. The mechanism underlying atrophy appears to involve a shift in protein synthesis from the endoplasmic reticulum to the mitochondria via mortalin-mediated mechanisms. Arrhythmias and QT Interval Prolongation: Instances of arrhythmias have been recurrently documented, although generally nonlethal, in both Russian and American space missions. Long-duration spaceflight has been associated with the prolongation of the QT interval, particularly in extended missions. Radiation Effects: Exposure of the heart to the proton and heavy ion radiation pervasive in deep space contributes to coronary artery degeneration, augmented aortic stiffness, and carotid intima thickening through collagen-mediated processes. Moreover, it accelerates the onset of atherosclerosis and triggers proinflammatory responses. Reentry and Postflight Challenges: Upon reentry, astronauts frequently experience orthostatic intolerance and altered sympathetic responses, which bear potential hazards in scenarios requiring rapid mobilization or evacuation. Conclusion: Consequently, careful monitoring of these cardiac risks is imperative for forthcoming missions. While early studies illuminate the adaptability of the body to space travel's challenges, the intricacies of long-duration missions and their effects on the CV system necessitate continued investigation and vigilance to ensure astronaut health and mission success.

The Astrobiological Potential of the Uranian Moon System.

The 2023-2032 Planetary Science and Astrobiology Decadal Survey prioritized the Uranus Orbiter and Probe (UOP) mission concept as the next priority flagship mission. The UOP concept includes scientific studies of the Uranian moon system. Although the Uranian moons differ greatly from the ocean worlds in the Jovian and Saturnian systems, the emerging hypothesis is that some of them could at least sustain thin, potentially concentrated, oceans. Herein, we make a case that these moons are important and interesting targets of astrobiological research. Studying these worlds would provide critical astrobiological data related to their habitability, including origin, evolution, and potential death, as well as the formation and evolution of ocean worlds more broadly. There is a strong need for research that connects astrobiology to modeling and experimentation to better characterize the possible conditions of these worlds, and this will be critical in formulating and maximizing the potential science that could be done by a Uranus flagship mission.

Blood flow restriction: The acute effects of body tilting and reduced gravity analogues on limb occlusion pressure.

Blood flow restriction (BFR) has been identified as a potential countermeasure to mitigate physiological deconditioning during spaceflight. Guidelines recommend that tourniquet pressure be prescribed relative to limb occlusion pressure (LOP); however, it is unclear whether body tilting or reduced gravity analogues influence LOP. We examined LOP at the leg and arm during supine bedrest and bodyweight suspension (BWS) at 6° head-down tilt (HDT), horizontal (0°), and 9.5° head-up tilt (HUT) positions. Twenty-seven adults (age, 26 ± 5 years; height, 1.75 ± 0.08 m; body mass, 73 ± 12 kg) completed all tilts during bedrest. A subgroup (n = 15) additionally completed the tilts during BWS. In each position, LOP was measured twice in the leg and arm using the Delfi Personalized Tourniquet System after 5 min of rest and again after a further 5 min. The LOP at the leg increased significantly from 6° HDT to 9.5° HUT in bedrest and BWS by 9-15 mmHg (Cohen's d = 0.7-1.0). Leg LOP was significantly higher during BWS at horizontal and 9.5° HUT postures relative to the same angles during bedrest by 8 mmHg (Cohen's d = 0.6). Arm LOP remained unchanged between body tilts and analogues. Intraclass correlation coefficients for LOP measurements taken after an initial and subsequent 5 min rest period in all conditions ranged between 0.91-0.95 (leg) and 0.83-0.96 (arm). It is advised that LOP be measured before the application of a vascular occlusion in the same body tilt/setting to which it is applied to minimize discrepancies between the actual and prescribed tourniquet pressure.

Effects of weightlessness on the cardiovascular system: a systematic review and meta-analysis.

Background: The microgravity environment has a direct impact on the cardiovascular system due to the fluid shift and weightlessness that results in cardiac dysfunction, vascular remodeling, and altered Cardiovascular autonomic modulation (CAM), deconditioning and poor performance on space activities, ultimately endangering the health of astronauts. Objective: This study aimed to identify the acute and chronic effects of microgravity and Earth analogues on cardiovascular anatomy and function and CAM. Methods: CINAHL, Cochrane Library, Scopus, Science Direct, PubMed, and Web of Science databases were searched. Outcomes were grouped into cardiovascular anatomic, functional, and autonomic alterations, and vascular remodeling. Studies were categorized as Spaceflight (SF), Chronic Simulation (CS), or Acute Simulation (AS) based on the weightlessness conditions. Meta-analysis was performed for the most frequent outcomes. Weightlessness and control groups were compared. Results: 62 articles were included with a total of 963 participants involved. The meta-analysis showed that heart rate increased in SF [Mean difference (MD) = 3.44; p = 0.01] and in CS (MD = 4.98; p < 0.0001), whereas cardiac output and stroke volume decreased in CS (MD = -0.49; p = 0.03; and MD = -12.95; p < 0.0001, respectively), and systolic arterial pressure decreased in AS (MD = -5.20; p = 0.03). According to the qualitative synthesis, jugular vein cross-sectional area (CSA) and volume were greater in all conditions, and SF had increased carotid artery CSA. Heart rate variability and baroreflex sensitivity, in general, decreased in SF and CS, whereas both increased in AS. Conclusion: This review indicates that weightlessness impairs the health of astronauts during and after spaceflight, similarly to the effects of aging and immobility, potentially increasing the risk of cardiovascular diseases. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42020215515.

Sex similarities and divergences in systemic and muscle iron metabolism adaptations to extreme physical inactivity in rats.

BACKGROUND: Previous data in humans suggest that extreme physical inactivity (EPI) affects iron metabolism differently between sexes. Our objective was to deepen the underlying mechanisms by studying rats of both sexes exposed to hindlimb unloading (HU), the reference experimental model mimicking EPI. METHODS: Eight-week-old male and female Wistar rats were assigned to control (CTL) or hindlimb unloading (HU) conditions (n = 12/group). After 7 days of HU, serum, liver, spleen, and soleus muscle were removed. Iron parameters were measured in serum samples, and ICP-MS was used to quantify iron in tissues. Iron metabolism genes and proteins were analysed by RT-qPCR and Western blot. RESULTS: Compared with control males, control females exhibited higher iron concentrations in serum (+43.3%, p < 0.001), liver (LIC; +198%, P < 0.001), spleen (SIC; +76.1%, P < 0.001), and transferrin saturation (TS) in serum (+53.3%, P < 0.001), contrasting with previous observations in humans. HU rat males, but not females, exhibited an increase of LIC (+54% P < 0.001) and SIC (+30.1%, P = 0.023), along with a rise of H-ferritin protein levels (+60.9% and +134%, respectively, in liver and spleen; P < 0.05) and a decrease of TFRC protein levels (-36%; -50%, respectively, P < 0.05). HU males also exhibited an increase of splenic HO-1 and NRF2 mRNA levels, (p < 0.001), as well as HU females (P < 0.001). Concomitantly to muscle atrophy observed in HU animals, the iron concentration increased in soleus in females (+26.7, P = 0.004) while only a trend is observed in males (+17.5%, P = 0.088). In addition, the H-ferritin and myoglobin protein levels in soleus were increased in males (+748%, P < 0.001, +22%, P = 0.011, respectively) and in females (+369%, P < 0.001, +21.9%, P = 0.007, respectively), whereas TFRC and ferroportin (FPN) protein levels were reduced in males (-68.9%, P < 0.001, -76.8%, P < 0.001, respectively) and females (-75.9%, P < 0.001, -62.9%, P < 0.001, respectively). Interestingly, in both sexes, heme exporter FLVCR1 mRNA increased in soleus, while protein levels decreased (-39.9% for males P = 0.010 and -49.1% for females P < 0.001). CONCLUSIONS: Taken together, these data support that, in rats (1) extreme physical inactivity differently impacts the distribution of iron in both sexes, (2) splenic erythrophagocytosis could play a role in this iron misdistribution. The higher iron concentrations in atrophied soleus from both sexes are associated with a decoupling between the increase in iron storage proteins (i.e., ferritin and myoglobin) and the decrease in levels of iron export proteins (i.e., FPN and FLVCR1), thus supporting an iron sequestration in skeletal muscle under extreme physical inactivity.

Optimizing healthcare in space: the role of ultrasound imaging in medical conditions.

In the context of long-distance space travel, managing medical conditions presents unique challenges due to communication delays. Consequently, onboard physicians must possess proficiency in diagnostic tools such as ultrasound, which has demonstrated its efficacy in the Space. However, there is a notable lack of comprehensive discussion regarding its effectiveness in handling medical scenarios in the Space. This bibliometric and systematic review aims to provide an updated analysis of the evidence supporting the role of ultrasound imaging in diagnosing medical conditions within microgravity environments.

Synergistic interplay between radiation and microgravity in spaceflight-related immunological health risks.

Spaceflight poses a myriad of environmental stressors to astronauts´ physiology including microgravity and radiation. The individual impacts of microgravity and radiation on the immune system have been extensively investigated, though a comprehensive review on their combined effects on immune system outcomes is missing. Therefore, this review aims at understanding the synergistic, additive, and antagonistic interactions between microgravity and radiation and their impact on immune function as observed during spaceflight-analog studies such as rodent hindlimb unloading and cell culture rotating wall vessel models. These mimic some, but not all, of the physiological changes observed in astronauts during spaceflight and provide valuable information that should be considered when planning future missions. We provide guidelines for the design of further spaceflight-analog studies, incorporating influential factors such as age and sex for rodent models and standardizing the longitudinal evaluation of specific immunological alterations for both rodent and cellular models of spaceflight exposure.

Integrated analysis of miRNAome and transcriptome reveals that microgravity induces the alterations of critical functional gene modules via the regulation of miRNAs in short-term space-flown C. elegans.

Microgravity, as a unique hazardous factor encountered in space, can induce a series of harmful effects on living organisms. The impact of microgravity on the pivotal functional gene modules stemming from gene enrichment analysis via the regulation of miRNAs is not fully illustrated. To explore the microgravity-induced alterations in critical functional gene modules via the regulation of miRNAs, in the present study, we proposed a novel bioinformatics algorithm for the integrated analysis of miRNAome and transcriptome from short-term space-flown C. elegans. The samples of C. elegans were exposed to two space conditions, namely spaceflight (SF) and spaceflight control (SC) onboard the International Space Station for 4 days. Additionally, the samples of ground control (GC) were included for comparative analysis. Using the present algorithm, we constructed regulatory networks of functional gene modules annotated from differentially expressed genes (DEGs) and their associated regulatory differentially expressed miRNAs (DEmiRNAs). The results showed that functional gene modules of molting cycle, defense response, fatty acid metabolism, lysosome, and longevity regulating pathway were facilitated by 25 down-regulated DEmiRNAs (e.g., cel-miR-792, cel-miR-65, cel-miR-70, cel-lsy-6, cel-miR-796, etc.) in the SC vs. GC groups, whereas these modules were inhibited by 13 up-regulated DEmiRNAs (e.g., cel-miR-74, cel-miR-229, cel-miR-70, cel-miR-249, cel-miR-85, etc.) in the SF vs. GC groups. These findings indicated that microgravity could significantly alter gene expression patterns and their associated functional gene modules in short-term space-flown C. elegans. Additionally, we identified 34 miRNAs as post-transcriptional regulators that modulated these functional gene modules under microgravity conditions. Through the experimental verification, our results demonstrated that microgravity could induce the down-regulation of five critical functional gene modules (i.e., molting cycle, defense response, fatty acid metabolism, lysosome, and longevity regulating pathways) via the regulation of miRNAs in short-term space-flown C. elegans.