Effects Of Spaceflight Research Articles

Space Travel: The Radiation and Microgravity Effects on the Cardiovascular System.

Space flight modulates the functions of the cardiovascular system. The exposure to space conditions can alter the cerebral blood flow, as well as the venous return. Anemia, cardiac output changes, and increased activity of the sympathetic nervous system can also be seen. Understanding cardiac changes prepares astronauts for both better in-flight adaptations and long-term protection against cardiovascular diseases. The heart could undergo radio-degenerative effects when exposed to space radiation, increasing the risk of cardiovascular diseases in the long run. A high frequency of arrhythmias, such as ventricular/atrial premature complexes, have been reported during the Gemini and Apollo missions. Additionally, microgravity can lead to progressive degeneration of the myocytes and muscle atrophy with altered gene expression and calcium handling, along with impaired contractility. This review summarizes the potential cardiovascular effects of spaceflight and prevention measures.

Proteome of Dried Blood Spots of Cosmonauts during a 6-Month Flight

For successful exploration of near space, construction of planetary bases and exploration of the Solar System planets, it is necessary to fill the gaps in understanding the molecular mechanisms of the human body response to space flight (SF) conditions. Subsequently, this will make it possible to get closer to the discovery of potential molecular targets for protection against adverse processes occurring in the body under the influence of SF conditions. The aim of the work was to assess the effect of a 6-month space flight on the proteome of dried blood spots of cosmonauts. As a result of proteomic analysis, processes with highly and moderately enriched proteins were identified. Among them, processes with reliable dynamics were identified on the 7th day of SF, as well as on the 3rd and 6th months of flight: these are clusters of energy processes, presentation of molecules on the membrane, initiation of immune defense, proteostasis and metabolism. Biological processes were identified in which the representation of proteins decreased most significantly, which was reflected in a weakening of activity in the presentation of molecules on the membrane, the initiation of immune defense, as well as in the mechanisms of proteostasis in the acute period of adaptation to the factors of the initial stage of flight. It has been shown that there is a close interaction with proteins of the cytoskeleton organization that disappear or reappear in the dried blood spots proteome during flight, and that relate to processes whose activity significantly decreased during SF (immune system, proteostasis, metabolism).

Biopsychosocial Health Considerations for Astronauts in Long-Duration Spaceflight: A Narrative Review.

Long-duration spaceflights beyond low-Earth orbit, including missions to the Moon and Mars, pose significant health risks. Although biomedical approaches commonly appear in the literature, considering psychological and social factors alongside physiologic health offers a more holistic approach to astronaut care. Integrating the biopsychosocial (BPS) framework into medical planning addresses complex spaceflight challenges and aids in developing mitigation strategies. This review examined health risks associated with long-duration spaceflight within a BPS framework. Sources included governmental space agencies, academic textbooks, and relevant publications from multiple databases. Considering the National Aeronautics and Space Administration's Human Research Program's 5 main hazards, a conceptual model was developed to highlight the multifactorial BPS effects of spaceflight. In space, astronauts face unique environments and biological adaptations, including fluid shift, plasma volume loss, bone density loss, and muscle atrophy. Noise and the absence of natural light disrupt circadian rhythms, causing sleep disturbances and fatigue, which affect physical and mental health. Studies on crews in isolated and confined extreme environments reveal psychosocial challenges, including impaired mood and cognition, interpersonal tension, and miscommunication. International collaboration in spaceflight introduces differences in communication, problem solving, and social customs due to diverse cultural backgrounds. Upcoming long-distance missions likely will amplify these challenges. This review emphasizes BPS health considerations in long-duration spaceflight. It highlights the interplay among psychological, social, and biological factors, advocating for multidisciplinary teams and a holistic approach to astronaut health and mission planning and the potential added value of BPS perspectives in considering countermeasures.

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.

Citizen Science Approach for Searching and Curating Literature on the Effects of Spaceflight on Cardiovascular Outcomes in Rodents and Humans

Citizen Science Approach for Searching and Curating Literature on the Effects of Spaceflight on Cardiovascular Outcomes in Rodents and Humans

Cardiovascular effects of long-duration space flight.

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. 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. The displacement of fluid from the vascular system to the interstitium, driven by baroreceptor stimulation, results in a 10%-15% decline in plasma volume. 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. 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. 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. Upon reentry, astronauts frequently experience orthostatic intolerance and altered sympathetic responses, which bear potential hazards in scenarios requiring rapid mobilization or evacuation. 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.

Direct RNA sequencing of astronaut blood reveals spaceflight-associated m6A increases and hematopoietic transcriptional responses

The advent of civilian spaceflight challenges scientists to precisely describe the effects of spaceflight on human physiology, particularly at the molecular and cellular level. Newer, nanopore-based sequencing technologies can quantitatively map changes in chemical structure and expression at single molecule resolution across entire isoforms. We perform long-read, direct RNA nanopore sequencing, as well as Ultima high-coverage RNA-sequencing, of whole blood sampled longitudinally from four SpaceX Inspiration4 astronauts at seven timepoints, spanning pre-flight, day of return, and post-flight recovery. We report key genetic pathways, including changes in erythrocyte regulation, stress induction, and immune changes affected by spaceflight. We also present the first m6A methylation profiles for a human space mission, suggesting a significant spike in m6A levels immediately post-flight. These data and results represent the first longitudinal long-read RNA profiles and RNA modification maps for each gene for astronauts, improving our understanding of the human transcriptome’s dynamic response to spaceflight.

Effect of Spaceflight and Microgravity on the Musculoskeletal System: A Review.

With National Aeronautics and Space Administration's plans for longer distance, longer duration spaceflights such as missions to Mars and the surge in popularity of space tourism, the need to better understand the effects of spaceflight on the musculoskeletal system has never been more present. However, there is a paucity of information on how spaceflight affects orthopaedic health. This review surveys existing literature and discusses the effect of spaceflight on each aspect of the musculoskeletal system. Spaceflight reduces bone mineral density at rapid rates because of multiple mechanisms. While this seems to be recoverable upon re-exposure to gravity, concern for fracture in spaceflight remains as microgravity impairs bone strength and fracture healing. Muscles, tendons, and entheses similarly undergo microgravity adaptation. These changes result in decreased muscle mass, increased tendon laxity, and decreased enthesis stiffness, thus decreasing the strength of the muscle-tendon-enthesis unit with variable recovery upon gravity re-exposure. Spaceflight also affects joint health; unloading of the joints facilitates changes that thin and atrophy cartilage similar to arthritic phenotypes. These changes are likely recoverable upon return to gravity with exercise. Multiple questions remain regarding effects of longer duration flights on health and implications of these findings on terrestrial medicine, which should be the target of future research.

Spaceflight effects on human vascular smooth muscle cell phenotype and function

The cardiovascular system is strongly impacted by the hazards of spaceflight. Astronauts spending steadily increasing lengths of time in microgravity are subject to cardiovascular deconditioning resulting in loss of vascular tone, reduced total blood volume, and diminished cardiac output. Appreciating the mechanisms by which the cells of the vasculature are altered during spaceflight will be integral to understanding and combating these deleterious effects as the human presence in space advances. In this study, we performed RNA-Seq analysis coupled with review by QIAGEN Ingenuity Pathway Analysis software on human aortic smooth muscle cells (HASMCs) cultured for 3 days in microgravity and aboard the International Space Station to assess the transcriptomic changes that occur during spaceflight. The results of our RNA-Seq analysis show that SMCs undergo a wide range of transcriptional alteration while in space, significantly affecting 4422 genes. SMCs largely down-regulate markers of the contractile, synthetic, and osteogenic phenotypes including smooth muscle alpha actin (αSMA), matrix metalloproteinases (MMPs), and bone morphogenic proteins (BMPs). Additionally, components of several cellular signaling pathways were strongly impacted including the STAT3, NFκB, PI3K/AKT, HIF1α, and Endothelin pathways. This study highlights the significant changes in transcriptional behavior SMCs exhibit during spaceflight and puts these changes in context to better understand vascular function in space.

Conserved plant transcriptional responses to microgravity from two consecutive spaceflight experiments.

Understanding how plants adapt to the space environment is essential, as plants will be a valuable component of long duration space missions. Several spaceflight experiments have focused on transcriptional profiling as a means of understanding plant adaptation to microgravity. However, there is limited overlap between results from different experiments. Differences in experimental conditions and hardware make it difficult to find a consistent response across experiments and to distinguish the primary effects of microgravity from other spaceflight effects. Plant Signaling (PS) and Plant RNA Regulation (PRR) were two separate spaceflight experiments conducted on the International Space Station utilizing the European Modular Cultivation System (EMCS). The EMCS provided a lighted environment for plant growth with centrifugal capabilities providing an onboard 1 g control. An RNA-Seq analysis of shoot samples from PS and PRR revealed a significant overlap of genes differentially expressed in microgravity between the two experiments. Relative to onboard 1 g controls, genes involved in transcriptional regulation, shoot development, and response to auxin and light were upregulated in microgravity in both experiments. Conversely, genes involved in defense response, abiotic stress, Ca++ signaling, and cell wall modification were commonly downregulated in both datasets. The downregulation of stress responses in microgravity in these two experiments is interesting as these pathways have been previously observed as upregulated in spaceflight compared to ground controls. Similarly, we have observed many stress response genes to be upregulated in the 1 g onboard control compared to ground reference controls; however these genes were specifically downregulated in microgravity. In addition, we analyzed the sRNA landscape of the 1 g and microgravity (μ g) shoot samples from PRR. We identified three miRNAs (miR319c, miR398b, and miR8683) which were upregulated in microgravity, while several of their corresponding target genes were found to be downregulated in microgravity. Interestingly, the downregulated target genes are enriched in those encoding chloroplast-localized enzymes and proteins. These results uncover microgravity unique transcriptional changes and highlight the validity and importance of an onboard 1 g control.

Genome and clonal hematopoiesis stability contrasts with immune, cfDNA, mitochondrial, and telomere length changes during short duration spaceflight.

The Inspiration4 (I4) mission, the first all-civilian orbital flight mission, investigated the physiological effects of short-duration spaceflight through a multi-omic approach. Despite advances, there remains much to learn about human adaptation to spaceflight's unique challenges, including microgravity, immune system perturbations, and radiation exposure. To provide a detailed genetics analysis of the mission, we collected dried blood spots pre-, during, and post-flight for DNA extraction. Telomere length was measured by quantitative PCR, while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations. A robust bioinformatic pipeline was used for data analysis, including variant calling to assess mutational burden. Telomere elongation occurred during spaceflight and shortened after return to Earth. Cell-free DNA analysis revealed increased immune cell signatures post-flight. No significant clonal hematopoiesis of indeterminate potential (CHIP) or whole-genome instability was observed. The long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months post-flight. Our findings provide valuable insights into the physiological consequences of short-duration spaceflight, with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to Earth. CHIP sequencing data will serve as a reference point for studying the early development of CHIP in astronauts, an understudied phenomenon as previous studies have focused on career astronauts. This study will serve as a reference point for future commercial and non-commercial spaceflight, low Earth orbit (LEO) missions, and deep-space exploration.

ВЛИЯНИЕ КРАТКОСРОЧНОГО АНТИОРТОСТАТИЧЕСКОГО ВЫВЕШИВАНИЯ НА ОВАРИАЛЬНО-ГИПОФИЗАРНУЮ ОСЬ У МЫШЕЙ

With the increasing number of women-participants in piloted space programs, investigations of spaceflight effects on the female reproductive system are becoming vital. Purpose of the work is to determine thickness of the granulosa cells layer relative to the content of the luteinizing hormone (LH) receptor in antral follicles of the ovary, LH and a relative content of cytoskeletal proteins in the hypophysis of mice following suspension during the estrous cycle. SDS-PAGE and immunoblotting were used to define the relative proteins content. mRNAs were counted using RT-PCR. IHA was performed to measure thickness of the granulosa cells layer in ovarian sections. The results demonstrate an increase in the number of granulosa cells in the antral follicles of mice after 96-hr suspension, as well as in the relative content of the LH receptor and its mRNAs. However, the LH level in the hypophysis did not alter, even though we observed some changes in the content of cytoskeletal proteins, namely, an increase in the actin-binding proteins (alpha actinin 1 and 4) and a decrease in alpha tubulin and its acetylated form suggesting, probably, modification of the intracellular LH transport and release into blood.

Drosophila parasitoids go to space: Unexpected effects of spaceflight on hosts and their parasitoids

While fruit flies (Drosophila melanogaster) and humans exhibit immune system dysfunction in space, studies examining their immune systems' interactions with natural parasites in space are lacking. Drosophila parasitoid wasps modify blood cell function to suppress host immunity. In this study, naive and parasitized ground and space flies from a tumor-free control and a blood tumor-bearing mutant strain were examined. Inflammation-related genes were activated in space in both fly strains. Whereas control flies did not develop tumors, tumor burden increased in the space-returned tumor-bearing mutants. Surprisingly, control flies were more sensitive to spaceflight than mutant flies; many of their essential genes were downregulated. Parasitoids appeared more resilient than fly hosts, and spaceflight did not significantly impact wasp survival or the expression of their virulence genes. Previously undocumented mutant wasps with novel wing color and wing shape were isolated post-flight and will be invaluable for host-parasite studies on Earth.

Hindlimb unloading, a physiological model of microgravity, modifies the murine bone marrow IgM repertoire in a similar manner as aging but less strongly

BackgroundThe spaceflight environment is an extreme environment that affects the immune system of approximately 50% of astronauts. With planned long-duration missions, such as the deployment of the Lunar Gateway and possible interplanetary missions, it is mandatory to determine how all components of the immune system are affected, which will allow the establishment of countermeasures to preserve astronaut health. However, despite being an important component of the immune system, antibody-mediated humoral immunity has rarely been investigated in the context of the effects of the space environment. It has previously been demonstrated that 30 days aboard the BION-M1 satellite and 21 days of hindlimb unloading (HU), a model classically used to mimic the effects of microgravity, decrease murine B lymphopoiesis. Furthermore, modifications in B lymphopoiesis reported in young mice subjected to 21 days of HU were shown to be similar to those observed in aged mice (18–22 months). Since the primary antibody repertoire composed of IgM is created by V(D) J recombination during B lymphopoiesis, the objective of this study was to assess the degree of similarity between changes in the bone marrow IgM repertoire and in the V(D)J recombination process in 2.5-month-old mice subjected to 21 days of HU and aged (18 months) mice.ResultsWe found that in 21 days, HU induced changes in the IgM repertoire that were approximately 3-fold less than those in aged mice, which is a rapid effect. Bone remodeling and epigenetics likely mediate these changes. Indeed, we previously demonstrated a significant decrease in tibial morphometric parameters from day 6 of HU and a progressive reduction in these parameters until day 21 of HU, and it has been shown that age and microgravity induce epigenetic changes.ConclusionThese data reveal novel immune changes that are akin to advanced aging and underline the importance of studying the effects of spaceflight on antibody-mediated humoral immunity.

Neurocognitive Adaptations for Spatial Orientation and Navigation in Astronauts.

Astronauts often face orientation challenges while on orbit, which can lead to operator errors in demanding spatial tasks. In this study, we investigated the impact of long-duration spaceflight on the neural processes supporting astronauts' spatial orientation skills. Using functional magnetic resonance imaging (fMRI), we collected data from 16 astronauts six months before and two weeks after their International Space Station (ISS) missions while performing a spatial orientation task that requires generating a mental representation of one's surroundings. During this task, astronauts exhibited a general reduction in neural activity evoked from spatial-processing brain regions after spaceflight. The neural activity evoked in the precuneus was most saliently reduced following spaceflight, along with less powerful effects observed in the angular gyrus and retrosplenial regions of the brain. Importantly, the reduction in precuneus activity we identified was not accounted for by changes in behavioral performance or changes in grey matter concentration. These findings overall show less engagement of explicitly spatial neurological processes at postflight, suggesting astronauts make use of complementary strategies to perform some spatial tasks as an adaptation to spaceflight. These preliminary findings highlight the need for developing countermeasures or procedures that minimize the detrimental effects of spaceflight on spatial cognition, especially in light of planned long-distance future missions.

Changes in Vertebral Bone Density and Paraspinal Muscle Morphology Following Spaceflight and 1 Year Readaptation on Earth.

Astronauts have an increased risk of back pain and disc herniation upon returning to Earth. Thus, it is imperative to understand the effects of spaceflight and readaptation to gravity on the musculoskeletal tissues of the spine. Here we investigated whether ~6 months of spaceflight led to regional differences in bone loss within the vertebral body. Additionally, we evaluated the relationships between vertebral bone density and paraspinal muscle morphology before flight, after flight, and after readaptation on Earth. We measured vertebral trabecular bone mineral density (Tb.BMD), paraspinal muscle cross-sectional area (CSA), and muscle density in 17 astronauts using computed tomography (CT) images of the lumbar spine obtained before flight (before flight, n = 17), after flight (spaceflight, n = 17), and ~12 months of readaptation to gravitational loading on Earth (follow-up, n = 15). Spaceflight-induced declines in Tb.BMD were greater in the superior region of the vertebral body (-6.7%) than the inferior (-3.1%, p = 0.052 versus superior region) and transverse regions (-4.3%, p = 0.057 versus superior region). After a year of readaptation to Earth's gravity, Tb.BMD in the transverse region remained significantly below preflight levels (-4.66%, p = 0.0094). Paraspinal muscle CSA and muscle density declined -1.0% (p = 0.005) and -0.83% (p = 0.001) per month of spaceflight, respectively. Ultimately, bone loss in the superior vertebral body, along with fatty infiltration of paraspinal muscles and incomplete recovery even after a year of readaptation on Earth, may contribute to spinal pathology in long-duration astronauts. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Grip Force Control in 21-Day Dry Immersion

During space flight, the changes in the functions of the upper limbs can affect the quality of operator activity. At the same time, there are very few data on this topic, because most of the research is focused on the structure and functions of the lower extremities. The aim was to study the characteristics of the grip force control during the decrease of the support and proprioceptive sensory signals in the conditions of the ground-based model of the effects of space flight – dry immersion (DI). The duration of DI exposure was 21 days. 10 male volunteers performed tests using a hand dynamometer for maximal voluntary contraction, the maintenance of the reference force, the reproduction of this force from memory, and the grip force gradation test. The subjects performed this series of tests before exposure to DI, then on days 1, 3, 5, 10, 15, and 20 of DI, and days 1 and 3 of the recovery period. The results show that DI exposure led to an increase in proprioceptive sensitivity in the tasks without visual feedback when with open eyes from day 5 of DI the subjects were more mistaken in the reproduction of the reference force using the dominant hand. The sensory processing/modulation disorder under DI factors may cause this phenomenon.

The Effect of One-Year Seed Spaceflight Storage on Yield, Biochemical and Mineral Characteristics of Mature Leafy Vegetables Belonging to Brassicaceae, Apiaceae and Asteraceae Families

Spaceflight is known to produce genetic changes in seeds, usually accelerating aging, though species and varietal differences have been poorly investigated. Comparisons were carried out in terms of yield, biochemical characteristics and mineral composition between mature plants grown from seeds subjected to a one-year spaceflight, belonging to Brassicaceae (Brassica juncea and Eruca sativa), Apiaceae (Anethus graveolens, and Coriandrum sativum), and Asteraceae (Lactuca sativa, six cultivars) families, and non-treated control. Among the studied species, only Brassica juncea and Eruca sativa demonstrated a growth stimulation effect caused by seed spaceflight, while significant growth inhibition was recorded in Apiaceae plants and three cultivars of Lactuca sativa L. No differences in the total antioxidant activity (AOA), polyphenol and ascorbic acid content were detected between ‘space-treated’ and control plants. On the contrary, significant decrease in proline accumulation and increase in malonic dialdehyde and photosynthetic pigments levels were shown by Brassicaceae species. The effect of long-term seed spaceflight on the mineral composition of mature plants was reflected in the inhibition of accumulation of all 24 elements analyzed in Apiaceae plants, except for Se, whose concentration was higher in all ‘space-treated’ plants compared to the control. Spaceflight seed storage increased V levels in lettuce and decreased Na accumulation in all the investigated species. The results reveal species-dependent changes in the accumulation of macro-, micro- and toxic elements in Apiaceae, Brassicacea, and Asteraceae representatives due to spaceflight seed storage. The detected differences in plant elemental composition between ‘space’ treatment and control partly explain the corresponding yield gap and suggest a relationship between mineral status and adaptability. The highest beneficial effect of spaceflight seed storage on yield was recorded in Eruca sativa cultivar, Rusalochka.

Corticospinal excitability after 5-day Dry Immersion in women.

In light of the development of manned astronautics and the increasing participation of women in space flights, the question of female body adaptation to microgravity conditions becomes relevant. Currently, one of the important directions in this issue is to study the effects of support withdrawal as a factor of weightlessness on the human sensorimotor system. Dry Immersion is one of the well-known ground-based models, which adequately reproduces the main physiological effects of space flight. The aim of this study was to evaluate the changes in motor evoked potentials of the lower leg gravity-dependent muscles in women after a 5-day Dry Immersion. We analyzed evoked responses to transcranial and trans-spinal magnetic stimulation. In this method, areas of interest (the motor cortex and lumbosacral thickening of the spinal cord) are stimulated with an electromagnetic stimulus. The experiment was conducted with the participation of 16 healthy female volunteers with a natural menstrual cycle. The thresholds, amplitudes, and latencies of motor potentials evoked by magnetic stimulation were assessed. We showed that 5-day exposure to support withdrawal leads to a decrease in motor-evoked potential thresholds and central motor conduction time, although changes in motor response amplitudes were ambiguous. The data obtained correspond to the results of previous research on Dry Immersion effects on the sensorimotor system in men.

Human skeletal muscle tissue chip autonomous payload reveals changes in fiber type and metabolic gene expression due to spaceflight

Microphysiological systems provide the opportunity to model accelerated changes at the human tissue level in the extreme space environment. Spaceflight-induced muscle atrophy experienced by astronauts shares similar physiological changes to muscle wasting in older adults, known as sarcopenia. These shared attributes provide a rationale for investigating molecular changes in muscle cells exposed to spaceflight that may mimic the underlying pathophysiology of sarcopenia. We report the results from three-dimensional myobundles derived from muscle biopsies from young and older adults, integrated into an autonomous CubeLab™, and flown to the International Space Station (ISS) aboard SpaceX CRS-21 as part of the NIH/NASA funded Tissue Chips in Space program. Global transcriptomic RNA-Seq analyses comparing the myobundles in space and on the ground revealed downregulation of shared transcripts related to myoblast proliferation and muscle differentiation. The analyses also revealed downregulated differentially expressed gene pathways related to muscle metabolism unique to myobundles derived from the older cohort exposed to the space environment compared to ground controls. Gene classes related to inflammatory pathways were downregulated in flight samples cultured from the younger cohort compared to ground controls. Our muscle tissue chip platform provides an approach to studying the cell autonomous effects of spaceflight on muscle cell biology that may not be appreciated on the whole organ or organism level and sets the stage for continued data collection from muscle tissue chip experimentation in microgravity. We also report on the challenges and opportunities for conducting autonomous tissue-on-chip CubeLabTM payloads on the ISS.