Spaceflight is known to negatively impact bone health, but the duration of these effects remains unclear. These two case studies investigated bone microarchitecture, density, and remodelling up to 4 years after long-duration spaceflight, aiming to inform countermeasure development and guide future research efforts. High-resolution peripheral quantitative computed tomography (HR-pQCT) and dual X-ray absorptiometry (DXA) scans were conducted on two crew members at pre-flight and up to 48-months post-spaceflight. Both crew members exhibited significant bone loss in the tibia at return from spaceflight, while only one crew member showed losses in the radius. After 4 years of recovery, one crew member achieved full recovery, while the second experienced persistent trabecular deficits that were compensated by significant cortical thickening. These results provide insight into the need for tailored countermeasures and prolonged monitoring to optimize skeletal health for future long-duration space missions, with implications for bone health research on mechanical unloading and reloading.

Space ionizing radiation is a major risk factor for astronauts, yet its molecular mechanisms remain poorly understood. This study employs an integrative approach to investigate the effects of space ionizing radiation on molecules, modules, biological functions, associated diseases, and potential therapeutic drugs. Using paired samples from five donors subjected to acute ex vivo 2Gy gamma-ray irradiation, we analyzed miRNA and gene expression profiles in human peripheral blood lymphocytes collected 24 h post-exposure, combined with heterogeneous network analysis, identifying 179 key molecules (23 transcription factors, 10 miRNAs, and 146 genes) and 5 key modules. Functional enrichment analysis revealed associations with processes such as cell cycle regulation, cytidine deamination, cell differentiation, viral carcinogenesis, and apoptosis. Radiation was also significantly linked to neoplasms and digestive system diseases. Furthermore, we predicted 20 potential therapeutic compounds, including small molecules (e.g., Navitoclax) and Traditional Chinese Medicine ingredients (e.g., Genistin, Saikosaponin D), which may alleviate radiation-induced damage such as pulmonary fibrosis and oxidative stress. These findings provide novel insights into the molecular mechanisms of space ionizing radiation and may contribute to developing effective strategies to protect astronaut health during space missions.

We investigate the use of an atomic Fabry-Perot interferometer (FPI) with a pulsed non-interacting Bose-Einstein condensate (BEC) source as a space-based acceleration sensor. We derive an analytic approximation for the device’s transmission under a uniform acceleration, which we use to compute the device’s attainable acceleration sensitivity using the classical Fisher information. In the ideal case of a high-finesse FPI and an infinitely narrow momentum width atomic source, we find that when the device length is limited, the atomic FPI can achieve greater acceleration sensitivity than a Mach-Zender (MZ) interferometer of equivalent device length. Under the more realistic case of a finite momentum width source, we identify the ideal cavity length for the best sensitivity. Although the MZ interferometer now offers enhanced sensitivity within currently achievable parameter regimes, our analysis demonstrates that the atomic FPI holds potential as a promising future alternative if narrow momentum width atomic sources can be engineered.

The effects of galactic cosmic radiation on reproductive physiology remain largely unknown. We determined the impact of near-continuous low-dose-rate Californium-252 neutron irradiation (1 mGy/day) as a space-relevant analog on litter size and number of resorptions at embryonic day (E) 12.5 (n = 19 radiated dams, n = 20 controls) and litter size, number of resorptions, fetal growth, and placental signaling and transcriptome (RNA sequencing) at E18.5 (n = 21 radiated dams, n = 20 controls) in pregnant mice. A significantly increased early resorption rate and decreased placental weight were observed in irradiated mice. There were no statistically significant differences in litter size, fetal weight, length, or malformation rate between the groups. Near-continuous radiation had no significant effects on the mechanistic target of rapamycin (mTOR), endoplasmic reticulum stress or inflammatory signaling, rate of double-stranded DNA breaks, and had minimal effects on gene expression in the placenta. These data suggest that near-continuous, low-level galactic cosmic radiation has a limited impact on pregnancy outcomes.

Spaceflight-associated neuro-ocular syndrome (SANS) has been well documented in astronauts. However, its pathogenesis is not fully understood. New findings indicate the impaired outflow of the optic nerve cerebrospinal fluid may participate or contribute to some changes in SANS. In this perspective, we generated a hypothesis that the outflow of cerebrospinal fluid through the optic nerve sheath may be impaired under micro-gravity and then may potentially lead to SANS-related alterations.

Extended-duration human spaceflight necessitates a better understanding of the physiological impacts of microgravity. While the ground-based microgravity simulations identified low intensity vibration (LIV) as a possible countermeasure, how cells may respond to LIV under real microgravity remain unexplored. In this way, adaptation of LIV bioreactors for space remains limited, resulting in a significant gap in microgravity research. In this study, we introduce an LIV bioreactor designed specifically for the usage in the International Space Station. Our research covers the bioreactor’s design process and evaluation of the short-term viability of cells encapsulated in hydrogel-laden 3D printed scaffolds under 0.7 g, 90 Hz LIV. An LIV bioreactor compatible with the operation requirements of space missions provides a robust platform to study cellular effects of LIV under real microgravity conditions.

Space exploration’s advancement toward long-duration missions prompts intensified research on physiological effects. Despite adaptive physiological stability in some variables, persistent changes affect genome integrity, immune response, and cognitive function. Our study, utilizing multi-omics data from GeneLab, provides crucial insights investigating muscle atrophy during space mission. Leveraging NASA GeneLab’s data resources, we apply systems biology-based analyses, facilitating comprehensive understanding and enabling meta-analysis. Through transcriptomics, we establish a reference profile of biological processes underlying muscle atrophy, crucial for intervention development. We emphasize the often-overlooked role of glycosylation in muscle atrophy. Our research sheds light on fundamental molecular mechanisms, bridging gaps between space research and terrestrial conditions. This study underscores the importance of interdisciplinary collaboration and data-sharing initiatives like GeneLab in advancing space medicine research.

Microgravity (µG) experienced during space flights promotes adaptation in several astronauts’ organs and tissues, with skeletal muscles being the most affected. In response to reduced gravitational loading, muscles (especially, lower limb and antigravity muscles) undergo progressive mass loss and alteration in metabolism, myofiber size, and composition. Skeletal muscle precursor cells (MPCs), also known as satellite cells, are responsible for the growth and maintenance of muscle mass in adult life as well as for muscle regeneration following damage and may have a major role in µG-induced muscle wasting. Despite the great relevance for astronaut health, very few data are available about the effects of real µG on human muscles. Based on the MyoGravity project, this study aimed to analyze: (i) the cellular and transcriptional alterations induced by real µG in human MPCs (huMPCs) and (ii) the response of human skeletal muscle to normal gravitational loading after prolonged exposure to µG. We evaluated the transcriptomic changes induced by µG on board the International Space Station (ISS) in differentiating huMPCs isolated from Vastus lateralis muscle biopsies of a pre-flight astronaut and an age- and sex-matched volunteer, in comparison with the same cells cultured on the ground in standard gravity (1×g) conditions. We found that huMPCs differentiated under real µG conditions showed: (i) upregulation of genes related to cell adhesion, plasma membrane components, and ion transport; (ii) strong downregulation of genes related to the muscle contraction machinery and sarcomere organization; and (iii) downregulation of muscle-specific microRNAs (myomiRs). Moreover, we had the unique opportunity to analyze huMPCs and skeletal muscle tissue of the same astronaut before and 30 h after a long-duration space flight on board the ISS. Prolonged exposure to real µG strongly affected the biology and functionality of the astronaut’s satellite cells, which showed a dramatic reduction of responsiveness to activating stimuli and proliferation rate, morphological changes, and almost inability to fuse into myotubes. RNA-Seq analysis of post- vs. pre-flight muscle tissue showed that genes involved in muscle structure and remodeling are promptly activated after landing following a long-duration space mission. Conversely, genes involved in the myelination process or synapse and neuromuscular junction organization appeared downregulated. Although we have investigated only one astronaut, these results point to a prompt readaptation of the skeletal muscle mechanical components to the normal gravitational loading, but the inability to rapidly recover the physiological muscle myelination/innervation pattern after landing from a long-duration space flight. Together with the persistent functional deficit observed in the astronaut’s satellite cells after prolonged exposure to real µG, these results lead us to hypothesize that a condition of inefficient regeneration is likely to occur in the muscles of post-flight astronauts following damage.

Test subjects were assessed in a partial gravity environment during parabolic flight while they performed mission-critical activities that challenged their balance and locomotion. These functional activities included rising from a seated position and walking, jumping down, recovering from falls, and maintaining an upright stance. Twelve volunteers were tested during 10 parabolas that produced 0.25×g, 0.5×g, or 0.75×g, and at 1×g during level flight intervals between parabolas. Additionally, 14 other subjects were tested using identical procedures in a 1×g laboratory setting. Partial gravity altered the performance of settling after standing and navigating around obstacles. As gravity levels decreased, the time required to stand up, settle, walk, and negotiate obstacles, and the number of falls increased. Information obtained from these tests will allow space agencies to assess the vestibular, sensorimotor, and cardiovascular risks associated with different levels of partial gravity.

The analysis of cells frozen within the International Space Station (ISS) will provide crucial insights into the impact of the space environment on cellular functions and properties. The objective of this study was to develop a method for cryopreserving blood cells under the specific constraints of the ISS. In a ground experiment, mouse blood was directly mixed with a cryoprotectant and gradually frozen at −80 °C. Thawing the frozen blood sample resulted in the successful recovery of viable mononuclear cells when using a mixed solution of dimethylsulfoxide and hydroxyethyl starch as a cryoprotectant. In addition, we developed new freezing cases to minimize storage space utilization within the ISS freezer. Finally, we confirmed the recovery of major mononuclear immune cell subsets from the cryopreserved blood cells through a high dimensional analysis of flow cytometric data using 13 cell surface markers. Consequently, this ground study lays the foundation for the cryopreservation of viable blood cells on the ISS, enabling their analysis upon return to Earth. The application of this method in ISS studies will contribute to understanding the impact of space environments on human cells. Moreover, this method may find application in the cryopreservation of blood cells in situations where research facilities are inadequate.