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SOMA biosample collections during the Inspiration4 mission Sample types and downstream assays performed for multi-omic and clinical biomarkers. A variety of blood derivatives were collected via venipuncture. Samples that have not yet been sequenced are biobanked. EVP = extracellular vesicles and particles. Env = environment. Created with BioRender.com.
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Human spaceflight has historically been managed by government agencies, such as in the NASA Twins Study¹, but new commercial spaceflight opportunities have opened spaceflight to a broader population. In 2021, the SpaceX Inspiration4 mission launched the first all-civilian crew to low Earth orbit, which included the youngest American astronaut (aged...
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Citations
... The resulting data can be valuable for advancing terrestrial health care as well 17 . Omics technologies were applied to analyze the data from the NASA Twin study and, more recently, Inspiration4, the first all-civilian orbital spaceflight mission 12,18,19 . Sequencing was also used to analyze Clonal Hematopoiesis of Indeterminate potential mutations in a retrospective specimen cohort 20 . ...
... The GENESTAR protocol was designed to prioritize operational convenience, ensure continuity in biospecimen collection across missions, and seamlessly integrate into the schedules of astronauts and private space organizations. All the three multi-omics studies undertaken so far GEN-ESTAR, SOMA 18 and NASA-HRP 12 captures the core biospecimens so that the cohort of samples and data available to study the effects of space on human health are as inclusive as possible 12,19,25 while there are assays that GENESTAR and SOMA are not generating the exact datasets (16S for GENESTAR vs metagenomic WGS for SOMA; targeted proteomics vs untargeted proteomics) or that the GENESTAR is not generating lipidomics data immediately, the biospecimens collected and biobanked are available for later data generation from these assays. For the first time, in the GEN-ESTAR manual, a data dictionary, a LIMS-enabled biobank, and a customized provision for subjects to obtain CLIA WGS among the three protocols. ...
The surge in commercial and civilian spaceflight enables the systematic and longitudinal, large-scale biospecimen collection to understand the prospective effects of space travel on human health. The Genomics and Space Medicine (Space Omics) project at BCM-HGSC involves a comprehensive biospecimen collection plan from commercial/private space flight participants. The manuscript addresses the critical gaps in the biospecimen collection process including details of the informed consent process, a provision for subjects to obtain custom CLIA-WGS reports, a data dictionary and a LIMS enabled biobank. The manuscript also discusses the biospecimens collection, processing methodologies and nucleic acid suitability for Omics data generation. Results from Axiom-2 mission where, 339 biospecimens were collected using 'Genomic Evaluation of Space Travel and Research (GENESTAR)' manual, at two different sites, showed that 98% of the blood samples and 91.6% of the non-blood samples passed the QC requirements for Omics assays, underscoring the reliability and effectiveness of the GENESTAR manual.
... These findings underscore potential inflammation-related risks for astronauts after SF [4]. Additionally, SF alters the hormones associated with appetite and stress, likely contributing to oxidative stress [5]. Ghrelin, an antioxidant hormone, declined by 35% (Fig. 1k), while leptin, a proinflammatory and pro-oxidative agent, increased by 25% (Fig. 1l). ...
... Admittedly, we did not conduct cognitive/behavioral tests. However, a recent study demonstrated that a 3-day spaceflight is not potent enough to affect cognitive performance in civilians [5]. Other remaining questions to consider are whether SF has an impact on the neurohormonal assets of female and crew members of different ages. ...
... Orbital space tourism is divided into two different sub-categories. First there is the opportunity to stay inside the capsula for the entire stay of the touristic flight, which also means, that all activities will be located in and around the space flight vehicle, e.g. during the Inspiration 4 or Polaris Dawn Mission (Jones et al., 2024). Secondly, there is the opportunity as a tourist to use the space flight vehicle to reach an orbit and then stir towards a given structure in space, which can be for example a space station, like the international space station or a future space hotel. ...
... As the United States and China are the two leading countries in launch rates (Denis et al., 2020), as of 2024 space tourism is more popular in the US than in China. Additionally, operators like AXIOM Space are pushing the limits of space tourism with missions like Inspiration 4 or Polaris Dawn (Jones et al., 2024). ...
This article aims to give an overview and introduction into space tourism. Therefore, a selection of this field's literature represents the field's beginnings, major figures, and potential futures. Overall space tourism refers to the opportunity to experience space flights for non-professionals for leisure or recreational purposes. Established in the early 2000s when private individuals first ventured into space through collaborations with the Russian space agency, it becomes more popular today, with new companies entering the market. Since the beginning, major companies such as SpaceX, Blue Origin or Virgin Galactic have led the development of space tourism, with several nations also investing in the industry. Initially accessible only to wealthy individuals, the target group may expand as costs decrease due to reusable rocket technology. Especially suborbital space tourism which in contrast to orbital space is less expensive and will therefore become more easily available to the general public. Also, the increasing competition on the market, the development from infrastructure in the Low Earth Orbit, as well as evolving regulatory frameworks will further shape the industry's growth in the coming years. Future trends suggest a broader market with the potential for commercial space stations, space hotels, and even lunar or interplanetary travel.
... The potential for customers with health problems to participate in space tourism raises the necessity for further research in the field of space medicine, particularly in relation to the effects of space travel on individuals with pre-existing health conditions [200]. The Inspira-tion4 mission, which marked the first space voyage to be undertaken with an entirely civilian crew, was conducted in 2021 through the launch of SpaceX's Crew Dragon capsule into low Earth orbit [201]. During this mission, the crew remained in this orbit for a total duration of three days. ...
... Portable ultrasound measurements, cognitive and sensory motor tests, surveys, physiological data collected with a smart watch, and blood/saliva tests were performed to evaluate the effects of this short-term space flight on humans and observed inflammatory response, DNA damage, neurovestibular changes, telomere elongation, and immune changes. These changes were found to disappear after returning to Earth [201]. Furthermore, another study revealed that telomere length, which is known to increase during spaceflight, rapidly diminishes upon return to Earth [202]. ...
Purpose
Since the first human experience in space, the interest in space research and medicine to explore universe is growing day by day. The extreme space conditions mainly radiation and microgravity effects on human physiology, antimicrobial susceptibility, and efficacy, safety, and stability of drugs. Therefore, the aim of this review is to address the impact of extreme space conditions, mainly microgravity and radiation, on human physiology and highlights the need for future approaches by evaluating the effectiveness of strategies to prevent or mitigate health problems.
Methods
Published papers and NASA technical documents were searched in Pubmed and Google Scholar databases using the keywords ‘‘antimicrobial susceptibility or drug resistance or drug stability or innovations or pharmacokinetic or pharmacodynamics’’ and ‘‘radiation or microgravity or space environments or space medicine or space pharmacy’' to prepare this review.
Results
In this review, the challenges regarding physiological effects and drug-related problems are examined through the evaluation of extreme conditions in space. Medications used in spaceflight are summarized, and the role of pharmacists specializing in space medicine is briefly explained. Last but not least, to overcome the aforementioned issues, novel approaches have been addressed, such as personalised treatments, development of space-resistant formulations and various microbial applications.
Conclusions
Further research in the space medicine is required to facilitate the safe and healthy travel of humans to the Moon, Mars and other extraterrestrial destinations. One bear in mind that space research will contribute not only to the exploration of the universe, but also to the advancement of health and technological discoveries on Earth.
... To explore the physiological variations profiles of I4 crew, 13 kinds of biospecimen (including whole blood, serum, peripheral blood mononuclear cells [PBMCs], dried blood spots, skin biopsies, stool, etc.) were collected across 10 time points (including three pre-flight, three in-flight, one immediately post-flight, and three recovery time points) and the portable imaging devices, wearables, and multiomics analysis methods were conducted. 3 The collection and analysis of biological samples are summarized ( Figure 1) and some research highlights will be elaborated below. ...
... Eliciting protective genotype-phenotype relationships is also challenging because several gene variants linked to protective phenotypes can concurrently also be linked to negative, potentially fatal, phenotypes. For example, while overproduction of TERT is linked to decreased aging, it is also linked to cancer risk 88 ; while variants of PCSK9 are linked to decreased LDL and heart disease 89 , they are also linked to diabetes 90 and low cognition 91 ; while CCR5 variants are linked to decreased risks of cancer 92 , HIV 93 and diseases of the heart 94 , liver 95 , and brain 96 , they also correspond to increased risks of various viruses like West Nile virus 97 ; and while CTNNB1 overproduction is linked to radiation resistance 98 , it is also linked to increased cancer risk 99 . To complicate the matter, downstream effects of gene variants can interact with each other; this is the case with SOST and LRP5, both related to bone health 100 . ...
... In this paper, we reviewed an example set of published alleles purportedly linked to protective effects, the biochemical pathways of which could inform therapeutic compound discovery and nutrition, exercise, and lifestyle recommendations to protect health during spaceflight missions and potentially during postflight recovery and stationing on planetary surfaces, including the Moon and Mars 138 . This guide can also help individuals on Earth in high-stress and environmentally challenging scenarios, such as first responders, cave explorers, radiation workers, deep-sea investigators, or commercial astronauts like the Inspiration4, Axoim Space, and Polaris Dawn missions 91,[139][140][141][142][143][144][145][146][147] . Alongside any untapped potential to enhance both terrestrial and aerospace precision healthcare, investigation of such alleles poses significant technical and ethical challenges. ...
Common and rare alleles are now being annotated across millions of human genomes, and omics technologies are increasingly being used to develop health and treatment recommendations. However, these alleles have not yet been systematically characterized relative to aerospace medicine. Here, we review published alleles naturally found in human cohorts that have a likely protective effect, which is linked to decreased cancer risk and improved bone, muscular, and cardiovascular health. Although some technical and ethical challenges remain, research into these protective mechanisms could translate into improved nutrition, exercise, and health recommendations for crew members during deep space missions.
... Sample collection methods for the four SpaceX Inspiration4 civilian crewmembers have been detailed in full 71,108 . Briefly, human peripheral blood mononuclear cells (PBMCs) were isolated from K2 EDTA tubes using Ficoll separation. ...
Telomeres are repetitive nucleoprotein complexes at chromosomal termini essential for maintaining genome stability. Telomeric RNA, or TERRA, is a previously presumed long noncoding RNA of heterogeneous lengths that contributes to end-capping structure and function, and facilitates telomeric recombination in tumors that maintain telomere length via the telomerase-independent Alternative Lengthening of Telomeres (ALT) pathway. Here, we investigated TERRA in the radiation-induced DNA damage response (DDR) across astronauts, high-altitude climbers, healthy donors, and cellular models. Similar to astronauts in the space radiation environment and climbers of Mt. Everest, in vitro radiation exposure prompted increased transcription of TERRA, while simulated microgravity did not. Data suggest a specific TERRA DDR to telomeric double-strand breaks (DSBs), and provide direct demonstration of hybridized TERRA at telomere-specific DSB sites, indicative of protective TERRA:telomeric DNA hybrid formation. Targeted telomeric DSBs also resulted in accumulation of TERRA foci in G2-phase, supportive of TERRA’s role in facilitating recombination-mediated telomere elongation. Results have important implications for scenarios involving persistent telomeric DNA damage, such as those associated with chronic oxidative stress (e.g., aging, systemic inflammation, environmental and occupational radiation exposures), which can trigger transient ALT in normal human cells, as well as for targeting TERRA as a therapeutic strategy against ALT-positive tumors.
... The NASA Twins study along with the JAXA Cell-Free Epigenome and Inspiration4 data reported here and elsewhere (Figs. 6 and 7) highlight the emerging ability to conduct omic analyses on astronaut samples 27,39,55 . We propose the use of omics data to investigate the development of aging-like phenomena in spaceflight, which can also help improve our understanding of aging metrics like clonal hematopoiesis 56 , and also link to a wide array of new data from the SOMA package of data and papers 48,53,55,55,[57][58][59][60][61][62][63][64][65] . ...
Human space exploration poses inherent risks to astronauts’ health, leading to molecular changes that can significantly impact their well-being. These alterations encompass genomic instability, mitochondrial dysfunction, increased inflammation, homeostatic dysregulation, and various epigenomic changes. Remarkably, these changes bear similarities to those observed during the aging process on Earth. However, our understanding of the connection between these molecular shifts and disease development in space remains limited. Frailty syndrome, a clinical syndrome associated with biological aging, has not been comprehensively investigated during spaceflight. To bridge this knowledge gap, we leveraged murine data obtained from NASA’s GeneLab, along with astronaut data gathered from the JAXA and Inspiration4 missions. Our objective was to assess the presence of biological markers and pathways related to frailty, aging, and sarcopenia within the spaceflight context. Through our analysis, we identified notable changes in gene expression patterns that may be indicative of the development of a frailty-like condition during space missions. These findings suggest that the parallels between spaceflight and the aging process may extend to encompass frailty as well. Consequently, further investigations exploring the utility of a frailty index in monitoring astronaut health appear to be warranted.
... Corroborating gene regulatory changes associated with hair cycle were also reported in an analysis of hair follicle samples from 10 astronauts in a Japan Aerospace Exploration Agency (JAXA) study 13 , yet reports of skin physiological changes in astronauts, including dermal atrophy, have been mixed 14,15 . In a recent analysis of astronaut skin punch biopsies taken before and after the 3-day commercial Inspiration4 (i4) mission 16 , gene expression changes within different layers of the skin were explored alongside microbiome changes, revealing signatures of increased inflammation and mitochondrial dysregulation across skin compartments, and gene regulatory changes associated with activation of DNA damage response (DDR) processes, T cell immunity, and increased barrier disruption in the outer epidermal layer of the skin 17 . ...
Background
Spaceflight poses a unique set of challenges to humans and the hostile spaceflight environment can induce a wide range of increased health risks, including dermatological issues. The biology driving the frequency of skin issues in astronauts is currently not well understood.
Methods
To address this issue, we used a systems biology approach utilizing NASA’s Open Science Data Repository (OSDR) on space flown murine transcriptomic datasets focused on the skin, biochemical profiles of 50 NASA astronauts and human transcriptomic datasets generated from blood and hair samples of JAXA astronauts, as well as blood samples obtained from the NASA Twins Study, and skin and blood samples from the first civilian commercial mission, Inspiration4.
Results
Key biological changes related to skin health, DNA damage & repair, and mitochondrial dysregulation are identified as potential drivers for skin health risks during spaceflight. Additionally, a machine learning model is utilized to determine gene pairings associated with spaceflight response in the skin. While we identified spaceflight-induced dysregulation, such as alterations in genes associated with skin barrier function and collagen formation, our results also highlight the remarkable ability for organisms to re-adapt back to Earth via post-flight re-tuning of gene expression.
Conclusion
Our findings can guide future research on developing countermeasures for mitigating spaceflight-associated skin damage.
... The first all-civilian crew of the SpaceX Inspiration4 (i4) short-term mission (3 days) embarked aboard the Dragon capsule and reached a high altitude (575 km) on the Earth orbit, with the crew being exposed to spaceflight hazards such as radiation, microgravity, and confinement in hostile space environment. The mission provided a platform for mapping human response to acute spaceflight in an unprecedented detail with the largest number of processed biological samples from a space mission, thereby allowing the longitudinal profiling of multi-omic clinical responses across genomics, proteomics, metabolomics, microbiome, and transcriptomics measurements (Jones et al., 2024;Houerbi et al., 2024). ...
