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1.
Cells ; 13(13)2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38995005

RESUMO

Space travel presents multiple risks to astronauts such as launch, radiation, spacewalks or extravehicular activities, and microgravity. The lungs are composed of a combination of air, blood, and tissue, making it a complex organ system with interactions between the external and internal environment. Gravity strongly influences the structure of the lung which results in heterogeneity of ventilation and perfusion that becomes uniform in microgravity as shown during parabolic flights, Spacelab, and Skylab experiments. While changes in lung volumes occur in microgravity, efficient gas exchange remains and the lungs perform as they would on Earth; however, little is known about the cellular response to microgravity. In addition to spaceflight and real microgravity, devices, such as clinostats and random positioning machines, are used to simulate microgravity to study cellular responses on the ground. Differential expression of cell adhesion and extracellular matrix molecules has been found in real and simulated microgravity. Immune dysregulation is a known consequence of space travel that includes changes in immune cell morphology, function, and number, which increases susceptibility to infections. However, the majority of in vitro studies do not have a specific respiratory focus. These studies are needed to fully understand the impact of microgravity on the function of the respiratory system in different conditions.


Assuntos
Pulmão , Voo Espacial , Ausência de Peso , Humanos , Pulmão/fisiologia , Ausência de Peso/efeitos adversos , Animais
2.
J Environ Sci (China) ; 146: 237-240, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38969451

RESUMO

Exploring the vast extraterrestrial space is an inevitable trend with continuous human development. Water treatment and reuse are crucial in the limited and closed space that is available in spaceships or long-term use space bases that will be established in the foreseeable future. Dedicated water treatment technologies have experienced iterative development for more than 60 years since the first manned spaceflight was successfully launched. Herein, we briefly review the related wastewater characteristics and the history of water treatment in space stations, and we focus on future challenges and perspectives, aiming at providing insights for optimizing wastewater treatment technologies and closing the water cycle in future.


Assuntos
Eliminação de Resíduos Líquidos , Águas Residuárias , Purificação da Água , Eliminação de Resíduos Líquidos/métodos , Purificação da Água/métodos , Voo Espacial
3.
Nat Commun ; 15(1): 4778, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862479

RESUMO

Impairment of the central nervous system (CNS) poses a significant health risk for astronauts during long-duration space missions. In this study, we employed an innovative approach by integrating single-cell multiomics (transcriptomics and chromatin accessibility) with spatial transcriptomics to elucidate the impact of spaceflight on the mouse brain in female mice. Our comparative analysis between ground control and spaceflight-exposed animals revealed significant alterations in essential brain processes including neurogenesis, synaptogenesis and synaptic transmission, particularly affecting the cortex, hippocampus, striatum and neuroendocrine structures. Additionally, we observed astrocyte activation and signs of immune dysfunction. At the pathway level, some spaceflight-induced changes in the brain exhibit similarities with neurodegenerative disorders, marked by oxidative stress and protein misfolding. Our integrated spatial multiomics approach serves as a stepping stone towards understanding spaceflight-induced CNS impairments at the level of individual brain regions and cell types, and provides a basis for comparison in future spaceflight studies. For broader scientific impact, all datasets from this study are available through an interactive data portal, as well as the National Aeronautics and Space Administration (NASA) Open Science Data Repository (OSDR).


Assuntos
Encéfalo , Neurônios , Voo Espacial , Animais , Camundongos , Feminino , Encéfalo/metabolismo , Encéfalo/patologia , Neurônios/metabolismo , Transcriptoma , Neurogênese , Análise de Célula Única , Camundongos Endogâmicos C57BL , Transmissão Sináptica , Ausência de Peso/efeitos adversos , Astrócitos/metabolismo , Estresse Oxidativo , Perfilação da Expressão Gênica , Multiômica
4.
Nat Commun ; 15(1): 4964, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862509

RESUMO

The SpaceX Inspiration4 mission provided a unique opportunity to study the impact of spaceflight on the human body. Biospecimen samples were collected from four crew members longitudinally before (Launch: L-92, L-44, L-3 days), during (Flight Day: FD1, FD2, FD3), and after (Return: R + 1, R + 45, R + 82, R + 194 days) spaceflight, spanning a total of 289 days across 2021-2022. The collection process included venous whole blood, capillary dried blood spot cards, saliva, urine, stool, body swabs, capsule swabs, SpaceX Dragon capsule HEPA filter, and skin biopsies. Venous whole blood was further processed to obtain aliquots of serum, plasma, extracellular vesicles and particles, and peripheral blood mononuclear cells. In total, 2,911 sample aliquots were shipped to our central lab at Weill Cornell Medicine for downstream assays and biobanking. This paper provides an overview of the extensive biospecimen collection and highlights their processing procedures and long-term biobanking techniques, facilitating future molecular tests and evaluations.As such, this study details a robust framework for obtaining and preserving high-quality human, microbial, and environmental samples for aerospace medicine in the Space Omics and Medical Atlas (SOMA) initiative, which can aid future human spaceflight and space biology experiments.


Assuntos
Bancos de Espécimes Biológicos , Voo Espacial , Manejo de Espécimes , Humanos , Manejo de Espécimes/métodos , Astronautas
6.
Nat Commun ; 15(1): 4814, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862469

RESUMO

A detailed understanding of how spaceflight affects human health is essential for long-term space exploration. Liquid biopsies allow for minimally-invasive multi-omics assessments that can resolve the molecular heterogeneity of internal tissues. Here, we report initial results from the JAXA Cell-Free Epigenome Study, a liquid biopsy study with six astronauts who resided on the International Space Station (ISS) for more than 120 days. Analysis of plasma cell-free RNA (cfRNA) collected before, during, and after spaceflight confirms previously reported mitochondrial dysregulation in space. Screening with 361 cell surface marker antibodies identifies a mitochondrial DNA-enriched fraction associated with the scavenger receptor CD36. RNA-sequencing of the CD36 fraction reveals tissue-enriched RNA species, suggesting the plasma mitochondrial components originated from various tissues. We compare our plasma cfRNA data to mouse plasma cfRNA data from a previous JAXA mission, which had used on-board artificial gravity, and discover a link between microgravity and the observed mitochondrial responses.


Assuntos
Antígenos CD36 , Ácidos Nucleicos Livres , DNA Mitocondrial , Voo Espacial , Ausência de Peso , DNA Mitocondrial/genética , DNA Mitocondrial/sangue , Humanos , Ácidos Nucleicos Livres/sangue , Animais , Camundongos , Antígenos CD36/metabolismo , Antígenos CD36/genética , Mitocôndrias/metabolismo , Mitocôndrias/genética , Masculino , Astronautas , RNA/metabolismo , RNA/genética , Biópsia Líquida/métodos , RNA Mitocondrial/metabolismo , RNA Mitocondrial/genética , Feminino , Pessoa de Meia-Idade , Adulto
7.
Nat Commun ; 15(1): 4954, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862516

RESUMO

Spaceflight induces an immune response in astronauts. To better characterize this effect, we generated single-cell, multi-ome, cell-free RNA (cfRNA), biochemical, and hematology data for the SpaceX Inspiration4 (I4) mission crew. We found that 18 cytokines/chemokines related to inflammation, aging, and muscle homeostasis changed after spaceflight. In I4 single-cell multi-omics data, we identified a "spaceflight signature" of gene expression characterized by enrichment in oxidative phosphorylation, UV response, immune function, and TCF21 pathways. We confirmed the presence of this signature in independent datasets, including the NASA Twins Study, the I4 skin spatial transcriptomics, and 817 NASA GeneLab mouse transcriptomes. Finally, we observed that (1) T cells showed an up-regulation of FOXP3, (2) MHC class I genes exhibited long-term suppression, and (3) infection-related immune pathways were associated with microbiome shifts. In summary, this study reveals conserved and distinct immune disruptions occurring and details a roadmap for potential countermeasures to preserve astronaut health.


Assuntos
Análise de Célula Única , Voo Espacial , Transcriptoma , Animais , Feminino , Masculino , Humanos , Camundongos , Astronautas , Citocinas/metabolismo , Linfócitos T/imunologia , Fatores Sexuais , Perfilação da Expressão Gênica , Fosforilação Oxidativa
8.
Commun Biol ; 7(1): 692, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862620

RESUMO

Organismal adaptations to spaceflight have been characterized at the molecular level in model organisms, including Drosophila and C. elegans. Here, we extend molecular work to energy metabolism and sex hormone signaling in mice and humans. We found spaceflight induced changes in insulin and estrogen signaling in rodents and humans. Murine changes were most prominent in the liver, where we observed inhibition of insulin and estrogen receptor signaling with concomitant hepatic insulin resistance and steatosis. Based on the metabolic demand, metabolic pathways mediated by insulin and estrogen vary among muscles, specifically between the soleus and extensor digitorum longus. In humans, spaceflight induced changes in insulin and estrogen related genes and pathways. Pathway analysis demonstrated spaceflight induced changes in insulin resistance, estrogen signaling, stress response, and viral infection. These data strongly suggest the need for further research on the metabolic and reproductive endocrinologic effects of space travel, if we are to become a successful interplanetary species.


Assuntos
Estrogênios , Insulina , Voo Espacial , Animais , Insulina/metabolismo , Estrogênios/metabolismo , Humanos , Camundongos , Masculino , Feminino , Transcriptoma , Transdução de Sinais , Camundongos Endogâmicos C57BL , Metabolismo Energético/genética , Resistência à Insulina/genética , Fígado/metabolismo , Adulto , Regulação da Expressão Gênica
10.
Emerg Med Clin North Am ; 42(3): 695-709, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38925783

RESUMO

The safety and health of individuals who may be exposed to the spaceflight environment are first and foremost cared for through prevention. This environment, which encompasses microgravity, radiation, and alternobaric factors, can have physiologic impacts on every human system. Available medical care and resources in the spaceflight environment are currently limited by mass and volume constraints, with available medical resources thereby focusing on a patient's stabilization and evacuation. An understanding of the spaceflight environment and its possible effects is crucial for the treatment of individuals prior to, during, and after spaceflight.


Assuntos
Voo Espacial , Ausência de Peso , Humanos , Ausência de Peso/efeitos adversos , Medicina Aeroespacial , Astronautas
11.
Astrobiology ; 24(6): 579-589, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38917419

RESUMO

The 21st century is likely to be the first century in which large-scale short- and long-term space missions become common. Accordingly, an ever-increasing body of research is focusing on understanding the effects of current and future space expeditions on human physiology in health and disease. Yet the complex experimental environment, the small number of participants, and the high cost of space missions are among the primary factors that hinder a better understanding of the impact of space missions on human physiology. The goal of our research was to develop a cost-effective, compact, and easy-to-manipulate system to address questions related to human health and disease in space. This initiative was part of the Ramon SpaceLab program, an annual research-based learning program designed to cultivate high school students' involvement in space exploration by facilitating experiments aboard the International Space Station (ISS). In the present study, we used the nematode Caenorhabditis elegans (C. elegans), a well-suited model organism, to investigate the effect of space missions on neurodegeneration-related processes. Our study specifically focused on the level of aggregation of Huntington's disease-causing polyglutamine stretch-containing (PolyQ) proteins in C. elegans muscles, the canonical system for studying neurodegeneration in this organism. We compared animals expressing PolyQ proteins grown onboard the ISS with their genetically identical siblings grown on Earth and observed a significant difference in the number of aggregates between the two populations. Currently, it is challenging to determine whether this effect stems from developmental or morphological differences between the cultures or is a result of life in space. Nevertheless, our results serve as a proof of concept and open a new avenue for utilizing C. elegans to address various open questions in space studies, including the effects of space conditions on the onset and development of neurodegenerative diseases.


Assuntos
Caenorhabditis elegans , Voo Espacial , Animais , Peptídeos/metabolismo , Doenças Neurodegenerativas/patologia , Humanos
12.
Nat Microbiol ; 9(7): 1661-1675, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38862604

RESUMO

Maintenance of astronaut health during spaceflight will require monitoring and potentially modulating their microbiomes. However, documenting microbial shifts during spaceflight has been difficult due to mission constraints that lead to limited sampling and profiling. Here we executed a six-month longitudinal study to quantify the high-resolution human microbiome response to three days in orbit for four individuals. Using paired metagenomics and metatranscriptomics alongside single-nuclei immune cell profiling, we characterized time-dependent, multikingdom microbiome changes across 750 samples and 10 body sites before, during and after spaceflight at eight timepoints. We found that most alterations were transient across body sites; for example, viruses increased in skin sites mostly during flight. However, longer-term shifts were observed in the oral microbiome, including increased plaque-associated bacteria (for example, Fusobacteriota), which correlated with immune cell gene expression. Further, microbial genes associated with phage activity, toxin-antitoxin systems and stress response were enriched across multiple body sites. In total, this study reveals in-depth characterization of microbiome and immune response shifts experienced by astronauts during short-term spaceflight and the associated changes to the living environment, which can help guide future missions, spacecraft design and space habitat planning.


Assuntos
Astronautas , Bactérias , Metagenômica , Microbiota , Voo Espacial , Humanos , Estudos Longitudinais , Microbiota/imunologia , Bactérias/classificação , Bactérias/genética , Bactérias/imunologia , Masculino , Perfilação da Expressão Gênica , Adulto , Pessoa de Meia-Idade , Feminino , Transcriptoma , Multiômica
14.
Science ; 384(6701): 1159-1160, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38870298

RESUMO

New studies include health data collected from space tourists on first privately funded orbital mission.


Assuntos
Astronautas , Voo Espacial , Humanos , Risco
15.
Nat Commun ; 15(1): 4774, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862473

RESUMO

Mounting ambitions and capabilities for public and private, non-government sector crewed space exploration bring with them an increasingly diverse set of space travelers, raising new and nontrivial ethical, legal, and medical policy and practice concerns which are still relatively underexplored. In this piece, we lay out several pressing issues related to ethical considerations for selecting space travelers and conducting human subject research on them, especially in the context of non-governmental and commercial/private space operations.


Assuntos
Voo Espacial , Humanos , Voo Espacial/ética , Astronautas
16.
Nat Commun ; 15(1): 4862, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862464

RESUMO

As spaceflight becomes more common with commercial crews, blood-based measures of crew health can guide both astronaut biomedicine and countermeasures. By profiling plasma proteins, metabolites, and extracellular vesicles/particles (EVPs) from the SpaceX Inspiration4 crew, we generated "spaceflight secretome profiles," which showed significant differences in coagulation, oxidative stress, and brain-enriched proteins. While >93% of differentially abundant proteins (DAPs) in vesicles and metabolites recovered within six months, the majority (73%) of plasma DAPs were still perturbed post-flight. Moreover, these proteomic alterations correlated better with peripheral blood mononuclear cells than whole blood, suggesting that immune cells contribute more DAPs than erythrocytes. Finally, to discern possible mechanisms leading to brain-enriched protein detection and blood-brain barrier (BBB) disruption, we examined protein changes in dissected brains of spaceflight mice, which showed increases in PECAM-1, a marker of BBB integrity. These data highlight how even short-duration spaceflight can disrupt human and murine physiology and identify spaceflight biomarkers that can guide countermeasure development.


Assuntos
Coagulação Sanguínea , Barreira Hematoencefálica , Encéfalo , Homeostase , Estresse Oxidativo , Voo Espacial , Animais , Humanos , Encéfalo/metabolismo , Barreira Hematoencefálica/metabolismo , Camundongos , Coagulação Sanguínea/fisiologia , Masculino , Secretoma/metabolismo , Camundongos Endogâmicos C57BL , Vesículas Extracelulares/metabolismo , Proteômica/métodos , Biomarcadores/metabolismo , Biomarcadores/sangue , Feminino , Adulto , Proteínas Sanguíneas/metabolismo , Pessoa de Meia-Idade , Leucócitos Mononucleares/metabolismo , Proteoma/metabolismo
17.
Nat Commun ; 15(1): 4773, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862494

RESUMO

Spaceflight can change metabolic, immunological, and biological homeostasis and cause skin rashes and irritation, yet the molecular basis remains unclear. To investigate the impact of short-duration spaceflight on the skin, we conducted skin biopsies on the Inspiration4 crew members before (L-44) and after (R + 1) flight. Leveraging multi-omics assays including GeoMx™ Digital Spatial Profiler, single-cell RNA/ATAC-seq, and metagenomics/metatranscriptomics, we assessed spatial gene expressions and associated microbial and immune changes across 95 skin regions in four compartments: outer epidermis, inner epidermis, outer dermis, and vasculature. Post-flight samples showed significant up-regulation of genes related to inflammation and KRAS signaling across all skin regions. These spaceflight-associated changes mapped to specific cellular responses, including altered interferon responses, DNA damage, epithelial barrier disruptions, T-cell migration, and hindered regeneration were located primarily in outer tissue compartments. We also linked epithelial disruption to microbial shifts in skin swab and immune cell activity to PBMC single-cell data from the same crew and timepoints. Our findings present the inaugural collection and examination of astronaut skin, offering insights for future space missions and response countermeasures.


Assuntos
Inflamação , Proteínas Proto-Oncogênicas p21(ras) , Pele , Voo Espacial , Humanos , Pele/imunologia , Pele/metabolismo , Pele/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Inflamação/imunologia , Inflamação/genética , Inflamação/metabolismo , Masculino , Análise de Célula Única , Adulto , Pessoa de Meia-Idade , Feminino , Metagenômica/métodos , Perfilação da Expressão Gênica , Multiômica
18.
Nat Commun ; 15(1): 4795, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862487

RESUMO

Microgravity is associated with immunological dysfunction, though the mechanisms are poorly understood. Here, using single-cell analysis of human peripheral blood mononuclear cells (PBMCs) exposed to short term (25 hours) simulated microgravity, we characterize altered genes and pathways at basal and stimulated states with a Toll-like Receptor-7/8 agonist. We validate single-cell analysis by RNA sequencing and super-resolution microscopy, and against data from the Inspiration-4 (I4) mission, JAXA (Cell-Free Epigenome) mission, Twins study, and spleens from mice on the International Space Station. Overall, microgravity alters specific pathways for optimal immunity, including the cytoskeleton, interferon signaling, pyroptosis, temperature-shock, innate inflammation (e.g., Coronavirus pathogenesis pathway and IL-6 signaling), nuclear receptors, and sirtuin signaling. Microgravity directs monocyte inflammatory parameters, and impairs T cell and NK cell functionality. Using machine learning, we identify numerous compounds linking microgravity to immune cell transcription, and demonstrate that the flavonol, quercetin, can reverse most abnormal pathways. These results define immune cell alterations in microgravity, and provide opportunities for countermeasures to maintain normal immunity in space.


Assuntos
Leucócitos Mononucleares , Análise de Célula Única , Voo Espacial , Simulação de Ausência de Peso , Animais , Feminino , Humanos , Masculino , Camundongos , Imunidade Inata , Inflamação/imunologia , Células Matadoras Naturais/imunologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Aprendizado de Máquina , Camundongos Endogâmicos C57BL , Quercetina/farmacologia , Transdução de Sinais , Linfócitos T/imunologia , Ausência de Peso
19.
Nat Commun ; 15(1): 4923, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862484

RESUMO

Missions into Deep Space are planned this decade. Yet the health consequences of exposure to microgravity and galactic cosmic radiation (GCR) over years-long missions on indispensable visceral organs such as the kidney are largely unexplored. We performed biomolecular (epigenomic, transcriptomic, proteomic, epiproteomic, metabolomic, metagenomic), clinical chemistry (electrolytes, endocrinology, biochemistry) and morphometry (histology, 3D imaging, miRNA-ISH, tissue weights) analyses using samples and datasets available from 11 spaceflight-exposed mouse and 5 human, 1 simulated microgravity rat and 4 simulated GCR-exposed mouse missions. We found that spaceflight induces: 1) renal transporter dephosphorylation which may indicate astronauts' increased risk of nephrolithiasis is in part a primary renal phenomenon rather than solely a secondary consequence of bone loss; 2) remodelling of the nephron that results in expansion of distal convoluted tubule size but loss of overall tubule density; 3) renal damage and dysfunction when exposed to a Mars roundtrip dose-equivalent of simulated GCR.


Assuntos
Radiação Cósmica , Voo Espacial , Animais , Humanos , Camundongos , Radiação Cósmica/efeitos adversos , Ratos , Masculino , Rim/patologia , Rim/efeitos da radiação , Rim/metabolismo , Nefropatias/patologia , Nefropatias/etiologia , Ausência de Peso/efeitos adversos , Astronautas , Camundongos Endogâmicos C57BL , Proteômica , Feminino , Marte , Simulação de Ausência de Peso/efeitos adversos
20.
Nat Commun ; 15(1): 4952, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862505

RESUMO

Future multi-year crewed planetary missions will motivate advances in aerospace nutrition and telehealth. On Earth, the Human Cell Atlas project aims to spatially map all cell types in the human body. Here, we propose that a parallel Human Cell Space Atlas could serve as an openly available, global resource for space life science research. As humanity becomes increasingly spacefaring, high-resolution omics on orbit could permit an advent of precision spaceflight healthcare. Alongside the scientific potential, we consider the complex ethical, cultural, and legal challenges intrinsic to the human space omics discipline, and how philosophical frameworks may benefit from international perspectives.


Assuntos
Astronautas , Voo Espacial , Humanos , Genômica/métodos , Corpo Humano
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