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Abstract 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.

Abstract In recent decades of spaceflight, inadequate caloric intake has posed significant nutritional challenges, contributing to muscle degradation, weakened immune and cardiovascular systems during and after space missions. This challenge becomes more acute on longer exploration missions, where transporting all food for the entire mission becomes a logistical challenge. This places immense pressure on the food system, requiring energy-dense, varied, stable, and palatable food options. Prolonged storage can lead to nutrient degradation, reducing their bioavailability and bioaccessibility to astronauts. Research is essential not only to improve the quality and stability of space food but also to enhance nutrient bioavailability, thereby reducing weight and volume of food. Muscle and bone loss represent major risks during extended spaceflight, prompting extensive efforts to find exercise countermeasures. However, increased exercise requires additional energy intake, and finding the optimal balance between energy needs and the preservation of muscle and bone mass is challenging. Currently, there is no reliable way to measure total energy expenditure and activity-related energy expenditures in real-time. Systematic research is necessary to develop onboard technology for accurate energy expenditure and body composition monitoring. This research should aim to establish an optimal exercise regimen that balances energy requirements while maintaining astronaut strength and minimizing food transport. In summary, this overview outlines key actions needed for future exploration missions to maintain body mass and physical strength of space travellers. It addresses the requirements for food processing and preservation, considerations for space food formulation and production, and the essential measures to be implemented.

Introduction: Long-term sodium balance studies show that sodium can be temporarily stored and released in tissues, mediated by circaseptan rhythms of aldosterone and cortisol. This complicates the reliability of a single 24-h urine collection to estimate individual sodium intake. We investigated whether repeated timed urine collection with and without correction for plasma aldosterone is a more accurate alternative for estimating daily sodium intake. Methods: We conducted a post hoc analysis of a metabolic ward study in which 16 healthy male adults consumed a diet with a fixed sodium content (50 or 200 mmol/day) for 7 days. Each day, urine was collected in 4 intervals (7:00–13:00 h, 13:00–19:00 h, 19:00–23:00 h, and 23:00–07:00 h). Plasma aldosterone was measured at 6:30 h, 12:30 h, and 18:30 h. Sodium intakes were estimated by various formulas using 3 timed urines of day 5–7. Results: During a 200-mmol daily sodium intake, sodium intake estimates based on three repeated timed urine samples and the Toft equation differed 10 [IQR: 3–14], 8 [6–19], 36 [16–49], and 20 [10–43] mmol from the actual intake for intervals 7:00–13:00 h, 13:00–19:00 h, 19:00–23:00 h, 23:00–7:00 h, respectively. These measurements did not significantly differ from a single 24-h urine (20 [12–55] mmol). During a 50-mmol daily sodium intake, repeated timed urine collection performed worse than a single 24-h urine collection. On both diets, correction for plasma aldosterone increased accuracy and sodium intake estimates were significantly more accurate than a single 24-h urine. Conclusion: In a controlled environment, repeated timed urine collection corrected for plasma aldosterone is more accurate than a single 24-h urine collection.

Abstract Although we have sent humans into space for more than 50 years crucial questions regarding kidney physiology, volume regulation and osmoregulation remain unanswered. The complex interactions between the renin-angiotensin-aldosterone system, the sympathetic nervous system, osmoregulatory responses, glomerular function, tubular function, and environmental factors such as sodium and water intake, motion sickness and ambient temperature make it difficult to establish the exact effect of microgravity and the subsequent fluid shifts and muscle mass loss on these parameters. Unfortunately, not all responses to actual microgravity can be reproduced with head-down tilt bed rest studies, which complicates research on Earth. Better understanding of the effects of microgravity on kidney function, volume regulation and osmoregulation are needed with the advent of long-term deep space missions and planetary surface explorations during which orthostatic intolerance complaints or kidney stone formation can be life-threatening for astronauts. Galactic cosmic radiation may be a new threat to kidney function. In this review, we summarise and highlight the current understandings of the effects of microgravity on kidney function, volume regulation and osmoregulation and discuss knowledge gaps that future studies should address.

Abstract Long-duration spaceflight impacts human physiology, including well documented immune system dysregulation. The space food system has the potential to serve as a countermeasure to maladaptive physiological changes during spaceflight. However, the relationship between dietary requirements, the food system, and spaceflight adaptation requires further investigation to adequately define countermeasures and prioritize resources on future spaceflight missions. We evaluated the impact of an enhanced spaceflight diet, with increased quantity and variety of fruits, vegetables, fish, and other foods rich in flavonoids and omega-3 fatty acids, compared to a standard spaceflight diet on multiple health and performance outcomes in 16 subjects over four 45-day closed chamber missions in the NASA Human Exploration Research Analog (HERA). Subjects consuming the enhanced spaceflight diet had lower cholesterol levels, lower stress (i.e. cortisol levels), better cognitive speed, accuracy, and attention, and a more stable microbiome and metatranscriptome than subjects consuming the standard diet. Although no substantial changes were observed in the immune response, there were also no immune challenges, such as illness or infection, so the full benefits of the diet may not have been apparent in these analog missions. These results indicate that a spaceflight diet rich in fruits, vegetables, and omega-3 fatty acids produces significant health and performance benefits even over short durations. Further investigation is required to fully develop dietary countermeasures to physiological decrements observed during spaceflight. These results will have implications for food resource prioritization on spaceflight missions.

Abstract Astronauts on the International Space Station are exposed to levels of atmospheric carbon dioxide (CO2) above typical terrestrial levels. We explored the possibility that increased levels of ambient CO2 further stimulate bone resorption during bed rest. We report here data from 2 ground-based spaceflight analog studies in which 12 male and 7 female subjects were placed in a strict 6° head-down tilt (HDT) position for either 30 days at 0.5% ambient CO2 or 60 days with nominal environmental exposure to CO2. Bone mineral density (BMD) and bone mineral content (BMC) were determined using dual-energy X-ray absorptiometry (DXA). Blood and urine were collected before and after HDT for biochemical analysis. No change was detected in either BMD or BMC, as expected given the study duration. Bone resorption markers increased after bed rest as expected; however, elevated CO2 had no additive effect. Elevated CO2 did not affect concentrations of minerals in serum and urine. Serum parathyroid hormone and 1,25-dihydroxyvitamin D were both reduced after bed rest, likely secondary to calcium efflux from bone. In summary, exposure to 0.5% CO2 for 30 days did not exacerbate the typical bone resorption response observed after HDT bed rest. Furthermore, results from these strict HDT studies were similar to data from previous bed rest studies, confirming that strict 30–60 days of HDT can be used to evaluate changes in bone metabolism. This is valuable in the continuing effort to develop and refine efficacious countermeasure protocols to mitigate bone loss during spaceflight in low-Earth orbit and beyond.

Here, the authors use sedimentary DNA, pollen, fungal spores, chironomids, and microcharcoal from an alpine lake core to reconstruct vegetation across 12,000 years. They find that vegetation responded to climate in the early Holocene, followed by a shift to human activity from 6000 years onward corresponding with an increase in deforestation and agropastoralism.

Abstract Determining the extent of bone recovery after prolonged spaceflight is important for understanding risks to astronaut long-term skeletal health. We examined bone strength, density, and microarchitecture in seventeen astronauts (14 males; mean 47 years) using high-resolution peripheral quantitative computed tomography (HR-pQCT; 61 μm). We imaged the tibia and radius before spaceflight, at return to Earth, and after 6- and 12-months recovery and assessed biomarkers of bone turnover and exercise. Twelve months after flight, group median tibia bone strength (F.Load), total, cortical, and trabecular bone mineral density (BMD), trabecular bone volume fraction and thickness remained − 0.9% to − 2.1% reduced compared with pre-flight (p ≤ 0.001). Astronauts on longer missions (> 6-months) had poorer bone recovery. For example, F.Load recovered by 12-months post-flight in astronauts on shorter (

Space travelers are exposed to microgravity (µg), which induces enhanced bone loss compared to the age-related bone loss on Earth. Microgravity promotes an increased bone turnover, and this obstructs space exploration. This bone loss can be slowed down by exercise on treadmills or resistive apparatus. The objective of this systematic review is to provide a current overview of the state of the art of the field of bone loss in space and possible treatment options thereof. A total of 482 unique studies were searched through PubMed and Scopus, and 37 studies met the eligibility criteria. The studies showed that, despite increased bone formation during µg, the increase in bone resorption was greater. Different types of exercise and pharmacological treatments with bisphosphonates, RANKL antibody (receptor activator of nuclear factor κβ ligand antibody), proteasome inhibitor, pan-caspase inhibitor, and interleukin-6 monoclonal antibody decrease bone resorption and promote bone formation. Additionally, recombinant irisin, cell-free fat extract, cyclic mechanical stretch-treated bone mesenchymal stem cell-derived exosomes, and strontium-containing hydroxyapatite nanoparticles also show some positive effects on bone loss.

The upcoming exploration missions will imply a much longer duration than any of the missions flown so far. In these missions, physiological adaptation to the new environment leads to changes in different body systems, such as the cardiovascular and musculoskeletal systems, metabolic and neurobehavioral health and immune function. To keep space travelers healthy on their trip to Moon, Mars and beyond and their return to Earth, a variety of countermeasures need to be provided to maintain body functionality. From research on the International Space Station (ISS) we know today, that for instance prescribing an adequate training regime for each individual with the devices available in the respective spacecraft is still a challenge. Nutrient supply is not yet optimal and must be optimized in exploration missions. Food intake is intrinsically linked to changes in the gut microbiome composition. Most of the microbes that inhabit our body supply ecosystem benefit to the host-microbe system, including production of important resources, bioconversion of nutrients, and protection against pathogenic microbes. The gut microbiome has also the ability to signal the host, regulating the processes of energy storage and appetite perception, and influencing immune and neurobehavioral function. The composition and functionality of the microbiome most likely changes during spaceflight. Supporting a healthy microbiome by respective measures in space travelers might maintain their health during the mission but also support rehabilitation when being back on Earth. In this review we are summarizing the changes in the gut microbiome observed in spaceflight and analog models, focusing particularly on the effects on metabolism, the musculoskeletal and immune systems and neurobehavioral disorders. Since space travelers are healthy volunteers, we focus on the potential of countermeasures based on pre- and probiotics supplements.

Recent studies have established that dysregulation of the human immune system and the reactivation of latent herpesviruses persists for the duration of a 6-month orbital spaceflight. It appears certain aspects of adaptive immunity are dysregulated during flight, yet some aspects of innate immunity are heightened. Interaction between adaptive and innate immunity also seems to be altered. Some crews experience persistent hypersensitivity reactions during flight. This phenomenon may, in synergy with extended duration and galactic radiation exposure, increase specific crew clinical risks during deep space exploration missions. The clinical challenge is based upon both the frequency of these phenomena in multiple crewmembers during low earth orbit missions and the inability to predict which specific individual crewmembers will experience these changes. Thus, a general countermeasure approach that offers the broadest possible coverage is needed. The vehicles, architecture, and mission profiles to enable such voyages are now under development. These include deployment and use of a cis-Lunar station (mid 2020s) with possible Moon surface operations, to be followed by multiple Mars flyby missions, and eventual human Mars surface exploration. Current ISS studies will continue to characterize physiological dysregulation associated with prolonged orbital spaceflight. However, sufficient information exists to begin consideration of both the need for, and nature of, specific immune countermeasures to ensure astronaut health. This article will review relevant in-place operational countermeasures onboard ISS and discuss a myriad of potential immune countermeasures for exploration missions. Discussion points include nutritional supplementation and functional foods, exercise and immunity, pharmacological options, the relationship between bone and immune countermeasures, and vaccination to mitigate herpes (and possibly other) virus risks. As the immune system has sentinel connectivity within every other physiological system, translational effects must be considered for all potential immune countermeasures. Finally, we shall discuss immune countermeasures in the context of their individualized implementation or precision medicine, based on crewmember specific immunological biases.

For the prevention and treatment of bone loss related diseases, focus has been put on naturally derived substances such as polyphenols. Based on human intervention studies, this review gives an overview of the effects of dietary significant polyphenols (flavonoids, hydroxycinnamic acids, and stilbenes) on bone turnover. Literature research was conducted using PubMed database and articles published between 01/01/2008 and 31/12/2018 were included (last entry: 19/02/2019). Randomized controlled trials using oral polyphenol supplementation, either of isolated polyphenols or polyphenols-rich foods with healthy subjects or study populations with bone disorders were enclosed. Twenty articles fulfilled the inclusion criteria and the average study quality (mean Jadad score: 4.5) was above the pre-defined cut-off of 3.0. Evidence from these studies does not allow an explicit conclusion regarding the effects of dietary important polyphenols on bone mineral density and bone turnover markers. Differences in study population, habitual diet, lifestyle factors, applied polyphenols, used doses, and polyphenol bioavailability complicate the comparison of study outcomes.

The space flight environment is known to induce bone loss and, subsequently, calcium loss. The longer the mission, generally the more bone and calcium are lost. This review provides a history of bone and calcium studies related to space flight and highlights issues related to calcium excretion that the space program must consider so that urine can be recycled. It also discusses a novel technique using natural stable isotopes of calcium that will be helpful in the future to determine calcium and bone balance during space flight.

Astronauts consume fewer calories during spaceflight and return to earth with an increased risk of orthostatic intolerance. Whether a caloric deficiency modifies orthostatic responses is not understood. Thus, we determined the effects of a hypocaloric diet (25% caloric restriction) during 6° head down bedrest (an analog of spaceflight) on autonomic neural control during lower body negative pressure (LBNP). Nine healthy young men completed a randomized crossover bedrest study, consisting of four (2 weeks each) interventions (normocaloric bedrest, normocaloric ambulatory, hypocaloric bedrest, hypocaloric ambulatory), each separated by 5 months. Muscle sympathetic nerve activity (MSNA) was recorded at baseline following normocaloric and hypocaloric interventions. Heart rate (HR) and arterial pressure were recorded before, during, and after 3 consecutive stages (7 min each) of LBNP (-15, -30, -45 mmHg). Caloric and posture effects during LBNP were compared using two-way ANOVA with repeated measures. There was a strong trend toward reduced basal MSNA following caloric restriction alone (normcaloric vs. hypocaloric: 22±3 vs. 14±4 burst/min, p = 0.06). Compared to the normocaloric ambulatory, both bedrest and caloric restriction were associated with lower systolic blood pressure during LBNP (p

Aim. We hypothesized that 4 days of normal daily activity after 21 days of experimental bed rest (BR) will not reverse BR induced impaired glucose tolerance. Design. Glucose tolerance of seven male, healthy, untrained test subjects (age: 27.6 (3.3) years (mean (SD)); body mass: 78.6 (6.4) kg; height: 1.81 (0.04) m; VO2 max: 39.5 (5.4) ml/kg body mass/min) was studied. They stayed twice in the metabolic ward (crossover design), 21 days in bed and 7 days before and after BR each. Oral glucose tolerance tests were applied before, on day 21 of BR, and 5 and 14 days after BR. Results. On day 21 of BR, AUC120 min of glucose concentration was increased by 28.8 (5.2)% and AUC120 min of insulin by 35.9 (10.2)% (glucose: P