Search

Introduction: Bone loss is one of the greatest physiological challenges for extended-duration space missions. The ability of exercise to counteract weightlessness-induced bone loss has been studied extensively, but to date, it has proven ineffective. We evaluated the effectiveness of a combination of two countermeasures-treadmill exercise while inside a lower body negative pressure (LBNP) chamber-on bone loss during a 30-day bed rest study. Materials and Methods: Eight pairs of identical twins were randomized into sedentary (SED) or exercise/LBNP (EX/LBNP) groups. Blood and urine samples were collected before, several times during, and after the 30-day bed rest period. These samples were analyzed for markers of bone and calcium metabolism. Repeated measures ANOVA was used to determine statistical significance. Because identical twins were used, both time and group were treated as repeated variables. Results: Markers of bone resorption were increased during bed rest in samples from sedentary subjects, including the collagen cross-links and serum and urinary calcium concentrations. For N-telopeptide and deoxypyridinoline, there were significant (p < 0.05) interactions between group (SED versus EX/LBNP) and phase of the study (sample collection point). Pyridinium cross-links were increased above pre-bed rest levels in both groups, but the EX/LBNP group had a smaller increase than the SED group. Markers of bone formation were unchanged by bed rest in both groups. Conclusions: These data show that this weight-bearing exercise combined with LBNP ameliorates some of the negative effects of simulated weightlessness on bone metabolism. This protocol may pave the way to counteracting bone loss during spaceflight and may provide valuable information about normal and abnormal bone physiology here on Earth.

Human alpha herpesviruses herpes simplex virus (HSV-1) and varicella zoster virus (VZV) establish latency in various cranial nerve ganglia and often reactivate in response to stress-associated immune system dysregulation. Reactivation of Epstein Barr virus (EBV), VZV, HSV-1, and cytomegalovirus (CMV) is typically asymptomatic during spaceflight, though live/infectious virus has been recovered and the shedding rate increases with mission duration. The risk of clinical disease, therefore, may increase for astronauts assigned to extended missions (>180 days). Here, we report, for the first time, a case of HSV-1 skin rash (dermatitis) occurring during long-duration spaceflight. The astronaut reported persistent dermatitis during flight, which was treated onboard with oral antihistamines and topical/oral steroids. No HSV-1 DNA was detected in 6-month pre-mission saliva samples, but on flight day 82, a saliva and rash swab both yielded 4.8 copies/ng DNA and 5.3 × 104 copies/ng DNA, respectively. Post-mission saliva samples continued to have a high infectious HSV-1 load (1.67 × 107 copies/ng DNA). HSV-1 from both rash and saliva samples had 99.9% genotype homology. Additional physiological monitoring, including stress biomarkers (cortisol, dehydroepiandrosterone (DHEA), and salivary amylase), immune markers (adaptive regulatory and inflammatory plasma cytokines), and biochemical profile markers, including vitamin/mineral status and bone metabolism, are also presented for this case. These data highlight an atypical presentation of HSV-1 during spaceflight and underscore the importance of viral screening during clinical evaluations of in-flight dermatitis to determine viral etiology and guide treatment. [ABSTRACT FROM AUTHOR]

Following long‐duration spaceflight, some astronauts exhibit ophthalmic structural changes referred to as Spaceflight Associated Neuro‐ocular Syndrome (SANS). Optic disc edema is a common sign of SANS. The origin and effects of SANS are not understood as signs of SANS have not manifested in previous spaceflight analog studies. In the current spaceflight analog study, 11 subjects underwent 30 days of strict head down‐tilt bed rest in elevated ambient carbon dioxide (HDBR+CO2). Using functional magnetic resonance imaging (fMRI), we acquired resting‐state fMRI data at 6 time points: before (2), during (2), and after (2) the HDBR+CO2 intervention. Five participants developed optic disc edema during the intervention (SANS subgroup) and 6 did not (NoSANS group). This occurrence allowed us to explore whether development of signs of SANS during the spaceflight analog impacted resting‐state functional connectivity during HDBR+CO2. In light of previous work identifying genetic and biochemical predictors of SANS, we further assessed whether the SANS and NoSANS subgroups exhibited differential patterns of resting‐state functional connectivity prior to the HDBR+CO2 intervention. We found that the SANS and NoSANS subgroups exhibited distinct patterns of resting‐state functional connectivity changes during HDBR+CO2 within visual and vestibular‐related brain networks. The SANS and NoSANS subgroups also exhibited different resting‐state functional connectivity prior to HDBR+CO2 within a visual cortical network and within a large‐scale network of brain areas involved in multisensory integration. We further present associations between functional connectivity within the identified networks and previously identified genetic and biochemical predictors of SANS. Subgroup differences in resting‐state functional connectivity changes may reflect differential patterns of visual and vestibular reweighting as optic disc edema develops during the spaceflight analog. This finding suggests that SANS impacts not only neuro‐ocular structures, but also functional brain organization. Future prospective investigations incorporating sensory assessments are required to determine the functional significance of the observed connectivity differences. [ABSTRACT FROM AUTHOR]

Long-duration spaceflight is known to cause immune dysregulation in astronauts. Biomarkers of immune system function are needed to determine both the need for and effectiveness of potential immune countermeasures for astronauts. Whereas plasma cytokine concentrations are a well-established biomarker of immune status, salivary cytokine concentrations are emerging as a sensitive indicator of stress and inflammation. For this study, to aid in characterizing immune dysregulation during spaceflight, plasma and saliva cytokines were monitored in astronauts before, during and after long-duration spaceflight onboard the International Space Station. Blood was collected from 13 astronauts at 3 timepoints before, 5 timepoints during and 3 timepoints after spaceflight. Saliva was collected from 6 astronauts at 2 timepoints before spaceflight, 2 timepoints during and 3 timepoints following spaceflight. Samples were analyzed using multiplex array technology. Significant increases in the plasma concentration of IL-3, IL-15, IL-12p40, IFN-α2, and IL-7 were observed during spaceflight compared to before flight baseline. Significant decreases in saliva GM-CSF, IL-12p70, IL-10 and IL-13 were also observed during spaceflight as compared to compared to before flight baseline concentrations. Additionally, plasma TGFβ1 and TGFβ2 concentrations tended to be consistently higher during spaceflight, although these did not reach statistical significance. Overall, the findings confirm an in-vivo hormonal dysregulation of immunity, appearing pro-inflammatory and Th1 in nature, persists during long-duration orbital spaceflight. These biomarkers may therefore have utility for monitoring the effectiveness of biomedical countermeasures for astronauts, with potential application in terrestrial research and medicine. [ABSTRACT FROM AUTHOR]

Introduction: In 2010, experts in osteoporosis and bone densitometry were convened by the Space Life Sciences Directorate at NASA Johnson Space Center to identify a skeletal outcome in astronauts after spaceflight that would require a clinical response to address fracture risk. After reviewing astronaut data, experts expressed concern over discordant patterns in loss and recovery of bone mineral density (BMD) after spaceflight as monitored by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). The pilot study described herein demonstrates the use of QCT to evaluate absence of recovery in hip trabecular BMD by QCT as an indicator of a clinically actionable response. Methodology: QCT and DXA scans of both hips were performed on 10 astronauts: once preflight and twice postflight about 1 wk and 1 yr after return. If trabecular BMD had not returned to baseline (i.e., within QCT measurement error) in 1 or both hips 1 yr after flight, then another QCT hip scan was obtained at 2 yr after flight. Results: Areal BMD by DXA recovered in 9 of 10 astronauts at 1 yr postflight while incomplete recovery of trabecular BMD by QCT was evident in 5 of 10 astronauts and persisted in 4 of the 5 astronauts 2 yr postflight. Conclusion: As an adjunct to DXA, QCT is needed to detect changes to hip trabecular BMD after spaceflight and to confirm complete recovery. Incomplete recovery at 2 yr should trigger the need for further evaluation and possible intervention to mitigate premature fragility and fractures in astronauts following long-duration spaceflight. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The objectives of this study were to evaluate the efficacy of two separate countermeasures, exercise and protein supplementation, to prevent muscle strength and lean tissue mass losses during 60 days of bed rest (BR) in women and whether countermeasure efficacy was influenced by pre-BR muscular fitness (strength, endurance, tissue mass). Twenty-four women were assigned to an exercise (EX, n = 8), a no-exercise control (CON, n = 8), or a no-exercise protein supplementation group (PROT, n = 8). EX performed supine treadmill exercise within lower body negative pressure 3-4 days/wk and maximal concentric and eccentric supine leg- and calf-press exercises 2-4 days/wk. PROT consumed a diet with elevated protein content compared with CON and EX (1.6 vs. 1.0 g·kg(-1)·day(-1)). Knee and calf isokinetic strength and endurance, isotonic leg-press strength, and leg lean mass were measured before and after BR. Post-BR knee extensor strength and endurance, ankle strength, and leg lean mass were significantly greater and leg-press strength tended to be higher in EX than in CON and PROT. Post-BR measures in PROT were not different than those in CON. Exercise countermeasure efficacy was less, and strength, endurance, and leg lean mass losses in CON and PROT were greater, in subjects who were more fit pre-BR. An exercise protocol combining resistive and aerobic exercise training protects against losses in strength, endurance, and leg lean mass in women during BR, while a nutritional countermeasure without exercise was not effective. Exercise countermeasures may require individualization to protect higher levels of strength and endurance. [ABSTRACT FROM AUTHOR]

The ability to rapidly detect changes in bone mineral balance (BMB) would be of great value in the early diagnosis and evaluation of therapies for metabolic bone diseases such as osteoporosis and some cancers. However, measurements of BMB are hampered by difficulties with using biochemical markers to quantify the relative rates of bone resorption and formation and the need to wait months to years for altered BMB to produce changes in bone mineral density large enough to resolve by X-ray densitometry. We show here that, in humans, the natural abundances of Ca isotopes in urine change rapidly in response to changes in BMB. In a bed rest experiment, use of high-precision isotope ratio MS allowed the onset of bone loss to be detected in Ca isotope data after about 1 wk, long before bone mineral density has changed enough to be detectable with densitometry. The physiological basis of the relationship between Ca isotopes and BMB is sufficiently understood to allow quantitative translation of changes in Ca isotope abundances to changes in bone mineral density using a simple model. The rate of change of bone mineral density inferred from Ca isotopes is consistent with the rate observed by densitometry in long-term bed rest studies. Ca isotopic analysis provides a powerful way to monitor bone loss, potentially making it possible to diagnose metabolic bone disease and track the impact of treatments more effectively than is currently possible. [ABSTRACT FROM AUTHOR]

Bone loss is a well-documented change during and after long-duration spaceflight. Many types of countermeasures to bone loss have been proposed, including vitamin K supplementation. The objective of this series of studies was to measure change in vitamin K status in response to microgravity under a variety of spaceflight and spaceflight analog (model) conditions, including long-duration spaceflight studies ( n = 15), three bed rest studies ( n = 15, 49, and 24), and a 14-day saturation dive ( n = 6). In crew members who flew 2-6 months on the International Space Station, in-flight and postflight plasma phylloquinone concentrations were unchanged from the preflight mean. Consistent with this finding, urinary γ-carboxyglutamic acid (GLA), a measure of vitamin K-dependent protein turnover, did not change in response to flight. Serum undercarboxylated osteocalcin (%ucOC), a measure of vitamin K function, was generally unchanged in response to flight. Spaceflight findings were corroborated by findings of no changes in phylloquinone, urinary GLA, or %ucOC during or after bed rest in three separate bed rest studies (21-90 days in duration) or after a 14-day saturation dive. The data presented here do not support either a need for vitamin K supplementation during spaceflight or the suggestion of using vitamin K as a bone loss countermeasure in spaceflight. © 2011 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

From the basic impact of nutrient intake on health maintenance to the psychosocial benefits of mealtime, the role of nutrition in space is evident. In this discussion, dietary intake data from three space programs, Apollo, Space Shuttle, and Skylab, are presented. Data examination reveals that energy and fluid intakes are almost always lower than predicted. Nutrition in space has many areas of impact, including provision of required nutrients and maintenance of endocrine, immune, and musculoskeletal systems. Long-duration missions will require quantitation of nutrient requirements for maintenance of health and protection against the effects of microgravity. Psychosocial aspects of nutrition will also be important for more productive missions and crew morale. Realization of the full role of nutrition during spaceflight is critical for the success of extended-duration missions. Research conducted to determine the impact of spaceflight on human physiology and subsequent nutritional requirements will also have direct and indirect applications in Earth-based nutrition research. [ABSTRACT FROM AUTHOR]

The National Aeronautics and Space Administration (NASA) Twins Study created an integrative molecular profile of an astronaut during NASA's first 1-year mission on the International Space Station (ISS) and included comparisons to an identical Earth-bound twin. The unique biochemical profiles observed when landing on Earth after such a long mission (e.g., spikes in interleukin-1 [IL-1]/6/10, c-reactive protein [CRP], C-C motif chemokine ligand 2 [CCL2], IL-1 receptor antagonist [IL-1ra], and tumor necrosis factor alpha [TNF-α]) opened new questions about the human body's response to gravity and how to plan for future astronauts, particularly around initiation or resolution of inflammation. Here, single-cell, multi-omic (100-plex epitope profile and gene expression) profiling of peripheral blood mononuclear cells (PBMCs) showed changes to blood cell composition and gene expression post-flight, specifically for monocytes and dendritic cell precursors. These were consistent with flight-induced cytokine and immune system stress, followed by skeletal muscle regeneration in response to gravity. Finally, we examined these profiles relative to 6-month missions in 28 other astronauts and detail potential pharmacological interventions for returning to gravity in future missions. • IL-6, IL-10, IL-1ra, CCL2, and CRP rose significantly on landing after a year in space • IL-6 and IL-1ra are potential targets for pharmacological intervention in astronauts • These cytokines are also associated with muscle regeneration in response to gravity • Muscle-generated IL-6 drives classic signaling cascades in an anti-inflammatory role Gertz et al. present a re-analysis of the landing data from the NASA Twins Study, suggesting that the biochemical signature reflects muscle regeneration after atrophy rather than a detrimental inflammatory response. This is mediated through muscle-derived IL-6 anti-inflammatory cascades. Single-cell analysis supports this role. Potential pharmacological interventions are also discussed. [ABSTRACT FROM AUTHOR]

• Spaceflight hazards include radiation, isolation, confinement, and altered gravity, which can have detrimental effects on behavior and cognition. • Food and nutrition interact with hazards of spaceflight, and can serve as countermeasures to mitigate negative effects. • Antioxidants and phytochemicals in food can affect neuroinflammation, behavior, and cognition. • After determining foods, nutrients, and amounts to optimize their protective effects, other constraints (e.g., stability, acceptability, safety) will need to be addressed before these can be used on exploration-class missions. Multi-year crewed space exploration missions are now on the horizon; therefore, it is important that we understand and mitigate the physiological effects of spaceflight. The spaceflight hazards—radiation, isolation, confinement, and altered gravity—have the potential to contribute to neuroinflammation and produce long-term cognitive and behavioral effects—while the fifth hazard, distance from earth, limits capabilities to mitigate these risks. Accumulated evidence suggests that nutrition has an important role in optimizing cognition and reducing the risk of neurodegenerative diseases caused by neuroinflammation. Here we review the nutritional perspective of how these spaceflight hazards affect the astronaut's brain, behavior, performance, and sensorimotor function. We also assess potential nutrient/nutritional countermeasures that could prevent or mitigate spaceflight risks and ensure that crewmembers remain healthy and perform well during their missions. Just as history has taught us the importance of nutrition in terrestrial exploration, we must understand the role of nutrition in the development and mitigation of spaceflight risks before humans can successfully explore beyond low-Earth orbit. [ABSTRACT FROM AUTHOR]

• Orbital spaceflight induces immune alterations consisting of reductions in T, NK cell function, elevated salivary stress hormones and the persistent reactivation of latent herpesviruses. • Spaceflight immune dysregulation is likely caused by some synergy of mission associated factors, including physiological and psychological stress, radiation, microgravity. • The international Space Station initiated construction in 1998 and since core construction has been completed a variety of biomedical countermeasures have been deployed including improved aerobic and resistive exercise equipment, psychological support for crewmembers, more frequent resupply and nutritional supplementation. • Immunity has been monitored for ISS astronauts for nearly 12 years and the data reveal a significant improvement for most immune and stress parameters, largely attributed to the biomedical countermeasures which have already been deployed. The International Space Station (ISS) has continued to evolve from an operational perspective and multiple studies have monitored both stress and the immune system of ISS astronauts. Alterations were ascribed to a potentially synergistic array of factors, including microgravity, radiation, psychological stress, and circadian misalignment. Comparing similar data across 12 years of ISS construction and operations, we report that immunity, stress, and the reactivation of latent herpesviruses have all improved in ISS astronauts. Major physiological improvements seem to have initiated approximately 2012, a period coinciding with improvements onboard ISS including cargo delivery and resupply frequency, personal communication, exercise equipment and protocols, food quality and variety, nutritional supplementation, and schedule management. We conclude that spaceflight associated immune dysregulation has been positively influenced by operational improvements and biomedical countermeasures onboard ISS. Although an operational challenge, agencies should therefore incorporate, within vehicle design limitations, these dietary, operational, and stress-relieving countermeasures into deep space mission planning. Specific countermeasures that have benefited astronauts could serve as a therapy augment for terrestrial acquired immunodeficiency patients. [ABSTRACT FROM AUTHOR]

The article presents a study which aims to compare the musculoskeletal effects of resistance exercise training using the Advanced Resistive Exercise Device (ARED) with the results of training with free weight (FW). It notes that musculoskeletal effects resulting from ARED exercise were not different in a significant manner to the effects of training with FW. It concludes that ARED training will be a more effective countermeasure than interim Resistive Exercise Device (iRED) training for spaceflight-induced deconditioning.

We appreciate the reviewers' time and recommendations, and have revised the manuscript to clarify questions. The changes are summarized here. • Energy equivalent meal replacement bars (MRBs) could conserve resources in isolated and confined operational environments. • MRB implementation was associated with reduced caloric intake, weight loss, and impacts to behavioral health. • Limited variety in flavor and texture, menu fatigue, and daily MRB implementation contribute to these negative impacts. • Meal replacement is operationally feasible and moderately acceptable for short-duration (<30d) missions. Strategies that reduce food system mass without negatively impacting food intake, acceptability, and resulting astronaut health and performance are essential for mission success in extreme operational environments such as space exploration. Here, we report the impact of substituting the spaceflight standard breakfast with energy equivalent, calorically-dense meal replacement bars (MRBs) on consumption, acceptability, and satiety and on associations with physical and behavioral health outcomes in high-performing subjects completing 30-day missions in the isolated and confined operational environment of NASA's Human Exploration Research Analog (HERA) habitat. MRB implementation was associated with reduced daily caloric intake, weight loss, and decrements in mood and neurobehavioral functioning, with no significant impacts on somatic symptoms and physical functioning. Food acceptability ratings suggest that flavor, texture, and menu fatigue attributed to limited variety are contributing factors, which are exacerbated by a daily implementation schedule. Meal replacement strategies for short-duration missions are operationally feasible, moderately acceptable, and can contribute to the practical goal of mass reduction, but more work is needed to define and optimize flavors, variety, and implementation schedules that sustain adequate nutrition, physical and behavioral health, and operational performance over time in isolated, confined, and extreme mission environments. [ABSTRACT FROM AUTHOR]