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NASA NTRS2005

Nutrition for Space Exploration

Nutrition has proven to be critical throughout the history of human exploration, on both land and water. The importance of nutrition during long-duration space exploration is no different. Maintaining optimal nutritional status is critical for all bodily systems, especially in light of the fact that that many are also affected by space flight itself. Major systems of concern are bone, muscle, the cardiovascular system, the immune system, protection against radiation damage, and others. The task ahead includes defining the nutritional requirements for space travelers, ensuring adequacy of the food system, and assessing crew nutritional status before, during, and after flight. Accomplishing these tasks will provide significant contributions to ensuring crew health on long-duration missions. In addition, development and testing of nutritional countermeasures to effects of space flight is required, and assessment of the impact of other countermeasures (such as exercise and pharmaceuticals) on nutrition is also critical for maintaining overall crew health. Vitamin D stores of crew members are routinely low after long-duration space flight. This occurs even when crew members take vitamin D supplements, suggesting that vitamin D metabolism may be altered during space flight. Vitamin D is essential for efficient absorption of calcium, and has numerous other benefits for other tissues with vitamin D receptors. Protein is a macronutrient that requires additional study to define the optimal intake for space travelers. Administration of protein to bed rest subjects can effectively mitigate muscle loss associated with disuse, but too much or too little protein can also have negative effects on bone. In another bed rest study, we found that the ratio of protein to potassium was correlated with the level of bone resorption: the higher the ratio, the more bone resorption. These relationships warrant further study to optimize the beneficial effect of protein on both bone and muscle during space flight. Omega3 fatty acids are currently being studied as a means of protecting against radiation-induced cancer. They have also recently been implicated as having a role in mitigating the physical wasting, or cachexia, caused by cancer. The mechanism of muscle loss associated with this type of cachexia is similar to the mechanism of muscle loss during disuse or space flight. Omega3 fatty acids have already been shown to have protective effects on bone and cardiovascular function. Omega3 fatty acids could be an ideal countermeasure for space flight because they have protective effects on multiple systems. A definition of optimal nutrient intake requirements for long-duration space travel should also include antioxidants. Astronauts are exposed to numerous sources of oxidative stress, including radiation, elevated oxygen exposure during extravehicular activity, and physical and psychological stress. Elevated levels of oxidative damage are related to increased risk for cataracts, cardiovascular disease, and cancer. Many groundbased studies show the protective effects of antioxidants against oxidative damage induced by radiation or oxygen. Balancing the diet with foods that have high levels of antioxidants would be another ideal countermeasure because it should have minimal side effects on crew health. Antioxidant supplements, however, are often used without having data on their effectiveness or side effects. High doses of supplements have been associated with bone and cardiovascular problems, but research on antioxidant effects during space flight has not been conducted. Much work must be done before we can send crews on exploration missions. Nutrition is often assumed to be the simple provision of food items that will be stable throughout the mission. As outlined briefly above, the situation is much more complex than food provision. As explorers throughout history have found, failure to truly understand the role of nutrition can be catastrophic. When huns are in environments unlike any they have seen before, this is more true than ever.

Smith, Scott M.↗

NASA NTRS2009

Microbial Risk Assessment

Historically, microbiological spaceflight requirements have been established in a subjective manner based upon expert opinion of both environmental and clinical monitoring results and the incidence of disease. The limited amount of data, especially from long-duration missions, has created very conservative requirements based primarily on the concentration of microorganisms. Periodic reevaluations of new data from later missions have allowed some relaxation of these stringent requirements. However, the requirements remain very conservative and subjective in nature, and the risk of crew illness due to infectious microorganisms is not well defined. The use of modeling techniques for microbial risk has been applied in the food and potable water industries and has exceptional potential for spaceflight applications. From a productivity standpoint, this type of modeling can (1) decrease unnecessary costs and resource usage and (2) prevent inadequate or inappropriate data for health assessment. In addition, a quantitative model has several advantages for risk management and communication. By identifying the variable components of the model and the knowledge associated with each component, this type of modeling can: (1) Systematically identify and close knowledge gaps, (2) Systematically identify acceptable and unacceptable risks, (3) Improve communication with stakeholders as to the reasons for resource use, and (4) Facilitate external scientific approval of the NASA requirements. The modeling of microbial risk involves the evaluation of several key factors including hazard identification, crew exposure assessment, dose-response assessment, and risk characterization. Many of these factors are similar to conditions found on Earth; however, the spaceflight environment is very specialized as the inhabitants live in a small, semi-closed environment that is often dependent on regenerative life support systems. To further complicate modeling efforts, microbial dose-response characteristics may be affected by a potentially dysfunctional crew immune system during a mission. In addition, microbial virulence has been shown to change under certain conditions during spaceflight, further complicating dose-response characterization. An initial study of the applicability of microbial risk assessment techniques was performed using Crew Health Care System (CHeCS) operational data from the International Space Station potable water systems. The risk of infection from potable water was selected as the flight systems and microbial ecology are well defined. This initial study confirmed the feasibility of using microbial risk assessment modeling for spaceflight systems. While no immediate threat was detected, the study identified several medically significant microorganisms that could pose a health risk if uncontrolled. The study also identified several specific knowledge gaps in making a risk assessment and noted that filling these knowledge gaps is essential as the risk estimates may change by orders of magnitude depending on the answers. The current phase of the microbial risk assessment studies focuses on the dose-response relationship of specific infectious agents, focusing on Salmonella enterica Typhimurium, Pseudomonas spp., and Escherichia coli, as their evaluation will provide a better baseline for determining the overall hazard characterization. The organisms were chosen as they either have been isolated on spacecraft or have an identified route of infection during a mission. The characterization will utilize dose-response models selected either from the peer-reviewed literature and/or by using statistical approaches. Development of these modeling and risk assessment techniques will help to optimize flight requirements and to protect the safety, health, and performance of the crew.

Ott, C. M.↗

NASA NTRS1991

An investigation of the effect of surface impurities on the adsorption kinetics of hydrogen chemisorbed onto iron

The goal was to develop an understanding of heterogeneous kinetic processes for those molecular species which produce gaseous hydrogen degradation of the mechanical properties of metallic structural materials. Although hydrogen degradation of metallic materials is believed to result from dissolved protonic hydrogen, the heterogeneous hydrogen interface transport processes often dominate the kinetics of the degradation process. The initial step in the interface transport process is the dissociative chemisorption of the molecular species at the metal surface followed by hydrogen absorption into and transport through the bulk. Modern advanced aerospace applications often require the use of structural materials in high pressure hydrogen environments at temperatures which range from low cryogenic temperatures to very high temperatures (1300 K and greater). Materials proposed for these applications, such as the titanium aluminides, beta-titanium alloys, nickel- and cobalt-based superalloys, molybdenum-rhenium alloys, beryllium, and various beryllides, need to possess a high degree of immunity from hydrogen induced degradation of mechanical properties. In the present program, the interaction of hydrogen with the surfaces of alpha-2 (Ti3Al) titanium aluminide, gamma (TiAl) titanium aluminide, and beryllium were studied. The interaction of low pressure hydrogen with gamma titanium aluminide and beryllium was found to be relatively weak, in the sense that adsorption leads to a low surface concentration of dissociated hydrogen, i.e., the chemisorption process is reversible at room temperature (300 K) for gamma titanium aluminide and the sticking coefficient for chemisorption is extremely small for beryllium. Hydrogen was found to interact readily with alpha-2 titanium aluminide to form a stable surface hydride at 300 K. These results correlate well with other recent studies which show that the mechanical properties for alpha-2 titanium aluminide are readily degraded in hydrogen while gamma titanium aluminide exhibits less degradation and beryllium essentially no degradation. The interaction of oxygen with the surface of these materials has been studied, also, in the present program.

Shanabarger, Mickey R.↗

NASA NTRS2002

Determination of the Absolute Number of Cytokine mRNA Molecules within Individual Activated Human T Cells

A primary function of activated T cells is the expression and subsequent secretion of cytokines, which orchestrate the differentiation of other lymphocytes, modulate antigen presenting cell activity, and alter vascular endothelium to mediate an immune response. Since many features of immune regulation probably result from modest alterations of endogenous rates of multiple interacting processes, quantitative analysis of the frequency and specific activity of individual T cells is critically important. Using a coordinated set of quantitative methods, the absolute number of molecules of several key cytokine mRNA species in individual T cells has been determined. The frequency of human blood T cells activated in vitro by mitogens and recall protein antigens was determined by intracellular cytokine protein staining, in situ hybridization for cytokine mRNA, and by limiting dilution analysis for cytokine mRNA+ cells. The absolute number of mRNA molecules was simultaneously determined in both homogenates of the entire population of cells and in individual cells obtained by limiting dilution, using a quantitative, competitive RT-PCR assay. The absolute numbers of mRNA molecules in a population of cells divided by the frequency of individual positive cells, yielded essentially the same number of mRNA molecules per cell as direct analysis of individual cells by limiting dilution analysis. Mean numbers of mRNA per positive cell from both mitogen and antigen activated T cells, using these stimulation conditions, were 6000 for IL-2, 6300 for IFN-gamma, and 1600 for IL-4.

Karr, Laurel J.↗

NASA NTRS2002

Loss of signal transduction and inhibition of lymphocyte locomotion in a ground-based model of microgravity

Inflammatory adherence to, and locomotion through the interstitium is an important component of the immune response. Conditions such as microgravity and modeled microgravity (MMG) severely inhibit lymphocyte locomotion in vitro through gelled type I collagen. We used the NASA rotating wall vessel bioreactor or slow-turning lateral vessel as a prototype for MMG in ground-based experiments. Previous experiments from our laboratory revealed that when lymphocytes (human peripheral blood mononuclear cells [PBMCs]) were first activated with phytohemaglutinin followed by exposure to MMG, locomotory capacity was not affected. In the present study, MMG inhibits lymphocyte locomotion in a manner similar to that observed in microgravity. Phorbol myristate acetate (PMA) treatment of PBMCs restored lost locomotory capacity by a maximum of 87%. Augmentation of cellular calcium flux with ionomycin had no restorative effect. Treatment of lymphocytes with mitomycin C prior to exposure to MMG, followed by PMA, restored locomotion to the same extent as when nonmitomycin C-treated lymphocytes were exposed to MMG (80-87%), suggesting that deoxyribonucleic acid replication is not essential for the restoration of locomotion. Thus, direct activation of protein kinase C (PKC) with PMA was effective in restoring locomotion in MMG comparable to the normal levels seen in Ig cultures. Therefore, in MMG, lymphocyte calcium signaling pathways were functional, with defects occurring at either the level of PKC or upstream of PKC.

NASA Discipline Cell Biology↗

NASA NTRSDate not supplied

Mitochondria Dysfunction Central in Driving Health Risks Associated with Spaceflight

Background: Determining the biological impact of spaceflight through novel approaches is essential to reduce the health risks to astronauts for long-term space missions. The current established health risks due to spaceflight are only reflecting known symptomatic and physiologic responses and do not reflect early onset of other potential diseases. There are many unknown variables which still need to be identified to fully understand the health impacts due to the environmental factors in space. Materials and Methods: One method to uncover potential novel biological mechanisms responsible for health risks in astronauts is by utilizing NASA’s GeneLab platform (genelab.nasa.gov). GeneLab is public repository that hosts multiple omics datasets generated from space biology experiments that include experiments flown in space, simulated cosmic radiation experiments, and simulated microgravity experiments. This presentation will provide an example of analysis and novel hypothesis generation that is being produced with GeneLab datasets. A comprehensive multi-omics approach was implemented correlating transcriptomics, proteomics, metabolomics, and methylation analysis. Results: We found that cells have stronger overall biological response than the tissues to spaceflight, with mitochondrial activity and innate immunity pathways being heavily impacted. NASA Twin Study results are consistent with a specific alteration in mitochondrial ATP production. Our results indicate that the space environment can directly induce mitochondrial damage, with mitochondrial dysfunctions being a cause for chronic inflammation and both being involved in the development of metabolic disorders that cause changes in lipid metabolism. We also found biological changes occurring during spaceflight with cell cycle, circadian rhythm and olfactory activity pathways can also influence and be influenced by alterations on mitochondrial activity

Afshin Beheshti↗

NASA NTRSDate not supplied

Dry Saliva Development-Artemis

Prior to the deployment of prolonged deep space missions which may carry increased crew health risks, it is essential to determine the effect that missions beyond the Van Allen Belt will have on physiology. Historically the National Aeronautics and Space Administration (NASA), Human Research Program (HRP) has developed, conducted, and delivered research findings and countermeasures that will maintain the health and safety of crews aboard the International Space Station (ISS) in anticipation of future exploration class missions. To support these objectives, research operations on ISS typically include the collection and storage of human physiological samples and their return to Earth for analysis. Transition to Gateway and Artemis lunar exploration will limit the available up mass and biosample return capability resulting in new challenges to monitor crew health during the mission. The Artemis lunar missions provide a perfect opportunity to assess new technology that could support crew biosample return that is compatible with the severe operational constraints of Artemis mission design. Dried biosample chemistry analysis is a potential technology that can enable the collection of samples and tracking of crew health during these exploration class missions. The development and implementation of dried biosample chemistry technology for tracking immune health, viral reactivation and hormone fluctuations provide a simple alternative strategy for sample collection and sample return (light weight non-conditioned stowage option) for the continuation of human research during Artemis missions. Saliva is established as an informative biosample that has both its own unique available analytes as well as others that are also present in blood. Saliva is already routinely collected from ISS astronauts for the detection of stress hormones and latent virus DNA. The ‘Dry Saliva’ book sample collection/storage protocol, already successfully deployed to ISS, represents a perfect method for collecting biosamples from Gateway and Artemis astronauts because it requires a simple, non-invasive sample collection protocol, minimum volume, and uses non-conditioned storage. We are currently conducting an expanded stability study of the dry saliva analyte platform to include additional stress hormones, cytokines, antimicrobial proteins, and latent virus DNA as well as other markers of immunity and inflammation. Validation testing on parabolic flight will establish collection methods for saliva and blood to dry sampling substrates to finalize the collection protocols for flight. For the new expanded analyte stability study, a short-term stability study with time points out to 14 days has been completed with analysis underway to determine whether additional analytes could be recovered, as well as assessing the best storage conditions for the samples collected. In parallel, a long-term stability study is being conducted out to 1 year to improve the stability of some unstable analytes. To this end, the NASA Johnson Space Center’s Immunology/Virology lab is currently finalizing the saliva dry chemistry platform, including assay compatibility and stability studies. This technology is approved to be implemented, as part of the ‘Biomarkers’ study, during Artemis II through Artemis IV lunar missions.

Mayra Nelman-Gonzalez↗

NASA NTRS2006

Microgravity and Immunity: Changes in Lymphocyte Gene Expression

Earlier studies had shown that modeled and true microgravity (MG) cause multiple direct effects on human lymphocytes. MG inhibits lymphocyte locomotion, suppresses polyclonal and antigen-specific activation, affects signal transduction mechanisms, as well as activation-induced apoptosis. In this study we assessed changes in gene expression associated with lymphocyte exposure to microgravity in an attempt to identify microgravity-sensitive genes (MGSG) in general and specifically those genes that might be responsible for the functional and structural changes observed earlier. Two sets of experiments targeting different goals were conducted. In the first set, T-lymphocytes from normal donors were activated with antiCD3 and IL2 and then cultured in 1g (static) and modeled MG (MMG) conditions (Rotating Wall Vessel bioreactor) for 24 hours. This setting allowed searching for MGSG by comparison of gene expression patterns in zero and 1 g gravity. In the second set - activated T-cells after culturing for 24 hours in 1g and MMG were exposed three hours before harvesting to a secondary activation stimulus (PHA) thus triggering the apoptotic pathway. Total RNA was extracted using the RNeasy isolation kit (Qiagen, Valencia, CA). Affymetrix Gene Chips (U133A), allowing testing for 18,400 human genes, were used for microarray analysis. In the first set of experiments MMG exposure resulted in altered expression of 89 genes, 10 of them were up-regulated and 79 down-regulated. In the second set, changes in expression were revealed in 85 genes, 20 were up-regulated and 65 were down-regulated. The analysis revealed that significant numbers of MGS genes are associated with signal transduction and apoptotic pathways. Interestingly, the majority of genes that responded by up- or down-regulation in the alternative sets of experiments were not the same, possibly reflecting different functional states of the examined T-lymphocyte populations. The responder genes (MGSG) might play an essential role in adaptation to MG and/or be responsible for pathologic changes encountered in Space and thus represent potential targets for molecular-based countermeasures

Risin, D.↗

NASA NTRS2014

Probiotics in the Space Food System: Delivery, Microgravity Effects, and the Potential Benefit to Crew Health

As mission distance and duration increase, the need grows for non‐invasive disease prevention and immunomodulation, especially given the limited medical response capability expected for these missions and the immune dysregulation documented in crew. Additionally, changes in diet, lifestyle, antibiotic usage, and the environmental stresses during spaceflight may alter crewmembers' intestinal microbiome. The addition of probiotic bacteria to the space food system is expected to confer immunostimulatory benefits on crewmembers, with the potential to counteract the immune dysregulation that has been documented in spaceflight. Based on previous studies that demonstrated unique microbiological responses to the low shear environment of spaceflight, probiotic organisms hold the potential to induce enhanced beneficial responses through mechanisms, such as beneficial interactions with human immune cells and repression of colonization of pathogens on the mucosa. The work presented here will begin to address two research gaps related to providing probiotics in spaceflight: 1) delivery, and 2) the effect of the low shear microgravity environment on probiotic attributes. The probiotic Lactobacillus acidophilus was selected for investigation due to its wide commercial use and documented benefits that include inhibition of virulence related gene expression in pathogens and mucosal stimulation of immune cells. The delivery system for probiotics has not been determined for spaceflight, where the food system is shelf stable and the lack of refrigeration prevents the use of traditional dairy delivery methods. In order to demonstrate the potential of the space food system to deliver viable probiotic bacteria to crewmembers, the probiotic L. acidophilus was packaged in high barrier flight packaging in nonfat dry milk (NFDM) or retained in commercial capsule form. Viable cells were enumerated over 8 months of storage at 22, 4, and ‐80ºC. The survival of L. acidophilus rehydrated in NFDM, in a PBS control, and directly from the capsule was also evaluated following stress challenge with simulated gastric and intestinal juices to determine the method that would deliver the most viable cells to the intestine, where they would be expected to confer beneficial effects. L. acidophilus was found to be stable to gastric and intestinal juice challenge when delivered in rehydrated NFDM, even after two hours of exposure. In comparison, L. acidophilus was reduced by 1‐5 logs when exposed to gastric and intestinal juice directly and when rehydrated in a PBS control. Shelf life data indicated that L. acidophilus would require refrigerated or frozen storage to remain viable at adequate levels over the multi‐year storage periods required for spaceflight. This study suggests that the protective effect provided by the dairy matrix, and not merely rehydration prior to consumption, extends probiotic viability and stress tolerance during storage in spaceflight and in simulated digestion conditions more adequately than a capsule. In addition to effective delivery, it is essential to understand the microgravity effects on the stress tolerances and genetic expression of probiotic bacteria to enable optimization of growth, survival, strain selection, and conferred benefits in spaceflight. In our current study, ground‐based characterization of the growth, stress response, and transcriptomic response of L. acidophilus will be accomplished using the low shear modeled microgravity (LSMMG) culture environment in the rotating wall vessel (RWV). We hypothesize that L. acidophilus will maintain or improve its growth and stress response following culture in the LSMMG environment, and that transcriptomic analysis will define the associated molecular mechanism(s), resulting in the ability to optimize strain selection.

Castro, S. L.↗

NASA NTRSDate not supplied

Isolation Standard Measures: A Set of Validated and Feasible Measurements Ensuring Comparability Across Isolation and Confinement Studies

Isolation and confinement studies have been essential to the preparation of crewed long-duration space missions, acting as analogues that facilitate the study of psychological and physiological responses to isolation and confinement. They also serve as opportunities for the development, testing, and validation of countermeasures and coping methods to handle the challenges that arise in such scenarios. Due to the small sample sizes in combination with high inter-individual variability, single isolation campaigns are not always sufficient for obtaining statistically significant scientific findings. To address this issue and improve comparability between different studies, the need for standardized measures to be collected in all future isolation and confinement studies was identified. Additionally, these measures should also be shown to be generally valid, reliable, feasible and acceptable in analogue and spaceflight environments. Standard measures in isolation and confinement studies allow for more direct comparisons of results and synthesis of data across isolation and confinement studies as well as provide an important step toward standard measures in spaceflight. An international expert group with representatives from different space agencies worldwide was brought together to define a core set of standard measures for isolation and confinement studies. This paper provides an overview of the expert group’s recommendations for international standard measures for future isolation and confinement studies, along with subsequent updates coordinated by the International Countermeasures Working Group (ICMWG), which was established as a sub-Working Group under the International Space Life Sciences Working Group (ISLSWG). Additional experts were consulted by the ICMWG partner agencies as required. The collection of the described set of isolation standard measures will provide data on the following parameters: sleep, mood, psychological state, psychophysiology, cognitive performance, stress and the immune system, general health and well-being, team measures, nutritional measures, and environmental conditions. For each measure, recommendations were made about duration and frequency of administration, along with specific implementation recommendations in relation to the duration of the isolation study. The set of isolation standard measures will be reassessed every two years at a minimum to ensure they are up to date and reflect the current state-of-the-art.

Isolation↗