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NASA NTRS2007

Autonomous Medical Care for Exploration Class Space Missions

The US-based health care system of the International Space Station (ISS) contains several subsystems, the Health Maintenance System, Environmental Health System and the Countermeasure System. These systems are designed to provide primary, secondary and tertiary medical prevention strategies. The medical system deployed in Low Earth Orbit (LEO) for the ISS is designed to enable a "stabilize and transport" concept of operations. In this paradigm, an ill or injured crewmember would be rapidly evacuated to a definitive medical care facility (DMCF) on Earth, rather than being treated for a protracted period on orbit. The medical requirements of the short (7 day) and long duration (up to 6 months) exploration class missions to the Moon are similar to LEO class missions with the additional 4 to 5 days needed to transport an ill or injured crewmember to a DCMF on Earth. Mars exploration class missions are quite different in that they will significantly delay or prevent the return of an ill or injured crewmember to a DMCF. In addition the limited mass, power and volume afforded to medical care will prevent the mission designers from manifesting the entire capability of terrestrial care. NASA has identified five Levels of Care as part of its approach to medical support of future missions including the Constellation program. In order to implement an effective medical risk mitigation strategy for exploration class missions, modifications to the current suite of space medical systems may be needed, including new Crew Medical Officer training methods, treatment guidelines, diagnostic and therapeutic resources, and improved medical informatics.

Hamilton, Douglas↗

NASA NTRS1996

High Leverage Space Transportation System Technologies for Human Exploration Missions to the Moon and Beyond

The feasibility of returning humans to the Moon by 2004, the 35th anniversary of the Apollo 11 landing, is examined assuming the use of existing launch vehicles (the Space Shuttle and Titan 4B), a near term, advanced technology space transportation system, and extraterrestrial propellant--specifically 'lunar-derived' liquid oxygen or LUNOX. The lunar transportation system (LTS) elements consist of an expendable, nuclear thermal rocket (NTR)-powered translunar injection (TLI) stage and a combination lunar lander/Earth return vehicle (LERV) using cryogenic liquid oxygen and hydrogen (LOX/LH2) chemical propulsion. The 'wet' LERV, carrying a crew of 2, is configured to fit within the Shuttle orbiter cargo bay and requires only modest assembly in low Earth orbit. After Earth orbit rendezvous and docking of the LERV with the Titan 4B-launched NTR TLI stage, the initial mass in low Earth orbit (IMLEO) is approx. 40 t. To maximize mission performance at minimum mass, the LERV carries no return LOX but uses approx. 7 t of LUNOX to 'reoxidize' itself for a 'direct return' flight to Earth followed by an 'Apollo-style' capsule recovery. Without LUNOX, mission capability is constrained and the total LTS mass approaches the combined Shuttle-Titan 4B IMLEO limit of approx. 45 t even with enhanced NTR and chemical engine performance. Key technologies are discussed, lunar mission scenarios described, and LTS vehicle designs and characteristics are presented. Mission versatility provided by using a small 'all LH2' NTR engine or a 'LOX-augmented' derivative, either individually or in clusters, for outer planet robotic orbiter, small Mars cargo, lunar 'commuter', and human Mars exploration class missions is also briefly discussed.

Borowski, Stanley K.↗

NASA NTRS2024

Ensuring Safe Decision-Making on the Moon and Mars: Cognitive Performance Assessment for Exploration Class Mission EVA

Extravehicular activity (EVA) is one of the most dangerous and cognitively demanding actions that astronauts can execute, and the cognitive demands associated with future partial gravity EVA on the Moon and Mars are expected to be higher compared to microgravity EVA currently conducted from the International Space Station (ISS). Decrements in cognitive performance present an important risk to crew safety during exploration mission class EVA. Yet there is currently insufficient data to characterize cognitive performance prior to, during, and following EVA. Furthermore, it is still unclear which cognitive domains are most important for conducting mission critical decisions with crew safety implications. To address this gap, we conducted a cognitive task analysis (CTA) of EVA to characterize the procedures, the cognitive demands required, and the critical safety decisions associated with decrements in cognitive performance. We used the applied cognitive task analysis method as outlined by Militello and Hutton (1998) and conducted interviews with subject matter experts (SMEs) in EVA at NASA Johnson Space Center in summer 2024. Interviews focused on exploration EVA and elicited feedback from SMEs on the cognitive skills required for specific EVA tasks including cognitive strategies, critical cues, and decision-making strategies. A cognitive demands table was assembled to consolidate and synthesize the information from all interviews. The information from this cognitive task analysis will inform ongoing work to identify the key cognitive domains for safe decision-making during exploration mission class EVA on the Moon and Mars. This work will importantly provide a link between cognitive domains identified in the cognitive task analysis and operationally-relevant performance metrics collected during spaceflight and simulation EVA that can be tracked and assessed by NASA mission operations. Ultimately, this work will aid in the development and application of exploration class cognitive performance monitoring capabilities to improve safe decision-making and inform EVA planning on future spaceflight missions to the Moon and Mars.

Steven R Anderson↗

NASA NTRSDate not supplied

A 1 MW Solar Electric and Chemical Propulsion Vehicle for Piloted Mars Opposition Class Missions

Previous investigations have extensively explored crew missions to and from Mars, with a prevailing approach termed the 'conjunction' class, necessitating an approximately 500-day stay at Mars for a cost-effective return. However, this configuration results in a mission duration exceeding 1000 days (roughly 3 years). In order to reduce crew health and surface operations risks, a shortened mission duration of 850 days is being explored by using a short ~30 day Mars surface stay and a ‘opposition’ class approach. A non-nuclear approach is possible by combining solar electric propulsion and a chemical stage. While past mission concepts for the conjunction missions also used solar electric propulsion they limited the SEP power to <700 kW. In order to achieve the 850 day round trip more SEP power is needed. A 1MW class SEP-Chem vehicle was found sufficient to perform the 850 day mission. The biggest challenge for the design will be the large, high power solar arrays, mainly from their deployment and stability. This work describes the design of the SEP-Chem vehicle, assembled in a Near Rectilinear Halo Orbit (NRHO) and employing super-heavy class and the Space Launch System (SLS) launchers.

SEP-Chem↗

NASA NTRSDate not supplied

Developing Mars-Based Clinical Scenarios for an Earth Independent Medical Operations (EIMO) – Based Decision Support Service

As crewed missions move beyond Low-Earth Orbit, pre-mission planning cannot fully buy down the medical risks of exploration-class missions. Martian missions, where increased hazards exist, (such as long-duration spaceflight, surface-level EVA operations, and communications delays) will require a paradigm shift in the structure of a medical system. An Earth-Independent Medical Operations-based Medical System (EIMO-MS) will need to optimize four critical domains to help provide medical care: utilization of Pre-Mission Planning, augmentation of Acute and Prolonged Medical Decision Making, automated tracking of Resource Management, and assistance in Task Load Balance. The ideal EIMO-MS will be able to accomplish this goal by having an interactive, adaptable interface that will be able to provide real-time medical services. It must respond based on the level of crewmember training, medical situation, and available medical and non-medical resources. To showcase the capabilities and requirements of such a sophisticated automated MS, a series of clinical scenarios of escalating complexity were developed with clinical and systems engineering input. These scenarios describe in clinical detail what a theoretical future medical system, enhanced with multiple information streams (such as a medical database, an AI-based Decision Support System, real-time monitoring, enhanced in-situ laboratory imaging, etc.) can achieve in conjunction with a trained and experienced crew. Scenarios are comprised of: a context section including objectives and applicable spaceflight environment, a highlighted assumptions section, a clinical narrative section, and a systems engineering activity diagram demonstrating the integrated Medical System (MS). The “swim lanes” of the activity diagram act as the logistical core of each scenario and show how the MS will interact with the crew, ground support, and other in-flight systems. The Design Reference Mission that is used for the scenarios is based on existing reference mission profiles [1] with a projected 30-sol stay on the Martian surface. Scenarios span the spectrum from planned evaluations, minor medical care, urgent care, surgical guidance, critical and expectant management, and behavioral health care. Mission complexity will exponentially increase during deep space and Mars exploration-class missions, and medical support for these missions will likewise need to increase in autonomy and adaptability. The integrated system that will support these missions will need to provide assistance in a variety of anticipated and unforeseen scenarios. These medical scenarios, guided by clinician input, are initial steps in crafting the requirements for an EIMO-based medical system. By working in a systems engineering framework, requirements and capabilities can be extracted and mapped while maintaining a clinical core.

Prashant Parmar↗

NASA NTRS1984

Mars exploration, Venus swingby and conjunction class mission modes, time period 2000 to 2045

Trajectory and mission requirement data are presented for Earth-Mars opposition class and conjunction class round trip stopover mission opportunities available during the time period year 2000 to year 2045. The opposition class mission employs the gravitational field of Venus to accelerate the space vehicle on either the outbound or inbound leg. The gravitational field of Venus was used to reduce the propulsion requirement associated with the opposition class mission. Representative space vehicle systems are sized to compare the initial mass required in low Earth orbit of one mission opportunity with another mission opportunity. The interplanetary space vehicle is made up of the spacecraft and the space vehicle acceleration system. The space vehicle acceleration system consists of three propulsion stages. The first propulsion stage performs the Earth escape maneuver; the second stage brakes the spacecraft and Earth braking stage into the Mars elliptical orbit and effects the escape maneuver from the Mars elliptical orbit. The third propulsion stage brakes the mission module into an elliptical orbit at Earth return. The interplanetary space vehicle was assumed to be assembled in and depart from the space station circular orbit.

Mars Exploration↗

NASA NTRSDate not supplied

Ensuring Safe Decision-Making on the Moon and Mars: Cognitive Performance Assessment for Exploration Class Mission EVA

Extravehicular activity (EVA) is one of the most dangerous and cognitively demanding actions that astronauts can execute, and the cognitive demands associated with future partial gravity EVAs on the Moon and Mars are expected to be higher compared to microgravity EVAs currently conducted from the International Space Station. Decrements in cognitive performance present an important risk to crew safety during exploration mission class EVA. Yet there is currently insufficient data to characterize cognitive performance prior to, during, and following EVA. Furthermore, it is still unclear which cognitive domains are most important for conducting mission critical decisions with crew safety implications. To address this gap, we conducted a cognitive task analysis (CTA) of EVA to characterize the procedures, the cognitive demands required, and the critical safety decisions associated with decrements in cognitive performance. We conducted a cognitive task analysis with 15 astronauts and subject matter experts in EVA operations and research. Interviews focused on surface exploration EVA and elicited feedback from experts on the cognitive skills required for specific EVA tasks, including cognitive strategies, critical cues, and decision-making strategies. A cognitive demands table was assembled to consolidate and synthesize the information from all interviews. The information from this cognitive task analysis informs ongoing exploration EVA for Moon to Mars. This work identifies the specific cognitive challenges that astronauts are likely to encounter during surface exploration EVA, and provides the foundation for: (1) prioritized and targeted cognitive performance measurement and functional performance tests, (2) EVA simulation design at varying levels of cognitive workload, and (3) the development of training and other technologies that can improve safe decision-making and inform EVA planning on future spaceflight missions to the Moon and Mars.

Steven R Anderson↗

NASA NTRS2009

Aerocapture Guidance and Performance at Mars for High-Mass Systems

The Mars Entry, Descent, and Landing System Analysis (EDL-SA) project has been tasked with performing systems analysis to identify the optimal technologies required to land a 20-50 MT Exploration-class mission on Mars. It has been shown that it is not possible to safely land these large systems using heritage Mars EDL systems, or analogous Earth or Moon EDL systems. In 2007, NASA conducted a Mars Exploration Architecture Study which included an in depth review of the science motivations and engineering technology requirements for a human Mars mission campaign. This study resulted in an update to the Mars Design Reference Architecture (DRA 5.0). Among the primary findings and recommendations was the conclusion that landing of large payloads (greater than 1 MT) on the surface of Mars remains a key architectural challenge. Additionally, research and system studies of fundamental EDL technologies were highly recommended. The EDL-SA project identified the candidate technologies and assembled them into full capture and EDL sequences so that simulations could be developed to evaluate them. The chosen architectures combine the various technologies of interest in eight different ways. For aerocapture, only two scenarios were considered. The first is a rigid mid-L/D aeroshell (AS), which is represented in architectures 1, 4, 5, and 7. This scenario calls for a vehicle that flies at a 55-degree angle of attack, resulting in ballistic coefficient and L/D values of 490 kg/m 2 and 0.43, respectively. The second is a lifting hypersonic inflatable aerodynamic decelerator (HIAD), which is represented in architectures 2, 6, and 8. This scenario requires the vehicle to fly at a 22.2- degree angle of attack, which correlates to an L/D of 0.3 and was sized to provide a ballistic coefficient of 165 kg/m 2 . Architecture 3 is an all-propulsive sequence, and is not considered in this study.

Zumwalt, Carlie H.↗

NASA NTRS2013

A Mission Concept: Re-Entry Hopper-Aero-Space-Craft System on-Mars (REARM-Mars)

Future missions to Mars that would need a sophisticated lander, hopper, or rover could benefit from the REARM Architecture. The mission concept REARM Architecture is designed to provide unprecedented capabilities for future Mars exploration missions, including human exploration and possible sample-return missions, as a reusable lander, ascend/descend vehicle, refuelable hopper, multiple-location sample-return collector, laboratory, and a cargo system for assets and humans. These could all be possible by adding just a single customized Re-Entry-Hopper-Aero-Space-Craft System, called REARM-spacecraft, and a docking station at the Martian orbit, called REARM-dock. REARM could dramatically decrease the time and the expense required to launch new exploratory missions on Mars by making them less dependent on Earth and by reusing the assets already designed, built, and sent to Mars. REARM would introduce a new class of Mars exploration missions, which could explore much larger expanses of Mars in a much faster fashion and with much more sophisticated lab instruments. The proposed REARM architecture consists of the following subsystems: REARM-dock, REARM-spacecraft, sky-crane, secure-attached-compartment, sample-return container, agile rover, scalable orbital lab, and on-the-road robotic handymen.

Davoodi, Faranak↗

NASA NTRS2014

MSL Entry, Descent, and Landing Instrumentation: Return on Investment

On Aug 5, 2012 the Mars Science Laboratory (MSL) Entry, Descent, and Landing Instrumentation (MEDLI) suite on MSL entry vehicle heatshield suc-cessfully returned surface pressure and in-depth temperature data.1,2 The MEDLI data has given scientists and engineers an unprecedented ability to reconstruct entry environment, atmospheric density, and flight trajectory, and flight validation of predic-tions vehicle aerodynamics and thermal protection system (TPS) performance. This presentation will dis-cuss key findings from MEDLI, some of which are being applied to improve definition of aerothermal environment and TPS sizing margins for existing NASA entry missions. The postflight analysis has shown that a significant thermal protection mass saving upon redesign is possible for an MSL-class vehicle. The success of MEDLI has also demonstrated and qualified robust flight instrumentation technologies at very low risk to the mission. The potential benefits of MEDLI to planetary exploration and sample return missions, as well as to exploration class missions to Mars will be presented.

MEDLI↗

NASA NTRS2007

Assessing the Biohazard Potential of Putative Martian Organisms for Exploration Class Human Space Missions

Exploration Class missions to Mars will require precautions against potential contamination by any native microorganisms that may be incidentally pathogenic to humans. While the results of NASA's Viking biology experiments of 1976 have been generally interpreted as inconclusive for surface organisms, the possibility of native surface life has never been ruled out and more recent studies suggest that the case for biological interpretation of the Viking Labeled Release data may now be stronger than it was when the experiments were originally conducted. It is possible that, prior to the first human landing on Mars, robotic craft and sample return missions will provide enough data to know with certainty whether or not future human landing sites harbor extant life forms. However, if native life is confirmed, it will be problematic to determine whether any of its species may present a medical risk to astronauts. Therefore, it will become necessary to assess empirically the risk that the planet contains pathogens based on terrestrial examples of pathogenicity and to take a reasonably cautious approach to bio-hazard protection. A survey of terrestrial pathogens was conducted with special emphasis on those pathogens whose evolution has not depended on the presence of animal hosts. The history of the development and implementation of Apollo anticontamination protocol and recent recommendations of the NRC Space Studies Board regarding Mars were reviewed. Organisms can emerge in nature in the absence of indigenous animal hosts and both infectious and non-infectious human pathogens are theoretically possible on Mars. The prospect of Martian surface life, together with the existence of a diversity of routes by which pathogenicity has emerged on Earth, suggests that the possibility of human pathogens on Mars, while low, is not zero. Since the discovery and study of Martian life can have long-term benefits for humanity, the risk that Martian life might include pathogens should not be an obstacle to human exploration. As a precaution, however, it is recommended that EVA suits be decontaminated when astronauts enter surface habitats when returning from field activity and that biosafety protocol approximating laboratory BSL 2 be developed for astronauts working in laboratories on the Martian surface. Quarantine of astronauts and Martian materials arriving on Earth should also be part of a human Mars mission and this and the surface biosafety program should be integral to human expeditions from the earliest stages of the mission planning.

Warmflash, David↗

NASA NTRS2011

Defining the Relationship Between Biomarkers of Oxidative and Inflammatory Stress and the Risk for Atherosclerosis in Astronauts During and After Long-Duration Spaceflight

Future human space travel will primarily consist of long-duration missions aboard the International Space Station (ISS) or exploration class missions to Mars, its moons, or nearby asteroids. These missions will expose astronauts to increased risk of oxidative and inflammatory damage primarily from radiation, but also from psychological stress, reduced physical activity, diminished nutritional status, and, in the case of extravehicular activity, hyperoxic exposure. There is evidence that increased oxidative damage and inflammation can accelerate the development of atherosclerosis. PURPOSE The purpose of this proposal is to identify biomarkers of oxidative and inflammatory stress and to correlate them to indices of atherosclerosis risk before, during, and after long-duration spaceflight. METHODS To meet the objectives of the study, we will study astronauts before, during, and up to 5 years after long-duration missions aboard ISS. Biomarkers of oxidative and inflammatory stress, some of which we have previously shown to be elevated with spaceflight, will be measured before, during, and after spaceflight. Arterial structure will be monitored using ultrasound to measure carotid intima-medial thickness before, during, and after weightlessness. Carotid intima-medial thickness has been shown to be a better indicator than Framingham Risk scores for prediction of atherosclerosis. Arterial function will be monitored using brachial flow-mediated dilation before flight and after landing. Brachial flow-mediated dilation is a good index of endothelium-dependent vasodilation, which is a sensitive predictor of atherosclerotic risk. This is the first study to propose assessing atherosclerotic risk using biochemical, structural, and functional measures before, during, and immediately after spaceflight and structural functional measures for up to 5 years after landing. EXPECTED RESULTS We hypothesize that these biomarkers of oxidative and inflammatory stress will be increased with spaceflight and will correlate with increased carotid intima-medial thickness in- and postflight and with decreased flow-mediated dilation after the mission. Furthermore, we hypothesize that measures of oxidative stress will return to baseline after flight, but that biomarkers of inflammatory stress and vascular indices of atherosclerosis risk will remain elevated.

Lee, Stuart M. C.↗

NASA NTRS2014

Defining the Relationship between Biomarkers of Oxidative and Inflammatory Stress and the Risk for Atherosclerosis in Astronauts during and after Long-duration Spaceflight

Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. These missions will expose astronauts to increased risk of oxidative and inflammatory damage from a variety of sources, including radiation, psychological stress, reduced physical activity, diminished nutritional status, and hyperoxic exposure during extravehicular activity. Evidence exists that increased oxidative damage and inflammation can accelerate the development of atherosclerosis. PURPOSE The purpose of this investigation is to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and investigate if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. This is the first study to propose assessing atherosclerotic risk using biochemical, structural, and functional measures before, during, and immediately after spaceflight, and structural and functional measures for up to 5 years after landing. METHODS We will study 12 astronauts before, during, and up to 5 years after long-duration ISS missions. A panel of biomarkers of oxidative and inflammatory stress will be measured twice before flight, early (flight days 15 and 60) and late (2 weeks before landing) during the mission, and early in the postflight recovery phase (approx 3 days after landing). Arterial structure and vascular compliance will be measured at the same times and also at 1, 3, and 5 years after landing (surveillance). Arterial function will be measured using the same preflight, postflight, and surveillance schedule as arterial structure and vascular compliance measures, but will not be measured inflight. Biomarkers, some of which we have previously shown to be elevated with spaceflight, will be measured in venous blood samples and 24-h (in-flight) and 48-h (pre- and post-flight) urine pools. Arterial structure will be assessed from measures of carotid intima-media thickness, which have been shown to be better indicators of atherosclerotic than the Framingham Risk Score. Arterial function will be assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and is a sensitive predictor of atherosclerotic risk. Arterial pulse pressure measured in the brachial artery and stroke volume measured from cardiac ultrasound will be used to assess hemodynamic status, cardiac function, and systemic vascular compliance. Three astronauts are actively participating in the preflight data collection and training activities. One astronaut has completed all preflight activities and will participate in the first in-flight data collection sessions by the end of 2013. The first post-flight data collection sessions will occur in the spring of 2014. EXPECTED RESULTS We hypothesize that biomarkers of oxidative and inflammatory stress will increased with spaceflight and will correlate with increased carotid intima-media thickness during and after flight and with decreased flow-mediated dilation after the mission. Furthermore, we hypothesize that measures of oxidative stress will return to baseline after flight, but biomarkers of inflammatory stress and vascular indices of atherosclerotic risk will remain elevated.

Lee, Stuart M. C.↗

NASA NTRS2014

Fluid Shifts Before, During and After Prolonged Space Flight and Their Association with Intracranial Pressure and Visual Impairment

Future human space travel will primarily consist of long duration missions onboard the International Space Station or exploration class missions to Mars, its moons, or nearby asteroids. Current evidence suggests that long duration missions might increase risk of permanent ocular structural and functional changes, possibly due to increased intracranial pressure resulting from a spaceflight-induced cephalad (headward) fluid shift.

Stenger, Michael↗

NASA NTRS2011

Mission Implementation Constraints on Planetary Muon Radiography

Cost: Use heritage hardware, especially use a tested landing system to reduce cost (Phoenix or MSL EDL stage). The sky crane technology delivers higher mass to the surface and enables reaching targets at higher elevation, but at a higher mission cost. Rover vs. Stationary Lander: Rover-mounted instrument enables tomography, but the increased weight of the rover reduces the allowable payload weight. Mass is the critical design constraint for an instrument for a planetary mission. Many factors that are minor factors or do not enter into design considerations for terrestrial operation are important for a planetary application. (Landing site, diurnal temperature variation, instrument portability, shock/vibration)

entry, descent, and landing (EDL)↗

NASA NTRS2016

Defining the Relationship Between Biomarkers of Oxidation and Inflammatory Stress and the Risk for Atherosclerosis in Astronauts During and After Long-Duration Spaceflight

Lee, Stuart M. C.↗

NASA NTRS2016

Metabolomic and Genomic Markers of Atherosclerosis as Related to Oxidative Stress, Inflammation, and Vascular Function in Twin Astronauts

Background: Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. Astronauts participating in long-duration missions may be at an increased risk of oxidative stress and inflammatory damage due to radiation, psychological stress, altered physical activity, nutritional insufficiency, and hyperoxia during extravehicular activity. By studying one identical twin during his 1-year ISS mission and one ground-based twin, this work extends a current NASA-funded investigation to determine whether these spaceflight factors contribute to an accelerated progression of atherosclerosis. This study of twins affords a unique opportunity to examine the spaceflight-related atherosclerosis risk independent of the confounding factors associated with different genotypes. Purpose: The purpose of this investigation is to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and determine if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. These physiological and biochemical data will be extended by using an exploratory approach to investigate the relationship between intermediate phenotypes and risk factors for atherosclerosis and the metabolomic signature from plasma and urine samples. Since metabolites are often the indirect products of gene expression, we will simultaneously assess gene expression and DNA methylation in leukocytes. Hypothesis: We predict that the space-flown twin will experience elevated biomarkers of oxidative stress and inflammatory damage, altered arterial structure and function, accelerated telomere shortening, dysregulation of genes associated with oxidative stress and inflammation, and a metabolic profile shift that is associated with elevated atherosclerosis risk factors. Conversely, these will not be observed in the ground-based twin. Methods: We will measure blood and urine biomarkers of oxidative stress and inflammation as well as arterial structure and function (carotid intima-medial thickness and brachial artery flow-mediated dilation) in one twin astronaut before, during, and after long-duration spaceflight and in his twin serving as a ground-based control. Furthermore, we will measure metabolomics (targeted and untargeted approaches) and genomic markers (DNA methylation, mRNA gene expression, telomere length) to elucidate the molecular mechanisms involved. A panel of biomarkers of oxidative and inflammatory stress will be measured in venous blood samples and 24-hour (in-flight) and 48-hour (pre- and post-flight) urine pools twice before flight, early (flight days 15 and 60) and late (2 weeks before landing) during the mission, and early in the post-flight recovery phase (approximately 3-5 days after landing). Arterial structure, assessed from measures of intima-media thickness, will be measured at the same times. Arterial function will be assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and a sensitive predictor of atherosclerotic risk, only before and after spaceflight. Discussion: Pre- and in-flight data collection is in progress for the space-flown twin, and similar data have been obtained from the ground-based twin. Blood and urine samples will be batch processed when received from ISS after the conclusion of the 1-year mission. Results from these individual subjects will be compared to the larger complement of subjects participating in the companion study currently ongoing in ISS astronauts.

Lee, Stuart M. C.↗

NASA NTRS2017

Metabolomic and Genomic Markers of Atherosclerosis as Related to Oxidative Stress, Inflammation, and Vascular Function in Twin Astronauts

BACKGROUND: Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. Astronauts participating in long-duration missions may be at an increased risk of oxidative stress and inflammatory damage due to radiation, psychological stress, altered physical activity, nutritional insufficiency, and hyperoxia during extravehicular activity. By studying one identical twin during his 1-year ISS mission and his ground-based twin, this work extends a current NASA-funded investigation to determine whether these spaceflight factors contribute to an accelerated progression of atherosclerosis. This study of twins affords a unique opportunity to examine spaceflight-related atherosclerosis risk that is independent of the confounding factors associated with different genotypes. PURPOSE: The purpose of this investigation was to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and determine if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. These physiological and biochemical data will be extended by using an exploratory approach to investigate the relationship between intermediate phenotypes and risk factors for atherosclerosis and the metabolomic signature from plasma and urine samples. Since metabolites are often the indirect products of gene expression, we simultaneously assessed gene expression and DNA methylation in leukocytes. HYPOTHESIS: We predict that, compared to the ground-based twin, the space-flown twin will experience elevated biomarkers of oxidative stress and inflammatory damage, altered arterial structure and function, accelerated telomere shortening, dysregulation of genes associated with oxidative stress and inflammation, and a metabolic profile shift that is associated with elevated atherosclerosis risk factors. METHODS: In the space-flown twin, a panel of biomarkers of oxidative and inflammatory stress were measured in venous blood samples and in 24-h (in-flight) and 48-h (pre- and post-flight) urine pools collected twice before flight, six times during the mission (~FD15, 75, 180, 240, 300, 335), and early in the post-flight recovery phase (3-5 days after landing). We also measured metabolomic (targeted and untargeted approaches) and genomic markers (DNA methylation, mRNA gene expression, telomere length) in these samples. Arterial structure, assessed from measures of intima-media thickness, also were measured using standard clinical ultrasound at the same time points. Arterial function was assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and a sensitive predictor of atherosclerotic risk, only before and after spaceflight. All of the same measures were obtained in the ground-based twin, but less frequently. DISCUSSION: All data collection has been completed for both the space-flown twin and the ground-based twin. Vascular structure and function measures have been analyzed, blood and urine samples have been batch-processed. Results from these individuals will be compared to each other, to data from other Twin Study investigations, and to the larger complement of subjects participating in the companion study currently ongoing in ISS astronauts.

Lee, Stuart M. C.↗