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NASA NTRS1999

Tissue Engineering Organs for Space Biology Research

Long-term manned space flight requires a better understanding of skeletal muscle atrophy resulting from microgravity. Atrophy most likely results from changes at both the systemic level (e.g. decreased circulating growth hormone, increased circulating glucocorticoids) and locally (e.g. decreased myofiber resting tension). Differentiated skeletal myofibers in tissue culture have provided a model system over the last decade for gaining a better understanding of the interactions of exogenous growth factors, endogenous growth factors, and muscle fiber tension in regulating protein turnover rates and muscle cell growth. Tissue engineering these cells into three dimensional bioartificial muscle (BAM) constructs has allowed us to extend their use to Space flight studies for the potential future development of countermeasures.

Vandenburgh, H. H.↗

NASA NTRS2000

Neural-Thyroid Interaction on Skeletal Isomyosin in Zero Gravity

The primary goal of the project was to develop a ground based model to first study the role of the nerve and of thyroid hormone (T3) in the regulation of body growth and skeletal muscle growth and differentiation in rodents. A primary objective was to test the hypothesis that normal weight bearing activity is essential for the development of antigravity, slow twitch skeletal muscle and the corresponding slow myosin heavy chain (MHC) gene; whereas, T3 was obligatory for general body and muscle growth and the establishment of fast MHC phenotype in typically fast locomoter muscles. These ground based experiments would provide both the efficacy and background for a spaceflight experiment (referred to as the Neurolab Mission) jointly sponsored by the NIH and NASA.

Baldwin, Kenneth M.↗

NASA NTRS2002

Skeletal Adaptation to Daily Activity: A Biochemical Perspective

Musculoskeletal forces generated by normal daily activity on Earth maintain the functional and structural properties of muscle and bone throughout most of one's adult life. A reduction in the level of cumulative daily loading caused by space flight, bed rest or spinal cord injury induces rapid muscle atrophy, functional changes in muscle, and bone resorption in regions subjected to the reduced loading. Bone cells in culture and bone tissue reportedly respond to a wide variety of non-mechanical and mechanical stimuli ranging, from electromagnetic fields, and hormones to small amplitude, high frequency vibrations, fluid flow, strain rate, and stress/strain magnitude. However, neither the transduction mechanism that transforms the mechanical input into a muscle or bone metabolic response nor the characteristics, of the loading history that directly or indirectly stimulates the cell is known. Identifying the factors contributing to the input stimulus will have a major impact on the design of effective countermeasures for long duration space flight. This talk will present a brief overview of current theories of bone remodeling and functional adaptation to mechanical loading. Work from our lab will be presented from the perspective of daily cumulative loading on Earth and its relationship to bone density and structure. Our objective is to use the tibia and calcaneus as model bone sites of cortical and cancellous bone adaptation, loaded daily by musculoskeletal forces in equilibrium with the ground reaction force. All materials that will be discussed are in the open scientific literature.

Whalen, Robert T.↗

NASA NTRS2002

Constitutive properties of hypertrophied myocardium: cellular contribution to changes in myocardial stiffness

Recent studies have suggested that pressure overload hypertrophy (POH) alters the viscoelastic properties of individual cardiocytes when studied in isolation. However, whether these changes in cardiocyte properties contribute causally to changes in the material properties of the cardiac muscle as a whole is unknown. Accordingly, a selective, isolated, acute change in cardiocyte constitutive properties was imposed in an in vitro system capable of measuring the resultant effect on the material properties of the composite cardiac muscle. POH caused an increase in both myocardial elastic stiffness, from 20.5 +/- 1.3 to 28.4 +/- 1.8, and viscous damping, from 15.2 +/- 1.1 to 19.8 +/- 1.5 s (normal vs. POH, P < 0.05), respectively. Recent studies have shown that cardiocyte constitutive properties could be acutely altered by depolymerizing the microtubules with colchicine. Colchicine caused a significant decrease in the viscous damping in POH muscles (19.8 +/- 1.5 s at baseline vs. 14.7 +/- 1.3 s after colchicine, P < 0.05). Therefore, myocardial material properties can be altered by selectively changing the constitutive properties of one element within this muscle tissue, the cardiocyte. Changes in the constitutive properties of the cardiocytes themselves contribute to the abnormalities in myocardial stiffness and viscosity that develop during POH.

Non-NASA Center↗

NASA NTRS1997

An overview of the issues: physiological effects of bed rest and restricted physical activity

Reduction of exercise capacity with confinement to bed rest is well recognized. Underlying physiological mechanisms include dramatic reductions in maximal stroke volume, cardiac output, and oxygen uptake. However, bed rest by itself does not appear to contribute to cardiac dysfunction. Increased muscle fatigue is associated with reduced muscle blood flow, red cell volume, capillarization and oxidative enzymes. Loss of muscle mass and bone density may be reflected by reduced muscle strength and higher risk for injury to bones and joints. The resultant deconditioning caused by bed rest can be independent of the primary disease and physically debilitating in patients who attempt to reambulate to normal active living and working. A challenge to clinicians and health care specialists has been the identification of appropriate and effective methods to restore physical capacity of patients during or after restricted physical activity associated with prolonged bed rest. The examination of physiological responses to bed rest deconditioning and exercise training in healthy subjects has provided significant information to develop effective rehabilitation treatments. The successful application of acute exercise to enhance orthostatic stability, daily endurance exercise to maintain aerobic capacity, or specific resistance exercises to maintain musculoskeletal integrity rather than the use of surgical, pharmacological, and other medical treatments for clinical conditions has been enhanced by investigation and understanding of underlying mechanisms that distinguish physical deconditioning from the disease. This symposium presents an overview of cardiovascular and musculoskeletal deconditioning associated with reduced physical work capacity following prolonged bed rest and exercise training regimens that have proven successful in ameliorating or reversing these adverse effects.

NASA Program Space Physiology and Countermeasures↗

NASA NTRS1994

Spaceflight and protein metabolism, with special reference to humans

Human space missions have shown that human spaceflight is associated with a loss of body protein. Specific changes include a loss of lean body mass, decreased muscle mass in the calves, decreased muscle strength, and changes in plasma proteins and amino acids. The major muscle loss is believed to be associated with the antigravity (postural) muscle. The most significant loss of protein appears to occur during the first month of flight. The etiology is believed to be multifactorial with contributions from disuse atrophy, undernutrition, and a stress type of response. This article reviews the results of American and Russian space missions to investigate this problem in humans, monkeys, and rats. The relationship of the flight results with ground-based models including bedrest for humans and hindlimb unweighting for rats is also discussed. The results suggest that humans adapt to spaceflight much better than either monkeys or rats.

Review↗

NASA NTRS1992

Abnormalities in intracellular calcium regulation and contractile function in myocardium from dogs with pacing-induced heart failure

24 d of rapid ventricular pacing induced dilated cardiomyopathy with both systolic and diastolic dysfunction in conscious, chronically instrumented dogs. We studied mechanical properties and intracellular calcium (Ca2+i) transients of trabeculae carneae isolated from 15 control dogs (n = 32) and 11 dogs with pacing-induced cardiac failure (n = 26). Muscles were stretched to maximum length at 30 degrees C and stimulated at 0.33 Hz; a subset (n = 17 control, n = 17 myopathic) was loaded with the [Ca2+]i indicator aequorin. Peak tension was depressed in the myopathic muscles, even in the presence of maximally effective (i.e., 16 mM) [Ca2+] in the perfusate. However, peak [Ca2+]i was similar (0.80 +/- 0.13 vs. 0.71 +/- 0.05 microM; [Ca2+]o = 2.5 mM), suggesting that a decrease in Cai2+ availability was not responsible for the decreased contractility. The time for decline from the peak of the Cai2+ transient was prolonged in the myopathic group, which correlated with prolongation of isometric contraction and relaxation. However, similar end-diastolic [Ca2+]i was achieved in both groups (0.29 +/- 0.05 vs. 0.31 +/- 0.02 microM), indicating that Cai2+ homeostasis can be maintained in myopathic hearts. The inotropic response of the myopathic muscles to milrinone was depressed compared with the controls. However, when cAMP production was stimulated by pretreatment with forskolin, the response of the myopathic muscles to milrinone was improved. Our findings provide direct evidence that abnormal [Ca2+]i handling is an important cause of contractile dysfunction in dogs with pacing-induced heart failure and suggest that deficient production of cAMP may be an important cause of these changes in excitation-contraction coupling.

Non-NASA Center↗

NASA NTRS2004

Elevated Skin Blood Flow Influences Near Infrared Spectroscopy Measurements During Supine Rest

Near infrared spectroscopy is a non-invasive technique that allows determination of tissue oxygenation/blood flow based on spectrophotometric quantitation of oxy- and deoxyhemoglobin present within a tissue. This technique has gained acceptance as a means of detecting and quantifying changes in tissue blood flow due to physiological perturbation, such as that which is elicited in skeletal muscle during exercise. Since the NIRS technique requires light to penetrate the skin and subcutaneous fat in order to reach the muscle of interest, changes in skin blood flow may alter the NIRS signal in a fashion unrelated to blood flow in the muscle of interest. The aim of this study was to determine the contribution of skin blood flow to the NIRS signal obtained from resting vastus lateralis muscle of the thigh.

Lee, Stuart M. C.↗

NASA NTRS2005

Incidence of associated events during the performance of invasive procedures in healthy human volunteers

Metabolic investigations often utilize arteriovenous sampling and muscle biopsy. These investigations represent some risk to the subject. We examined 369 studies performed in the General Clinical Research Center between January 1994 and May 2003 for events related to femoral catheterization and muscle biopsies. Incidents were further examined by age (younger: 18-59 yr, n=133; and older: 60-76 yr, n=28). There were no clinically defined major complications associated with either procedure. The incidence of femoral catheter repositioning or reinsertion was higher in the older group (25.5 vs. 9.7%). There was no difference in the incidence of premature removal of catheters, ecchymosis or hematoma, or the persistence of pain after discharge. The occurrence of all incidents did not increase with multiple catheterizations. Muscle biopsy was associated with infrequent ecchymosis or hematoma in both groups (1.1 and 3.6% in younger and older groups, respectively). Both procedures entail a small likelihood of a vagallike response (3.3% overall), resulting in nausea, dizziness, and rarely a loss of consciousness. These results indicate that, in skilled hands and a defined clinical setting, the incidents associated with femoral catheterization and muscle biopsy in healthy volunteers are reasonable and largely controllable.

NASA Discipline Musculoskeletal↗

NASA NTRS2004

Hematopoietic Stem Cell Therapy as a Counter-Measure for Human Exploration of Deep Space

Human exploration of deep space depends, in part, on our ability to counter severe/invasive disorders that astronauts experience in space environments. The known symptoms include hematological/cardiac abnormalities,bone and muscle losses, immunodeficiency, neurological disorders, and cancer. Exploiting the extraordinary plasticity of hematopoietic stem cells (HSCs), which differentiate not only to all types of blood cells, but also to various tissues, we have advanced a hypothesis that ome of the space-caused disorders maybe amenable to hematopoietis stem cell therapy(HSCT) so as to maintain promote human exploration of deep space. Using mouse models of human anemia beta-thaiassemia) as well as spaceflight (hindlimb unloading system), we have obtained feasibility results of HSCT for space anemia, muscle loss, and immunodeficiency. For example, in the case of HSCT for muscle loss, the beta-galactosidese marked HSCs were detected in the hindlimbs of unloaded mouse following transplantation by -X-gal wholemaunt staining procedure. Histochemicaland physical analyses indicated structural contribution of HSCs to the muscle. HSCT for immunodeficiency was investigated ising beta-galactosidese gene-tagged Escherichia coli as the infectious agent. Results of the X-gal staining procedure indicated the rapeutic role of the HSCT. To facilitate the HSCT in space, growth of HSCs were optimized in the NASA Rotating Wall Vessel (RWV) culture systems, including Hydrodynamic Focusing Bioreactor (HFB).

Ohi, S.↗

NASA NTRS1977

Help for Crippled Children

Children with cerebral palsy have nervous system defects which lead to muscular spasticity and loss of coordination. Many of these children have great difficulty walking because certain muscles are in a constant state of contraction. Surgical techniques can lengthen muscles or tendons to improve the child's walking pattern, but it is vital to diagnose accurately the particular spasticity problem of each patient; the individual muscles causing the handicap vary greatly from child to child. It is difficult by physical examination alone to determine precisely which muscle groups are most involved. Biotelemetry has provided a solution. For the past two years, the Children's Hospital at Standord, assisted by NASA and the Stanford Biomedical Application Team, has been applying biotelemetry to the cerebral palsy problem.

Source record↗

NASA NTRS2010

Relationships Among Lower Body Strength, Power, and Performance of Functional Tasks

There is a large degree of variability among crewmembers with respect to decrements in muscle strength and power following long duration spaceflight, ranging from 0 to approx.30% reductions. The purpose of this study was to investigate the influence of varying decrements in lower body muscle strength and power (relative to body weight) on the performance of 2 occupationally relevant tasks (ladder climb and supine egress & walk). Seventeen participants with leg strength similar to US crewmembers performed a leg press power test, an isokinetic knee extension strength test and they were asked to complete the 2 functional tasks as quickly as possible. On additional test days the participants were asked to repeat the functional tasks under 3 conditions where a different external load was applied each time using a weighted suit in order to experimentally manipulate participants strength/body weight and power/body weight ratios. The weight in the suit ranged from 20-120% of body weight and was distributed in proportion to limb segment weights to minimize changes in center of gravity. The ladder task consisted of climbing 40 rungs on a ladder treadmill as fast as possible. The supine egress & walk task consisted of rising from a supine position and walking through an obstacle course. Results show a relatively linear relationship between strength/body weight and task time and power/body weight with task time such that the fastest performance times are associated with higher strength and power with about half the variance in task time is accounted for by a single variable (either strength or power). For the average person, a 20% reduction in power/body weight (from 18 to 14.4 W/kg) induces an increase (slowing) of about 10 seconds in the ladder climb task from 14 to 24 seconds (approx.70%) and a slowing of the supine egress & walk task from 14 to 21 seconds (approx.50%). Similar relationships were observed with strength/body weight and task performance. For the average person, a 20% reduction in strength/body weight (from 2.1 to 1.7 Nm/kg) resulted in a slowing of the ladder climb from 10.5 to 24 seconds (approx.128%) and a slowing of the supine egress & walk from 11 to 20 seconds (approx.82%). These data suggest that the single variable of either low body muscle strength or power, relative to body weight is predictive of about 50% of the variance in task performance time, and that considerable slowing in task performance is associated with relatively typical decrements in muscle performance seen with long duration spaceflight. The observation of a relatively linear relationship between strength/power and task time suggests that across the full spectrum of initial crew strengths and typical decrements in strength previously observed, that task performance would be expected to be slowed following long duration spaceflight. These data will be confirmed in actual spaceflight with subsequent studies.

Ploutz-Snyder, Lori↗

NASA NTRS2011

Musculoskeletal Modeling Component of the NASA Digital Astronaut Project

The NASA Digital Astronaut Project s (DAP) objective is to provide computational tools that support research of the physiological response to low gravity environments and analyses of how changes cause health and safety risks to the astronauts and to the success of the mission. The spaceflight risk associated with muscle atrophy is impaired performance due to reduced muscle mass, strength and endurance. Risks of early onset of osteoporosis and bone fracture are among the spaceflight risks associated with loss of bone mineral density. METHODS: Tools under development include a neuromuscular model, a biomechanical model and a bone remodeling model. The neuromuscular model will include models of neuromuscular drive, muscle atrophy, fiber morphology and metabolic processes as a function of time in space. Human movement will be modeled with the biomechanical model, using muscle and bone model parameters at various states. The bone remodeling model will allow analysis of bone turnover, loss and adaptation. A comprehensive trade study was completed to identify the current state of the art in musculoskeletal modeling. The DAP musculoskeletal models will be developed using a combination of existing commercial software and academic research codes identified in the study, which will be modified for use in human spaceflight research. These individual models are highly dependent upon each other and will be integrated together once they reach sufficient levels of maturity. ANALYSES: The analyses performed with these models will include comparison of different countermeasure exercises for optimizing effectiveness and comparison of task requirements and the state of strength and endurance of a crew member at a particular time in a mission. DISCUSSION: The DAP musculoskeletal model has the potential to complement research conducted on spaceflight induced changes to the musculoskeletal system. It can help with hypothesis formation, identification of causative mechanisms and supplementing small data samples.

Lewandowski, B. E.↗

NASA NTRS2012

Nature's Autonomous Oscillators

Nonlinearity is required to produce autonomous oscillations without external time dependent source, and an example is the pendulum clock. The escapement mechanism of the clock imparts an impulse for each swing direction, which keeps the pendulum oscillating at the resonance frequency. Among nature's observed autonomous oscillators, examples are the quasi-biennial oscillation and bimonthly oscillation of the Earth atmosphere, and the 22-year solar oscillation. The oscillations have been simulated in numerical models without external time dependent source, and in Section 2 we summarize the results. Specifically, we shall discuss the nonlinearities that are involved in generating the oscillations, and the processes that produce the periodicities. In biology, insects have flight muscles, which function autonomously with wing frequencies that far exceed the animals' neural capacity; Stretch-activation of muscle contraction is the mechanism that produces the high frequency oscillation of insect flight, discussed in Section 3. The same mechanism is also invoked to explain the functioning of the cardiac muscle. In Section 4, we present a tutorial review of the cardio-vascular system, heart anatomy, and muscle cell physiology, leading up to Starling's Law of the Heart, which supports our notion that the human heart is also a nonlinear oscillator. In Section 5, we offer a broad perspective of the tenuous links between the fluid dynamical oscillators and the human heart physiology.

Mayr, H. G.↗

NASA NTRS2015

Digital Astronaut Project Biomechanical Models: Biomechanical Modeling of Squat, Single-Leg Squat and Heel Raise Exercises on the Hybrid Ultimate Lifting Kit (HULK)

The NASA Digital Astronaut Project (DAP) implements well-vetted computational models to predict and assess spaceflight health and performance risks, and to enhance countermeasure development. The DAP Musculoskeletal Modeling effort is developing computational models to inform exercise countermeasure development and to predict physical performance capabilities after a length of time in space. For example, integrated exercise device-biomechanical models can determine localized loading, which will be used as input to muscle and bone adaptation models to estimate the effectiveness of the exercise countermeasure. In addition, simulations of mission tasks can be used to estimate the astronaut's ability to perform the task after exposure to microgravity and after using various exercise countermeasures. The software package OpenSim (Stanford University, Palo Alto, CA) (Ref. 1) is being used to create the DAP biomechanical models and its built-in muscle model is the starting point for the DAP muscle model. During Exploration missions, such as those to asteroids and Mars, astronauts will be exposed to reduced gravity for extended periods. Therefore, the crew must have access to exercise countermeasures that can maintain their musculoskeletal and aerobic health. Exploration vehicles may have very limited volume and power available to accommodate such capabilities, even more so than the International Space Station (ISS). The exercise devices flown on Exploration missions must be designed to provide sufficient load during the performance of various resistance and aerobic/anaerobic exercises while meeting potential additional requirements of limited mass, volume and power. Given that it is not practical to manufacture and test (ground, analog and/or flight) all candidate devices, nor is it always possible to obtain data such as localized muscle and bone loading empirically, computational modeling can estimate the localized loading during various exercise modalities performed on a given device to help formulate exercise prescriptions and other operational considerations. With this in mind, NASA's Digital Astronaut Project (DAP) is supporting the Advanced Exercise Concepts (AEC) Project, Exercise Physiology and Countermeasures (ExPC) laboratory and NSBRI-funded researchers by developing and implementing well-validated computational models of exercises with advanced exercise device concepts. This report focuses specifically on lower-body resistance exercises performed with the Hybrid Ultimate Lifting Kit (HULK) device as a deliverable to the AEC Project.

health↗

NASA NTRS2017

Biomechanical Modeling Analysis of Loads Configuration for Squat Exercise

INTRODUCTION: Long duration space travel will expose astronauts to extended periods of reduced gravity. Since gravity is not present to assist loading, astronauts will use resistive and aerobic exercise regimes for the duration of the space flight to minimize loss of bone density, muscle mass and aerobic capacity that occurs during exposure to a reduced gravity environment. Unlike the International Space Station (ISS), the area available for an exercise device in the next generation of spacecraft for travel to the Moon or to Mars is limited and therefore compact resistance exercise device prototypes are being developed. The Advanced Resistive Exercise Device (ARED) currently on the ISS is being used as a benchmark for the functional performance of these new devices. Biomechanical data collection and computational modeling aid the device design process by quantifying the joint torques and the musculoskeletal forces that occur during exercises performed on the prototype devices. METHODS The computational models currently under development utilize the OpenSim [1] software platform, consisting of open source code for musculoskeletal modeling, using biomechanical input data from test subjects for estimation of muscle and joint loads. The OpenSim Full Body Model [2] is used for all analyses. The model incorporates simplified wrap surfaces, a new knee model and updated lower body muscle parameters derived from cadaver measurements and magnetic resonance imaging of young adults. The upper body uses torque actuators at the lumbar and extremity joints. The test subjects who volunteer for this study are instrumented with reflective markers for motion capture data collection while performing squat exercising on the Hybrid Ultimate Lifting Kit (HULK) prototype device (ZIN Technologies, Middleburg Heights, OH). Ground reaction force data is collected with force plates under the feet, and device loading is recorded through load cells internal to the HULK. Test variables include the applied device load and the dual cable long bar or single cable T-bar interface between the test subject and the device. Data is also obtained using free weights with the identical loading for a comparison to the resistively loaded exercise device trials. The data drives the OpenSim biomechanical model, which has been scaled to match the anthropometrics of the test subject, to calculate the body loads. RESULTS Lower body kinematics, joint moments, joint forces and muscle forces are obtained from the OpenSim biomechanical analysis of the squat exercises under different loading conditions. Preliminary results from the model for the loading conditions will be presented as will hypotheses developed for follow on work.

Human Factors Engineering↗

NASA NTRS2020

Circulating miRNA Signature Predicts Health Risks Associated with Cancer and Spaceflight

Biological risks associated with space radiation and microgravity are major concerns for long-term space travel. Through a Systems Biology approach, our previous NASA work has shown both TGF signaling pathways and miRNAs have a critical impact on defining health risks with and without space irradiation. We hypothesize that circulating microRNA (miRNA) signatures are driving microvascular disease and muscle degeneration associated with accelerating aging and will be enhanced by exposure to the space environment (radiation and microgravity). We are investigating this hypothesis with both in vivo and in vitro models to test novel antagonist therapies to these miRNA signatures as countermeasures to reduce space radiation-induced health risks. A comprehensive Systems Biology approach is utilized to examine the influence by high atomic number by high (H) atomic number (Z) and energy (E) (HZE) irradiation. To simulate low-dose exposure due to galactic cosmic rays (GCR), we used ions, energy, and doses determined by a NASA consensus formula of 7 different ions to represent GCR (referred to as GCR sim model). To similate high-dose radiation exposure due to solar particle events (SPE), we used a solar particle event (SPE) sim model which gave a total dose of 1Gy protons with energy ranges from 50MeV to 150MeV. C57BL/6 wild-type female mice were utilized for the irradiations with our established simulated microgravity model (hindlimb suspension model) and an in vitro 3D microvasculature tissue model under simulated microgravity (clinostat) conditions was also irradiated. To expand on the circulating miRNA signature determined from our preliminary data, we determined a group of conserved miRNAs which are commonly being regulated in the majority of the organs and tissues throughout the host using our established techniques. MiRNA-sequencing was done on serum (at time of sacrifice), liver, heart, and muscle (soleus muscle) tissue for all radiation groups. Additional validation of the key miRNAs was performed by droplet digital PCR (ddPCR). This revealed a key circulating miRNA signature (consisting of multiple miRNAs) impacting cardiovascular and muscular disease risk. Further in vitro experiments with CRISPR/Cas9 system to knockout the key miRNA signatures, novel self-delivering antagomirs, overexpression of the miRNAs test the functional impact of the miRNA signatures on both microvascular disease and muscle degeneration due to space irradiation. The current work has started to allow the possible development of a novel minimally invasive miRNA based radioprotector to be used as a countermeasure for space radiation. Collectively, understanding of how whole body space radiation impacts microvascular and tissue degeneration through circulating miRNAs will greatly enhance health risk prognostication and provide possible new mechanisms for protection against space radiation. This work is supported by the Translational Research Institute through NASA Cooperative Agreement NNX16AO69A (T-0404) awarded to AB.

Beheshti, Afshin↗

NASA NTRS2024

iGCE and MitoFlyght Spaceflight Missions: Unraveling Oxidative Stress Responses in Space

Thriving In DEep Space (TIDES) initiative aims to comprehensively understand how hostile environments such as the Moon and Mars affect human physiology. Here we present two NASA-selected spaceflight experiments under the TIDES portfolio, iGCE (Integrated Gravity Continuum Experiment) and MitoFlyght (Mitochondrial Investigation of Oxidative Stress in Flies). We hypothesize that exposure to spaceflight conditions induces oxidative stress responses that negatively impact physiology. The iGCE mission employs two well-established spaceflight models, Drosophila melanogaster and C.elegans, using Redwire’s Multi-use Variable-g Platform (MVP) hardware to assess changes in cardiac, muscle, and nervous systems across five different gravities: Hypergravity (2g), Earth (1g), Mars (0.37g), Moon (0.16g), and microgravity (ug). This mission focuses on uncovering alterations in protein homeostasis, autophagy, and mitochondrial function conserved across species. In the MitoFlyght mission to the ISS, Drosophila will be housed in the Vented Fly Box (VFB). This mission evaluates the oxidative stress response and autophagic pathway in muscle, heart, and nervous system. Additionally, we will (a) use the genetic mutant, Tor7/P to test whether increased autophagy is beneficial or a maladaptive response to the spaceflight stressors, and (b) utilize fly lines with tissue-specific expression (neuronal, muscle, and cardiac) of an antioxidant gene, SOD2 (superoxide dismutase) as a potential countermeasure. Data from these missions will be compared with previous LEO-based datasets to identify shared signatures. Furthermore, cross-species analysis of the transcriptomic data from other invertebrate and vertebrate spaceflight studies will help determine evolutionarily conserved pathways perturbed by space stressors. Overall, both these missions aim to provide crucial insights into the mechanisms underlying oxidative stress responses, synaptic changes, and heart and muscle deficits, facilitating the identification of diagnostic and therapeutic targets to mitigate the adverse health effects of long-duration space habitation. Ultimately, this research will enhance our ability to thrive in deep space and inform future missions.

Janani Iyer↗