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At least 127 records · Page 7

NASA project 1: Full-body dynamometer

In space, where the body does only a fraction of work it does on earth, muscle atrophy is a major concern. The bones and the muscles will begin to deteriorate after a short stay in weightlessness. Bone decalcification appears to be a major problem with extensive living in microgravity. Resistance exercise is not only essential to prevent muscle atrophy in space, it also helps to keep bone decalcification in check. For a space station, where the astronauts are expected to live for months at a time, exercise is especially important. Experts recommend about an hour and a half to two hours of exercise per day to keep the muscles in good condition in microgravity. The exercises will not only keep the astronauts in excellent physical condition, it will also make it easier for them to readjust to earth's gravity on return. The stationary bicycle and the treadmill have been the astronauts' primary sources of exercise since the 1970's. The major problem with both the stationary bicycle and the treadmill is that while they may keep the leg muscles from deteriorating in microgravity, they do little for muscles in the upper body. The National Aeronautics and Space Administration (NASA) is currently developing a full-body dynamometer (FBD), which will provide the astronauts with a full-body workout. It will also test the astronauts for muscle atrophy and rehabilitate the weakened muscle. The specification and the function structure for the FBD is presented.

Lu, Li-Dai↗

Six Month Report on Tissue Cultured Avian Skeletal Myofibers in the STL/A Module Aboard STS-77

Space travel is know to effect skeletal muscle, causing rapid and pronounced atrophy in humans and animals, even when strenuous exercise is used as a countermeasure. The cellular and molecular bases of this atrophy are unknown. Space travel may cause muscle atrophy by a direct effect on the muscle fibers and/or indirectly by reducing circulating levels of growth factors such as growth hormone. The recent development of a tissue culture incubator system for Shuttle Middeck basic science experiments [Space Tissue Loss (STL) Module] by the Walter Reed Army Institute of Research (WRAIR) allows the study of the effects of space travel directly on isolated skeletal myofibers. Avian bioartificial skeletal muscle 'organoids' containing differentiated skeletal myofibers and connective tissue fibroblasts were flown aboard the Space Shuttle (Space Transportation System, STS) on Flight STS-77, a repeat of a similar experiment flown on STS-66. The results from these two flight experiments show for the first time that space travel has a direct effect on skeletal muscle cells separate from any systemic effects resulting from altered circulating growth factors.

Vandenburgh, Herman H.↗

Time Course of the Response of Myofibrillar and Sarcoplasmic Protein Metabolism to Unweighting of the Soleus Muscle

Contributions of altered in vivo protein synthesis and degradation to unweighting atrophy of the soleus muscle in tail-suspended young female rats were analyzed daily for up to 6 days. Specific changes in myofibrillar and sarcoplasmic proteins were also evaluated to assess their contributions to the loss of total protein. Synthesis of myofibrillar and sarcoplasmic proteins was estimated by intramuscular (IM) injection and total protein by intraperitoneal (IP) injection of flooding doses of H-3-phenylaianine. Total protein loss was greatest during the first 3 days following suspension and was a consequence of the loss of myofibrillar rather than sarcoplasmic proteins. However, synthesis of total myofibrillar and sarcoplasmic proteins diminished in parallel beginning in the first 24 hours. Therefore sarcoplasmic proteins must be spared due to a decrease in their degradation. In contrast, myofibrillar protein degradation increased, thus explaining the elevated degradation of the total pool. Following 72 hours of suspension, protein synthesis remained low, but the rate of myofibrillar protein loss diminished, suggesting a slowing of degradation. These various results show acute loss of protein during unweighting atrophy is a consequence of decreased synthesis and increased degradation of myofibrillar proteins, and sarcoplasmic proteins are spared due to slower degradation, likely explaining the sparing of plasma membrane receptors. Based on other published data, we propose that the slowing of atrophy after the initial response may be attributed to an increased effect of insulin.

Munoz, Kathryn A.↗

Cyclic Adenosine Monophosphate Accumulation and beta-Adrenergic Binding in Unweighted and Denervated Rat Soleus Muscle

Unweighting, but not denervation, of muscle reportedly "spares" insulin receptors, increasing insulin sensitivity. Unweighting also increases beta-adrenergic responses of carbohydrate metabolism. These differential characteristics were studied further by comparing cyclic adenosine monophosphate (cAMP) accumulation and beta-adrenergic binding in normal and 3-day unweighted or denervated soleus muscle. Submaximal amounts of isoproterenol, a p-agonist, increased cAMP accumulation in vitro and in vivo (by intramuscular (IM) injection) to a greater degree (P less than .05) in unweighted muscles. Forskolin or maximal isoproterenol had similar in vitro effects in all muscles, suggesting increased beta-adrenergic sensitivity following unweighting. Increased sensitivity was confirmed by a greater receptor density (B(sub max)) for iodo-125(-)-pindolol in particulate preparations of unweighted (420 x 10(exp -18) mol/mg muscle) than of control or denervated muscles (285 x 10(exp-18) mol/mg muscle). The three dissociation constant (Kd) values were similar (20.3 to 25.8 pmol/L). Total binding capacity (11.4 fmol/muscle) did not change during 3 days of unweighting, but diminished by 30% with denervation. This result illustrates the "sparing" and loss of receptors, respectively, in these two atrophy models. In diabetic animals, IM injection of insulin diminished CAMP accumulation in the presence of theophylline in unweighted muscle (-66% +/- 2%) more than in controls (-42% +'- 6%, P less than .001). These results show that insulin affects CAMP formation in muscle, and support a greater in vivo insulin response following unweighting atrophy. These various data support a role for lysosomal proteolysis in denervation, but not in unweighting, atrophy.

Kirby, Christopher R.↗

Growth Factors and Tension-Induced Skeletal Muscle Growth

The project investigated biochemical mechanisms to enhance skeletal muscle growth, and developed a computer based mechanical cell stimulator system. The biochemicals investigated in this study were insulin/(Insulin like Growth Factor) IGF-1 and Steroids. In order to analyze which growth factors are essential for stretch-induced muscle growth in vitro, we developed a defined, serum-free medium in which the differentiated, cultured avian muscle fibers could be maintained for extended periods of time. The defined medium (muscle maintenance medium, MM medium) maintains the nitrogen balance of the myofibers for 3 to 7 days, based on myofiber diameter measurements and myosin heavy chain content. Insulin and IGF-1, but not IGF-2, induced pronounced myofiber hypertrophy when added to this medium. In 5 to 7 days, muscle fiber diameters increase by 71 % to 98% compared to untreated controls. Mechanical stimulation of the avian muscle fibers in MM medium increased the sensitivity of the cells to insulin and IGF-1, based on a leftward shift of the insulin dose/response curve for protein synthesis rates. (54). We developed a ligand binding assay for IGF-1 binding proteins and found that the avian skeletal muscle cultures produced three major species of 31, 36 and 43 kD molecular weight (54) Stretch of the myofibers was found to have no significant effect on the efflux of IGF-1 binding proteins, but addition of exogenous collagen stimulated IGF-1 binding protein production 1.5 to 5 fold. Steroid hormones have a profound effect on muscle protein turnover rates in vivo, with the stress-related glucocorticoids inducing rapid skeletal muscle atrophy while androgenic steroids induce skeletal muscle growth. Exercise in humans and animals reduces the catabolic effects of glucocorticoids and may enhance the anabolic effects of androgenic steroids on skeletal muscle. In our continuing work on the involvement of exogenrus growth factors in stretch-induced avian skeletal muscle growth, we have performed experiments to determine whether mechanical stimulation of cultured avian muscle cells alters their response to anabolic steroids or glucocorticoids. In static cultures, testosterone had no effect on muscle cell growth, but 5alpha-dihydrotestosterone and the synthetic steroid stanozolol increased cell growth by up to 18% and 30%, respectively, after a three day exposure. We completed development of a new IBM-based mechanical cell stimulator system to provide greater flexibility in operating and monitoring our experiments. Our previous long term studies on myofiber growth were designed around a perfusion system of our own design. We have recently changed to performing these studies using a modified CELLCO cartridge bioreactor system Z since it has been certified as the ground-based model for the Shuttle's Space Tissue Loss (STL) F= Cell Culture Module. The current goals of this aspect of the project are three fold: 1) to design a Z cell culture system for studying avian skeletal myofiber atrophy on the Shuttle and Space Station; 0 2) to expand the use of bioreactors to cells which do not grow in either suspension or attached to the hollow fibers; and 3) to combine the bioreactor system with our computerized mechanical cell stimulator to have a better in vitro model to study tension/gravity/stretch regulation of skeletal muscle size. Preliminary studies also reported on involved : (1) how release of tension can induce rapid atrophy of tissues cultured avian skeletal muscle cells, and (2) a mechanism to transfer and maintain avian skeletal muscle organoids in modified cartridges in the Space Tissue Loss Module.

Vandenburgh, Herman H.↗

Tissue Engineered Skeletal Myofibers can Directly "Sense" Gravitational Force Changes

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. Embryonic avian muscle cells were isolated and BAMs tissue engineered as described previously. The myoblasts proliferate and fuse into aligned postmitotic myofibers after ten to fourteen days in vitro. A cylindrical muscle-like structure containing several thousand myofibers is formed which is approximately 30 mm in length, 2-3 mm in diameter, and attached at each end. For the Space Shuttle experiments, the BAMs were transferred to 55 mL bioreactor cartridges (6 BAMs/cartridge). At Kennedy Space Center, the cartridges were mounted in two Space Tissue Loss (STL) Modules (three to four cartridges per Module) and either maintained as ground controls or loaded in a Mid-Deck locker of the Space Shuttle. The BAM cartridges were continuously perfused during the experiment at 1.5 mL/ min with tissue culture medium. Eighteen BAMs were flown for nine days on Mission STS66 while eighteen BAMs served as ground controls. The complete experiment was repeated on Mission STS77 with twenty four BAMs in each group. BAMs could be maintained in a healthy state for at least 30 days in the perfusion bioreactor cartridges. The BAM muscle fibers directly detected both the loss of gravity and the reloading effects of 1 x g. While total cellular metabolism and total protein degradation rates were not altered during 9 to 10 days in Space, protein synthesis rates were significantly reduced and resulted in significant myofiber atrophy compared to ground controls. One g reloading of the flight muscle cells post-flight significantly increased protein synthesis rates and the synthesis rates of myosin heavy chain, fibronectin, and collagen. Tissue cultured muscle cells can directly "sense" changes in gravity and provide a valid model to begin the study of countermeasures. Based on our ground based experiments, and the experiments of others, growth hormone and/or insulin-like growth factors are attractive protein therapeutics which may assisting attenuating skeletal muscle wasting in space. Our laboratory is developing a new cell-based delivery system for this and other potential therapeutic factors for attenuating muscle and bone wasting.

Vandenburgh, Herman H.↗

Bion 11 Spaceflight Project: Effect of Weightlessness on Single Muscle Fiber Function in Rhesus Monkeys

Although it is well known that microgravity induces considerable limb muscle atrophy, little is known about how weightlessness alters cell function. In this study, we investigated how weightlessness altered the functional properties of single fast and slow striated muscle fibers. Physiological studies were carried out to test the hypothesis that microgravity causes fiber atrophy, a decreased peak force (Newtons), tension (Newtons/cross-sectional area) and power, an elevated peak rate of tension development (dp/dt), and an increased maximal shortening velocity (V(sub o)) in the slow type I fiber, while changes in the fast-twitch fiber are restricted to atrophy and a reduced peak force. For each fiber, we determined the peak force (P(sub o)), V(sub o), dp/dt, the force-velocity relationship, peak power, the power-force relationship, the force-pCa relationship, and fiber stiffness. Biochemical studies were carried out to assess the effects of weightlessness on the enzyme and substrate profile of the fast- and slow-twitch fibers. We predicted that microgravity would increase resting muscle glycogen and glycolytic metabolism in the slow fiber type, while the fast-twitch fiber enzyme profile would be unaltered. The increased muscle glycogen would in part result from an elevated hexokinase and glycogen synthase. The enzymes selected for study represent markers for mitochondrial function (citrate synthase and 0-hydroxyacyl-CoA dehydrogenase), glycolysis (Phosphofructokinase and lactate dehydrogenase), and fatty acid transport (Carnitine acetyl transferase). The substrates analyzed will include glycogen, lactate, adenosine triphosphate, and phosphocreatine.

Fitts, Robert H.↗

Attenuation of skeletal muscle wasting with recombinant human growth hormone secreted from a tissue-engineered bioartificial muscle

Skeletal muscle wasting is a significant problem in elderly and debilitated patients. Growth hormone (GH) is an anabolic growth factor for skeletal muscle but is difficult to deliver in a therapeutic manner by injection owing to its in vivo instability. A novel method is presented for the sustained secretion of recombinant human GH (rhGH) from genetically modified skeletal muscle implants, which reduces host muscle wasting. Proliferating murine C2C12 skeletal myoblasts stably transduced with the rhGH gene were tissue engineered in vitro into bioartificial muscles (C2-BAMs) containing organized postmitotic myofibers secreting 3-5 microg of rhGH/day in vitro. When implanted subcutaneously into syngeneic mice, C2-BAMs delivered a sustained physiologic dose of 2.5 to 11.3 ng of rhGH per milliliter of serum. rhGH synthesized and secreted by the myofibers was in the 22-kDa monomeric form and was biologically active, based on downregulation of a GH-sensitive protein synthesized in the liver. Skeletal muscle disuse atrophy was induced in mice by hindlimb unloading, causing the fast plantaris and slow soleus muscles to atrophy by 21 to 35% ( < 0.02). This atrophy was significantly attenuated 41 to 55% (p < 0.02) in animals that received C2-BAM implants, but not in animals receiving daily injections of purified rhGH (1 mg/kg/day). These data support the concept that delivery of rhGH from BAMs may be efficacious in treating muscle-wasting disorders.

NASA Discipline Musculoskeletal↗

Apoptosis: a mechanism contributing to remodeling of skeletal muscle in response to hindlimb unweighting

The role of apoptosis in the elimination of myonuclei during hindlimb unloading-induced atrophy and the inhibition of apoptosis in the prevention of muscle atrophy were examined. The number of nuclei demonstrating double-stranded DNA fragmentation seen by terminal deoxynucleotidyl transferase (TDT) histochemical staining, an indicator of apoptosis, was significantly increased after 14 days of suspension. Double staining with TDT and antilaminin immunohistochemistry revealed that some TDT-positive nuclei were within the fiber lamina and were most likely myonuclei. The number of fibers containing morphologically abnormal nuclei was also significantly greater in suspended compared with control rats. Combined treatment with growth hormone and insulin-like growth factor I (GH/ IGF-I) and resistance exercise attenuated the increase in TDT-positive nuclei (approximately 26%, P > 0.05) and significantly decreased the number of fibers with morphologically abnormal nuclei. The data suggest that 1) "programmed nuclear death" contributes to the elimination of myonuclei and/or satellite cells from atrophying fibers, and 2) GH/IGF-I administration plus muscle loading ameliorates the apoptosis associated with hindlimb unloading.

Non-NASA Center↗

Effect of spaceflight on the functional, biochemical, and metabolic properties of skeletal muscle

This paper summarizes the effects of spaceflight on the functional, morphological, and biochemical properties of human and rodent skeletal muscle. The findings suggest that following as little as 5-6 in space there are deficits in both human and rodent motor capacity, strength, and endurance properties of skeletal muscle. The reduced strength is associated, in part, with a reduction in muscle mass as reflected in smaller cross-sectional areas of both fast- and slow-twitch fibers. Available evidence in animal models suggests that slow-twitch fibers are more sensitive to the atrophying process. Accompanying the atrophy is a transformation of slow to fast protein phenotype involving myosin heavy chain and sarcoplasmic reticulum protein isoforms. These transformations appear to be regulated, in part, by pretranslational processes. Data on the oxidative capacity of rodent skeletal muscle suggest a bias toward preferential utilization of carbohydrate as the primary substrate. These collective findings suggest that skeletal muscles comprised chiefly of slow fibers are highly dependent on gravity for the normal expression of protein mass and slow phenotype. Future studies need to focus on elucidating the mechanisms associated with the atrophy response, as well as identifying suitable exercise and other countermeasures capable of preserving the structural and functional integrity of skeletal muscle.

NASA Discipline Musculoskeletal↗

Metabolic responses to head-down suspension in hypophysectomized rats

Rats exposed to head-down suspension (HDS) exhibit reductions in maximal O2 consumption (VO2max) and atrophy of select hindlimb muscles. This study tested the hypothesis that an endocrine-deficient rat exposed to HDS would not exhibit reductions in VO2max or hindlimb muscle mass. Hypophysectomized (HYPX) and sham-operated (SHAM) rats were tested for VO2max before and after 28 days of HDS or cage control (CC) conditions. No significant reductions in VO2max were observed in HYPX rats. In contrast, SHAM-HDS rats exhibited a significant reduction in absolute (-16%) and relative (-29%) measures of aerobic capacity. Time course experiments revealed a reduction in VO2max in SHAM-HDS rats within 7 days, suggesting that cardiovascular adjustments to HDS occurred in the 1st wk. HDS was associated with atrophy of the soleus (-42%) in SHAM rats, whereas HYPX rats exhibited atrophy of the soleus (-36%) and plantaris (-13%). SHAM-HDS rats had significantly lower (-38%) soleus citrate synthase activities per gram muscle mass than SHAM-CC, but no significant differences existed between HYPX-HDS and -CC rats. HDS rats had an impaired ability to thermoregulate, as indicated by significantly greater temperature increases per unit run time, compared with their CC counterparts. Pretreatment plasma epinephrine levels were significantly lower in HYPX than in SHAM rats. Norepinephrine concentration was similar for all groups except HYPX-HDS, in which it was significantly higher. HDS had no significant effect on thyroxine or triiodothyronine. SHAM-HDS rats had significantly lower concentrations of testosterone and growth hormone.(ABSTRACT TRUNCATED AT 250 WORDS).

NASA Discipline Number 14-10↗

Neuromuscular Adaptations to Reduced Use

This viewgraph presentation reviews the studies done to reduce neuromuscular strength loss during unilateral lower limb suspension (ULLS). Since there are animals that undergo fairly long periods of muscular disuse without any or minimal muscular atrophy, there is an answer to that might be applicable to human in situations that require no muscular use to diminish the effects of muscular atrophy. Three sets of ULLS studies were reviewed indicated that muscle strength decreased more than the muscle mass. The study reviewed exercise countermeasures to combat the atrophy, including: ischemia maintained during Compound muscle action potential (CMAP), ischemia and low load exercise, Japanese kaatsu, and the potential for rehabilitation or situations where heavy loading is undesirable. Two forms of countermeasures to unloading have been successful, (1) high-load resistance training has maintained muscle mass and strength, and low load resistance training with blood flow restriction (LL(sub BFR)). The LL(sub BFR) has been shown to increase muscle mass and strength. There has been significant interest in Tourniquet training. An increase in Growth Hormone(GH) has been noted for LL(sub BFR) exercise. An experimental study with 16 subjects 8 of whom performed ULLS, and 8 of whom performed ULLS and LL(sub BFR) exercise three times per week during the ULLS. Charts show the results of the two groups, showing that performing LL(sub BFR) exercise during 30 days of ULLS can maintain muscle size and strength and even improve muscular endurance.

Ploutz-Snyder, Lori↗

Muscle Volume Increases Following 16 Weeks of Resistive Exercise Training with the Advanced Resistive Exercise Device (ARED) and Free Weights

Space flight-induced muscle atrophy, particularly in the postural and locomotorymuscles, may impair task performance during long-duration space missions and planetary exploration. High intensity free weight (FW) resistive exercise training has been shown to prevent atrophy during bed rest, a space flight analog. NASA developed the Advanced Resistive Exercise Device (ARED) to simulate the characteristics of FW exercise (i.e. constant mass, inertial force) and to be used as a countermeasure during International Space Station (ISS) missions. PURPOSE: To compare the efficacy of ARED and FW training to induce hypertrophy in specific muscle groups in ambulatory subjects prior to deploying ARED on the ISS. METHODS: Twenty untrained subjects were assigned to either the ARED (8 males, 3 females) or FW (6 males, 3 females) group and participated in a periodizedtraining protocol consisting of squat (SQ), heel raise (HR), and deadlift(DL) exercises 3 d wk-1 for 16 wks. SQ, HR, and DL muscle strength (1RM) was measured before, after 8 wks, and after 16 wks of training to prescribe exercise and measure strength changes. Muscle volume of the vastigroup (V), hamstring group (H), hip adductor group (ADD), medial gastrocnemius(MG), lateral gastrocnemius(LG), and deep posterior muscles including soleus(DP) was measured using MRI pre-and post-training. Consecutive cross-sectional images (8 mm slices with a 2 mm gap) were analyzed and summed. Anatomical references insured that the same muscle sections were analyzed pre-and post-training. Two-way repeated measures ANOVAs (p<0.05) were used to test for differences in muscle strength and volume between training devices. RESULTS: SQ, HR, and DL 1RM increased in both FW (SQ: 49+/-6%, HR: 12+/-2%, DL: 23+/-4%) and ARED (SQ: 31+/-4%, HR: 18+/-2%, DL: 23+/-3%) groups. Both groups increased muscle volume in the V (FW: 13+/-2%, ARED: 10+/-2%), H (FW: 3+/-1%, ARED: 3+/-1 %), ADD (FW: 15=/-2%, ARED: 10+/-1%), LG (FW: 7+/-2%, ARED: 4+/-1%), MG (FW: 7+/-2%, ARED: 5+/-2%), and DP (FW: 2+/-1%; ARED: 2+/-1%) after training. There were no between group differences in muscle strength or volume. CONCLUSIONS: The increase in muscle volume and strength following ARED training is not different than FW training. With the training effects similar to FW and a 600 lb load capacity, ARED likely will protect against muscle atrophy in microgravity.

Nash, R. E.↗

Beneficial Effects of Metabolic Supression for Adoptation and Survival in Space Environment

NASA in its plans to send humans to distant destination such as Mars faces the health and physiological performance problems caused by microgravity and space radiation. While most of the environmental conditions in spacecraft during flight can be made to mimic terrestrial conditions, microgravity cannot yet be managed. This space environmental factor has a major impact on the body’s biological system forcing alterations, in order to adapt to this new environment. Most space flight and ground-based studies suggest that prolonged exposure to microgravity leads to significant skeletal muscle atrophy, bone loss, and results in suppression of total metabolism. Due to microgravity, unloaded crewmembers lose up to 1.5% of their skeletal mass and 1.8% of bone strength each month during ISS missions. Remarkably many animals, including human-size bears, which are largely inactive during the 6 to 8 months of hibernation, show no loss in bone mass and much less muscle atrophy than would be anticipated over such a prolonged period of physical inactivity. This suggests that while in a suppressed metabolic state animals have unique natural mechanisms to prevent muscle disuse and bone atrophy. The molecular mechanisms underlying these important adaptations are not yet known. Radiation exposure is the second health hazard encountered during spaceflight that can cause radiation sickness, cancer or death. This study provides new evidence that metabolic activity levels play a critical role in radioprotection. Metabolic suppression, as an adaptive response of cells to minimize damage caused by radiation, enables cells to reduce cellular dysfunction and damage, and prolong their survival despite persistent oxidative stress. Thus mechanistic understanding of metabolism offers a means for sustaining astronauts in long-duration missions. The ultimate goals of this study are to demonstrate that induced metabolic suppression in animals and humans will profoundly reduce their sensitivity to the damaging effects of radiation and microgravity as well as other kinds of stresses caused by spaceflight. The beneficial effects of suppressed metabolism induced by different factors such as temperature, nutrition, and medications, will not only mitigate the most detrimental hazards of spaceflight but also radically reduce mission life support requirements and spaceflight logistics.

Galicia, E.↗

Robust and Mass Efficient Thermal Protection Systems for Future Venus Missions

Several international Venus missions, both orbiter, and in-situ probe are in the works after a prolonged absence. Future missions are expected to be long-duration lander missions and balloon missions to investigate the cloud layer. The entry mass for these in-situ missions will be significantly higher, and the aeroshell will be larger, than previous missions. Two cardinal requirements govern the selection and use of thermal protection systems (TPS), namely, robustness to assure mission safety during entry and mass efficiency so that the useful mass for science is maximized. One cannot trade mission safety for mass when it comes to TPS. The robustness of the TPS is a paramount requirement as it is a single point of system failure. At the same time, TPS mass is carried for the entire mission duration prior to entry, and any excess TPS mass is at the cost of science payload. Future missions will benefit enormously from TPS options with mass and performance benefits far beyond advanced carbon-carbon (ACC) that is currently proposed for the DAVINCI mission. NASA STMD, and SMD jointly invested in the development of 3-D woven thermal protection systems in the last decade, and as a result, the Heat-shield for Extreme Entry Environment Technology (HEEET) TPS has been matured to TRL 6. It is ready for future mission use including Venus. The HEEET project focused on developing a broad technology base, applicable for missions not only to Venus, but also to Saturn, the Ice Giants, and higher speed sample return missions such as Mars Sample Return requiring extreme robustness due to bio-hazards. The dual-layer HEEET (DL-HEEET) is proven to be extremely robust. DL-HEEET performed well in arc jet and laser testing conditions where heritage carbon-phenolic failed. HEEET also proved to be more mass efficient compared to Carbon-Phenolic. Recently, the principal author was invited to present his perspectives to the 2023-2032 Planetary Sciences Decadal Venus subcommittee on the current state of TPS for future Venus missions [1]. In addition to pointing out successful TPS and other developments in the last decade in support of entry systems, the principal author made two findings: 1) importance of and need to sustain TPS capabilities that took nearly a decade to develop and 2) the opportunity to further optimize TPS mass without sacrificing robustness to further enable future in-situ missions. This talk will focus on the above two recommendations and provide the rationale for them. The intent of the talk is to seek advocacy from the VEXAG community for the criticality of TPS sustainment and the benefits of 3D woven TPS optimization. TPS Capability Sustainment: HEEET development was necessitated by the atrophy of heritage carbon-phenolic. Atrophy has impacted other TPS materials as well. Avcoat, the TPS that successfully allowed astronauts to explore the Moon in the 1960s and 70s, took nearly a decade and $10’sM to recover in support of Orion/Artemis. One of the most used TPS materials, SLA 561V, had to be recovered prior to its use on Mars Pathfinder. Phenolic Impregnated Carbon Ablator (PICA), the TPS that replaced SLA 561V on MSL, has undergone multiple replacements and recovery due to constituent rayon changes. Recently, NASA invested in a domestic rayon replacement program and also invested in FMI to consolidate PICA capability for NASA missions, as a result of FMI’s decision to discontinue commercial FiberForm, which is needed for PICA. TPS used for planetary missions are unique and have no other commercial or defense use. In addition, low mission cadence is also a driver for TPS atrophy. Hence, NASA, as the steward, must take steps to ensure and sustain TPS capabilities. In this talk, we outline steps NASA can take to keep abreast of emerging risks and target risk mitigation steps to ensure TPS capability sustainment for Venus and other extreme environment missions. Next Generation of Mass efficient and Robust TPS: NASA invested in an alternate TPS to PICA based on felt-technology called Conformal-PICA which has the potential to save 30% - 50% mass over PICA. The development was discontinued at a Technology Readiness Level (TRL) of ~ 5. 3D Mid-Density Carbon Phenolic (3MDCP) is a single layer variant of HEEET, based on the insulating layer only (SL-HEEET) and currently baselined for the Mars Sample Return Mission Earth Entry System due to its mass efficiency (30% more mass efficient than DL- HEEET). Currently, SL-HEEET is limited to aeroshell diameters of < 1.3m. The SL-HEEET was compared to DL-HEEET in the recent ADVENT flag-ship class mission study in support of the Planetary Science Decadal. SL HEEET was the recommended TPS based on 30% mass savings for both the balloon and lander missions. Given C-PICA and SL-HEEET have superior reliability and mass efficiency, advocacy from VEXAG is sought for completing their further development to TRL 5/6 in this decade so as to enable TPS readiness for future missions.

Thermal Protection Systems↗

Dual Genes of Muscle Cell Senescence: Unraveling the Radiation-Induced Roles of HDAC4 and MORC2a

As the human race ventures further into space and plans missions to explore the Moon and the expanse that lies ahead, addressing health challenges that may hinder exploration becomes an imperative task. However, limited research exists on the molecular mechanisms within skeletal muscle cells in response to long-term radiation-induced oxidative stress. Upon analyzing GLDS-426 from the GeneLab Repository, upregulation of the DNA damage response gene HDAC4 in space radiation conditions with 1G was observed, where radiation-induced oxidative stress increased DNA damage. DNA damage response gene MORC2a was found to be downregulated in space radiation conditions in 1G with a culture treatment of nanoceria, an antioxidant that alleviates the effects of oxidative stress and causes less DNA damage. Literature review further indicated that MORC2a recruits HDAC4 at the promoter to prevent the transcription of p21. Upregulation of p21 has been linked to cell senescence and muscle atrophy on Earth, but no research has studied its changes in radiation conditions. To address the knowledge gap regarding the HDAC4/MORC2a pathway impact on p21 expression in radiation, our experiment aims to silence HDAC4 and MORC2a in the Mus musculus C2C12 cell culture line. These cultures will be exposed to radiation to assess the effects on cellular senescence (Aim 1). Additionally, we will silence p21 and subject the cell cultures to radiation to measure muscle cell proliferation (Aim 2). Muscle atrophy in future long-term space missions can contribute to the risk of degenerative diseases and hinder the completion of tasks in space. Furthermore, exploring the impact of these genes on muscle atrophy may provide therapeutic insights for individuals experiencing skeletal muscle degeneration and elderly individuals affected by sarcopenia.

GL4HS↗

Age, vascular disease, and Alzheimer’s disease pathologies in amyloid negative elderly adults

Background: We recently reported that CSF phosphorylated tau (p-Tau 181 ) relative to Aβ 40 (CSF p-Tau/Aβ 40 ratio) was less noisy and increased associations with Alzheimer’s disease (AD) biomarkers compared to CSF p-Tau 181 alone. While elevations of CSF p-Tau/Aβ 40 can occur in amyloid-β (Aβ) negative (Aβ-) individuals, the factors associated with these elevations and their role in neurodegeneration and cognitive decline are unknown. We aim to explore factors associated with elevated tau in CSF, and how these elevated tau are related to neurodegeneration and cognitive decline in the absence of Aβ positivity. Methods: We examined relationships between CSF p-Tau/Aβ 40 , and CSF Aβ 42 /Aβ 40 , Aβ PET, and white matter hyperintensities (WMH) as well as vascular risk factors in 149 cognitively unimpaired and 52 impaired individuals who were presumably not on the Alzheimer’s disease (AD) pathway due to negative Aβ status on both CSF and PET. Subgroups had 18 F-fluorodeoxyglucose (FDG) PET and adjusted hippocampal volume (aHCV), and longitudinal measures of CSF, aHCV, FDG PET, and cognition data, so we examined CSF p-Tau/Aβ 40 associations with these measures as well. Results: Elevated CSF p-Tau/Aβ 40 was associated with older age, male sex, greater WMH, and hypertension as well as a pattern of hippocampal atrophy and temporoparietal hypometabolism characteristic of AD. Lower CSF Aβ 42 /Aβ 40 , higher WMH, and hypertension but not age, sex, Aβ PET, APOE-ε4 status, body mass index, smoking, and hyperlipidemia at baseline predicted CSF p-Tau/Aβ 40 increases over approximately 5 years of follow-up. The relationship between CSF p-Tau/Aβ 40 and subsequent cognitive decline was partially or fully explained by neurodegenerative measurements. Conclusions: These data provide surprising clues as to the etiology and significance of tau pathology in the absence of Aβ. It seems likely that, in addition to age, both cerebrovascular disease and subthreshold levels of Aβ are related to this tau accumulation. Crucially, this phenotype of CSF tau elevation in amyloid-negative individuals share features with AD such as a pattern of metabolic decline and regional brain atrophy.

60 APPLIED LIFE SCIENCES↗

Effect of short-term microgravity and long-term hindlimb unloading on rat cardiac mass and function

The purpose of this study was to test the hypothesis that exposure to short-term microgravity or long-term hindlimb unloading induces cardiac atrophy in male Sprague-Dawley rats. For the microgravity study, rats were subdivided into four groups: preflight (PF, n = 12); flight (Fl, n = 7); flight cage simulation (Sim, n = 6), and vivarium control (Viv, n = 7). Animals in the Fl group were exposed to 7 days of microgravity during the Spacelab 3 mission. Animals in the hindlimb-unloading study were subdivided into three groups: control (Con, n = 20), 7-day hindlimb-unloaded (7HU, n = 10), and 28-day hindlimb-unloaded (28HU, n = 19). Heart mass was unchanged in adult animals exposed to 7 days of actual microgravity (PF 1.33 +/- 0.03 g; Fl 1.32 +/- 0.02 g; Sim 1.28 +/- 0.04 g; Viv 1.35 +/- 0.04 g). Similarly, heart mass was unaltered with hindlimb unloading (Con 1.40 +/- 0.04 g; 7HU 1.35 +/- 0.06 g; 28HU 1.42 +/- 0.03 g). Hindlimb unloading also had no effect on the peak rate of rise in left ventricular pressure, an estimate of myocardial contractility (Con 8,055 +/- 385 mmHg/s; 28HU 8,545 +/- 755 mmHg/s). These data suggest that cardiac atrophy does not occur after short-term exposure to microgravity and that neither short- nor long-term simulated microgravity alters cardiac mass or function.

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