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At least 19 records

The molecular responses of skeletal muscle satellite cells to continuous expression of IGF-1: implications for the rescue of induced muscular atrophy in aged rats

Approximately 50% of humans older than 85 years have physical frailty due to weak skeletal muscles. This indicates a need for determining mechanisms to combat this problem. A critical cellular factor for postnatal muscle growth is a population of myogenic precursor cells called satellite cells. Given the complex process of sarcopenia, it has been postulated that, at some point in this process, a limited satellite cell proliferation potential could become rate-limiting to the regrowth of old muscles. It is conceivable that if satellite cell proliferative capacity can be maintained or enhanced with advanced age, sarcopenia could potentially be delayed or prevented. Therefore, the purposes of this paper are to describe whether IGF-I can prevent muscular atrophy induced by repeated cycles of hindlimb immobilization, increase the in vitro proliferation in satellite cells from these muscles and, if so, the molecular mechanisms by which IGF-I mediates this increased proliferation. Our results provide evidence that IGF-I can enhance aged muscle regrowth possibly through increased satellite cell proliferation. The results also suggest that IGF-I enhances satellite cell proliferation by decreasing the cell cycle inhibitor, p27Kip1, through the PI3'-K/Akt pathway. These data provide molecular evidence for IGF-I's rescue effect upon aging-associated skeletal muscle atrophy.

NASA Discipline Musculoskeletal↗

Bed Rest Muscular Atrophy

A major debilitating response from prolonged bed rest (BR) is muscle atrophy, defined as a "decrease in size of a part of tissue after full development has been attained: a wasting away of tissue as from disuse, old age, injury or disease". Part of the complicated mechanism for the dizziness, increased body instability, and exaggerated gait in patients who arise immediately after BR may be a result of not only foot pain, but also of muscular atrophy and associated reduction in lower limb strength. Also, there seems to be a close association between muscle atrophy and bone atrophy. A discussion of many facets of the total BR homeostatic syndrome has been published. The old adage that use determines form which promotes function of bone (Wolff's law) also applies to those people exposed to prolonged BR (without exercise training) in whom muscle atrophy is a consistent finding. An extreme case involved a 16-year-old boy who was ordered to bed by his mother in 1932: after 50 years in bed he had "a lily-white frame with limbs as thin as the legs of a ladder-back chair". These findings emphasize the close relationship between muscle atrophy and bone atrophy. In addition to loss of muscle mass during deconditioning, there is a significant loss of muscle strength and a decrease in protein synthesis. Because the decreases in force (strength) are proportionately greater than those in fiber size or muscle cross-sectional area, other contributory factors must be involved; muscle fiber dehydration may be important.

Greenleaf, John E.↗

Monitoring Biomarkers for Muscular Atrophy Using an Electrochemical Chip for Astronaut Space Health

Skeletal muscle atrophy is a serious health problem for astronauts in long-duration space flight under microgravity conditions. Preventative measures against muscle atrophy require specific exercise and dietary regimens. Preemptive measurements to improve treatment have the potential to streamline these regimens, decreasing their daily footprint and increasing astronaut quality of life. The objective of our proposed project is to (1) develop a fully integrated disposable microelectrode array chip (with the size of a stamp) that can be interfaced with a handheld electronic system for simultaneous detection of the a panel of biomarkers to monitor the progression of skeletal muscle atrophy due to disuse under microgravity in long-duration spaceflights; and (2) use such quantitative information to guide the combined countermeasures of physical exercise and pharmaceuticals (i.e. specific protease inhibitors) so that the intensity, duration and frequency of exercise can be reduced. Note: The presentation includes voice commentary and plays best as a slide show. The voice begins once the presentation starts, and only requires the user to click to the next slide each time. With a run time of ~15 mins.

Biosensor↗

Monitoring Biomarkers for Muscular Atrophy using an Electronic Chip for Astronaut Health

Skeletal muscle atrophy is a serious health problem for astronauts in long-duration space flight under microgravity conditions. Preventative measures against muscle atrophy require specific exercise and dietary regimens. Preemptive measurements to improve treatment have the potential to streamline these regimens, decreasing their daily footprint and increasing astronaut quality of life. The objective of our proposed project is to (1) develop a fully integrated disposable microelectrode array chip (with the size of a stamp) that can be interfaced with a handheld electronic system for simultaneous detection of the a panel of biomarkers to monitor the progression of skeletal muscle atrophy due to disuse under microgravity in long-duration spaceflights; and (2) use such quantitative information to guide the combined countermeasures of physical exercise and pharmaceuticals (i.e. specific protease inhibitors) so that the intensity, duration and frequency of exercise can be reduced.

Biosensing↗

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↗

A Biomechanical Comparison of 1-G and Fully-Loaded Simulated Zero-Gravity Locomotion

Exercise will almost certainly play an integral part in minimizing the bone mineral loss and muscular atrophy that occur during spaceflight. It has been hypothesized that an effective exercise regimen can be developed to elicit loads on the lower extremities and require muscle actions which resemble those encountered on Earth. The Penn State Zero-Gravity Simulator (PSZS) is a device which suspends subjects horizontally from multiple latex cords, with each cord negating the weight of a limb segment. A treadmill mounted on the wall under the PSZS enables subjects to run in simulated 0G. Subjects wear a harness to which a number of springs, which provide a gravity replacement load, are connected. The opposite end of each spring is connected to the side of the treadmill. During exercise, astronauts currently wear a similar harness in which the spring tethering load pulls at both the waist and shoulders. Ground reaction forces, muscular activations, and joint angles of the left leg during overground, treadmill, and fully-loaded zero-gravity simulated (ZLS) locomotion were assessed in order to gain insight into the effectiveness of the exercise regimen used by NASA to prevent the muscular atrophy and bone demineralization which occur in weightlessness. There were three hypotheses to this research. It was hypothesized that there will be no differences in peak ground reaction forces and peak loading rates between overground gait and gait in the full body weight loaded conditions in the ZLS. A second hypothesis was that that there will be no differences in hip, knee, and ankle joint positions between walking or running overground, on a standard treadmill, and in full bodyweight loaded conditions in the ZLS. The third hypothesis was that the muscular activations, as a percentage of maximal voluntary contraction, will be similar between walking or running overground, on a standard treadmill, and in full body-weight loaded conditions in the ZLS.

McCrory, Jean L.↗

The combined influence of stretch, mobility and electrical stimulation in the prevention of muscle fiber atrophy caused hypokinesia and hypodynamia

The morphological and biochemical changes which occur in the hind limb muscles of the rat in response to hypokinesia and hypodynamia were investigated. Hind limb cast fixation and suspension techniques were employed to study the musclar atrophy after five days of hypokinesia and hypodynamia induced by suspension, appreciable muscular atrophy was apparent, particularly in the anti-gravity muscles. The effect of passive stretching and electrical stimulation on muscle atrophy was studied. Changes in muscle protein mass were assessed with spectrophotometric and radioactive techniques. Passive stretch is shown to counteract muscle disuse atrophy. The change in the numbers of specific muscle fibers in atrophied muscles is discussed.

Goldspink, G.↗

Exposure to Microgravity for 30 Days Onboard Bion M1 Caused Muscle Atrophy and Decreased Regeneration in the Mouse Femoral Quadriceps

Mechanical unloading of muscle during spaceflight in microgravity is known to cause muscular atrophy, changes in muscle fiber type composition, gene expression, and reductions in regenerative muscle growth. Although limited data exists for long-term effects of microgravity in human muscle, these processes have mostly been studied in rodents for short periods of time. Here we report on how 30-day, long-term, mechanical unloading in microgravity affects mouse muscle of the femoral Quadriceps group. To conduct these studies we used muscle tissue from 6 mice from the NASA Biospecimen Sharing Program conducted in collaboration with the Institute for Biomedical Problems of the Russian Academy of Sciences, during the Russian Bion M1 biosatellite mission in 2013. Muscle morphology observed in histological sections shows signs of extensive atrophy and regenerative hypoplasia. Specifically, we observed a two-fold decrease in the number of myonuclei, their central location, low density of myofibers and myofibrils, in fragmentation and swelling of myofibers. Despite obvious atrophy, muscle regeneration nevertheless appears to have continued after 30 days in microgravity as evidenced by thin and short newly formed myofibers. Many of them however showed evidence of apoptotic, TUNEL positive cells and myofibrils degradation, suggesting long-term unloading in microgravity affects late stages of myofiber differentiation. Ground asynchronous and vivarium control animals showed normal, well-developed tissue structure with sufficient blood and nerve supply and evidence of regenerative formation of new myofibers free of apoptotic nuclei. Myonuclei stress response in spaceflight animals was detected by positive nuclear immunolocalization of c-jun and c-myc proteins. Regenerative activity of satellite cells in muscles is detected in mice of all animal groups, by pax7, MyoD, and myogenin immunostaining and myogenin PCR analysis. In summary, long-term spaceflight in microgravity causes significant atrophy and degeneration of the femoral Quadriceps muscle group, and it may interfere with muscle regenerative processes by inducing apoptosis in newly-formed myofibrils during their differentiation phase.

Grigoryan, E. N.↗

Influence of performance on gene expression in skeletal muscle: effects of forced inactivity

Joint immobilization and hindlimb suspension are used to examine muscle protein expression and mRNA quantities in rats. A decrease in protein synthesis was not associated with alteration in alpha-actin mRNA, cytochrome c mRNA, or beta-myosin heavy chain mRNA early in treatment. Percentage declines after seven days are compared with early treatment quantities to determine acute and chronic response to muscular atrophy.

Non-NASA Center↗

Centrosome and microtubule instability in aging Drosophila cells

Several cytoskeletal changes are associated with aging which includes alterations in muscle structure leading to muscular atrophy, and weakening of the microtubule network which affects cellular secretion and maintenance of cell shape. Weakening of the microtubule network during meiosis in aging oocytes can result in aneuploidy or trisomic zygotes with increasing maternal age. Imbalances of cytoskeletal organization can lead to disease such as Alzheimer's, muscular disorders, and cancer. Because many cytoskeletal diseases are related to age we investigated the effects of aging on microtubule organization in cell cultures of the Drosophila cell model system (Schneider S-1 and Kc23 cell lines). This cell model is increasingly being used as an alternative system to mammalian cell cultures. Drosophila cells are amenable to genetic manipulations and can be used to identify and manipulate genes which are involved in the aging processes. Immunofluorescence, scanning, and transmission electron microscopy were employed for the analysis of microtubule organizing centers (centrosomes) and microtubules at various times after subculturing cells in fresh medium. Our results reveal that centrosomes and the microtubule network becomes significantly affected in aging cells after 5 days of subculture. At 5-14 days of subculture, 1% abnormal out of 3% mitoses were noted which were clearly distinguishable from freshly subcultured control cells in which 3% of cells undergo normal mitosis with bipolar configurations. Microtubules are also affected in the midbody during cell division. The midbody in aging cells becomes up to 10 times longer when compared with midbodies in freshly subcultured cells. During interphase, microtubules are often disrupted and disorganized, which may indicate improper function related to transport of cell organelles along microtubules. These results are likely to help explain some cytoskeletal disorders and diseases related to aging.

Non-NASA Center↗

Urinary excretion of cortisol from rhesus monkeys (Macaca mulatta) habituated to restraint

Use of monkeys in research has often required that they be restrained in a chair. However, chair restraint can elicit an initial neuroendocrine stress response. Also, inactivity associated with restraint can induce muscular atrophy. We proposed that prior habituation of monkeys to chair restraint would attenuate these neuroendocrine responses without causing substantial muscle wasting. Four rhesus monkeys (Macaca mulatta) were trained and habituated to a restraint chair specifically designed for spaceflight. During the study, monkeys were placed in metabolic cages for 7 days (prerestraint, Phase I), placed in a chair restraint for 18 days (Phase II), and then returned to their metabolic cages for 5 days (postrestraint, Phase III). Urine was collected between 0700-1100 daily, and measurements of cortisol, creatinine, and electrolyte concentrations were adjusted for hourly excretion rates. Body weights of the monkeys did not change between start of the prerestraint and postrestraint phases (10.3 +/- 0.8 vs. 10.3 +/- 0.9 kg, respectively). During the 3 phases, mean excretion rate of cortisol did not change (24.1 +/- 10.3, 26.7 +/- 7.7, and 19.3 +/- 5.8 microg/h, respectively). Mean excretion rate of creatinine (37.3 +/- 7.5, 37.5 +/- 12.2, and 36.9 +/- 17.1 mg/h, respectively), Na+ (3.3 +/- 1.2, 3.2 +/- 1.2, 2.2 +/- 1.8 mmol/h, respectively), and K+ (5.3 +/- 1.8, 5.4 +/- 1.6, and 4.3 +/- 2.8 mmol/h, respectively) were also not altered. Lack of an increase in excreted urinary cortisol suggested that prior habituation to chair restraint attenuated neuroendocrine responses reported previously. Also, the chair restraint method used appeared to allow adequate activity, because the monkeys did not have indices of muscle wasting.

NASA Center ARC↗

Recovery of skeletal muscle after 3 mo of hindlimb immobilization in rats

During immobilization, skeletal muscle undergoes decreases in size and strength with concomitant atrophic and degenerative changes in slow-twitch muscle fibers. Currently there are no objective data in slow-twitch muscle demonstrating recovery of biochemical or physiological indices following termination of immobilization. The purpose of this study was to determine whether the soleus, a slow-twitch muscle, could recover normal biochemical or physiological levels following termination of immobilization. Adenosine triphosphate, glycogen, and protein concentration (mg/g wet wt) all significantly decreased following 90 days of hindlimb immobilization, but these three values returned to control levels by the 60th recovery day. Similarly, soleus muscle wet weight and protein content (mg protein/muscle) returned to control levels by the 14th recovery day. In contrast, maximal isometric tension did not return to normal until the 120th day. These results indicate that following muscular atrophy, which was achieved through 90 days of hindlimb immobilization, several biochemical and physiological values in skeletal muscle are recovered at various times after the end of immobilization.

Booth, F. W.↗

Hindlimb immobilization - Length-tension and contractile properties of skeletal muscle

Casts were placed around rat feet in plantar flexion position to immobilize the soleus muscle in a shortened position, while the other foot was fixed in dorsal flexion to set the extensor digitorum longus in a shortened position. The total muscular atrophy and contractile properties were measured at 1, 2, 4, 7, 14, 21, 28, 35, and 42 days after immobilization, with casts being replaced every two weeks. The slow twitch soleus and the fast-twitch vastus lateralis and longus muscles were excised after termination of the experiment. The muscles were then stretched and subjected to electric shock to elicit peak tetanic tension and peak tetanic tension development. Force velocity features of the three muscles were assayed in a series of afterloaded contractions and fiber lengths were measured from subsequently macerated muscle. All muscles atrophied during immobilization, reaching a new steady state by day 21. Decreases in fiber and sarcomere lengths were also observed.

Witzmann, F. A.↗

Acid phosphatase and protease activities in immobilized rat skeletal muscles

The effect of hind-limb immobilization on selected Iysosomal enzyme activities was studied in rat hing-limb muscles composed primarily of type 1. 2A, or 2B fibers. Following immobilization, acid protease and acid phosphatase both exhibited signifcant increases in their activity per unit weight in all three fiber types. Acid phosphatase activity increased at day 14 of immobilization in the three muscles and returned to control levels by day 21. Acid protease activity also changed biphasically, displaying a higher and earlier rise than acid phosphatase. The pattern of change in acid protease, but not acid phosphatase, closely parallels observed muscle wasting. The present data therefore demonstrate enhanced proteolytic capacity of all three fiber types early during muscular atrophy. In addition, the data suggest a dependence of basal hydrolytic and proteolytic activities and their adaptive response to immobilization on muscle fiber composition.

Witzmann, F. A.↗

Exercise/recreation facility for a Lunar or Mars analog

Discussed here is a project to design an exercise/recreation station for an earth based simulator of a lunar or Martian habitat. Specifically, researchers designed a stationary bicycle that will help people keep fit and prevent muscular atrophy while stationed in space. To help with motivation and provide an element of recreation during the workout, the bicycle is enhanced by a virtual reality system. The system will simulate various riding situations and the choice of mountain bike or road bike. The bike employs a magnetic brake that provides continuously changing tension to simulate actual riding conditions. This braking system will be interfaced directly with the virtual reality system. Also integrated into the virtual reality system will be a monitoring system that regulates heart rate, work rate, and other functions during the course of the session.

Source record↗

Exercise/recreation facility for a lunar or Mars analog

The University of Idaho, NASA/USRA project for the 1990-91 school year is an exercise/recreation station for an Earth-based simulator of a lunar or martian habitat. Specifically, a stationary bicycle that will help people keep fit and prevent muscular atrophy while stationed in space was designed. To help with motivation and provide an element of recreation during the workout, the bicycle is to be enhanced by a virtual reality system. The system simulates various riding situations, including the choice of a mountain bike or a road bike. The bike employs a magnetic brake that provides continuously changing tension to simulate actual riding conditions. This braking system is interfaced directly with the virtual reality system. Also, integrated into the virtual reality display will be a monitoring system that regulates heart rate, work rate, and other functions during the course of the session.

Source record↗

Microgravity effects on 'postural' muscle activity patterns

Changes in neuromuscular activation patterns associated with movements made in microgravity can contribute to muscular atrophy. Using electromyography (EMG) to monitor 'postural' muscles, it was found that free floating arm flexions made in microgravity were not always preceded by neuromuscular activation patterns normally observed during movements made in unit gravity. Additionally, manipulation of foot sensory input during microgravity arm flexion impacted upon anticipatory postural muscle activation.

Layne, Charles S.↗