Journal of Applied Physiology Ad Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Appl Physiol 106: 1159-1168, 2009. First published January 15, 2009; doi:10.1152/japplphysiol.91578.2008 Free Article
8750-7587/09 $8.00
This Article
Free upon publication Free Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow All Versions of this Article:
106/4/1159    most recent
91578.2008v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Trappe, S.
Right arrow Articles by Fitts, R. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Trappe, S.
Right arrow Articles by Fitts, R. H.

Exercise in space: human skeletal muscle after 6 months aboard the International Space Station

Scott Trappe,1 David Costill,1 Philip Gallagher,1 Andrew Creer,1 Jim R. Peters,2 Harlan Evans,3 Danny A. Riley,4 and Robert H. Fitts2

1Human Performance Laboratory, Ball State University, Muncie, Indiana; 2Department of Biological Sciences, Marquette University, Milwaukee, Wisconsin; 3Wyle Laboratories, Houston, Texas; and 4Medical College of Wisconsin, Milwaukee, Wisconsin

Submitted 8 December 2008 ; accepted in final form 12 January 2009


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
The aim of this investigation was to document the exercise program used by crewmembers (n = 9; 45 ± 2 yr) while aboard the International Space Station (ISS) for 6 mo and examine its effectiveness for preserving calf muscle characteristics. Before and after spaceflight, we assessed calf muscle volume (MRI), static and dynamic calf muscle performance, and muscle fiber types (gastrocnemius and soleus). While on the ISS, crewmembers had access to a running treadmill, cycle ergometer, and resistance exercise device. The exercise regimen varied among the crewmembers with aerobic exercise performed ~5 h/wk at a moderate intensity and resistance exercise performed 3–6 days/wk incorporating multiple lower leg exercises. Calf muscle volume decreased (P < 0.05) 13 ± 2% with greater (P < 0.05) atrophy of the soleus (–15 ± 2%) compared with the gastrocnemius (–10 ± 2%). Peak power was 32% lower (P < 0.05) after spaceflight. Force-velocity characteristics were reduced (P < 0.05) –20 to –29% across the velocity spectrum. There was a 12–17% shift in myosin heavy chain (MHC) phenotype of the gastrocnemius and soleus with a decrease (P < 0.05) in MHC I fibers and a redistribution among the faster phenotypes. These data show a reduction in calf muscle mass and performance along with a slow-to-fast fiber type transition in the gastrocnemius and soleus muscles, which are all qualities associated with unloading in humans. Future long-duration space missions should modify the current ISS exercise prescription and/or hardware to better preserve human skeletal muscle mass and function, thereby reducing the risk imposed to crewmembers.

microgravity; muscle biopsy; fiber type; gastrocnemius; soleus; magnetic resonance imaging

WITH HUMANS CURRENTLY OCCUPYING the International Space Station (ISS) for 6 mo and space exploration missions of 1–3 yr on the horizon, preservation of crewmember health and fitness is a major objective of the international space community. Exercise has been the primary utility used by the space agencies in an effort to protect cardiovascular, bone, and skeletal muscle health while in space for extended stays. The first multifaceted exercise program implemented in space was during the 28- to 84-day Skylab missions in the 1970s. Using a cycle ergometer and a variety of rudimentary exercise equipment, Skylab crewmembers generally maintained cardiovascular capacity while showing decrements in lower leg muscle circumference and performance (23). Since Skylab, the available data from humans that have flown in space for 6 mo or longer show that muscle mass and performance are not protected despite exercise countermeasures (16, 17, 20, 46). An exercise program that has historically been variable and limited by hardware most likely explains these findings. However, detailed information on the actual exercise program performed during long-duration space missions is sparse, thus making it difficult to quantitatively assess the effectiveness of the exercise countermeasure to protect against skeletal muscle atrophy. This information is critical to guide the countermeasure program forward for future long-duration space missions.

The aim of the current study was to document the exercise program used by crewmembers aboard the ISS and examine its effectiveness for preserving skeletal muscle size and function. Our focus was on the calf muscles, since they have been shown to atrophy more than other leg and upper body muscles with unloading (12, 21). To obtain a comprehensive profile of skeletal muscle before and after flight, we utilized magnetic resonance imaging (MRI) to assess muscle volume, static and dynamic muscle testing to assess muscle performance, and muscle biopsies from the gastrocnemius and soleus to assess fiber type, contractile function, and microanatomy. The focus of the current report is to overview the exercise program, muscle volume, muscle performance, and fiber type profile of the nine crewmembers tested. The single muscle fiber physiology and muscle microanatomy are being presented in separate reports by our research team. Since there was not a specific exercise protocol that was followed by all crewmembers, we present exercise and muscle data from each crewmember to provide better insight on the exercise program and skeletal muscle findings.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
Overall study design.   Access to the crewmembers began ~6 mo before launch. In this time period the familiarization and testing sequence was staggered to obtain the desired test measures outlined in the Introduction. The testing timelines for all of the measurements varied slightly due to crew training procedures in the U.S. and Russia. All pretesting procedures in the U.S. occurred at Johnson Space Center. With the exception of three crewmembers who landed at Kennedy Space Center, the crews landed in Russia. The initial postlanding procedures took place in Star City, Russia (muscle biopsy, MRI, initial muscle performance evaluations). For the Florida landing, the initial postlanding procedures took place at Kennedy Space Center. Approximately 1 wk after the Russia landings, U.S. crewmembers returned to Houston, TX, where the remaining muscle performance measures were performed. Russian crewmembers remained in Russia for the remaining whole muscle performance evaluations. Two identical muscle performance devices were used to accommodate the testing at Johnson Space Center and The Russian Space Center. For the descriptions of the testing sequence described below, prelaunch is designated as L minus (L–) and postlanding (recovery) is designated as R plus (R+) with the day pre- or postflight indicated.

Subjects.   Ten crewmembers participated in this investigation. For the analysis presented, one crewmember had incomplete data sets and was not included. The subject population consisted of American astronauts and Russian cosmonauts. The subjects' (n = 9) age, height, weight, and days in space were 45 ± 2 yr, 176 ± 2 cm, 81 ± 3 kg, and 177 ± 4 days (range = 161–192 days), respectively. An overview of each crewmember's exercise history in the weeks preceding their launch is shown in Table 1.


View this table:
[in this window]
[in a new window]

  		Table 1. Preflight conditioning biographies

 
Before volunteering to participate in this skeletal muscle research, all crewmembers were briefed on the project objectives and testing procedures by a member of the investigative team. Crewmembers were informed of the risks and benefits with the research and gave their written consent to protocols approved by the Human Subjects Institutional Review Boards at Ball State University, Marquette University, and the National Aeronautics and Space Administration (NASA; Johnson Space Center). This study was conducted in accordance with the Declaration of Helsinki.

Exercise in space.   During the 6 mo the crewmembers were on the ISS, they had access to a treadmill (treadmill with vibration isolation system), two bicycle ergometers (cycle ergometer with vibration isolation system and a Velosiped, i.e., Russian bicycle exercise device), and an interim resistive exercise device (iRED). The crewmembers also had access to bungee cords, which they could use to provide resistance-type exercise for various muscle groups.

The treadmill device could be used in a passive (subject driven) or active (motorized) mode of operation, which was selected by the crewmember during each exercise session. Crewmembers used a subject-loading device to fix themselves to the treadmill, which provided varying levels of loading relative to body weight (typical load was ~70% of body weight) during use. In this way, the crewmembers could complete running or walking exercise while partially loaded. The bicycle ergometers provided typical loading in 1-W increments up to 350 W and had clipless pedals for securing their feet. The iRED is an elastomer-based resistance exercise device consisting of two canisters capable of producing up to ~68 kg of force per canister. Additional bungee cords can also be attached to increase the load characteristics. A known limitation of the iRED is the inability to precisely set and quantify workloads. A more detailed profile of the iRED has been previously reported (25).

The operational guidelines prescribed that crewmembers exercise while in space with up to 2.5 h allocated per day for 6 of 7 days of the week. The 2.5-h period included time needed for hardware setup, stowage, and personal hygiene. The exercise prescription was not fixed or targeted to a specific level of performance for a given physiological system. The exercise program was structured to allow for personal preference from the crewmembers along with guidance from trainers and staff within NASA and the Russian Space Agency. To track the exercise profile while in space, crewmembers kept logbooks of their physical activity. In addition, analog data from the devices (treadmill and cycle ergometer) were downloaded (when the downlink was operational) at various times while on-orbit and accounted for ~65% of the treadmill and cycle ergometer data. Members of our investigative team personally interviewed each crewmember after their mission. The combination of these three elements (logbook, downloaded data, and personal interviews) comprised the database that enabled us to profile the exercise program conducted by each crewmember while in space.

Muscle volume.   To determine muscle volume of the calf muscle, MRI was performed on crewmembers 40 ± 3 (L–40) days before launch and 4 ± 1 (R+4) days after returning from the ISS. An additional MRI was obtained on each crewmember 19 ± 2 (R+19) days after returning from space. All preflight MRI scans were conducted in Clear Lake, TX, and all postflight (R+4) MRI scans were conducted in Moscow, Russia. The postflight R+19 scans were divided between scanners depending on the location of the crewmembers at the testing time point. The subjects were scanned feet first in the supine position. The subject was supine at least 30 min before the acquisition to standardize body fluid shifts (5, 20). The lower leg was suspended at the heel and knee so that the calf muscle was hanging freely. On the GE scanner (Clear Lake, TX), the distal patella was used as the bony landmark for the starting point of the scan. On the Siemens scanner (Cardiology Research Center, Moscow, Russia), the leg was landmarked in the center of the calf and the scan covered approximately the same anatomic region with the actual position set using a scout scan. The scan sequence was a spin echo sequence with 32 continuous slices, 10 mm thick, TR 800 ms, and TE 14 ms using the body coil with a field of view (FOV) of 300 mm (occasionally a FOV of 350 mm when needed to include both legs). This sequence was run twice to increase the probability of having a quality set of images.

To check on the calibration of the scanners and to intercalibrate between scanners, a set of phantoms were scanned each time an astronaut/cosmonaut was scanned with the same sequence, except the FOV was 400 mm. These phantoms were Plexiglas cylinders (5-in. diameter, 12-in. length) filled with doped water. These were used to correct the nominal areas and intercalibrate the scanners.

The MR images were transferred electronically from the scanner to a personal computer (iMac G5) at Ball State University and analyzed with NIH Image software (Image J, version 1.34; NIH, Bethesda, MD) using manual planimetry. A detailed description of the basic manual planimetry procedures for the calf has been outlined previously (2, 40). Calf muscle volume was assessed from the caput fibulae to the lower portion of the soleus. For each slice, the cross-sectional area of the muscles of interest (medial gastrocnemius, lateral gastrocnemius, and soleus) was traced five times and the average used for the muscle volume calculation. Muscle volume (cm3) was calculated by multiplying the cross-sectional area of each muscle by the appropriate slice thickness. The left leg of each subject was used for all measurements. The same investigator completed all measurements. The images were coded to blind the investigator as to which images were pre- or postflight.

Muscle performance.   Maximal voluntary contraction and isokinetic strength of the left leg calf muscles was assessed using a torque-velocity dynamometer as previously described (37, 38). Each crewmember performed two familiarization sessions before preflight trials. Before launch, each crewmember performed four complete testing sessions over an ~4-mo period (L–127 ± 13, L–87 ± 13, L–40 ± 4, and L–27 ± 1). Postflight, torque-velocity dynamometer measurements were obtained at R+7 and R+13 for all subjects.

The calf muscle strength protocol consisted of two parts: 1) maximal isometric strength at ankle angles of 80°, 90°, and 100° (with 90° a neutral position) and 2) force-velocity measurements at 30, 60, 120, 180, 240, and 300°/s. With rest periods included, the total test time was ~30 min. At each isometric ankle angle, the subjects performed two 50% efforts for warm-up followed by one maximal effort lasting 5 s. At each isokinetic test velocity, a series of four warm-up contractions at ~50% effort were performed to familiarize the subjects to the test velocity and movement. After this warm-up, subjects were asked to perform four maximal plantar flexion contractions at the corresponding angular velocity. These contractions occurred with ~1 s between repetitions. In addition, no preload was applied to the muscle. A 2-min rest period occurred between each test velocity. Peak torque, independent of angle, at a given velocity was taken as the highest value obtained for each of the four contractions.

Muscle biopsy.   A muscle biopsy (6) was obtained from the lateral head of the gastrocnemius and soleus muscle of each crewmember before launch (L–55 ± 2) and on landing day (R+0). The landing day muscle biopsy was generally performed mid to late afternoon ~6–8 h after landing. Crewmembers were transported to the main medical operations facilities for observation. After a period of personal activities the crewmembers were brought to the data collection facility for the muscle biopsies. Crewmembers had performed very light ambulatory activities before the muscle biopsy procedure.

Each muscle biopsy sample was sectioned into several longitudinal pieces for various analyses [single-fiber physiology, single-fiber myosin heavy chain (MHC) analysis, single-fiber biochemistry, and microanatomy experiments]. This report presents the single-fiber MHC analysis from the gastrocnemius and soleus muscles.

Single muscle fiber MHC analysis.   Single muscle fiber segments (~4 mm) were isolated from a muscle bundle and solubilized in 80 µl of 1% SDS sample buffer and stored at –20°C until assayed (45). Briefly, samples were run overnight at 4°C on a Hoefer SE 600 gel electrophoresis unit (San Francisco, CA) utilizing a 3.5% (wt/vol) acrylamide stacking gel with a 5% separating gel. After electrophoresis, the gels were silver stained as described by Giulian et al. (14). MHC isoforms were identified according to migration rate.

Nutritional profile.   During flight, consumption of food and fluid was monitored according to the same schedule, but subjects used an automated bar code scanning system in which each individually packaged food item was labeled. The in-flight diet was designed to meet the nutritional requirements for ISS missions as established by NASA and the Russian Space Agency (28). Neither diet nor activity levels were restricted during any of the sampling periods. In-flight consumption data were stored in the bar code reader and downloaded to the ground.

Nutrient content of the pre- and postflight foods was calculated using the Nutrient Data System for Research (NDSR; versions 4.02/30 through 5.0/35), developed by the Nutrition Coordinating Center (University of Minnesota, Minneapolis, MN) (24). Nutrient content of the in-flight foods was calculated from food chemical data generated by the NASA JSC Water and Food Analytical Laboratory.

Statistical analysis.   The effect of spaceflight on whole muscle volume (MRI) and function [all isokinetic speeds and maximal voluntary contraction (MVC) angles] was analyzed using a one-way repeated-measures ANOVA for each variable. A significant time effect was interpreted using pairwise comparisons combined with the Bonferroni adjustment. Whole muscle volume comparisons between the soleus and gastrocnemius muscles were conducted using a two-way (time x muscle) repeated-measures ANOVA. Single-muscle fiber type changes were conducted using a two-tailed t-test for each MHC type. The Pearson correlation test was used for the correlation analyses. Significance was set at P < 0.05. All data are means ± SE.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
Exercise training profile.   A summary of the aerobic exercise performed while in space is shown in Table 2. There was a wide range of aerobic training performed by the crewmembers. Aerobic exercise (cycle + treadmill) approached ~5 h/wk or ~50 min/day. On average, subjects completed 138 ± 26 min/wk of cycle exercise that generally ranged between 100 and 150 W. While in orbit, crewmembers used the cycle ergometer ~60% of mission days. Four of the crewmembers (subjects A, B, C, and G) used the cycle ergometer ~81% (range = 70–90%) or more of mission days, whereas four others (subjects D, F, H, and I) averaged ~37% (range = 28–41%) of mission days, and one crewmember (subject E) did minimal cycling. For the treadmill exercise, subjects averaged 146 ± 34 min/wk on a level grade at a speed ranging from 2.1 to 5.5 miles/h. The treadmill appeared to be used less frequently compared with the cycle ergometer, accounting for <50% of total mission days. However, there was a wide range of treadmill use, with four crewmembers (subjects B, E, G, and H) having a high volume (>200 min/wk) of walking/running activities. The other five crewmembers (subjects A, C, D, F, and I) used the treadmill much less (≤85 min/wk).


View this table:
[in this window]
[in a new window]

  		Table 2. Summary of aerobic exercise performed while on the ISS

 
A summary of the resistance exercise performed while in space is shown in Table 3. Generally, all crewmembers performed a suite of leg exercise routines consisting of squats, heel raises, and dead lifts. The program varied for each crewmember, with everyone performing resistance exercise at least 3 days/wk and several conducting resistance training 5–6 days/wk. During the resistance training sessions, crewmembers averaged 3–6 sets of 12–20 repetitions for each leg exercise. We were unable to get an accurate account of the time involved with the resistance exercise. Based on the number of contractions and assuming a 2-s count for concentric and eccentric contractions (from video), we estimate crewmembers spent more than 1 h/wk with the leg muscles under tension during resistance exercise.


View this table:
[in this window]
[in a new window]

  		Table 3. Summary of resistance exercise performed while on the ISS

 
Based on the exercise database and available videos of crewmembers while exercising (cycling, running, and lifting), we were able to estimate the number of muscle contractions performed while in space (Table 4). On average, crewmembers performed more than 435,000 muscle contractions per leg during scheduled exercise while in space. As noted earlier, the exercise program was highly variable with a low of ~200,000 (subject C) and a high approaching 1 million (subject B) muscle contractions for each leg. Generally, crewmembers performed exercise 6 of 7 days/wk. Of the total time in orbit (~4,248 h), the exercise program presented (minus setup, stowage, and hygiene) constituted ~3.4% of the time. When sleep, workday schedule, and leisure time were considered, the estimate for exercise time increased to 7–10% of the available time for the crewmembers while in space.


View this table:
[in this window]
[in a new window]

  		Table 4. Summary of muscle contractions performed and time commitment for the exercise training regimen performed during the 6 mo in space

 
Muscle volume.   A summary of calf muscle volume before and after space flight is shown in Table 5. The gastrocnemius (medial and lateral) and soleus muscle were smaller (P < 0.05) after 6 mo in space. Combined, the gastrocnemius and soleus atrophied (P < 0.05) –13 ± 2% pre- to postflight. The soleus (–15 ± 2%) atrophied more (P < 0.05) than the gastrocnemius (–10 ± 2%) pre- to postflight (Fig. 1). One crewmember (subject E) had insignificant (–1%) atrophy after the flight. Two of the crewmembers (subjects A and F) lost more than 20% of their calf muscle mass. Of the remaining six crewmembers, five lost more than 10% calf muscle mass.


View this table:
[in this window]
[in a new window]

  		Table 5. Calf muscle volume before and after spaceflight

 

Figure 1
View larger version (14K):
[in this window]
[in a new window]

  		Fig. 1. Percent change in gastrocnemius and soleus muscle volume from preflight to postflight recovery days 4 (R+4) and 19 (R+19). *P < 0.05 vs. preflight. {dagger}P < 0.05 vs. gastrocnemius.

 
At R+19 after landing, the gastrocnemius was still 5–6% atrophied, but this was not significant. Conversely, the soleus was still reduced (P < 0.05) compared with preflight, averaging –9 ± 1% for all crewmembers. Although calf muscle volume was still reduced –8 ± 2%, it represented a partial recovery from the more immediate (R+4) flight measurement.

Muscle performance.   A summary of each crewmember's calf muscle performance for MVC at one angle (neutral position) and a slow (60°/s) and fast (180°/s) isokinetic speed are shown in Table 6. MVC was reduced (P < 0.05) –14 ± 2% at R+7 and remained lower (–13 ± 5%; P < 0.05) at R+13. All nine crewmembers had a decline in MVC (range = –7 to –22%) with flight. At R+13, seven of the nine crewmembers were lower (range = –9 to –33%), with two crewmembers (subjects A and H) having a 5–10% increase compared with preflight.


View this table:
[in this window]
[in a new window]

  		Table 6. Calf muscle performance profile before and after spaceflight

 
At the slow isokinetic speed (60°/s) there was a –20 ± 3% loss (P < 0.05), which was sustained (–19 ± 4; P < 0.05) at R+13. This pattern was also evident at the faster (180°/s) isokinetic speed with a 25 ± 10% reduction at R+7 and R+13. For both the slow and fast speeds, eight of the nine subjects had a decrease in muscle performance.

A force-velocity curve for all subjects from pre- to postflight (R+7) is shown in Fig. 2. On average, force-velocity characteristics were reduced –20 to –29% across the velocity spectrum (P < 0.05). Peak power was 134 ± 11, 91 ± 10, and 94 ± 13 W preflight, R+7, and R+13, respectively. On average, peak power declined 32% with spaceflight (P < 0.05).


Figure 2
View larger version (14K):
[in this window]
[in a new window]

  		Fig. 2. Calf muscle force-velocity profile before and after spaceflight. *P < 0.05 vs. preflight.

 
Muscle fiber type.   We isolated and analyzed the MHC profile on a total of 4,328 single muscle fibers from the gastrocnemius and soleus muscles before and after flight. The breakdown was 1,960 muscle fibers (1,109 preflight, 851 postflight) for the gastrocnemius and 2,368 muscle fibers (1,277 preflight, 1,091 postflight) for the soleus.

The average MHC profile of the gastrocnemius and soleus muscles from the crewmembers before and after space flight is shown in Fig. 3. Individual data from the gastrocnemius and soleus of each crewmember are shown in Tables 7 and 8, respectively. One individual (subject B) had a small muscle biopsy sample and therefore was not included in these analyses. The gastrocnemius had a 12% decrease (P < 0.05) in MHC I fibers and an increase (P < 0.05) in MHC I/IIa (+4%) hybrid fibers and MHC IIa fibers (+9%). Seven of the eight subjects had a decrease in MHC I fibers (range = –6 to –31%). There were minimal MHC IIx and MHC I/IIa/IIx fibers detected in the pre- and postflight muscle samples. The 4% increase in hybrid muscle fibers appears to be the result of the MHC I/IIa hybrid fiber type.


Figure 3
View larger version (14K):
[in this window]
[in a new window]

  		Fig. 3. Myosin heavy chain (MHC) composition of the gastrocnemius and soleus muscles before and after spaceflight. Hybrid, all fibers with more than one MHC isoform. *P < 0.05 vs. preflight.

 

View this table:
[in this window]
[in a new window]

  		Table 7. Gastrocnemius fiber type distribution before and after spaceflight

 

View this table:
[in this window]
[in a new window]

  		Table 8. Soleus fiber type distribution before and after spaceflight

 
On average, the soleus had a 17% decrease (P < 0.05) in MHC I fibers. The shift away from MHC I fibers was distributed among the other fiber types (MHC I/IIa, IIa, IIa/IIx), with a nonsignificant increase of 4–5% within each MHC phenotype. Combined, the soleus had a 12% increase (P < 0.05) in hybrid MHC isoforms. Three of the crewmembers (subjects D, E, and I) did not have any major alterations in fiber type of the soleus. Four of the crewmembers (subjects A, C, F, and G) had a decrease in soleus MHC I fibers that ranged from –20 to –44%.

Nutrition.   Crewmembers had a daily average caloric intake of 2,377 ± 118 kcal (range = 1,874–2,902 kcal). The dietary percent breakdown of carbohydrate, fat, and protein was 48, 33, and 18%, respectively.

Energy expenditure estimations during exercise.   We made the following estimates for aerobic and resistance exercise: 1) cycling in space at the workload generally performed by the ISS crewmembers (100–150 W) has been reported to be ~1.5–2.0 l/min (39), which would be equivalent to 7.5–10.0 kcal/min. Since we were unable to make a direct estimate for the treadmill exercise, we assumed an oxygen uptake similar to the cycle exercise: 2) a maximal resistance exercise bout of three sets of eight repetitions has a net caloric cost of 90 kcal (8). Given the less intense loading of the iRED and factoring for a greater number of contractions per set (12–20 repetitions), we used a conservative estimate of 70 kcal per set. Given the multiple resistance exercise routines using the lower legs, we estimate ~200 kcal per session.

Correlations.   A positive correlation between initial muscle volume and absolute muscle volume loss was observed (r2 = 0.48, P < 0.05) and is shown in Fig. 4. A negative correlation between treadmill exercise volume (min/wk) and absolute muscle mass loss was observed (r2 = –0.34, P = 0.09) and is shown in Fig. 5. From Fig. 5, it can be noted that when treadmill volume was <100 min/wk, there was a wide range in muscle mass loss (>100 cm3). When treadmill volume was 200–300 min/wk, there was less muscle mass loss (≤62 cm3). For total aerobic exercise volume (treadmill + cycle ergometer), a poor correlation was observed (r2 = 0.08, nonsignificant) in relation to muscle mass loss. A direct correlation between the decrease in calf muscle strength and mass was not found.


Figure 4
View larger version (13K):
[in this window]
[in a new window]

  		Fig. 4. Correlation between calf muscle volume before spaceflight and calf muscle volume loss with spaceflight.

 

Figure 5
View larger version (13K):
[in this window]
[in a new window]

  		Fig. 5. Correlation between treadmill exercise time (min/wk) while on the International Space Station and calf muscle volume loss (cm3) with spaceflight.

 

   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
This study provides a detailed overview of the exercise performed by nine crewmembers while on the ISS for 6 mo. We examined the benefits of this exercise program for protecting various aspects of skeletal muscle mass and performance. The main finding from this project was that the exercise program did not completely protect the calf muscles. We observed a substantial decrease in calf muscle mass and performance along with a slow-to-fast fiber-type transition in the gastrocnemius and soleus muscles, which are all traits associated with unloading in humans. These data suggest that changes to the exercise countermeasure program are required to more fully protect human skeletal muscle while crewmembers are in space for extended periods.

The in-flight exercise program performed among the crewmembers we tested had a large disparity in volume and mode of activity that was impacted by operational constraints outside of our control. The postflight testing timeline was driven by operational considerations, other research protocols, and crewmember availability. The muscle biopsies were obtained on R+0 within a few hours of landing with minimal reambulation, which was ideal given the constraints of spaceflight research. The initial measures of muscle volume (using MRI) on R+4 were as close to landing day as logistically possible and provided an excellent snapshot of muscle volume after 6 mo in space. The initial measures of muscle performance on R+7 and subsequent muscle testing in weeks 2 and 3 after landing may have been influenced by muscle soreness and the varied physical activity routines performed by the crewmembers.

The average amount of muscle mass lost (–13%) with spaceflight was slightly less than with previous long-duration stays on the Russian Space Station Mir (–17%) (20). The current ISS and previous Mir calf muscle volume loss is about one-half that of long-duration (60- to 120-day) bed rest studies showing a ~29% decrease among the control subjects without countermeasures (2, 21, 27, 40). These data imply that the exercise in space is having a beneficial effect but is not complete, with the soleus being more difficult to protect than the gastrocnemius. From the MRI and exercise data and estimates of caloric intake and energy expenditure, four factors (in addition to the microgravity environment) appear to be contributing to the calf muscle volume findings. The first is the calf muscle volume before spaceflight. Our data suggest that the crewmembers with larger calf muscles had a greater degree of atrophy with long-duration spaceflight (Fig. 4). Second, the volume of treadmill exercise may have provided a level of protection for calf muscle mass. The three individuals (subjects B, E, and H) who performed >200 min/wk on the treadmill lost about one-third of the calf muscle volume (–43 ± 19 cm3) compared with crewmembers who used the treadmill <100 min/wk (–135 ± 16 cm3). As a percentage, this translated into a –7 ± 3% muscle loss for the high-volume treadmill users and –17 ± 2% for the low-volume treadmill users. Interestingly, two of the high-volume treadmill users who lost the least amount of muscle mass (subjects B and E) also had the smallest calf muscles before flight. Third, when the treadmill is used in passive mode, more force is needed to drive the belt during walking/running activities and may help protect against calf muscle atrophy. Finally, inadequate caloric intake may have contributed to the muscle atrophy. These combined factors (initial muscle volume, amount of treadmill exercise, mode of treadmill use, and negative caloric balance) likely contributed to the varied muscle mass findings in this investigation.

A substantial decline (–20 to –29%) in calf muscle performance with spaceflight was noted for both static (9 of 9 subjects) and dynamic (8 of 9 subjects) muscle actions. These data are in close agreement with the decline in muscle performance after 84 days on Skylab (–25%) (23) and 180 days on the Mir (–35%) (17, 46). The decline in muscle performance following long-duration stays in space is less than in bed-rested subjects (~40% loss) without countermeasures (2, 15, 27, 40), suggesting that the ISS exercise program did provide a modest level of protection. However, the magnitude of loss in muscle performance was still quite large and covered a broad range of muscle performance from high-tension, slow movements to faster, more explosive movements. The overall reduction in muscle performance was sustained 2 wk after landing, with three of the crewmembers having a further decline in muscle performance at R+13. We speculate that the varied recovery in muscle performance was related to muscle soreness and muscle damage from reloading in a 1-G environment. This idea is well supported by data in humans and rodents showing a high incidence of muscle fiber ruptures in the initial hours of reambulation after unloading (44) and deficits in force-power characteristics that persist for several days/weeks (22, 42). The lack of recovery in muscle performance was in contrast to the partial recovery of muscle mass. The fact that the decline in muscle strength could not be completely accounted for by decline in muscle mass after flight and recovery is supported by numerous previous ground-based unloading studies (1, 2, 4, 9, 10, 19, 33, 40). The low relationship between muscle strength and size with unloading has been partially explained by a decrease in neural drive (2, 3, 26, 33) and alterations in muscle fiber quantity and quality (18, 34, 35, 41, 43).

The muscle biopsy data presented are the first from humans following a long-duration spaceflight. We observed a 12–17% shift in MHC phenotype of the gastrocnemius and soleus muscles after 6 mo on the ISS. The MHC shift was primarily driven by a decrease in MHC I fibers with a redistribution among the faster phenotypes. Overall, the change in gastrocnemius MHC phenotype among the crewmembers was more uniform compared with the soleus. Three crewmembers had no major shift in soleus MHC, whereas the other crewmembers had a robust slow-to-fast MHC transition. In particular, two crewmembers (subjects A and F) had massive changes in their soleus MHC profile. These same two crewmembers also had the largest change (>20%) in soleus muscle volume. For the remainder of the crewmembers, there was a wide mixture of results in the MHC profile relating to changes in muscle mass and muscle performance, with no clear relationship among these parameters and the exercise program.

The idea of a slow-to-fast muscle fiber transition with unloading is well documented in rodent (7, 32) and human (13, 47) muscles. Edgerton and colleagues (11, 47) reported a modest slow-to-fast muscle fiber transition (6–8%) in the vastus lateralis following short-term (5 and 11 days) spaceflight (11, 47). After a 17-day spaceflight, our laboratories did not observe any major shifts in gastrocnemius or soleus muscle fiber types (41, 43), which was likely attributed to the volume of high-intensity calf muscle testing throughout the flight (38). With long-duration bed rest (90 days), there was a larger decrease in MHC I fibers of 15–20% in the vastus lateralis and soleus muscles, with a large increase in the proportion of fibers containing the MHC IIx phenotype (>20%) (13, 36). Collectively, these data suggest that the exercise performed while on the ISS had some benefit for the myocellular components. This concept is supported by the fact that that ISS postflight muscle samples did not have a large increase in the MHC IIx phenotype and that the magnitude of shift away from MHC I fibers was slightly attenuated compared with previous long-duration bed rest studies. However, for some crewmembers, the shift in MHC phenotype was greater than observed following long-duration bed rest with no countermeasures.

Although nutrition was not the focus of this investigation, we were able to obtain a basic nutritional profile of the crewmembers while they were on the ISS. Voluntary energy intake while in space has been reported to be reduced by ~20% (29, 31) and poses additional concern for muscle wasting. Together, the aerobic and resistance exercise for the crewmembers in the current study would account for 2,850–4,200 additional kcal/week. Our 430–600 kcal/day estimate is in good agreement with previous reports from the ISS (16). A previous energy expenditure report of humans working in space with no exercise countermeasures was ~31 kcal·kg–1·day–1 (30). Interestingly, the daily energy intake of the crewmembers we studied was ~30 kcal·kg–1·day–1, which would be 17–23% below the predicted caloric need (35–37 kcal·kg–1·day–1) when the exercise is considered.

Although we could not quantify the intensity of the resistance exercise with any certainty, the iRED device has known loading limitations (25) that likely contributed to the high-volume, low-intensity resistance exercise program employed by the crewmembers. In the last decade, a large amount of data from short- and long-term ground-based unloading studies in humans have provided strong evidence for the use of high-intensity resistance exercise to protect against skeletal muscle atrophy. Recently, we observed that a balanced high-intensity resistance (2–3 days/wk) and aerobic (~4 days/wk) exercise program was more effective for preserving skeletal muscle characteristics during extended bed rest (34, 35, 40) compared with the current ISS study. The high-intensity resistance exercise performed during bed rest resulted in the leg muscles being under tension ~7 min/wk, compared with >60 min/wk in crewmembers on the ISS. The concurrent exercise prescription constituted 1.75% of the bed rest period and ~13,250 muscle contractions per week (34), which is considerably less than the 3.4% of time in space and ~17,300 muscle contractions per week that was dedicated to exercise on the ISS. The additional 4,000 muscle contractions per week translate into 100,000 more muscle contractions during a 6-mo mission and highlight that quality (i.e., intensity) is more effective than quantity for protecting skeletal muscle size and performance during long-duration unloading.

The exercise and muscle data gathered from the nine crewmembers while on the ISS for 6 mo clearly support that changes to the exercise prescription are necessary to protect skeletal muscle with long-duration space missions. In addition to the risk associated with reduced muscle performance, the decrease in muscle mass and contractile phenotype shift has risk implications for sensory-motor deficits and skeletal muscle health (i.e., fuel use, reduced oxidative capacity, fatigue, insulin resistance). The exercise program performed on the ISS was mainly of moderate intensity. Including hardware that had greater loading capabilities for high-intensity exercise as well as monitoring the crewmembers periodically during spaceflight would allow the exercise program to be modified accordingly. Applying these principles to the manned space program would lead to a more effective exercise program for skeletal muscle, reduce the risk imposed to the crewmembers, and likely reduce the total time necessary for exercise while in space.


   GRANTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
ACKNOWLEDGMENTS
 REFERENCES
 
This research was support by NASA Grant EC400-NCC9-116.


   ACKNOWLEDGMENTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
REFERENCES
 
We thank the astronauts and cosmonauts who graciously gave their time and energy to this research. We thank Simone Thomas, Elkin Romero, Alicia Forrester, the flight surgeons, and the numerous unnamed people who assisted our research team at the National Aeronautics and Space Administration (NASA) and Russian Space Agency. Also, we thank Gary Lee for technical support for the muscle performance device, Adrian Leblanc and V. Sinisyn for assistance with the MRI scans in the U.S. and Russia, Adam Konopka for technical assistance with the MRI analysis, Scott Smith for assistance with the nutritional profile of the crewmembers, and Janell Romatowski for assistance in facilitating data acquisition and analysis.


   FOOTNOTES
 

Address for reprint requests and other correspondence: S. Trappe, Human Performance Laboratory, Ball State Univ., Muncie, IN 47306 (e-mail: strappe{at}bsu.edu)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 

  1. Adams GR, Hather BM, Dudley GA. Effect of short-term unweighting on human skeletal muscle strength and size. Aviat Space Environ Med 65: 1116–1121, 1994.[Medline]
  2. Alkner BA, Tesch PA. Knee extensor and plantar flexor muscle size and function following 90 days of bed rest with or without resistance exercise. Eur J Appl Physiol 93: 294–305, 2004.[CrossRef][Web of Science][Medline]
  3. Berg HE, Dudley GA, Haggmark T, Ohlsen H, Tesch PA. Effects of lower limb unloading on skeletal muscle mass and function in humans. J Appl Physiol 70: 1882–1885, 1991.[Abstract/Free Full Text]
  4. Berg HE, Larsson L, Tesch PA. Lower limb skeletal muscle function after 6 wk of bed rest. J Appl Physiol 82: 182–188, 1997.[Abstract/Free Full Text]
  5. Berg HE, Tedner B, Tesch PA. Changes in lower limb muscle cross-sectional area and tissue fluid volume after transition from standing to supine. Acta Physiol Scand 148: 379–385, 1993.[Web of Science][Medline]
  6. Bergstrom J. Muscle electrolytes in man. Scand J Clin Lab Invest 14, Suppl 68: 7–110, 1962.[Web of Science][Medline]
  7. Caiozzo VJ, Haddad F, Baker MJ, Herrick RE, Prietto N, Baldwin KM. Microgravity-induced transformations of myosin isoforms and contractile properties of skeletal muscle. J Appl Physiol 81: 123–132, 1996.[Abstract/Free Full Text]
  8. Caruso JF, Hernandez DA. Net caloric cost of a 3-set flywheel ergometer resistance exercise paradigm. J Strength Cond Res 16: 567–572, 2002.[CrossRef][Web of Science][Medline]
  9. Convertino VA, Doerr DF, Mathes KL, Stein SL, Buchanan P. Changes in volume, muscle compartment, and compliance of the lower extremities in man following 30 days of exposure to simulated microgravity. Aviat Space Environ Med 60: 653–658, 1989.[Medline]
  10. Dudley GA, Duvoisin MR, Convertino VA, Buchanan P. Alterations of the in vivo torque-velocity relationship of human skeletal muscle following 30 days exposure to simulated microgravity. Aviat Space Environ Med 60: 659–663, 1989.[Medline]
  11. Edgerton VR, Zhou MY, Ohira Y, Klitgaard H, Jiang B, Bell G, Harris B, Saltin B, Gollnick PD, Roy RR, Day MK, Greenisen M. Human fiber size and enzymatic properties after 5 and 11 days of spaceflight. J Appl Physiol 78: 1733–1739, 1995.[Abstract/Free Full Text]
  12. Fitts RH, Riley DR, Widrick JJ. Physiology of a microgravity environment invited review: microgravity and skeletal muscle. J Appl Physiol 89: 823–839, 2000.[Abstract/Free Full Text]
  13. Gallagher P, Trappe S, Harber M, Creer A, Mazzetti S, Trappe T, Alkner B, Tesch P. Effects of 84-days of bed rest and resistance training on single muscle fibre myosin heavy chain distribution in human vastus lateralis and soleus muscles. Acta Physiol Scand 185: 61–69, 2005.[CrossRef][Web of Science][Medline]
  14. Giulian GG, Moss RL, Greaser M. Improved methodology for analysis and quantitation of proteins on one-dimensional silver-stained slab gels. Anal Biochem 129: 277–287, 1983.[CrossRef][Web of Science][Medline]
  15. Koryak Y. The effects of long-term simulated microgravity on neuromuscular performance in men and women. Eur J Appl Physiol Occup Physiol 79: 168–175, 1999.[CrossRef][Web of Science][Medline]
  16. Kozlovskaya IB, Grigoriev AI. Russian system of countermeasures on board of the International Space Station (ISS): the first results. Acta Astronaut 55: 233–237, 2004.[CrossRef][Web of Science][Medline]
  17. Lambertz D, Perot C, Kaspranski R, Goubel F. Effects of long-term spaceflight on mechanical properties of muscles in humans. J Appl Physiol 90: 179–188, 2001.[Abstract/Free Full Text]
  18. Larsson L, Li X, Berg HE, Frontera WR. Effects of removal of weight-bearing function on contractility and myosin isoform composition in single human skeletal muscle cells. Pflügers Arch 432: 320–328, 1996.[CrossRef][Web of Science][Medline]
  19. LeBlanc A, Gogia P, Schneider V, Krebs J, Schonfeld E, Evans H. Calf muscle area and strength changes after five weeks of horizontal bed rest. Am J Sports Med 16: 624–629, 1988.[Abstract/Free Full Text]
  20. LeBlanc A, Lin C, Shackelford L, Sinitsyn V, Evans H, Belichenko O, Schenkman B, Kozlovskaya I, Oganov V, Bakulin A, Hedrick T, Feeback D. Muscle volume, MRI relaxation times (T2), and body composition after spaceflight. J Appl Physiol 89: 2158–2164, 2000.[Abstract/Free Full Text]
  21. LeBlanc AD, Schneider VS, Evans HJ, Pientok C, Rowe R, Spector E. Regional changes in muscle mass following 17 weeks of bed rest. J Appl Physiol 73: 2172–2178, 1992.[Abstract/Free Full Text]
  22. Narici M, Kayser B, Barattini P, Cerretelli P. Effects of 17-day spaceflight on electrically evoked torque and cross-sectional area of the human triceps surae. Eur J Appl Physiol 90: 275–282, 2003.[CrossRef][Web of Science][Medline]
  23. Rummel JA, Sawin CF, Michel EL, Buderer MC, Thornton WT. Exercise and long duration spaceflight through 84 days. J Am Med Womens Assoc 30: 173–187, 1975.[Medline]
  24. Schakel SF, Sievert YA, Buzzard IM. Sources of data for developing and maintaining a nutrient database. J Am Diet Assoc 88: 1268–1271, 1988.[Web of Science][Medline]
  25. Schneider SM, Amonette WE, Blazine K, Bentley J, Lee SM, Loehr JA, Moore AD Jr, Rapley M, Mulder ER, Smith SM. Training with the International Space Station interim resistive exercise device. Med Sci Sports Exerc 35: 1935–1945, 2003.[CrossRef][Web of Science][Medline]
  26. Schulze K, Gallagher P, Trappe S. Resistance training preserves skeletal muscle function during unloading in humans. Med Sci Sports Exerc 34: 303–313, 2002.[CrossRef][Web of Science][Medline]
  27. Shackelford LC, LeBlanc AD, Driscoll TB, Evans HJ, Rianon NJ, Smith SM, Spector E, Feeback DL, Lai D. Resistance exercise as a countermeasure to disuse-induced bone loss. J Appl Physiol 97: 119–129, 2004.[Abstract/Free Full Text]
  28. Smith S, Zwart S. Nutritional biochemistry of spaceflight. Adv Clin Chem 46: 87–130, 2008.[CrossRef][Web of Science][Medline]
  29. Smith SM, Zwart SR, Block G, Rice BL, Davis-Street JE. The nutritional status of astronauts is altered after long-term space flight aboard the International Space Station. J Nutr 135: 437–443, 2005.[Abstract/Free Full Text]
  30. Stein TP, Leskiw MJ, Schluter MD. Diet and nitrogen metabolism during spaceflight on the shuttle. J Appl Physiol 81: 82–97, 1996.[Abstract/Free Full Text]
  31. Stein TP, Leskiw MJ, Schluter MD, Donaldson MR, Larina I. Protein kinetics during and after long-duration spaceflight on MIR. Am J Physiol Endocrinol Metab 276: E1014–E1021, 1999.[Abstract/Free Full Text]
  32. Talmadge RJ, Roy RR, Edgerton VR. Distribution of myosin heavy chain isoforms in non-weight-bearing rat soleus muscle fibers. J Appl Physiol 81: 2540–2546, 1996.[Abstract/Free Full Text]
  33. Tesch PA, Trieschmann JT, Ekberg A. Hypertrophy of chronically unloaded muscle subjected to resistance exercise. J Appl Physiol 96: 1451–1458, 2004.[Abstract/Free Full Text]
  34. Trappe S, Creer A, Minchev K, Slivka D, Louis E, Luden N, Trappe T. Human soleus single muscle fiber function with exercise or nutrition countermeasures during 60 days of bed rest. Am J Physiol Regul Integr Comp Physiol 294: R939–R947, 2008.[Abstract/Free Full Text]
  35. Trappe S, Creer A, Slivka D, Minchev K, Trappe T. Single muscle fiber function with concurrent exercise or nutrition countermeasures during 60 days of bed rest in women. J Appl Physiol 103: 1242–1250, 2007.[Abstract/Free Full Text]
  36. Trappe S, Trappe T, Gallagher P, Harber M, Alkner B, Tesch P. Human single muscle fibre function with 84 day bed-rest and resistance exercise. J Physiol 557: 501–513, 2004.[Abstract/Free Full Text]
  37. Trappe SW, Trappe TA, Lee GA, Costill DL. Calf muscle strength in humans. Int J Sports Med 22: 186–191, 2001.[CrossRef][Web of Science][Medline]
  38. Trappe SW, Trappe TA, Lee GA, Widrick JJ, Costill DL, Fitts RH. Comparison of a space shuttle flight (STS-78) and bed rest on human muscle function. J Appl Physiol 91: 57–64, 2001.[Abstract/Free Full Text]
  39. Trappe T, Trappe S, Lee G, Widrick J, Fitts R, Costill D. Cardiorespiratory responses to physical work during and following 17 days of bed rest and spaceflight. J Appl Physiol 100: 951–957, 2006.[Abstract/Free Full Text]
  40. Trappe TA, Burd NA, Louis ES, Lee GA, Trappe SW. Influence of concurrent exercise or nutrition countermeasures on thigh and calf muscle size and function during 60 days of bed rest in women. Acta Physiol (Oxf) 191: 147–159, 2007.[CrossRef][Medline]
  41. Widrick JJ, Knuth ST, Norenberg KM, Romatowski JG, Bain JL, Riley DA, Karhanek M, Trappe SW, Trappe TA, Costill DL, Fitts RH. Effect of a 17 day spaceflight on contractile properties of human soleus muscle fibres. J Physiol 516: 915–930, 1999.[Abstract/Free Full Text]
  42. Widrick JJ, Maddalozzo GF, Hu H, Herron JC, Iwaniec UT, Turner RT. Detrimental effects of reloading recovery on force, shortening velocity, and power of soleus muscles from hindlimb-unloaded rats. Am J Physiol Regul Integr Comp Physiol 295: R1585–R1592, 2008.[Abstract/Free Full Text]
  43. Widrick JJ, Romatowski JG, Norenberg KM, Knuth ST, Bain JL, Riley DA, Trappe SW, Trappe TA, Costill DL, Fitts RH. Functional properties of slow and fast gastrocnemius muscle fibers after a 17-day spaceflight. J Appl Physiol 90: 2203–2211, 2001.[Abstract/Free Full Text]
  44. Widrick JJ, Trappe SW, Romatowski JG, Riley DA, Costill DL, Fitts RH. Unilateral lower limb suspension does not mimic bed rest or spaceflight effects on human muscle fiber function. J Appl Physiol 93: 354–360, 2002.[Abstract/Free Full Text]
  45. Williamson DL, Godard MP, Porter DA, Costill DL, Trappe SW. Progressive resistance training reduces myosin heavy chain coexpression in single muscle fibers from older men. J Appl Physiol 88: 627–633, 2000.[Abstract/Free Full Text]
  46. Zange J, Muller K, Schuber M, Wackerhage H, Hoffmann U, Gunther RW, Adam G, Neuerburg JM, Sinitsyn VE, Bacharev AO, Belichenko OI. Changes in calf muscle performance, energy metabolism, and muscle volume caused by long-term stay on space station MIR. Int J Sports Med 18, Suppl 4: S308–S309, 1997.[CrossRef][Web of Science][Medline]
  47. Zhou MY, Klitgaard H, Saltin B, Roy RR, Edgerton VR, Gollnick PD. Myosin heavy chain isoforms of human muscle after short-term spaceflight. J Appl Physiol 78: 1740–1744, 1995.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
C. E. Pandorf, W. H. Jiang, A. X. Qin, P. W. Bodell, K. M. Baldwin, and F. Haddad
Calcineurin plays a modulatory role in loading-induced regulation of type I myosin heavy chain gene expression in slow skeletal muscle
Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2009; 297(4): R1037 - R1048.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
K. A. Zwetsloot, M. J. Laye, and F. W. Booth
Novel epigenetic regulation of skeletal muscle myosin heavy chain genes. Focus on "Differential epigenetic modifications of histones at the myosin heavy chain genes in fast and slow skeletal muscle fibers and in response to muscle unloading"
Am J Physiol Cell Physiol, July 1, 2009; 297(1): C1 - C3.
[Full Text] [PDF]

This Article
Free upon publication Free Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow All Versions of this Article:
106/4/1159    most recent
91578.2008v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Trappe, S.
Right arrow Articles by Fitts, R. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Trappe, S.
Right arrow Articles by Fitts, R. H.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2009 by the American Physiological Society.