Skeletal muscle morphology, satellite cells, and oxidative profile in relation to physical function and lifelong endurance training in very old men.

In the current study, we compared muscle morphology in three advanced aging cohorts that differed in physical function, including a unique cohort of lifelong endurance athletes. Biopsies from the vastus lateralis muscle of seven lifelong endurance athletes (EAs) aged 82-92 yr, and 19 subjects from the Uppsala Longitudinal Study of Adult Men (ULSAM) aged 87-91 yr were analyzed. ULSAM subjects were divided into high- (n = 9, HF) and low- (n = 10, LF) function groups based on strength and physical function tests. The analysis included general morphology, fiber type and cross-sectional area, capillarization, deficient cytochrome c oxidase (COX) activity, number of myonuclei and satellite cells, and markers of regeneration and denervation. Fibers with central nuclei and/or nuclear clumps were observed in all groups. EA differed from LF and HF by having a higher proportion of type I fibers, 52% more capillaries in relation to fiber area, fewer COX-negative fibers, and less variation in fiber sizes (all P < 0.05). There were no differences between the groups in the number of myonuclei and satellite cells per fiber, and no significant differences between LF and HF (P > 0.05). In conclusion, signs of aging were evident in the muscle morphology of all groups, but neither endurance training status nor physical function influenced signs of regeneration and denervation processes. Lifelong endurance training, but not higher physical function, was associated with higher muscle oxidative capacity, even beyond the age of 80.NEW & NOTEWORTHY Here we show that lifelong endurance training, but not physical function, is associated with higher muscle oxidative capacity, even beyond the age of 80 yr. Neither endurance training status nor physical function was significantly associated with satellite cells or markers of regeneration and denervation in muscle biopsies from these very old men.

Early accentuated muscle hypertrophy is strongly associated with myonuclear accretion.

The current study explored whether the marked hypertrophic response noted with a short-term unilateral concurrent exercise paradigm was associated with more prominent changes in myonuclei accretion, ribosome biogenesis, and capillarization compared with resistance exercise alone (RE). Ten men (age 25 ± 4 yr) performed aerobic and resistance exercise (AE + RE) for one leg while the other leg did RE. Muscle biopsies were obtained before and after 5 wk of training and subjected to fiber-type specific immunohistochemical analysis, and quantification of total RNA content and mRNA/rRNA transcript abundance. Type II fiber cross-sectional area (CSA) increased with both AE + RE (22%) and RE (16%), while type I fiber CSA increased mainly with AE + RE (16%). The change score tended to differ between legs for type I CSA (P = 0.099), and the increase in smallest fiber diameter was greater in AE + RE than RE (P = 0.029). The number of nuclei per fiber increased after AE + RE in both fiber types, and this increase was greater (P = 0.027) than after RE. A strong correlation was observed between changes in number of nuclei per fiber and fiber CSA in both fiber types, for both AE + RE and RE (r > 0.8, P < 0.004). RNA content increased after AE + RE (24%, P = 0.019), but the change-scores did not differ across legs. The capillary variables generally increased in both fiber types, with no difference across legs. In conclusion, the accentuated hypertrophic response to AE + RE was associated with more pronounced myonuclear accretion, which was strongly correlated with the degree of fiber hypertrophy. This suggests that myonuclear accretion could play a role in facilitating muscle hypertrophy also during very short training periods.

Three months of bed rest induce a residual transcriptomic signature resilient to resistance exercise countermeasures.

This study explored the muscle genome-wide response to long-term unloading (84-day bed rest) in 21 men. We hypothesized that a part of the bed rest-induced gene expression signature would be resilient to a concurrent flywheel resistance exercise (RE) countermeasure. Using DNA microarray technology analyzing 35 345 gene-level probe-sets, we identified 335 annotated probe-sets that were downregulated, and 315 that were upregulated after bed rest (P < .01). Besides a predictable differential expression of genes and pathways related to mitochondria (downregulation; false-discovery rates (FDR) <1E-04), ubiquitin system (upregulation; FDR = 3E-02), and skeletal muscle energy metabolism and structure (downregulation; FDR ≤ 3E-03), 84-day bed rest also altered circadian rhythm regulation (upregulation; FDR = 3E-02). While most of the bed rest-induced changes were counteracted by RE, 209 transcripts were resilient to the exercise countermeasure. Genes upregulated after bed rest were particularly resistant to training (P < .001 vs downregulated, non-reversed genes). Specifically, "Translation Factors," "Proteasome Degradation," "Cell Cycle," and "Nucleotide Metabolism" pathways were not normalized by RE. This study provides an unbiased high-throughput transcriptomic signature of one of the longest unloading periods in humans to date. Classical disuse-related changes in structural and metabolic genes/pathways were identified, together with a novel upregulation of circadian rhythm transcripts. In the context of previous bed rest campaigns, the latter seemed to be related to the duration of unloading, suggesting the transcriptomic machinery continues to adapt throughout extended disuse periods. Despite that the RE training offset most of the bed rest-induced muscle-phenotypic and transcriptomic alterations, we contend that the human skeletal muscle also displays a residual transcriptomic signature of unloading that is resistant to an established exercise countermeasure.

Muscle2View, a CellProfiler pipeline for detection of the capillary-to-muscle fiber interface and high-content quantification of fiber type-specific histology.

Because manual immunohistochemical analysis of features such as skeletal muscle fiber typing, capillaries, myonuclei, and fiber size-related parameters is time consuming and prone to user subjectivity, automatic computational methods could allow for faster and more objective evaluation. Here, we developed Muscle2View, a free CellProfiler-based pipeline that integrates all key fiber-morphological variables, including the novel quantification of the capillary-to-fiber interface, in one single tool. Provided that the images are of sufficient quality and the settings are configured for the specific study, the pipeline allows for automatic and unsupervised analysis of fiber borders, myonuclei, capillaries, and morphometric parameters in a fiber type-specific manner from large batches of images in <10 min/tissue sample. The novel identification of the capillary-to-fiber interface allowed for the calculation of microvascular factors such as capillary contacts (CC), individual capillary-to-fiber ratio (C/Fi), and capillary-to-fiber perimeter exchange (CFPE) index. When comparing the Muscle2View pipeline to manual or semiautomatic analysis, overall the results revealed strong correlations. For several variables, however, there were differences (5-15%) between values computed by manual counting and Muscle2View, suggesting that the methods should not necessarily be used interchangeably. Collectively, we demonstrate that the Muscle2View pipeline can provide unbiased and high-content analysis of muscle cross-sectional immunohistochemistry images. In addition to the classical morphological measurements, the Muscle2View can identify the complex capillary-to-fiber network and myonuclear density in a fiber type-specific manner. This robust analysis is done in one single run within a user-friendly and flexible environment based on the free and widely used image software CellProfiler.NEW & NOTEWORTHY Here, we developed a freely available CellProfiler-based pipeline termed Muscle2View, which provides unbiased, high-content analysis of muscle cross-sectional immunohistochemistry images. In addition to fiber typing, myonuclei counting, and the quantification of fiber type-specific morphological measurements, the Muscle2View pipeline can identify the complex capillary-to-fiber network from a batch of images within minutes. Thus, the Muscle2View is a viable tool for researchers aiming to quantify immunohistochemical variables from skeletal muscle biopsies.

Clinical Applications of Iso-Inertial, Eccentric-Overload (YoYo™) Resistance Exercise.

In the quest for a viable non-gravity dependent method to "lift weights" in space, our laboratory introduced iso-inertial resistance (YoYo™) exercise using spinning flywheel(s), more than 25 years ago. After being thoroughly tested in individuals subjected to various established spaceflight analogs, a multi-mode YoYo™ exercise apparatus was eventually installed on the International Space Station in 2009. The method, applicable to any muscle group, provides accommodated resistance and optimal muscle loading through the full range of motion of concentric actions, and brief episodes of eccentric overload. This exercise intervention has found terrestrial applications and shown success in enhancing sports performance and preventing injury and aiding neurological or orthopedic rehabilitation. Research has proven that this technique offers unique physiological responses not possible with other exercise hardware solutions. This paper provides a brief overview of research that has made use, and explored the efficacy, of this method in healthy sedentary or physically active individuals and populations suffering from muscle wasting, disease or injury. While the collective evidence to date suggests YoYo™ offers a potent stimulus to optimize the benefits of resistance exercise, systematic research to support clinical use of this method has only begun to emerge. Thus, we also offer perspectives on unresolved issues, unexplored applications for clinical conditions, and how this particular exercise paradigm could be implemented in future clinical research and eventually being prescribed. Fields of particular interest are those aimed at promoting muscle health by preventing injury or combating muscle wasting and neurological or metabolic dysfunction due to aging or illness, or those serving in rehabilitation following trauma and/or surgery.

Metabolic adaptations in skeletal muscle after 84 days of bed rest with and without concurrent flywheel resistance exercise.

As metabolic changes in human skeletal muscle after long-term (simulated) spaceflight are not well understood, this study examined the effects of long-term microgravity, with and without concurrent resistance exercise, on skeletal muscle oxidative and glycolytic capacity. Twenty-one men were subjected to 84 days head-down tilt bed rest with (BRE; n = 9) or without (BR; n = 12) concurrent flywheel resistance exercise. Activity and gene expression of glycogen synthase, glycogen phosphorylase (GPh), hexokinase, phosphofructokinase-1 (PFK-1), and citrate synthase (CS), as well as gene expression of succinate dehydrogenase (SDH), vascular endothelial growth factor (VEFG), peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1α), and myostatin, were analyzed in samples from m. vastus lateralis collected before and after bed rest. Activity and gene expression of enzymes controlling oxidative metabolism (CS, SDH) decreased in BR but were partially maintained in BRE. Activity of enzymes regulating anaerobic glycolysis (GPh, PFK-1) was unchanged in BR. Resistance exercise increased the activity of GPh. PGC-1α and VEGF expression decreased in both BR and BRE. Myostatin increased in BR but decreased in BRE after bed rest. The analyses of these unique samples indicate that long-term microgravity induces marked alterations in the oxidative, but not the glycolytic, energy system. The proposed flywheel resistance exercise was effective in counteracting some of the metabolic alterations triggered by 84-day bed rest. Given the disparity between gene expression vs. enzyme activity in several key metabolic markers, posttranscriptional mechanisms should be explored to fully evaluate metabolic adaptations to long-term microgravity with/without exercise countermeasures in human skeletal muscle.

Neuromuscular Adaptations Following 90 Days Bed Rest With or Without Resistance Exercise.

INTRODUCTION: This study examined the effects of long-term bed rest with or without a concurrent resistance exercise protocol on different muscle function indices of the knee extensors and their influence on previously shown atrophy, neural impairment, and slow-to-fast phenotype shift. METHODS: Nine men underwent 90 d of bed rest only (BR), while eight men in addition performed maximal supine squats every third day (BRE). Before and at day 1 and 5 following bed rest, surface quadriceps electromyographic (EMG) activity was measured during a sustained (60-s) submaximal isometric action and rate of force development (RFD) was assessed during a maximal isometric action, both in the supine squat position. Maximal torque was measured during isokinetic knee extensions at different angular velocities before and after (day 2 and 11) bed rest. RESULTS: EMG amplitude at a fixed submaximal load increased in BR, but not in BRE. The increase in amplitude during the sustained action was elevated in BR but not in BRE. RFD decreased in BR; this effect was attenuated day 1 and normalized day 5 in BRE. RFD expressed relative to maximal force was maintained in both groups. Angle-specific torque decreased equally for all velocities in BR. The decrease in isokinetic strength was attenuated day 2 in BRE. DISCUSSION: Phenotype changes were not reflected in muscle function measurements, probably because they were overridden by the effects of atrophy and neural adaptation. The protective effect of resistance exercise was more pronounced in tasks similar to the training action, inferring great impact of neural mechanisms. Alkner BA, Norrbrand L, Tesch PA. Neuromuscular adaptations following 90 days bed rest with or without resistance exercise. Aerosp Med Hum Perform. 2016; 87(7):610-617.

Muscle, functional and cognitive adaptations after flywheel resistance training in stroke patients: a pilot randomized controlled trial.

BACKGROUND: Resistance exercise (RE) improves neuromuscular function and physical performance after stroke. Yet, the effects of RE emphasizing eccentric (ECC; lengthening) actions on muscle hypertrophy and cognitive function in stroke patients are currently unknown. Thus, this study explored the effects of ECC-overload RE training on skeletal muscle size and function, and cognitive performance in individuals with stroke. METHODS: Thirty-two individuals with chronic stroke (≥6 months post-stroke) were randomly assigned into a training group (TG; n = 16) performing ECC-overload flywheel RE of the more-affected lower limb (12 weeks, 2 times/week; 4 sets of 7 maximal closed-chain knee extensions; <2 min of contractile activity per session) or a control group (CG; n = 16), maintaining daily routines. Before and after the intervention, quadriceps femoris volume, maximal force and power for each leg were assessed, and functional and dual task performance, and cognitive functions were measured. RESULTS: Quadriceps femoris volume of the more-affected leg increased by 9.4 % in TG. Muscle power of the more-affected, trained (48.2 %), and the less-affected, untrained limb (28.1 %) increased after training. TG showed enhanced balance (8.9 %), gait performance (10.6 %), dual-task performance, executive functions (working memory, verbal fluency tasks), attention, and speed of information processing. CG showed no changes. CONCLUSION: ECC-overload flywheel resistance exercise comprising 4 min of contractile activity per week offers a powerful aid to regain muscle mass and function, and functional performance in individuals with stroke. While the current intervention improved cognitive functions, the cause-effect relationship, if any, with the concomitant neuromuscular adaptations remains to be explored. TRIAL REGISTRATION: Clinical Trials NCT02120846.

Aerobic exercise augments muscle transcriptome profile of resistance exercise.

Recent reports suggest that aerobic exercise may boost the hypertrophic response to short-term resistance training. This study explored the effects of an acute aerobic exercise bout on the transcriptional response to subsequent resistance exercise. Ten moderately trained men performed ∼45 min cycling on one leg followed by 4 × 7 maximal knee extensions for each leg, 15 min later. Thus, one limb performed aerobic and resistance exercise (AE + RE) while the opposing leg did resistance exercise only (RE). Biopsies were obtained from the vastus lateralis muscle of each leg 3 h after the resistance exercise bout. Using DNA microarray, we analyzed differences [≥1.5-fold, false discovery rate (FDR) ≤10%] in gene expression profiles for the two modes of exercise. There were 176 genes up (127)- or downregulated (49) by AE + RE compared with RE. Among the most significant differentially expressed genes were established markers for muscle growth and oxidative capacity, novel cytokines, transcription factors, and micro-RNAs (miRNAs). The most enriched functional categories were those linked to carbohydrate metabolism and transcriptional regulation. Upstream analysis revealed that vascular endothelial growth factor, cAMP-response element-binding protein, Tet methylcytosine dioxygenase, and mammalian target of rapamycin were regulators highly activated by AE + RE, whereas JnK, NF-κß, MAPK, and several miRNAs were inhibited. Thus, aerobic exercise alters the skeletal muscle transcriptional signature of resistance exercise to initiate important gene programs promoting both myofiber growth and improved oxidative capacity. These results provide novel insight into human muscle adaptations to diverse exercise modes and offer the very first genomic basis explaining how aerobic exercise may augment, rather than compromise, muscle growth induced by resistance exercise.

Unilateral lower limb suspension: From subject selection to "omic" responses.

The unilateral lower limb suspension (ULLS) method was developed, introduced, and validated in the quest for a simple, effective, and highly reliable human analog to study the consequences of spaceflight on muscle size and function. Because withdrawal of weight bearing for no more than 2-3 days is sufficient to inflict disturbances in protein metabolism of postural muscles, it is imperative ULLS serves as a very powerful method to manifest skeletal muscle adaptations similar to those experienced in 0 g. Thus the rate of global muscle loss appears rather constant over the first 2 mo, amounting to about 2-3% per week. At the microscopic level, these changes are accompanied by a corresponding decrease in individual muscle fiber size. ULLS alters metabolism favoring more carbohydrate over fat substrate utilization. Altogether, these changes result in impaired work and endurance capacity of muscles being subjected to ULLS. Maximal voluntary force decreases out of proportion to the muscle loss, suggesting motor control is modified. Past reviews offer near exhaustive information on ULLS-induced responses with regard to the above changes. Hence, the current brief review describes more broadly the evolution of the ULLS model, from issues of subject recruitment and compliance control, to recent advances unraveling molecular mechanisms facilitating unloading-induced muscle wasting. Such knowledge is critical in designing future studies aimed at exploring and developing exercise countermeasures or other means to combat the debilitating effects on muscle experienced by astronauts during long-haul missions in Orbit.

Exercise Responses to Gravity-Independent Flywheel Aerobic and Resistance Training.

BACKGROUND: Although several exercise systems have been developed to mitigate the physiological deconditioning that occurs in microgravity, few have the capacity to positively impact multiple physiological systems and still meet the volume/mass requirements needed for missions beyond low Earth orbit. The purpose of this study was to test the gravity-independent Multi-Mode Exercise Device (M-MED) for both resistance (RE) and aerobic (AE) training stimuli. METHODS: Eight men and nine women (mean age 22.0 ± 0.4 yr) completed 5 wk of training on the M-MED: RE 4 × 7 squats 2 d/wk, and AE 4 × 4-min rowing bouts at ∼90% Vo2max 3 d/wk. Pre- and post-training data collection included an aerobic capacity test, MR imaging, strength testing, and vastus lateralis muscle biopsy. RESULTS: Vo2max increased 8%, 3RM strength 18%, and quadriceps femoris cross-sectional area (CSA) 10%. Knee extensor strength increased at all isokinetic speeds tested. Subjects also demonstrated improved fatigue resistance in knee extension. At the cellular and molecular level, the biopsy revealed increases in mixed myofiber CSA (13%), citrate synthase activity (26%), total RNA concentration (24%), IGF-I mRNA (77%), and Type IIa myosin heavy chain (MHC) mRNA (8%), and a concomitant decrease in Type IIx MHC mRNA (-23%). None of the changes were gender-specific. DISCUSSION: Both the functional outcomes and biomarker changes indicate that a very low volume of M-MED exercise results in robust adaptation in the cardiovascular and musculoskeletal systems. The M-MED has the potential to provide a wide range of countermeasure exercises and should be considered for testing in ground-based spaceflight simulation.

Effects of In-Season Inertial Resistance Training With Eccentric Overload in a Sports Population at Risk for Patellar Tendinopathy.

Gual, G, Fort-Vanmeerhaeghe, A, Romero-Rodríguez, D, and Tesch, PA. Effects of in-season inertial resistance training with eccentric overload in a sports population at risk for patellar tendinopathy. J Strength Cond Res 30(7): 1834-1842, 2016-Volleyball and basketball players can be considered as a population at risk for patellar tendinopathy. Given the paradox that eccentric training elicits therapeutic benefits yet might provoke such injury, we investigated the influence of a weekly bout of inertial squat resistance exercise offering eccentric overload on lower limb muscle power and patellar tendon complaints. Players of 8 (4 basketball and 4 volleyball) teams (38 women and 43 men) were randomly assigned to either the intervention (IG) or control (CG) group. Although IG and CG maintained scheduled in-season training routines over 24 weeks, IG, in addition, performed 1 weekly session of eccentric overload by 4 sets of 8 repetitions of the squat using flywheel inertial resistance. Victorian Institute of Sports Assessment patellar tendinopathy questionnaire (VISA-p), vertical countermovement jump, and squat power, both concentric (Squat-Con) and eccentric (Squat-Ecc), tests were performed before (T1), during (T2), and after (T3) the 24 weeks of intervention. Neither group suffered from patellar tendinopathy during the study period. VISA-p displayed no differences across groups at any measurement period. Countermovement jump scores significantly (p ≤ 0.05) differed between groups in favor of the IG. Both Squat-Con and Squat-Ecc mean scores from the IG were significantly (p < 0.01) higher than the CG. Adding a weekly eccentric overload squat training bout to a regular basketball and volleyball exercise routine enhances lower limb muscle power without triggering patellar tendon complaints. Future studies, using the current exercise paradigm, aim to explore its efficacy to prevent or combat patellar tendinopathy in sports calling for frequent explosive jumps.

Concurrent exercise on a gravity-independent device during simulated microgravity.

PURPOSE: The objective of this study is to examine the effect of a high-intensity concurrent training program using a single gravity-independent device on maintaining skeletal muscle function and aerobic capacity during short-term unilateral lower limb suspension (ULLS). METHODS: Nineteen subjects (10 males and 9 females; 21.0 ± 2.5 yr, 65.4 ± 12.2 kg) were separated into two groups: 1) 10-d ULLS only (n = 9) and 2) 10-d ULLS plus aerobic and resistance training (ULLS + EX, n = 10). Exercise was performed on a single gravity-independent Multi-Mode Exercise Device (M-MED) with alternating days of high-intensity interval aerobic training and maximal exertion resistance training. RESULTS: Aerobic capacity increased by 7% in ULLS + EX (P < 0.05). Knee extensor and ankle plantar flexor three-repetition maximum increased in the ULLS + EX group (P < 0.05), but this change was only different from ULLS in the plantar flexors (P < 0.05). Peak torque levels decreased with ULLS but were increased for the knee extensors and attenuated for the ankle plantar flexors with ULLS + EX (P < 0.05). A shift toward type IIx myosin heavy-chain mRNA occurred with ULLS and was reversed with ULLS + EX in the vastus lateralis (P < 0.05) but not the soleus. Myostatin and atrogin increased with ULLS in both the vastus lateralis and soleus, but this change was mitigated with ULLS + EX only in the vastus lateralis (P = 0.0551 for myostatin, P < 0.05 for atrogin). Citrate synthase was decreased in the soleus during ULLS but was increased with ULLS + EX (P < 0.05). CONCLUSION: These results indicate that an M-MED class countermeasure device appears to be effective at mitigating the deconditioning effects of microgravity simulated during a modified ULLS protocol.

Chronic stroke patients show early and robust improvements in muscle and functional performance in response to eccentric-overload flywheel resistance training: a pilot study.

BACKGROUND: Resistance exercise comprising eccentric (ECC) muscle actions enhances muscle strength and function to aid stroke patients in conducting daily tasks. The purpose of this study was to assess the efficacy of a novel ECC-overload flywheel resistance exercise paradigm to induce muscle and functional performance adaptations in chronic stroke patients. METHODS: Twelve patients (~8 years after stroke onset) performed 4 sets of 7 coupled concentric (CON) and ECC actions using the affected limb on a flywheel leg press (LP) device twice weekly for 8 weeks. Maximal CON and ECC isokinetic torque at 30, 60 and 90°/s, isometric knee extension and LP force, and CON and ECC peak power in LP were measured before and after training. Balance (Berg Balance Scale, BBS), gait (6-Min Walk test, 6MWT; Timed-Up-and-Go, TUG), functional performance (30-s Chair-Stand Test, 30CST), spasticity (Modified Ashworth Scale) and perceived participation (Stroke Impact Scale, SIS) were also determined. RESULTS: CON and ECC peak power increased in both the trained affected (34 and 44%; P < 0.01), and the untrained, non-affected leg (25 and 34%; P < 0.02). Power gains were greater (P = 0.008) for ECC than CON actions. ECC isokinetic torque at 60 and 90°/s increased in the affected leg (P < 0.04). The increase in isometric LP force for the trained, affected leg across tests ranged 10-20% (P < 0.05). BBS (P = 0.004), TUG (P = 0.018), 30CST (P = 0.024) and SIS (P = 0.058) scores improved after training. 6MWT and spasticity remained unchanged. CONCLUSIONS: This novel, short-term ECC-overload flywheel RE training regime emerges as a valid, safe and viable method to improve muscle function, balance, gait and functional performance in men and women suffering from chronic stroke.

Flywheel resistance exercise to maintain muscle oxidative potential during unloading.

BACKGROUND: As spaceflight compromises skeletal muscle oxidative and aerobic work capacity, this study assessed the efficacy of resistance exercise (RE) to counteract muscle metabolic perturbations induced by 5 wk unilateral lower limb unloading (UL). METHODS: There were 21 men and women (30-56 yr) who were randomly assigned to either UL with (Group, Grp; UL+RE; N = 10) or without (Grp UL; N = 11) concurrent RE. Iso-inertial RE comprised four sets of seven maximal coupled concentric-eccentric knee extensions executed 2-3 times per week. Percutaneous biopsies were obtained from m. vastus lateralis before and after either intervention. Levels of mRNA expression of factors regulating skeletal muscle oxidative capacity i.e., peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1alpha) and vascular endothelial growth factor (VEGF), and glycolytic capacity, i.e., phosphofructokinase (PFK), glycogen phosphorylase and synthase, hexokinase, and phosphorylase kinase alpha1, were subsequently analyzed. RESULTS: Grp UL showed decreased (36%) PGC-1alpha expression, increased (1.5-fold) PFK expression, and a trend toward decreased VEGF post-intervention. Grp UL+RE showed no changes. DISCUSSION: These results suggest that 5 wk unloading reduces skeletal muscle oxidative capacity and increases glycolytic enzyme activity. More importantly, only 12 bouts of high-force, low-volume resistance exercise attenuated these responses. Thus, the current resistance exercise paradigm emphasizing eccentric overload effectively counteracts unwarranted metabolic alterations induced by 5 wk unloading and may, therefore, aid in maintaining skeletal muscle integrity and endurance, and hence astronaut health and fitness during spaceflight.

Exercise-induced AMPK activation does not interfere with muscle hypertrophy in response to resistance training in men.

As aerobic exercise (AE) may interfere with adaptations to resistance exercise (RE), this study explored acute and chronic responses to consecutive AE (∼45 min cycling) and RE (4 × 7 maximal knee extensions) vs. RE only. Ten men performed acute unilateral AE + RE interspersed by 15 min recovery. The contralateral leg was subjected to RE. This exercise paradigm was then implemented in a 5-wk training program. Protein phosphorylation, gene expression, and glycogen content were assessed in biopsies obtained from the vastus lateralis muscle of both legs immediately before and 3 h after acute RE. Quadriceps muscle size and in vivo torque were measured, and muscle samples were analyzed for citrate synthase activity and glycogen concentration, before and after training. Acute AE reduced glycogen content (32%; P < 0.05) and increased (P < 0.05) phosphorylation of AMPK (1.5-fold) and rpS6 (1.3-fold). Phosphorylation of p70S6K and 4E-BP1 remained unchanged. Myostatin gene expression was downregulated after acute AE + RE but not RE. Muscle size showed greater (P < 0.05) increase after AE + RE (6%) than RE (3%) training. Citrate synthase activity (18%) and endurance performance (22%) increased (P < 0.05) after AE + RE but not RE. While training increased (P < 0.05) in vivo muscle strength in both legs, normalized and concentric torque increased after RE only. Thus AE activates AMPK, reduces glycogen stores, and impairs the progression of concentric force, yet muscle hypertrophic responses to chronic RE training appear not to be compromised.

Cardiovascular responses to rowing on a novel ergometer designed for both resistance and aerobic training in space.

BACKGROUND: Astronauts are required to perform both resistance and aerobic exercise while in orbit. This study assessed the aerobic energy yield and related physiological measurements using a nongravity dependent flywheel device designed for both resistance and aerobic exercise (RAD) in space. METHODS: Eight physically active men and women performed all-out rowing on the RAD. For comparison, exercise was also carried out employing a commercially available rowing ergometer (C2). RESULTS: Peak oxygen uptake during exercise using RAD and C2 averaged 3.11 +/- 0.49 and 3.18 +/- 0.50 L x min(-1), respectively. Similarly, peak plasma lactate concentration (9.6 vs. 11.2 mmol x L(-1)), heart rate (183 vs. 184 bpm), and rate of perceived exertion (15.8 vs. 16.0) were comparable across exercise using the two devices. DISCUSSION: Collectively, the results suggest that this novel exercise modality offers cardiovascular and metabolic responses, and thus aerobic exercise stimulus that is equally effective as that evoked by established technology for indoor rowing. Given the need for physiologically sound and highly effective exercise countermeasures that features small mass and envelope, and allows for resistance and aerobic exercise in a single apparatus, we believe this novel hardware should be considered for use in space.

Aerobic exercise does not compromise muscle hypertrophy response to short-term resistance training.

This study tested the hypothesis that chronic aerobic and resistance exercise (AE+RE) would elicit greater muscle hypertrophy than resistance exercise only (RE). Ten men (25 ± 4 yr) performed 5 wk unilateral knee extensor AE+RE. The opposing limb was subjected to RE. AE completed 6 hr prior to RE consisted of ~45 min one-legged cycle ergometry. RE comprised 4 × 7 maximal concentric-eccentric knee extensions. Various indexes of in vivo knee extensor function were measured before and after training. Magnetic resonance imaging (MRI) assessed m. quadricep femoris (QF) cross-sectional area (CSA), volume, and signal intensity (SI). Biopsies obtained from m. vastus lateralis determined fiber CSA, enzyme levels, and gene expression of myostatin, atrogin-1, MuRF-1, PGC-1α, and VEGF. Increases (P < 0.05) in isometric strength and peak power, respectively, were comparable in AE+RE (9 and 29%) and RE (11 and 24%). AE+RE showed greater increase (14%; P < 0.05) in QF volume than RE (8%). Muscle fiber CSA increased 17% after AE+RE (P < 0.05) and 9% after RE (P > 0.05). QF SI increased (12%; P < 0.05) after AE+RE, but not RE. Neither AE+RE nor RE showed altered mRNA levels. Citrate synthase activity increased (P < 0.05) after AE+RE. The results suggest that the increased aerobic capacity shown with AE+RE was accompanied by a more robust increase in muscle size compared with RE. Although this response was not carried over to greater improvement in muscle function, it remains that intense AE can be executed prior to RE without compromising performance outcome.

Aerobic exercise alters skeletal muscle molecular responses to resistance exercise.

PURPOSE: This study assessed the influence of an acute aerobic exercise bout on molecular responses to subsequent resistance exercise (RE). METHODS: Nine physically active men performed a 45-min one-legged cycle ergometry exercise and 4 × 7 maximal concentric-eccentric knee extensions for each leg 6 h later. Thus, one limb was subjected to aerobic and resistance exercise (AE+RE), and the contralateral limb to resistance exercise (RE) only. Knee extensor peak power was determined. Biopsies were obtained from the m vastus lateralis before (PRE) and 15 min (POST1) and 3 h after RE. Analysis determined glycogen content, mRNA levels (vascular endothelial growth factor, peroxisome proliferator-activated receptor-γ coactivator-1, muscle RING-finger protein-1, atrogin-1, myostatin), and phosphorylated proteins (mammalian target of rapamycin, p70S6 kinase, ribosomal protein S6, eukaryotic elongation factor 2). RESULTS: Peak power was similar in AE + RE and RE. After RE, the time course of glycogen utilization and protein signaling was similar across legs. However, phosphorylation of mammalian target of rapamycin and p70S6 kinase was elevated in AE + RE versus RE (main effect, P < 0.05). Vascular endothelial growth factor and peroxisome proliferator-activated receptor-γ coactivator-1 were higher in AE + RE than in RE at PRE and POST1 (P < 0.05). Myostatin was lower in AE + RE versus RE at PRE and POST1 (P < 0.05) and downregulated after resistance exercise only. Atrogin-1 was higher in AE + RE than in RE at PRE and POST1 (P < 0.05) and decreased after RE in AE + RE. Muscle RING-finger protein-1 was similar across legs. No difference for any marker was evident 3 h after RE. CONCLUSIONS: These results suggest that acute aerobic exercise alters molecular events regulating muscle protein turnover during the early recovery period from subsequent RE.

Quadriceps muscle use in the flywheel and barbell squat.

BACKGROUND: Resistance exercise has been proposed as an aid to counteract quadriceps muscle atrophy in astronauts during extended missions in orbit. While space authorities have advocated the squat exercise should be prescribed, no exercise system suitable for in-flight use has been validated with regard to quadriceps muscle use. We compared muscle involvement in the terrestrial "gold standard" squat using free weights and a nongravity dependent flywheel resistance exercise device designed for use in space. METHODS: The subjects were 10 strength-trained men who performed 5 sets of 10 repetitions using the barbell squat (BS; 10 repetition maximum) or flywheel squat (FS; each repetition maximal), respectively. Functional magnetic resonance imaging (MRI) and surface electromyography (EMG) techniques assessed quadriceps muscle use. Exercise-induced contrast shift of MR images was measured by means of transverse relaxation time (T2). EMG root mean square (RMS) was measured during concentric (CON) and eccentric (ECC) actions and normalized to EMG RMS determined during maximal voluntary contraction. RESULTS: The quadriceps muscle group showed greater exercise-induced T2 increase following FS compared with BS. Among individual muscles, the rectus femoris displayed greater T2 increase with FS (+24 +/- 14%) than BS (+8 +/- 4%). Normalized quadriceps EMG showed no difference across exercise modes. DISCUSSION: Collectively, the results of this study suggest that quadriceps muscle use in the squat is comparable, if not greater, with flywheel compared with free weight resistance exercise. Data appear to provide support for use of flywheel squat resistance exercise as a countermeasures adjunct during spaceflight.