scholarly journals Influence of ageing and essential amino acids on quantitative patterns of troponin T alternative splicing in human skeletal muscle

2015 ◽  
Vol 40 (8) ◽  
pp. 788-796 ◽  
Author(s):  
Joel Coble ◽  
Rudolf J. Schilder ◽  
Arthur Berg ◽  
Micah J. Drummond ◽  
Blake B. Rasmussen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Alternative Splicing ◽  
Resistance Exercise ◽  
Troponin T ◽  
Vastus Lateralis ◽  
Essential Amino Acids ◽  
Muscle Performance ◽  
Muscle Quality ◽  
Vastus Lateralis Muscle

Ageing is associated with a loss of skeletal muscle performance, a condition referred to as sarcopenia. In part, the age-related reduction in performance is due to a selective loss of muscle fiber mass, but mass-independent effects have also been demonstrated. An important mass-independent determinant of muscle performance is the pattern of expression of isoforms of proteins that participate in muscle contraction (e.g., the troponins). In the present study, we tested the hypothesis that ageing impairs alternative splicing of the pre-mRNA encoding fast skeletal muscle troponin T (TNNT3) in human vastus lateralis muscle. Furthermore, we hypothesized that resistance exercise alone or in combination with consumption of essential amino acids would attenuate age-associated effects on TNNT3 alternative splicing. Our results indicate that ageing negatively affects the pattern of TNNT3 alternative splicing in a manner that correlates quantitatively with age-associated reductions in muscle performance. Interestingly, whereas vastus lateralis TNNT3 alternative splicing was unaffected by a bout of resistance exercise 24 h prior to muscle biopsy, ingestion of a mixture of essential amino acids after resistance exercise resulted in a significant shift in the pattern of TNNT3 splice form expression in both age groups to one predicted to promote greater muscle performance. We conclude that essential amino acid supplementation after resistance exercise may provide a means to reduce impairments in skeletal muscle quality during ageing in humans.

scholarly journals Intake of branched-chain or essential amino acids attenuates the elevation in muscle levels of PGC-1α4 mRNA caused by resistance exercise

2016 ◽  
Vol 311 (1) ◽  
pp. E246-E251 ◽  
Author(s):  
Hedvig Samuelsson ◽  
Marcus Moberg ◽  
William Apró ◽  
Björn Ekblom ◽  
Eva Blomstrand
Keyword(s):  
Amino Acids ◽  
Protein Kinase ◽  
Resistance Exercise ◽  
Vastus Lateralis ◽  
Essential Amino Acids ◽  
Mitogen Activated Protein Kinase ◽  
Vastus Lateralis Muscle ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Branched Chain

The transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α is recognized as the master regulator of mitochondrial biogenesis. However, recently a novel isoform, PGC-1α4, that specifically regulates muscle hypertrophy was discovered. Because stimulation of mechanistic target of rapamycin complex 1 (mTORC1) activity is tightly coupled to hypertrophy, we hypothesized that activation of this pathway would upregulate PGC-1α4. Eight male subjects performed heavy resistance exercise (10 × 8–12 repetitions at ∼75% of 1 repetition maximum in leg press) on four different occasions, ingesting in random order a solution containing essential amino acids (EAA), branched-chain amino acids (BCAA), leucine, or flavored water (placebo) during and after the exercise. Biopsies were taken from the vastus lateralis muscle before and immediately after exercise, as well as following 90 and 180 min of recovery. Signaling through mTORC1, as reflected in p70S6 kinase phosphorylation, was stimulated to a greater extent by the EAA and BCAA than the leucine or placebo supplements. Unexpectedly, intake of EAA or BCAA attenuated the stimulatory effect of exercise on PGC-1α4 expression by ∼50% (from a 10- to 5-fold increase with BCAA and EAA, P < 0.05) 3 h after exercise, whereas intake of leucine alone did not reduce this response. The 60% increase ( P < 0.05) in the level of PGC-1α1 mRNA 90 min after exercise was uninfluenced by amino acid intake. Muscle glycogen levels were reduced and AMP-activated protein kinase α2 activity and phosphorylation of p38 mitogen-activated protein kinase enhanced to the same extent with all four supplements. In conclusion, induction of PGC-1α4 does not appear to regulate the nutritional (BCAA or EAA)-mediated activation of mTORC1 in human muscle.

scholarly journals Activation of the erythropoietin receptor in human skeletal muscle

2009 ◽  
Vol 161 (3) ◽  
pp. 427-434 ◽  
Author(s):  
Helene Rundqvist ◽  
Eric Rullman ◽  
Carl Johan Sundberg ◽  
Helene Fischer ◽  
Katarina Eisleitner ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cells ◽  
Human Skeletal Muscle ◽  
Acute Exercise ◽  
Vastus Lateralis ◽  
Muscle Fibers ◽  
Receptor Activation ◽  
Erythropoietin Receptor ◽  
Muscle Performance ◽  
Vastus Lateralis Muscle

Objective:Erythropoietin receptor (EPOR) expression in non-hematological tissues has been shown to be activated by locally produced and/or systemically delivered EPO. Improved oxygen homeostasis, a well-established consequence of EPOR activation, is very important for human skeletal muscle performance. In the present study we investigate whether human skeletal muscle fibers and satellite cells express EPOR and if it is activated by exercise.Design and methodsTen healthy males performed 65 min of cycle exercise. Biopsies were obtained from the vastus lateralis muscle and femoral arterio-venous differences in EPO concentrations were estimated.ResultsThe EPOR protein was localized in areas corresponding to the sarcolemma and capillaries. Laser dissection identified EPOR mRNA expression in muscle fibers. Also, EPOR mRNA and protein were both detected in human skeletal muscle satellite cells. In the initial part of the exercise bout there was a release of EPO from the exercising leg to the circulation, possibly corresponding to an increased bioavailability of EPO. After exercise, EPOR mRNA and EPOR-associated JAK2 phosphorylation were increased.ConclusionsInteraction with JAK2 is required for EPOR signaling and the increase found in phosphorylation is therefore closely linked to the activation of EPOR. The receptor activation by acute exercise suggests that signaling through EPOR is involved in exercise-induced skeletal muscle adaptation, thus extending the biological role of EPO into the skeletal muscle.

scholarly journals Nutritional and contractile regulation of human skeletal muscle protein synthesis and mTORC1 signaling

2009 ◽  
Vol 106 (4) ◽  
pp. 1374-1384 ◽  
Author(s):  
Micah J. Drummond ◽  
Hans C. Dreyer ◽  
Christopher S. Fry ◽  
Erin L. Glynn ◽  
Blake B. Rasmussen
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Resistance Exercise ◽  
Human Skeletal Muscle ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Essential Amino Acids ◽  
Skeletal Muscle Protein ◽  
Mtorc1 Signaling

In this review we discuss current findings in the human skeletal muscle literature describing the acute influence of nutrients (leucine-enriched essential amino acids in particular) and resistance exercise on muscle protein synthesis and mammalian target of rapamycin complex 1 (mTORC1) signaling. We show that essential amino acids and an acute bout of resistance exercise independently stimulate human skeletal muscle protein synthesis. It also appears that ingestion of essential amino acids following resistance exercise leads to an even larger increase in the rate of muscle protein synthesis compared with the independent effects of nutrients or muscle contraction. Until recently the cellular mechanisms responsible for controlling the rate of muscle protein synthesis in humans were unknown. In this review, we highlight new studies in humans that have clearly shown the mTORC1 signaling pathway is playing an important regulatory role in controlling muscle protein synthesis in response to nutrients and/or muscle contraction. We propose that essential amino acid ingestion shortly following a bout of resistance exercise is beneficial in promoting skeletal muscle growth and may be useful in counteracting muscle wasting in a variety of conditions such as aging, cancer cachexia, physical inactivity, and perhaps during rehabilitation following trauma or surgery.

scholarly journals Essential amino acids and muscle protein recovery from resistance exercise

2002 ◽  
Vol 283 (4) ◽  
pp. E648-E657 ◽  
Author(s):  
Elisabet Børsheim ◽  
Kevin D. Tipton ◽  
Steven E. Wolf ◽  
Robert R. Wolfe
Keyword(s):  
Amino Acids ◽  
Resistance Exercise ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Vastus Lateralis ◽  
Area Under The Curve ◽  
Essential Amino Acids ◽  
Constant Infusion ◽  
Protein Balance ◽  
Dose Dependent

This study tests the hypothesis that a dose of 6 g of orally administered essential amino acids (EAAs) stimulates net muscle protein balance in healthy volunteers when consumed 1 and 2 h after resistance exercise. Subjects received a primed constant infusion ofl-[2H5]phenylalanine andl-[1-13C]leucine. Samples from femoral artery and vein and biopsies from vastus lateralis were obtained. Arterial EAA concentrations increased severalfold after drinks. Net muscle protein balance (NB) increased proportionally more than arterial AA concentrations in response to drinks, and it returned rapidly to basal values when AA concentrations decreased. Area under the curve for net phenylalanine uptake above basal value was similar for the first hour after each drink (67 ± 17 vs. 77 ± 20 mg/leg, respectively). Because the NB response was double the response to two doses of a mixture of 3 g of EAA + 3 g of nonessential AA (NEAA) (14), we conclude that NEAA are not necessary for stimulation of NB and that there is a dose-dependent effect of EAA ingestion on muscle protein synthesis.

scholarly journals Skeletal muscle anabolic response to resistance exercise and essential amino acids is delayed with aging

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Micah J Drummond ◽  
Hans C Dreyer ◽  
Bart Pennings ◽  
Christopher S Fry ◽  
Shaheen Dhanani ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Resistance Exercise ◽  
Essential Amino Acids ◽  
Anabolic Response

scholarly journals Skeletal muscle protein anabolic response to resistance exercise and essential amino acids is delayed with aging

2008 ◽  
Vol 104 (5) ◽  
pp. 1452-1461 ◽  
Author(s):  
Micah J. Drummond ◽  
Hans C. Dreyer ◽  
Bart Pennings ◽  
Christopher S. Fry ◽  
Shaheen Dhanani ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Resistance Exercise ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Essential Amino Acids ◽  
Skeletal Muscle Protein ◽  
Eif2α Phosphorylation ◽  
Increased Risk ◽  
Old Men

Skeletal muscle loss during aging leads to an increased risk of falls, fractures, and eventually loss of independence. Resistance exercise is a useful intervention to prevent sarcopenia; however, the muscle protein synthesis (MPS) response to resistance exercise is less in elderly compared with young subjects. On the other hand, essential amino acids (EAA) increase MPS equally in both young and old subjects when sufficient EAA is ingested. We hypothesized that EAA ingestion following a bout of resistance exercise would stimulate anabolic signaling and MPS similarly between young and old men. Each subject ingested 20 g of EAA 1 h following leg resistance exercise. Muscle biopsies were obtained before and 1, 3, and 6 h after exercise to measure the rate of MPS and signaling pathways that regulate translation initiation. MPS increased early in young (1–3 h postexercise) and later in old (3–6 h postexercise). At 1 h postexercise, ERK1/2 MNK1 phosphorylation increased and eIF2α phosphorylation decreased only in the young. mTOR signaling (mTOR, S6K1, 4E-BP1, eEF2) was similar between groups at all time points, but MNK1 phosphorylation was lower at 3 h and AMP-activated protein kinase-α (AMPKα) phosphorylation was higher in old 1–3 h postexercise. We conclude that the acute MPS response after resistance exercise and EAA ingestion is similar between young and old men; however, the response is delayed with aging. Unresponsive ERK1/2 signaling and AMPK activation in old muscle may be playing a role in the delayed activation of MPS. Notwithstanding, the combination of resistance exercise and EAA ingestion should be a useful strategy to combat sarcopenia.

scholarly journals Impact of resistance exercise during bed rest on skeletal muscle sarcopenia and myosin isoform distribution

1998 ◽  
Vol 84 (1) ◽  
pp. 157-163 ◽  
Author(s):  
Marcas M. Bamman ◽  
Mark S. F. Clarke ◽  
Daniel L. Feeback ◽  
Robert J. Talmadge ◽  
Bruce R. Stevens ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Resistance Exercise ◽  
Vastus Lateralis ◽  
Bed Rest ◽  
Vastus Lateralis Muscle ◽  
Neural Activation ◽  
Type I ◽  
Cross Sectional ◽  
Maximum Voluntary Isometric Contraction ◽  
Leg Press

Bamman, Marcas M., Mark S. F. Clarke, Daniel L. Feeback, Robert J. Talmadge, Bruce R. Stevens, Steven A. Lieberman, and Michael C. Greenisen. Impact of resistance exercise during bed rest on skeletal muscle sarcopenia and myosin isoform distribution. J. Appl. Physiol. 84(1): 157–163, 1998.—Because resistance exercise (REx) and bed-rest unloading (BRU) are associated with opposing adaptations, our purpose was to test the efficacy of REx against the effects of 14 days of BRU on the knee-extensor muscle group. Sixteen healthy men were randomly assigned to no exercise (NoEx; n = 8) or REx ( n = 8). REx performed five sets of leg press exercise with 80–85% of one repetition maximum (1 RM) every other day during BRU. Muscle samples were removed from the vastus lateralis muscle by percutaneous needle biopsy. Myofiber distribution was determined immunohistochemically with three monoclonal antibodies against myosin heavy chain (MHC) isoforms (I, IIa, IIx). MHC distribution was further assessed by quantitative gel electrophoresis. Dynamic 1-RM leg press and unilateral maximum voluntary isometric contraction (MVC) were determined. Maximal neural activation (root mean squared electromyogram) and rate of torque development (RTD) were measured during MVC. Reductions ( P < 0.05) in type I (15%) and type II (17%) myofiber cross-sectional areas were found in NoEx but not in REx. Electrophoresis revealed no changes in MHC isoform distribution. The percentage of type IIx myofibers decreased ( P < 0.05) in REx from 9 to 2% and did not change in NoEx. 1 RM was reduced ( P < 0.05) by 9% in NoEx but was unchanged in REx. MVC fell by 15 and 13% in NoEx and REx, respectively. The agonist-to-antagonist root mean squared electromyogram ratio decreased ( P < 0.05) 19% in REx. RTD slowed ( P < 0.05) by 54% in NoEx only. Results indicate that REx prevented BRU-induced myofiber atrophy and also maintained training-specific strength. Unlike spaceflight, BRU did not induce shifts in myosin phenotype. The reported benefits of REx may prove useful in prescribing exercise for astronauts in microgravity.

scholarly journals Training state and skeletal muscle autophagy in response to 36 h of fasting

2018 ◽  
Vol 125 (5) ◽  
pp. 1609-1619 ◽  
Author(s):  
Maja Munk Dethlefsen ◽  
Lærke Bertholdt ◽  
Anders Gudiksen ◽  
Tomasz Stankiewicz ◽  
Jens Bangsbo ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Kinase ◽  
Human Skeletal Muscle ◽  
Vastus Lateralis ◽  
Adaptor Protein ◽  
Vastus Lateralis Muscle ◽  
Trained Subjects ◽  
Lateralis Muscle ◽  
Training State

The present study aimed at investigating fasting-induced responses in regulators and markers of autophagy in vastus lateralis muscle from untrained and trained human subjects. Untrained and trained subjects (based on maximum oxygen uptake, muscle citrate synthase activity, and oxidative phosphorylation protein level) fasted for 36 h with vastus lateralis muscle biopsies obtained at 2, 12, 24, and 36 h after a standardized meal. Fasting reduced ( P < 0.05) skeletal muscle microtubule-associated protein-1A/1B light chain 3 (LC3)I, LC3II, and adaptor protein sequestosome 1/p62 protein content in untrained subjects only. Moreover, skeletal muscle RAC-alpha serine/threonine-protein kinase (AKT)Thr308, AMP-activated protein kinase (AMPK)Thr172, and Unc-51-like autophagy-activating kinase-1 (ULK1)Ser555 phosphorylation state, as well as Bcl-2-interacting coiled-coil protein-1 (Beclin1) and ULK1Ser757 phosphorylation, was lower ( P < 0.05) in trained than untrained subjects during fasting. In addition, the plasma concentrations of several amino acids were higher ( P < 0.05) in trained than untrained subjects, and the plasma concentration profile of several amino acids was different in untrained and trained subjects during fasting. Taken together, these findings suggest that 36-h fasting has effects on some mediators of autophagy in untrained human skeletal muscle and that training state influences the effect of fasting on autophagy signaling and on mediators of autophagy in skeletal muscle. NEW & NOTEWORTHY This study showed that skeletal muscle autophagy was only modestly affected in humans by 36 h of fasting. Hence, 36-h fasting has effects on some mediators of autophagy in untrained human skeletal muscle, and training state influences the effect of fasting on autophagy signaling and on mediators of autophagy in skeletal muscle.

scholarly journals Remodeling the Skeletal Muscle Extracellular Matrix in Older Age—Effects of Acute Exercise Stimuli on Gene Expression

2020 ◽  
Vol 21 (19) ◽  
pp. 7089
Author(s):  
Matthias Gumpenberger ◽  
Barbara Wessner ◽  
Alexandra Graf ◽  
Marco V. Narici ◽  
Christian Fink ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Matrix ◽  
Resistance Exercise ◽  
Acute Exercise ◽  
Vastus Lateralis ◽  
Muscle Stiffness ◽  
Fold Change ◽  
Group Differences ◽  
Vastus Lateralis Muscle ◽  
Ecm Remodeling

With advancing age, the skeletal muscle extracellular matrix (ECM) undergoes fibrotic changes that may lead to increased muscle stiffness, injury susceptibility and strength loss. This study tested the potential of different exercises to counter these changes by stimulating the activity of genes associated with ECM remodeling. Twenty-six healthy men (66.9 ± 3.9 years) were stratified to two of four groups, performing unilateral (i) conventional resistance exercise, (ii) conventional resistance exercise followed by self-myofascial release (CEBR), (iii) eccentric-only exercise (ECC) or (iv) plyometric jumps (PLY). The non-trained leg served as control. Six hours post-exercise, vastus lateralis muscle biopsy samples were analyzed for the expression of genes associated with ECM collagen synthesis (COL1A1), matrix metallopeptidases (collagen degradation; MMPs) and peptidase inhibitors (TIMP1). Significant between-group differences were found for MMP3, MMP15 and TIMP1, with the greatest responses in MMP3 and TIMP1 seen in CEBR and in MMP15 in ECC. MMP9 (3.24–3.81-fold change) and COL1A1 (1.47–2.40-fold change) were increased in CEBR and PLY, although between-group differences were non-significant. The expression of ECM-related genes is exercise-specific, with CEBR and PLY triggering either earlier or stronger remodeling than other stimuli. Training studies will test whether execution of such exercises may help counter age-associated muscle fibrosis.

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