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

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.

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Supplemental dietary leucine and the skeletal muscle anabolic response to essential amino acids

Nutrition Reviews ◽

10.1111/j.1753-4887.2011.00420.x ◽

2011 ◽

Vol 69 (9) ◽

pp. 550-557 ◽

Cited By ~ 30

Author(s):

Stefan M Pasiakos ◽

James P McClung

Keyword(s):

Skeletal Muscle ◽

Amino Acids ◽

Essential Amino Acids ◽

Anabolic Response

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

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2014-0568 ◽

2015 ◽

Vol 40 (8) ◽

pp. 788-796 ◽

Cited By ~ 4

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.

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

Journal of Applied Physiology ◽

10.1152/japplphysiol.00021.2008 ◽

2008 ◽

Vol 104 (5) ◽

pp. 1452-1461 ◽

Cited By ~ 234

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.

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Myofibrillar Protein Abundance and Anabolic Signaling in Myotubes Depleted of E1 Alpha Subunit of Branched-Chain Ketoacid Dehydrogenase Complex

Current Developments in Nutrition ◽

10.1093/cdn/nzaa049_035 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 642-642

Author(s):

Glory Madu ◽

Olasunkanmi Adegoke

Keyword(s):

Skeletal Muscle ◽

Amino Acids ◽

Protein Content ◽

Muscle Protein ◽

Essential Amino Acids ◽

Myofibrillar Protein ◽

L6 Myotubes ◽

Branched Chain ◽

Ketoacid Dehydrogenase

Abstract Objectives Branched-chain amino acids (BCAAs) are essential amino acids that are crucial for skeletal muscle anabolism. Thus, alterations in their levels are associated with muscle atrophic diseases such as cancer, chronic inflammatory and neurological disorders. Others have linked impairments in BCAA metabolism to the development of insulin resistance and its sequelae. Compared to the effects of theses amino acids, much less is known on how impairment in BCAA catabolism affects skeletal muscle. BCAA catabolism starts with the reversible transamination by the mitochondrial enzyme branched-chain aminotransferase 2 (BCAT2). This is followed by the irreversible carboxylation, catalyzed by branched-chain ketoacid dehydrogenase (BCKD) complex. We have shown that BCAT2 and BCKD are essential for the differentiation of skeletal myoblasts into myotubes. Here, we investigated the effect of depletion of BCAT2 or of E1a subunit of BCKD in differentiated myotubes. Methods On day 4 of differentiation, L6 myotubes were transfected with the following siRNA oligonucleotides: scrambled (control), BCAT2, or E1a subunit of BCKD. Results Forty-eight hours after transfection, compared to control or BCAT2 siRNA group, we observed improved myotube structure in BCKD-depleted cells. BCKD depletion augmented myofibrillar protein levels: myosin heavy chain (MHC, 2-fold) and tropomyosin (4-fold), P < 0.05, n = 3. To further analyze the increase in myofibrillar protein content, we examined signaling through mTORC1 (mechanistic target of rapamycin complex 1), a vital complex necessary for skeletal muscle anabolism. BCKD depletion increased the phosphorylation of mTORC1 upstream activator AKT (52%, P < 0.05, n = 3), and of mTORC1 downstream substrates by 25%-86%, consistent with the increase in myofibrillar proteins. Finally, in myotubes treated with the catabolic cytokine (tumor necrosis factor-a), BCKD depletion tended to increase the abundance of tropomyosin (a myofibrillar protein). Conclusions We showed that depletion of BCKD enhanced myofibrillar protein content and anabolic signaling. If these data are confirmed in vivo, development of dietary and other interventions that target BCKD abundance or functions may promote muscle protein anabolism in individuals with muscle wasting conditions. Funding Sources MHRC, NSERC York U.

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mTORC1 Signaling in Individual Human Muscle Fibers Following Resistance Exercise in Combination With Intake of Essential Amino Acids

Frontiers in Nutrition ◽

10.3389/fnut.2019.00096 ◽

2019 ◽

Vol 6 ◽

Cited By ~ 12

Author(s):

Sebastian Edman ◽

Karin Söderlund ◽

Marcus Moberg ◽

William Apró ◽

Eva Blomstrand

Keyword(s):

Amino Acids ◽

Resistance Exercise ◽

Muscle Fibers ◽

Essential Amino Acids ◽

Human Muscle ◽

Mtorc1 Signaling ◽

Individual Human

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Effects of an Amino Acid/Creatine Energy Supplement on the Acute Hormonal Response to Resistance Exercise

International Journal of Sport Nutrition and Exercise Metabolism ◽

10.1123/ijsnem.17.6.608 ◽

2007 ◽

Vol 17 (6) ◽

pp. 608-623 ◽

Cited By ~ 11

Author(s):

Nicholas A. Ratamess ◽

Jay R. Hoffman ◽

Ryan Ross ◽

Miles Shanklin ◽

Avery D. Faigenbaum ◽

...

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Resistance Exercise ◽

Venous Blood ◽

Area Under The Curve ◽

Essential Amino Acids ◽

Total Testosterone ◽

Hormonal Response ◽

Energy Supplement ◽

And Performance

The authors aimed to examine the acute hormonal and performance responses to resistance exercise with and without prior consumption of an amino acid/creatine/energy supplement. Eight men performed a resistance-exercise protocol at baseline (BL), 20 min after consuming a supplement (S) consisting of essential amino acids, creatine, taurine, caffeine, and glucuronolactone or a maltodextrin placebo (P). Venous blood samples were obtained before and immediately after (IP), 15 min (15P), and 30 min (30P) after each protocol. Area under the curve of resistance-exercise volume revealed that BL was significantly less than S (10%) and P (8.6%). For fatigue rate, only S (18.4% ± 12.0%) was significantly lower than BL (32.9% ± 8.4%). Total testosterone (TT) and growth hormone (GH) were significantly elevated at IP and 15P in all conditions. The GH response was significantly lower, however, in S and P than in BL. The TT and GH responses did not differ between S and P. These results indicated that a supplement consisting of amino acids, creatine, taurine, caffeine, and glucuronolactone can modestly improve high-intensity endurance; however, the anabolic-hormonal response was not augmented.

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