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Making Sense of Muscle Protein Synthesis: A Focus on Muscle Growth During Resistance Training

Oliver C. Witard, Laurent Bannock, and Kevin D. Tipton

Muscle protein synthesis (MPS) is the metabolic process that describes the incorporation of amino acids into bound skeletal muscle proteins. Muscle proteins can be crudely classified into the contractile myofibrillar proteins (i.e., myosin, actin, tropomyosin, troponin) and the energy producing

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mTOR-Dependent Control of Skeletal Muscle Protein Synthesis

John C. Lawrence Jr.

Muscle mass is influenced by many factors including genetically programmed changes, hormonal state, level of activity, and disease processes. Ultimately, whether or not a muscle hypertrophies or atrophies is determined by a simple relationship between the rates of protein synthesis and degradation. When synthesis exceeds degradation, the muscle hypertrophies, and vice versa. In contrast to this simple relationship, the processes that control muscle protein synthesis and degradation are complex. Recently, significant progress has been made in understanding the biochemical mechanisms that control the rate of translation initiation, which is generally the limiting phase in protein synthesis.

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Celebrating the Professional Life of Professor Kevin D. Tipton (1961–2022)

Oliver C. Witard, Arny A. Ferrando, and Stuart M. Phillips

Stimulates Net Muscle Protein Synthesis Following Resistance Exercise” ( Elliot et al., 2006 ). The results from that paper still intrigue many today as to the mechanism underlying milk’s anabolic properties. While that publication may have been the first, it was most certainly not the last of Kevin’s senior

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Endocrine Responses During Overnight Recovery From Exercise: Impact of Nutrition and Relationships With Muscle Protein Synthesis

James A. Betts, Milou Beelen, Keith A. Stokes, Wim H.M. Saris, and Luc J.C. van Loon

Nocturnal endocrine responses to exercise performed in the evening and the potential role of nutrition are poorly understood. To gain novel insight, 10 healthy men ingested carbohydrate with (C+P) and without (C) protein in a randomized order and double-blind manner during 2 hr of interval cycling followed by resistancetype exercise and into early postexercise recovery. Blood samples were obtained hourly throughout 9 hr of postexercise overnight recovery for analysis of key hormones. Muscle samples were taken from the vastus lateralis before and after exercise and then again the next morning (7 a.m.) to calculate mixed-muscle protein fractional synthetic rate (FSR). Overnight plasma hormone concentrations were converted into overall responses (expressed as area under the concentration curve) and did not differ between treatments for either growth hormone (1,464 ± 257 vs. 1,432 ± 164 pg/ml · 540 min) or total testosterone (18.3 ± 1.2 vs. 17.9 ± 1.2 nmol/L · 540 min, C and C+P, respectively). In contrast, the overnight cortisol response was higher with C+P (102 ± 11 nmol/L · 540 min) than with C (81 ± 8 nmol/L · 540 min; p = .02). Mixed-muscle FSR did not differ between C and C+P during overnight recovery (0.062% ± 0.006% and 0.062% ± 0.009%/hr, respectively) and correlated significantly with the plasma total testosterone response (r = .7, p < .01). No correlations with FSR were apparent for the response of growth hormone (r = –.2, p = .4), cortisol (r = .1, p = .6), or the ratio of testosterone to cortisol (r = .2, p = .5). In conclusion, protein ingestion during and shortly after exercise does not modulate the endocrine response or muscle protein synthesis during overnight recovery.

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Control of Muscle Protein Synthesis as a Result of Contractile Activity and Amino Acid Availability: Implications for Protein Requirements

Michael J. Rennie

The major anabolic influences on muscle are feeding and contractile activity. As a result of feeding, anabolism occurs chiefly by increases in protein synthesis with minor changes in protein breakdown. Insulin has a permissive role in increasing synthesis, but the availability of amino acids is crucial for net anabolism. We have investigated the role of amino acids in stimulating muscle protein synthesis, the synergy between exercise and amino acid availability, and some of the signaling elements involved. The results suggest that muscle is acutely sensitive to amino acids, that exercise probably increases the anabolic effects of amino acids by a separate pathway, and that for this reason it is unlikely that accustomed physical exercise increases protein requirements.

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The Anabolic Response to Protein Ingestion During Recovery From Exercise Has No Upper Limit in Magnitude and Duration In Vivo in Humans: A Commentary

Oliver C. Witard and Samuel Mettler

,” recreationally active (but not resistance-trained), young men following resistance exercise. Moreover, this study demonstrated that the duration of the postprandial period is modulated by the dose of ingested protein contained within a meal, that is, the postexercise muscle protein synthesis (MPS) response to

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Endurance-Type Exercise Increases Bulk and Individual Mitochondrial Protein Synthesis Rates in Rats

Andrew M. Holwerda, Freek G. Bouwman, Miranda Nabben, Ping Wang, Janneau van Kranenburg, Annemie P. Gijsen, Jatin G. Burniston, Edwin C.M. Mariman, and Luc J.C. van Loon

-spread application of individual protein FSR measurements. We and others have applied deuterated water ( 2 H 2 O) to assess in vivo muscle protein synthesis rates over several days or weeks ( Holwerda et al., 2018a , 2018b ; Murphy et al., 2018 ; Robinson et al., 2011 ; Wilkinson et al., 2014 ). The endogenous

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Daily Myofibrillar Protein Synthesis Rates in Response to Low- and High-Frequency Resistance Exercise Training in Healthy, Young Men

Brandon J. Shad, Janice L. Thompson, James Mckendry, Andrew M. Holwerda, Yasir S. Elhassan, Leigh Breen, Luc J.C. van Loon, and Gareth A. Wallis

). However, most studies to date have examined the impact of resistance exercise training frequencies in the range of one to three times per week. It is possible that higher resistance exercise training frequencies (e.g., five times per week) are required to enhance muscle protein synthesis rates and

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Postexercise Dietary Protein Strategies to Maximize Skeletal Muscle Repair and Remodeling in Masters Endurance Athletes: A Review

Thomas M. Doering, Peter R. Reaburn, Stuart M. Phillips, and David G. Jenkins

Participation rates of masters athletes in endurance events such as long-distance triathlon and running continue to increase. Given the physical and metabolic demands of endurance training, recovery practices influence the quality of successive training sessions and, consequently, adaptations to training. Research has suggested that, after muscle-damaging endurance exercise, masters athletes experience slower recovery rates in comparison with younger, similarly trained athletes. Given that these discrepancies in recovery rates are not observed after non–muscle-damaging exercise, it is suggested that masters athletes have impairments of the protein remodeling mechanisms within skeletal muscle. The importance of postexercise protein feeding for endurance athletes is increasingly being acknowledged, and its role in creating a positive net muscle protein balance postexercise is well known. The potential benefits of postexercise protein feeding include elevating muscle protein synthesis and satellite cell activity for muscle repair and remodeling, as well as facilitating muscle glycogen resynthesis. Despite extensive investigation into age-related anabolic resistance in sedentary aging populations, little is known about how anabolic resistance affects postexercise muscle protein synthesis and thus muscle remodeling in aging athletes. Despite evidence suggesting that physical training can attenuate but not eliminate age-related anabolic resistance, masters athletes are currently recommended to consume the same postexercise dietary protein dose (approximately 20 g or 0.25 g/kg/meal) as younger athletes. Given the slower recovery rates of masters athletes after muscle-damaging exercise, which may be due to impaired muscle remodeling mechanisms, masters athletes may benefit from higher doses of postexercise dietary protein, with particular attention directed to the leucine content of the postexercise bolus.

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Effects of Resistance Training on the Rate of Muscle Protein Synthesis in Frail Elderly People

Jill N. Schulte and Kevin E. Yarasheski

Advancing age is associated with a reduction in skeletal muscle protein, muscle strength, muscle quality, and chemical modifications that may impair protein function. Sarcopenia has been coupled with physical disability, frailty, and a loss of independent function (5, 19). Using stable isotope tracer methodologies and mass spectrometric detection, we observed: (a) 76–92-year-old physically frail and 62–74-year-old middle-age adults have lower mixed muscle protein synthetic rates than 20–32-year-old men and women; (b) 2 weeks and 3 months of weightlifting exercise increased the synthetic rate of myosin heavy chain (MHC) and mixed muscle proteins to a similar magnitude in frail, middle-age, and young women and men; (c) Serum myostatin-immunoreactive protein levels were elevated in physically frail women and were inversely correlated with lean mass. This suggests that the protein synthetic machinery adapts rapidly to increased contractile activity and that the adaptive response(s) are maintained even in frail elders.