Basal Muscle Protein Synthesis Research Articles

Intramuscular injection of mesenchymal stem cells augments basal muscle protein synthesis after bouts of resistance exercise in male mice.

Skeletal muscle mass is critical for activities of daily living. Resistance training maintains or increases muscle mass, and various strategies maximize the training adaptation. Mesenchymal stem cells (MSCs) are multipotent cells with differential potency in skeletal muscle cells and the capacity to secrete growth factors. However, little is known regarding the effect of intramuscular injection of MSCs on basal muscle protein synthesis and catabolic systems after resistance training. Here, we measured changes in basal muscle protein synthesis, the ubiquitin-proteasome system, and autophagy-lysosome system-related factors after bouts of resistance exercise by intramuscular injection of MSCs. Mice performed three bouts of resistance exercise (each consisting of 50 maximal isometric contractions elicited by electrical stimulation) on the right gastrocnemius muscle every 48 h, and immediately after the first bout, mice were intramuscularly injected with either MSCs (2.0 × 106 cells) labeled with green fluorescence protein (GFP) or vehicle only placebo. Seventy-two hours after the third exercise bout, GFP was detected only in the muscle injected with MSCs with concomitant elevation of muscle protein synthesis. The injection of MSCs also increased protein ubiquitination. These results suggest that the intramuscular injection of MSCs augmented muscle protein turnover at the basal state after consecutive resistance exercise.

Short-term disuse does not affect postabsorptive or postprandial muscle protein fractional breakdown rates.

The decline in postabsorptive and postprandial muscle protein fractional synthesis rates (FSR) does not quantitatively account for muscle atrophy during uncomplicated, short-term disuse, when atrophy rates are the highest. We sought to determine whether 2days of unilateral knee immobilization affects mixed muscle protein fractional breakdown rates (FBR) during postabsorptive and simulated postprandial conditions. Twenty-three healthy, male participants (age: 22±1year; height: 179±1cm; body mass: 73.4±1.5kg; body mass index 22.8±0.5kg·m-2 ) took part in this randomized, controlled study. After 48h of unilateral knee immobilization, primed continuous intravenous l-[15 N]-phenylalanine and l-[ring-2 H5 ]-phenylalanine infusions were used for parallel determinations of FBR and FSR, respectively, in a postabsorptive (saline infusion; FAST) or simulated postprandial state (67.5mg·kg body mass-1 ·h-1 amino acid infusion; FED). Bilateral m. vastus lateralis biopsies from the control (CON) and immobilized (IMM) legs, and arterialized-venous blood samples, were collected throughout. Amino acid infusion rapidly increased plasma phenylalanine (59±9%), leucine (76±5%), isoleucine (109±7%) and valine (42±4%) concentrations in FED only (all P<0.001), which was sustained for the remainder of infusion. Serum insulin concentrations peaked at 21.8±2.2mU·L-1 at 15min in FED only (P<0.001) and were 60% greater in FED than FAST (P<0.01). Immobilization did not influence FBR in either FAST (CON: 0.150±0.018; IMM: 0.143±0.017%·h-1 ) or FED (CON: 0.134±0.012; IMM: 0.160±0.018%·h-1 ; all effects P>0.05). However, immobilization decreased FSR (P<0.05) in both FAST (0.071±0.004 vs. 0.086±0.007%·h-1 ; IMM vs CON, respectively) and FED (0.066±0.016 vs. 0.119±0.016%·h-1 ; IMM vs CON, respectively). Consequently, immobilization decreased net muscle protein balance (P<0.05) and to a greater extent in FED (CON: -0.012±0.025; IMM: -0.095±0.023%·h-1 ; P<0.05) than FAST (CON: -0.064±0.020; IMM: -0.072±0.017%·h-1 ). We conclude that merely 2days of leg immobilization does not modulate postabsorptive and simulated postprandial muscle protein breakdown rates. Instead, under these conditions the muscle negative muscle protein balance associated with brief periods of experimental disuse is driven near exclusively by reduced basal muscle protein synthesis rates and anabolic resistance to amino acid administration.

Postabsorptive muscle protein synthesis is higher in outpatients as compared to inpatients.

Several factors affect muscle protein synthesis (MPS) in the postabsorptive state. Extreme physical inactivity (e.g., bedrest) may reduce basal MPS, whereas walking may augment basal MPS. We hypothesized that outpatients would have a higher postabsorptive MPS than inpatients. To test this hypothesis, we conducted a retrospective analysis. We compared 152 outpatient participants who arrived at the research site the morning of the MPS assessment with 350 Inpatient participants who had an overnight stay in the hospital unit before the MPS assessment the following morning. We used stable isotopic methods and collected vastus lateralis biopsies ∼2 to 3 h apart to assess mixed MPS. MPS was ∼12% higher (P < 0.05) for outpatients than inpatients. Within a subset of participants, we discovered that after instruction to limit activity, outpatients (n = 13) took 800 to 900 steps in the morning to arrive at the unit, seven times more steps than inpatients (n = 12). We concluded that an overnight stay in the hospital as an inpatient is characterized by reduced morning activity and causes a slight but significant reduction in MPS compared with participants studied as outpatients. Researchers should be aware of physical activity status when designing and interpreting MPS results.NEW & NOTEWORTHY The postabsorptive muscle protein synthesis rate is lower in the morning after an overnight inpatient hospital stay compared with an outpatient visit. Although only a minimal amount of steps was conducted by outpatients (∼900), this was enough to increase postabsorptive muscle protein synthesis rate.

Resistance training but not leucine can reverse frailty by increasing basal muscle protein synthesis in older women consuming optimized protein intake

Resistance training but not leucine can reverse frailty by increasing basal muscle protein synthesis in older women consuming optimized protein intake

Aging Is Associated With Impaired Postprandial Response of Skeletal Muscle Protein Synthesis to High-Intensity Muscle Contraction in Mice.

The purpose of this study was to investigate whether aging alters the effect of nutritional status on contraction-induced muscle protein metabolism. In an overnight fasted or fed states, the right gastrocnemius muscle of young (3 months) and aged (24 months) male C57BL/6J mice was isometrically contracted via percutaneous electrical stimulation. The left gastrocnemius muscle served as a control. In the fasted state, there were no differences in basal or contraction-induced muscle protein synthesis between young and old mice. However, in the fed state, basal muscle protein synthesis was greater in young mice, and contraction increased muscle protein synthesis only in young mice. In the fed state, although phosphorylation of 4E-BP1 was similarly increased by contraction in both ages, the increase in phosphorylation of p70S6K was greater in young mice. Our results indicate that aging impairs the ability to integrate signals from muscle contraction and nutrition, leading to aging-induced anabolic resistance to muscle contraction in the postprandial state.

Determining the Influence of Habitual Dietary Protein Intake on Physiological Muscle Parameters in Youth and Older Age.

Protein ingestion is a potent stimulator of skeletal muscle protein synthesis (MPS). However, older adults demonstrate resistance to anabolic stimuli. Some evidence has demonstrated that a larger acute protein dose is required in older compared to younger adults to elicit the same synthetic response, suggesting that older adults should be consuming higher habitual dietary protein to optimise muscle mass. However, limited research has explored dietary habits in different age groups or the relationship between habitual dietary intake and mechanistic physiological parameters associated with muscle mass and function. This work investigated the effect of habitual dietary intake in young (n = 10, 25.9 (3.2y)) and older (n = 16, 70.2 (3.2y)) community-dwelling adults (16:10 male: female) on physiological muscle parameters. Dietary intake was assessed using four-day diet diaries. Post-absorptive MPS and MPS responses to feeding (4.25x basal metabolic rate; 16% protein) were determined in muscle biopsies of the m. vastus lateralis via stable isotope tracer ([1, 2−13C2]-leucine) infusions with mass-spectrometric analyses. Body composition was measured by dual-energy x-ray absorptiometry. Whole body strength was assessed via 1-repetition maximum assessments. No significant differences in habitual dietary intake (protein, fat, carbohydrate and leucine as g.kgWBLM−1.day−1) were observed between age groups. Whole-body lean mass (61.8 ± 9.9 vs. 49.8 ± 11.9 kg, p = 0.01) and knee-extensor strength (87.7 ± 28.3 vs. 56.8 ± 16.4 kg, p = 0.002) were significantly higher in young adults. Habitual protein intake (g.kg−1.day−1) was not associated with whole-body lean mass, upper-leg lean mass, whole-body strength, knee-extensor strength, basal MPS or fed-state MPS across both age groups. These findings suggest that differences in muscle mass and strength parameters between youth and older age are not explained by differences in habitual dietary protein intake. Further research with a larger sample size is needed to fully explore these relationships and inform on interventions to mitigate sarcopenia development.

Assessing the whole-body protein synthetic response to feeding in vivo in human subjects.

All tissues are in a constant state of turnover, with a tightly controlled regulation of protein synthesis and breakdown rates. Due to the relative ease of sampling skeletal muscle tissue, basal muscle protein synthesis rates and the protein synthetic responses to various anabolic stimuli have been well defined in human subjects. In contrast, only limited data are available on tissue protein synthesis rates in other organs. Several organs such as the brain, liver and pancreas, show substantially higher (basal) protein synthesis rates when compared to skeletal muscle tissue. Such data suggest that these tissues may also possess a high level of plasticity. It remains to be determined whether protein synthesis rates in these tissues can be modulated by external stimuli. Whole-body protein synthesis rates are highly responsive to protein intake. As the contribution of muscle protein synthesis rates to whole-body protein synthesis rates is relatively small considering the large amount of muscle mass, this suggests that other organ tissues may also be responsive to (protein) feeding. Whole-body protein synthesis rates in the fasted or fed state can be quantified by measuring plasma amino acid kinetics, although this requires the production of intrinsically labelled protein. Protein intake requirements to maximise whole-body protein synthesis may also be determined by the indicator amino acid oxidation technique, but the technique does not allow the assessment of actual protein synthesis and breakdown rates. Both approaches have several other methodological and inferential limitations that will be discussed in detail in this paper.

Muscle fiber capillarization is associated with various indices of skeletal muscle mass in healthy, older men.

Muscle fiber capillarization plays a fundamental role in the regulation of skeletal muscle mass maintenance. However, it remains unclear to what extent capillarization is related to various other skeletal muscle characteristics. In this study we determined whether muscle fiber capillarization is independently associated with measures of skeletal muscle mass, both on a whole-body and cellular level, and post-absorptive muscle protein synthesis rates in healthy older men. Forty-six healthy older (70±4 y) men participated in a trial during which basal muscle protein synthesis rates were assessed using stable isotope tracer methodology. Blood and muscle biopsy samples were collected to assess post-absorptive muscle protein synthesis rates over a 3-hour period. Immunohistochemistry was performed to determine various indices of muscle fiber capillarization, size, type distribution, and myonuclear content/domain size. Dual energy x-ray absorptiometry scans were performed to determine whole-body and appendicular lean tissue mass. Capillary-to-fiber ratio (C/Fi) and perimeter exchange (CFPE) index correlated with whole-body lean tissue mass (r=0.43, P<0.01 and r=0.25, P<0.10, respectively), appendicular lean tissue mass (r=0.52, P<0.001 and r=0.37, P<0.05, respectively) as well as appendicular lean tissue mass divided by body mass index (r=0.65, P<0.001 and r=0.62, P<0.001, respectively). Muscle fiber size correlated with C/Fi (r=0.45, P<0.01), but not with CFPE index. No associations were observed between different indices of muscle fiber capillarization and post-absorptive muscle protein synthesis rates in healthy, older men. The present study provides further evidence that muscle fiber capillarization may be a critical factor in the regulation of skeletal muscle maintenance in healthy older men.

Dysregulated Handling of Dietary Protein and Muscle Protein Synthesis After Mixed-Meal Ingestion in Maintenance Hemodialysis Patients

IntroductionSkeletal muscle loss is common in patients with renal failure who receive maintenance hemodialysis (MHD) therapy. Regular ingestion of protein-rich meals are recommended to help offset muscle protein loss in MHD patients, but little is known about the anabolic potential of this strategy.MethodsEight MHD patients (age: 56 ± 5 years; body mass index [BMI]: 32 ± 2 kg/m2) and 8 nonuremic control subjects (age: 50 ± 2 years: BMI: 31 ± 1 kg/m2) received primed continuous L-[ring-2H5]phenylalanine and L-[1-13C]leucine infusions with blood and muscle biopsy sampling on a nondialysis day. Participants consumed a mixed meal (546 kcal; 20-g protein, 59-g carbohydrates, 26-g fat) with protein provided as L-[5,5,5-2H3]leucine-labeled eggs.ResultsCirculating dietary amino acid availability was reduced in MHD patients (41 ± 5%) versus control subjects (61 ± 4%; P = 0.03). Basal muscle caspase-3 protein content was elevated (P = 0.03) and large neutral amino acid transporter 1 (LAT1) protein content was reduced (P = 0.02) in MHD patients versus control subjects. Basal muscle protein synthesis (MPS) was ∼2-fold higher in MHD patients (0.030 ± 0.005%/h) versus control subjects (0.014 ± 0.003%/h) (P = 0.01). Meal ingestion failed to increase MPS in MHD patients (absolute change from basal: 0.0003 ± 0.007%/h), but stimulated MPS in control subjects (0.009 ± 0.002%/h; P = 0.004).ConclusionsMHD patients demonstrated muscle anabolic resistance to meal ingestion. This blunted postprandial MPS response in MHD patients might be related to high basal MPS, which results in a stimulatory ceiling effect and/or reduced plasma dietary amino acid availability after mixed-meal ingestion.

Muscle Protein Anabolic Resistance to Essential Amino Acids Does Not Occur in Healthy Older Adults Before or After Resistance Exercise Training

The muscle protein anabolic response to contraction and feeding may be blunted in older adults. Acute bouts of exercise can improve the ability of amino acids to stimulate muscle protein synthesis (MPS) by activating mechanistic target of rapamycin complex 1 (mTORC1) signaling, but it is not known whether exercise training may improve muscle sensitivity to amino acid availability. The aim of this study was to determine if muscle protein anabolism is resistant to essential amino acids (EAAs) and whether resistance exercise training (RET) improves muscle sensitivity to EAA in healthy older adults. In a longitudinal study, 19 healthy older adults [mean ± SD age: 71±4 y body mass index (kg/m2): 28±3] were trained for 12 wk with a whole-body program of progressive RET (60-75% 1-repetition maximum). Body composition, strength, and metabolic health were measured pre- and posttraining. We also performed stable isotope infusion experiments with muscle biopsies pre- and posttraining to measure MPS and markers of amino acid sensing in the basal state and in response to 6.8 g of EAA ingestion. RET increased muscle strength by 16%, lean mass by 2%, and muscle cross-sectional area by 27% in healthy older adults (P<0.05). MPS and mTORC1 signaling (i.e., phosphorylation status of protein kinase B, 4E binding protein 1, 70-kDa S6 protein kinase, and ribosomal protein S6) increased after EAA ingestion (P<0.05) pre- and posttraining. RET increased basal MPS by 36% (P<0.05); however, RET did not affect the response of MPS and mTORC1 signaling to EAA ingestion. RET increases strength and basal MPS, promoting hypertrophy in healthy older adults. In these subjects, a small dose of EAAs stimulates muscle mTORC1 signaling and MPS, and this response to EAAs does not improve after RET. Our data indicate that anabolic resistance to amino acids may not be a problem in healthy older adults. This trial was registered at www.clinicaltrials.gov as NCT02999802.

Effect Of Resistance Exercise Training On Anabolic Resistance To Amino Acids In Healthy Older Adults

Aging attenuates the contraction-induced stimulation of muscle protein synthesis (MPS). This phenomenon is termed “anabolic resistance”, and may contribute to the slow loss of muscle mass with advancing age (sarcopenia). Some studies also reported anabolic resistance to amino acid/protein intake with aging. However, this notion has not been firmly established. Acute bouts of exercise can improve the ability of amino acids to stimulate MPS by activating mechanistic target of rapamycin complex 1 (mTORC1) signaling and translation initiation, but it is not known whether chronic exercise training may improve muscle sensitivity to amino acid availability. PURPOSE: The aim of this study was to determine if healthy older adults exhibit muscle anabolic resistance to essential amino acid intake (EAA), and whether resistance exercise training (RET) improves the muscle sensitivity to EAA. METHODS: To test our hypothesis 19 healthy older adults (65-80 years old) underwent a 12-week progressive resistance exercise training program (RET). Before and after training we measured muscle mass and strength, and performed stable isotope infusion experiments with muscle biopsies to determine MPS and markers of amino acid sensing in the basal state and in response to EAA ingestion. RESULTS: RET increased muscle strength (+15%), lean mass (+2%), and muscle cross sectional area (+17%) in healthy older adults (P<0.05). MPS and mTORC1 signaling (i.e., phosphorylation status of 4E-BP1, S6K1, and rpS6) increased following EAA ingestion (P<0.05). Basal MPS increased by 28% after RET (P<0.05). However, the amplitude of the response of MPS and mTORC1 signaling to EAA ingestion did not differ from pre-training values (P>0.05). CONCLUSION: Aging does not inhibit the EAA-stimulation of muscle mTORC1 signaling and MPS. In addition, RET did not increase the sensitivity of muscle to amino acids. Our data indicate that anabolic resistance to amino acids is not a significant problem in healthy older adults. We suggest that future work in conditions associated with more pronounced muscle wasting is necessary to determine whether exercise training can improve muscle sensitivity to amino acids or protein. Supported by NIH/NIA R56 AG051267, P30 AG024832, NIH/NCATS UL1 TR001439.

Measurement of Muscle, Tendon, Ligament, Cartilage, and Bone Protein Synthesis Rates In Vivo in Humans

IntroductionSkeletal muscle plasticity is reflected by a dynamic balance between protein synthesis and breakdown, with basal muscle protein synthesis rates typically ranging between 0.04 and 0.06 %/h. Though it is evident that other musculoskeletal tissues should also express some level of plasticity, protein synthesis rates of most of these tissues have never been assessed. The present study applies contemporary stable isotope methodology to assess basal muscle, tendon, ligament, bone, as well as cartilage protein synthesis rates in vivo in humans.MethodsSix otherwise healthy patients (62±3 y), scheduled to undergo unilateral total knee arthroplasty, were included in this study. Primed continuous intravenous infusions with L‐[ring‐13C6]‐Phenylalanine were initiated 2.5 h prior to surgery and continued during surgery. Throughout the surgical procedure the following tissue samples were obtained: muscle, tendon, cruciate ligaments, cartilage, bone, menisci, fat and synovium. Tissue‐specific fractional protein synthesis rates (%/h) were assessed by measuring the incorporation of labelled L‐[ring‐13C6]‐Phenylalanine in tissue protein and were compared with muscle tissue protein synthesis rates using a paired t test.ResultsProtein bound L‐[ring‐13C6]‐Phenylalanine enrichments did not differ substantially between the different musculoskeletal tissues and skeletal muscle, except for notch bone tissue (P&lt;0.01). Highest enrichment levels were observed in synovium derived protein (0.029±0.008 MPE) and lowest enrichment levels in patellar bone tissue protein (0.005±0.002 MPE). Tendon, bone, cartilage, fat, anterior cruciate ligament, posterior cruciate ligament, and menisci tissue protein synthesis rates averaged 0.06±0.01, 0.03±0.01, 0.04±0.01, 0.11±0.03, 0.07±0.02, 0.04±0.01, and 0.04±0.01 %/h, respectively, and did not significantly differ from skeletal muscle protein synthesis rates (0.04±0.01 %/h; P&gt;0.05). Synovium derived protein and notch bone tissue protein synthesis rates were respectively higher and lower compared to skeletal muscle protein synthesis rates (P&lt;0.05 and P&lt;0.01, respectively).ConclusionBasal protein synthesis rates in various musculoskeletal tissues are within the same range of skeletal muscle protein synthesis rates, with fractional muscle, tendon, bone, cartilage, ligament and menisci tissue protein synthesis rates ranging between 0.02 and 0.13 % per hour.Support or Funding InformationThis study received no specific grant from any funding agency.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Progressive resistance-loaded voluntary wheel running increases hypertrophy and differentially affects muscle protein synthesis, ribosome biogenesis, and proteolytic markers in rat muscle.

We examined if 6weeks of progressive resistance-loaded voluntary wheel running in rats induced plantaris, soleus, and/or gastrocnemius hypertrophy and/or affected markers of translational efficiency, ribosome biogenesis, and markers of proteolysis. For 6weeks, 8 male Sprague-Dawley rats (~9-10weeks of age, ~300-325g) rats were assigned to the progressive resistance-loaded voluntary wheel running model (EX), and ten rats were not trained (SED). For EX rats, the wheel-loading paradigm was as follows - days 1-7: free-wheel resistance, days 8-15: wheel resistance set to 20%-25% body mass, days 16-24: 40% body mass, days 25-32: 60% body mass, days 33-42: 40% body mass. Following the intervention, muscles were analysed for markers of translational efficiency, ribosome biogenesis, and muscle proteolysis. Raw gastrocnemius mass (+13%, p<.01), relative (body mass-corrected) gastrocnemius mass (+16%, p<.001), raw plantaris mass (+13%, p<.05), and relative plantaris mass (+15%, p<.01) were greater in EX vs. SED rats. In spite of gastrocnemius hypertrophy, EX animals presented a 54% decrease in basal muscle protein synthesis levels (p<.01), a 125% increase in pan 4EBP1 levels (p<.001) and a 31% decrease in pan eIF4E levels (p<.05). However, in relation to SED animals, EX animals presented a 70% increase in gastrocnemius c-Myc protein levels (p<.05). Most markers of translational efficiency and ribosome biogenesis were not altered in the plantaris or soleus muscles of EX vs. SED animals. Gastrocnemius F-box protein 32 and poly-ubiquinated protein levels were approximately 150% and 200% greater in SED vs. EX rats (p<.001). These data suggest that the employed resistance training model increases hind limb muscle hypertrophy, and this may be mainly facilitated through reductions in skeletal muscle proteolysis, rather than alterations in ribosome biogenesis or translational efficiency.

Habituation to low or high protein intake does not modulate basal or postprandial muscle protein synthesis rates: a randomized trial

Background: Muscle mass maintenance is largely regulated by basal muscle protein synthesis rates and the ability to increase muscle protein synthesis after protein ingestion. To our knowledge, no previous studies have evaluated the impact of habituation to either low protein intake (LOW PRO) or high protein intake (HIGH PRO) on the postprandial muscle protein synthetic response.Objective: We assessed the impact of LOW PRO compared with HIGH PRO on basal and postprandial muscle protein synthesis rates after the ingestion of 25 g whey protein.Design: Twenty-four healthy, older men [age: 62 ± 1 y; body mass index (in kg/m2): 25.9 ± 0.4 (mean ± SEM)] participated in a parallel-group randomized trial in which they adapted to either a LOW PRO diet (0.7 g · kg–1 · d−1; n = 12) or a HIGH PRO diet (1.5 g · kg–1 · d–1; n = 12) for 14 d. On day 15, participants received primed continuous l-[ring-2H5]-phenylalanine and l-[1-13C]-leucine infusions and ingested 25 g intrinsically l-[1-13C]-phenylalanine– and l-[1-13C]-leucine–labeled whey protein. Muscle biopsies and blood samples were collected to assess muscle protein synthesis rates as well as dietary protein digestion and absorption kinetics.Results: Plasma leucine concentrations and exogenous phenylalanine appearance rates increased after protein ingestion (P < 0.01) with no differences between treatments (P > 0.05). Plasma exogenous phenylalanine availability over the 5-h postprandial period was greater after LOW PRO than after HIGH PRO (61% ± 1% compared with 56% ± 2%, respectively; P < 0.05). Muscle protein synthesis rates increased from 0.031% ± 0.004% compared with 0.039% ± 0.007%/h in the fasted state to 0.062% ± 0.005% compared with 0.057% ± 0.005%/h in the postprandial state after LOW PRO compared with HIGH PRO, respectively (P < 0.01), with no differences between treatments (P = 0.25).Conclusion: Habituation to LOW PRO (0.7 g · kg–1 · d–1) compared with HIGH PRO (1.5 g · kg–1 · d–1) augments the postprandial availability of dietary protein–derived amino acids in the circulation and does not lower basal muscle protein synthesis rates or increase postprandial muscle protein synthesis rates after ingestion of 25 g protein in older men. This trial was registered at clinicaltrials.gov as NCT01986842.

Both basal and post-prandial muscle protein synthesis rates, following the ingestion of a leucine-enriched whey protein supplement, are not impaired in sarcopenic older males

Studying the muscle protein synthetic response to food intake in elderly is important, as it aids the development of interventions to combat sarcopenia. Although sarcopenic elderly are the target group for many of these nutritional interventions, no studies have assessed basal or post-prandial muscle protein synthesis rates in this population. To assess the basal and post-prandial muscle protein synthesis rates between healthy and sarcopenic older men. A total of 15 healthy (69±1y) and 15 sarcopenic (81±1y) older men ingested a leucine-enriched whey protein nutritional supplement containing 21g of protein, 9g of carbohydrate, and 3g of fat. Stable isotope methodology combined with frequent collection of blood and muscle samples was applied to assess basal and post-prandial muscle protein fractional synthetic rates. Handgrip strength, muscle mass, and gait speed were assessed to identify sarcopenia, according to international criteria. Basal mixed muscle protein fractional synthetic rates (FSR) averaged 0.040±0.005 and 0.032±0.003%/h (mean±SEM) in the sarcopenic and healthy group, respectively (P=0.14). Following protein ingestion, FSR increased significantly to 0.055±0.004 and 0.053±0.004%/h in the post-prandial period in the sarcopenic (P=0.003) and healthy groups (P<0.001), respectively, with no differences between groups (P=0.45). Furthermore, no differences were observed between groups in muscle protein synthesis rates during the early (0.058±0.007 vs 0.060±0.008%/h, sarcopenic vs healthy, respectively) and late (0.052±0.004 vs 0.048±0.003%/h) stages of the post-prandial period (P=0.93 and P=0.34, respectively). Basal muscle protein synthesis rates are not lower in sarcopenic older men compared to healthy older men. The ingestion of 21g of a leucine-enriched whey protein effectively increases muscle protein synthesis rates in both sarcopenic and healthy older men. Public trial registry number: NTR3047.

Ingestion of Wheat Protein Increases In Vivo Muscle Protein Synthesis Rates in Healthy Older Men in a Randomized Trial

Background: Muscle mass maintenance is largely regulated by basal muscle protein synthesis and the capacity to stimulate muscle protein synthesis after food intake. The postprandial muscle protein synthetic response is modulated by the amount, source, and type of protein consumed. It has been suggested that plant-based proteins are less potent in stimulating postprandial muscle protein synthesis than animal-derived proteins. However, few data support this contention.Objective: We aimed to assess postprandial plasma amino acid concentrations and muscle protein synthesis rates after the ingestion of a substantial 35-g bolus of wheat protein hydrolysate compared with casein and whey protein.Methods: Sixty healthy older men [mean ± SEM age: 71 ± 1 y; body mass index (in kg/m2): 25.3 ± 0.3] received a primed continuous infusion of L-[ring-13C6]-phenylalanine and ingested 35 g wheat protein (n = 12), 35 g wheat protein hydrolysate (WPH-35; n = 12), 35 g micellar casein (MCas-35; n = 12), 35 g whey protein (Whey-35; n = 12), or 60 g wheat protein hydrolysate (WPH-60; n = 12). Plasma and muscle samples were collected at regular intervals.Results: The postprandial increase in plasma essential amino acid concentrations was greater after ingesting Whey-35 (2.23 ± 0.07 mM) than after MCas-35 (1.53 ± 0.08 mM) and WPH-35 (1.50 ± 0.04 mM) (P < 0.01). Myofibrillar protein synthesis rates increased after ingesting MCas-35 (P < 0.01) and were higher after ingesting MCas-35 (0.050% ± 0.005%/h) than after WPH-35 (0.032% ± 0.004%/h) (P = 0.03). The postprandial increase in plasma leucine concentrations was greater after ingesting Whey-35 than after WPH-60 (peak value: 580 ± 18 compared with 378 ± 10 μM, respectively; P < 0.01), despite similar leucine contents (4.4 g leucine). Nevertheless, the ingestion of WPH-60 increased myofibrillar protein synthesis rates above basal rates (0.049% ± 0.007%/h; P = 0.02).Conclusions: The myofibrillar protein synthetic response to the ingestion of 35 g casein is greater than after an equal amount of wheat protein. Ingesting a larger amount of wheat protein (i.e., 60 g) substantially increases myofibrillar protein synthesis rates in healthy older men. This trial was registered at clinicaltrials.gov as NCT01952639.

Nutritional Support for Exercise-Induced Injuries.

Nutrition is one method to counter the negative impact of an exercise-induced injury. Deficiencies of energy, protein and other nutrients should be avoided. Claims for the effectiveness of many other nutrients following injuries are rampant, but the evidence is equivocal. The results of an exercise-induced injury may vary widely depending on the nature of the injury and severity. Injuries typically result in cessation, or at least a reduction, in participation in sport and decreased physical activity. Limb immobility may be necessary with some injuries, contributing to reduced activity and training. Following an injury, an inflammatory response is initiated and while excess inflammation may be harmful, given the importance of the inflammatory process for wound healing, attempting to drastically reduce inflammation may not be ideal for optimal recovery. Injuries severe enough for immobilization of a limb result in loss of muscle mass and reduced muscle strength and function. Loss of muscle results from reductions in basal muscle protein synthesis and the resistance of muscle to anabolic stimulation. Energy balance is critical. Higher protein intakes (2–2.5 g/kg/day) seem to be warranted during immobilization. At the very least, care should be taken not to reduce the absolute amount of protein intake when energy intake is reduced. There is promising, albeit preliminary, evidence for the use of omega-3 fatty acids and creatine to counter muscle loss and enhance hypertrophy, respectively. The overriding nutritional recommendation for injured exercisers should be to consume a well-balanced diet based on whole, minimally processed foods or ingredients made from whole foods. The diet composition should be carefully assessed and changes considered as the injury heals and activity patterns change.

Prolonged Adaptation to a Low or High Protein Diet Does Not Modulate Basal Muscle Protein Synthesis Rates - A Substudy.

BackgroundBased on controlled 36 h experiments a higher dietary protein intake causes a positive protein balance and a negative fat balance. A positive net protein balance may support fat free mass accrual. However, few data are available on the impact of more prolonged changes in habitual protein intake on whole-body protein metabolism and basal muscle protein synthesis rates.ObjectiveTo assess changes in whole-body protein turnover and basal muscle protein synthesis rates following 12 weeks of adaptation to a low versus high dietary protein intake.MethodsA randomized parallel study was performed in 40 subjects who followed either a high protein (2.4 g protein/kg/d) or low protein (0.4 g protein/kg/d) energy-balanced diet (30/35/35% or 5/60/35% energy from protein/carbohydrate/fat) for a period of 12 weeks. A subgroup of 7 men and 8 women (body mass index: 22.8±2.3 kg/m2, age: 24.3±4.9 y) were selected to evaluate the impact of prolonged adaptation to either a high or low protein intake on whole body protein metabolism and basal muscle protein synthesis rates. After the diet, subjects received continuous infusions with L-[ring-2H5]phenylalanine and L-[ring-2H2]tyrosine in an overnight fasted state, with blood samples and muscle biopsies being collected to assess post-absorptive whole-body protein turnover and muscle protein synthesis rates in vivo in humans.ResultsAfter 12 weeks of intervention, whole-body protein balance in the fasted state was more negative in the high protein treatment when compared with the low protein treatment (-4.1±0.5 vs -2.7±0.6 μmol phenylalanine/kg/h;P<0.001). Whole-body protein breakdown (43.0±4.4 vs 37.8±3.8 μmol phenylalanine/kg/h;P<0.03), synthesis (38.9±4.2 vs 35.1±3.6 μmol phenylalanine/kg/h;P<0.01) and phenylalanine hydroxylation rates (4.1±0.6 vs 2.7±0.6 μmol phenylalanine/kg/h;P<0.001) were significantly higher in the high vs low protein group. Basal muscle protein synthesis rates were maintained on a low vs high protein diet (0.042±0.01 vs 0.045±0.01%/h;P = 0.620).ConclusionsIn the overnight fasted state, adaptation to a low-protein intake (0.4 g/kg/d) does not result in a more negative whole-body protein balance and does not lower basal muscle protein synthesis rates when compared to a high-protein intake.Trial RegistrationClinicaltrials.gov NCT01551238.

Effect of age on basal muscle protein synthesis and mTORC1 signaling in a large cohort of young and older men and women

The rate of muscle loss with aging is higher in men than women. However, women have smaller muscles throughout the adult life. Protein content is a major determinant of skeletal muscle size. This study was designed to determine if age and sex differentially impact basal muscle protein synthesis and mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling. We performed a secondary data analysis on a cohort of 215 healthy, non-obese (BMI<30kg·m−2) young (18–40y; 74 men, 52 women) and older (60–87y; 57 men, 32 women) adults. The database contained information on physical characteristics, basal muscle protein fractional synthetic rate (FSR; n=215; stable isotope methodology) and mTORC1 signaling (n=125, Western blotting). FSR and mTORC1 signaling were measured at rest and after an overnight fast. mTORC1 and S6K1 phosphorylation were higher (p<0.05) in older subjects with no sex differences. However, there were no age or sex differences or interaction for muscle FSR (p>0.05). Body mass index, fat free mass, or body fat was not a significant covariate and did not influence the results. We conclude that age and sex do not influence basal muscle protein synthesis. However, basal mTORC1 hyperphosphorylation in the elderly may contribute to insulin resistance and the age-related anabolic resistance of skeletal muscle protein metabolism to nutrition and exercise.

Strategies to maintain skeletal muscle mass in the injured athlete: Nutritional considerations and exercise mimetics

The recovery from many injuries sustained in athletic training or competition often requires an extensive period of limb immobilisation (muscle disuse). Such periods induce skeletal muscle loss and consequent declines in metabolic health and functional capacity, particularly during the early stages (1–2 weeks) of muscle disuse. The extent of muscle loss during injury strongly influences the level and duration of rehabilitation required. Currently, however, efforts to intervene and attenuate muscle loss during the initial two weeks of injury are minimal. Mechanistically, muscle disuse atrophy is primarily attributed to a decline in basal muscle protein synthesis rate and the development of anabolic resistance to food intake. Dietary protein consumption is of critical importance for stimulating muscle protein synthesis rates throughout the day. Given that the injured athlete greatly reduces physical activity levels, maintaining muscle mass whilst simultaneously avoiding gains in fat mass can become challenging. Nevertheless, evidence suggests that maintaining or increasing daily protein intake by focusing upon the amount, type and timing of dietary protein ingestion throughout the day can restrict the loss of muscle mass and strength during recovery from injury. Moreover, neuromuscular electrical stimulation may be applied to evoke involuntary muscle contractions and support muscle mass maintenance in the injured athlete. Although more applied work is required to translate laboratory findings directly to the injured athlete, current recommendations for practitioners aiming to limit the loss of muscle mass and/or strength following injury in their athletes are outlined herein.