Comparison of 8-weeks of full versus split body resistance training on appetite and energy intake in non-obese untrained men.

To investigate the effects of 8-weeks of full versus split body resistance training (RT) on appetite and energy intake in non-obese untrained men. The participants were pair-matched based on their initial fat mass and then randomly allocated into one of two treatment groups: Full body (FB, n = 20), in which all muscle groups were trained in every session, or Split body (SB, n = 15), in which upper and lower muscle groups were trained alternated per session; both groups trained in non-consecutive days, three times per week with total number of sets performed equated between groups. Energy intake, body composition, and strength performance were evaluated at pre-training, and after 8-weeks of RT, as well as self-reported hunger, fullness, and desire to eat, that were assessed at fasted and feed states pre- and post-intervention. FB and SB resistance training increased fat-free mass (FFM) (p < 0.001); and FB induced greater maximal strength improvement (p = 0.027). At fasted state self-reported hunger increased, and fullness decreased, while in feed state desire to eat something fatty increased in both groups. Carbohydrate intake (p = 0.011) decreased in both groups. In conclusion, FB and SB training increased orexigenic drive (increasing hunger and decreasing fullness), however, total energy intake and fat mass did not change after 8-weeks of RT in non-obese untrained men.Registered under Brazilian Registry of Clinical Trials no. RBR-3wkcvyw.

Does Beta-Alanine Supplementation Potentiate Muscle Performance Following 6 Weeks of Blood Flow Restriction or Traditional Resistance Training?

We aimed to compare the effects of beta-alanine on Traditional Resistance Training (TRAD) or Blood Flow Restriction Training (BFR). METHODS: 19 subjects were randomly allocated to a Placebo (n = 10) or beta-alanine (n = 9) group. Subjects from both groups were trained unilaterally (unilateral arm curl) for six weeks, and each arm was trained using a different paradigm (BFR or TRAD). One repetition maximum (1RM) test measurements were performed before and after the strength training program. Work output was accessed as the total weight lifted (repetitions × weight lifted × sets) for the entire strength training program. RESULTS: 1RM or total weight lifted was not increased by beta-alanine supplementation. However, the TRAD-trained arm showed a significantly increased 1RM and total weight lifted compared to the BFR arm (p < 0.05). CONCLUSION: We conclude that in the short-term (6 weeks) and following the current experimental conditions, beta-alanine does not benefit BFR or TRAD in terms of total weight lifted (volume of training) or maximal strength (1RM).

Creatine supplementation combined with blood flow restriction training enhances muscle thickness and performance: a randomized, placebo-controlled, and double-blind study.

This study aimed to compare the effects of an 8-week creatine (CR) or placebo (PL) supplementation on muscle strength, thickness, endurance, and body composition employing different training paradigms with blood flow restriction (BFR) vs. traditional resistance training (TRAD). Seventeen healthy males were randomized between the PL (n = 9) and CR (n = 8) groups. Participants were trained unilaterally utilizing a within-between subject bicep curl exercise where each arm was allocated to TRAD or BFR for 8 weeks. Muscular strength, thickness, endurance, and body composition were evaluated. Creatine supplementation promoted increases in muscle thickness in TRAD and BFR compared with their placebo counterparts, however, without a significant difference between treatments (p = 0.349). TRAD training increased maximum strength (1 repetition maximum (1RM)) compared with BFR after 8 weeks of training (p = 0.021). Repetitions to failure at 30% of 1RM were increased in the BFR-CR group compared with the TRAD-CR group (p = 0.004). Repetitions to failure at 70% 1RM were increased from weeks 0-4 (p < 0.05) and 4-8 (p < 0.05) in all groups. Creatine supplementation exerted a hypertrophic effect when utilized with TRAD and BFR paradigms and increased muscle performance at 30% 1RM when utilized in conjunction with BFR. Therefore, creatine supplementation seems to amplify muscle adaptation following a BFR program. Registered in the Brazilian Registry of Clinical Trials (ReBEC), under the registration number: RBR-3vh8zgj.

Role of MST1 in the regulation of autophagy and mitophagy: implications for aging-related diseases

As a key mechanism to maintain cellular homeostasis under stress conditions, autophagy/mitophagy is related to the occurrence of metabolic disorders, neurodegenerative diseases, cancer, and other aging-related diseases, but the relevant signal pathways regulating autophagy have not been clarified. Mammalian sterile 20-like kinase 1 (MST1) is a central regulatory protein of many metabolic pathways involved in the pathophysiological processes of aging and aging-related diseases and has become a critical integrator affecting autophagic signaling. Recent studies show that MST1 not only suppresses autophagy through directly phosphorylating Beclin-1 and/or inhibiting the protein expression of silent information regulator 1 (SIRT1) in the cytoplasm, but also inhibits BCL2/adenovirus E1B protein-interacting protein 3 (BNIP3)–, FUN14 domain containing 1 (FUNDC1)–, and Parkin (Parkinson protein 2)–mediated mitophagy by interacting with factors such as Ras association domain family 1A (RASSF1A). Indeed, a common pharmacological strategy for anti-aging is to induce autophagy/mitophagy through MST1 inhibition. This article reviews the role and mechanism of MST1 in regulating autophagy during aging, to provide evidence for the development of drugs targeting MST1. (AU)

Acute Low-Dose Capsiate Supplementation Improves Upper Body Resistance Exercise Performance in Trained Men: A Randomized, Crossover and Double-Blind Study.

Objectives: The purpose of this study was to compare the effects of two acute doses of Capsiate (CAP; 6 vs. 12 mg) on upper body resistance exercise performance in trained men. Methods: Using a randomized, crossover and double-blind design, 20 resistance-trained males were supplemented with low-dose CAP (6 mg), high-dose CAP (12 mg) or placebo 45 minutes before exercise. Subjects performed 4 sets of bench press with repetitions to failure at 70% 1 repetition maximum (1RM) and 2 minutes of rest between each set. The ratings of perceived exertion (RPE) and blood lactate were analyzed at baseline and after exercise. Results: Total weight lifted was greater in the low CAP (2,454.6 ± 448.6 kg) compared to placebo (2,354.7 ± 458.6 kg, p = 0.039) and high CAP (2,309.3 ± 428.1 kg, p = 0.001). There was no significant difference between conditions for RPE (p = 0.155) and blood lactate (p = 0.434). Conclusion: In summary, 6 mg CAP increased total weight lifted and repetitions to failure on bench press exercise in trained men, while 12 mg did not present any effect.

Role of MST1 in the regulation of autophagy and mitophagy: implications for aging-related diseases.

As a key mechanism to maintain cellular homeostasis under stress conditions, autophagy/mitophagy is related to the occurrence of metabolic disorders, neurodegenerative diseases, cancer, and other aging-related diseases, but the relevant signal pathways regulating autophagy have not been clarified. Mammalian sterile 20-like kinase 1 (MST1) is a central regulatory protein of many metabolic pathways involved in the pathophysiological processes of aging and aging-related diseases and has become a critical integrator affecting autophagic signaling. Recent studies show that MST1 not only suppresses autophagy through directly phosphorylating Beclin-1 and/or inhibiting the protein expression of silent information regulator 1 (SIRT1) in the cytoplasm, but also inhibits BCL2/adenovirus E1B protein-interacting protein 3 (BNIP3)-, FUN14 domain containing 1 (FUNDC1)-, and Parkin (Parkinson protein 2)-mediated mitophagy by interacting with factors such as Ras association domain family 1A (RASSF1A). Indeed, a common pharmacological strategy for anti-aging is to induce autophagy/mitophagy through MST1 inhibition. This article reviews the role and mechanism of MST1 in regulating autophagy during aging, to provide evidence for the development of drugs targeting MST1.

Exercise May Promote Skeletal Muscle Hypertrophy via Enhancing Leucine-Sensing: Preliminary Evidence.

Several studies have indicated a positive effect of exercise (especially resistance exercise) on the mTOR signaling that control muscle protein synthesis and muscle remodeling. However, the relationship between exercise, mTOR activation and leucine-sensing requires further clarification. Two month old Sprague-Dawley rats were subjected to aerobic exercise (treadmill running at 20 m/min, 6° incline for 60 min) and resistance exercise (incremental ladder climbing) for 4 weeks. The gastrocnemius muscles were removed for determination of muscle fibers diameter, cross-sectional area (CSA), protein concentration and proteins involved in muscle leucine-sensing and protein synthesis. The results show that 4 weeks of resistance exercise increased the diameter and CSA of gastrocnemius muscle fibers, protein concentration, the phosphorylation of mTOR (Ser2448), 4E-BP1(Thr37/46), p70S6K (Thr389), and the expression of LeuRS, while aerobic exercise just led to a significant increase in protein concentration and the phosphorylation of 4E-BP1(Thr37/46). Moreover, no difference was found for Sestrin2 expression between groups. The current study shows resistance exercise, but not aerobic exercise, may increase muscle protein synthesis and protein deposition, and induces muscle hypertrophy through LeuRS/mTOR signaling pathway. However, further studies are still warranted to clarify the exact effects of vary intensities and durations of aerobic exercise training.

Chronic capsiate supplementation increases fat-free mass and upper body strength but not the inflammatory response to resistance exercise in young untrained men: a randomized, placebo-controlled and double-blind study.

BACKGROUND: Acute capsaicinoid and capsinoid supplementation has endurance and resistance exercise benefits; however, if these short-term performance benefits translate into chronic benefits when combined with resistance training is currently unknown. This study investigated changes of chronic Capsiate supplementation on muscular adaptations, inflammatory response and performance in untrained men. METHODS: Twenty untrained men were randomized to ingest 12 mg Capsiate (CAP) or placebo in a parallel, double-blind design. Body composition and performance were measured at pre-training and after 6 weeks of resistance training. An acute resistance exercise session test was performed pre and post-intervention. Blood samples were collected at rest and post-resistance exercise to analyze Tumor necrosis factor- (TNF-), Soluble TNF- receptor (sTNF-r), Interleukin-6 (IL-6) and Interleukin-10 (IL-10). RESULTS: Exercise and CAP supplementation increased fat-free mass in comparison to baseline by 1.5 kg (P < 0.001), however, the majority of the increase (1.0 kg) resulted from an increase in total body water. The CAP change scores for fat-free mass were significantly greater in comparison to the placebo (CAP ∆%= 2.1 ± 1.8 %, PLA ∆%= 0.7 ± 1.3 %, P = 0.043) and there was a significant difference between groups in the bench press exercise (P = 0.034) with greater upper body strength change score for CAP (∆%= 13.4 ± 9.1 %) compared to placebo (∆%= 5.8 ± 5.2 %), P = 0.041. CAP had no effect on lower body strength and no supplementation interactions were observed for all cytokines in response to acute resistance exercise (P > 0.05). CONCLUSION: Chronic Capsiate supplementation combined with resistance training during short period (6 weeks) increased fat-free mass and upper body strength but not inflammatory response and performance in young untrained men.

Advances in the Role of Leucine-Sensing in the Regulation of Protein Synthesis in Aging Skeletal Muscle.

Skeletal muscle anabolic resistance (i.e., the decrease in muscle protein synthesis (MPS) in response to anabolic stimuli such as amino acids and exercise) has been identified as a major cause of age-related sarcopenia, to which blunted nutrition-sensing contributes. In recent years, it has been suggested that a leucine sensor may function as a rate-limiting factor in skeletal MPS via small-molecule GTPase. Leucine-sensing and response may therefore have important therapeutic potential in the steady regulation of protein metabolism in aging skeletal muscle. This paper systematically summarizes the three critical processes involved in the leucine-sensing and response process: (1) How the coincidence detector mammalian target of rapamycin complex 1 localizes on the surface of lysosome and how its crucial upstream regulators Rheb and RagB/RagD interact to modulate the leucine response; (2) how complexes such as Ragulator, GATOR, FLCN, and TSC control the nucleotide loading state of Rheb and RagB/RagD to modulate their functional activity; and (3) how the identified leucine sensor leucyl-tRNA synthetase (LARS) and stress response protein 2 (Sestrin2) participate in the leucine-sensing process and the activation of RagB/RagD. Finally, we discuss the potential mechanistic role of exercise and its interactions with leucine-sensing and anabolic responses.

Appetite Is Suppressed After Full-Body Resistance Exercise Compared With Split-Body Resistance Exercise: The Potential Influence of Lactate and Autonomic Modulation.

ABSTRACT: Conrado de Freitas, M, Ricci-Vitor, AL, de Oliveira, JVNS, Quizzini, GH, Vanderlei, LCM, Silva, BSA, Zanchi, NE, Cholewa, JM, Lira, FS, and Rossi, FE. Appetite is suppressed after full-body resistance exercise compared with split-body resistance exercise: the potential influence of lactate and autonomic modulation. J Strength Cond Res 35(9): 2532-2540, 2021-The purposes of this study were to investigate the effects of full- vs. split-body resistance training on appetite and leptin response and to verify the potential involvement of lactate and autonomic modulation during this response in trained men. Twelve recreationally resistance-trained men (age = 26.1 ± 5.5 years) performed 3 randomized trials in 3 conditions: upper body (UB), lower body (LB), and full body (FB). The subjective rating of hunger was obtained through a visual analog scale. Leptin and lactate concentration were evaluated at rest, immediately after exercise, and during recovery. Heart rate variability in the time and frequency domains was recorded at baseline and during recovery (until 60 minutes after exercise) to assess autonomic modulation. The FB condition induced lower subjective hunger ratings than the UB at Post-1 hour (p < 0.05) and a significant difference in the area under the curve between conditions (p = 0.028) with lower hunger sensation for FB in relation to UB (p = 0.041). The FB presented greater lactate concentration and induced slower heart rate variability recovery in relation to UB and LB conditions (p < 0.05), and heart rate variability remained lower until 60 minutes after exercise compared with rest only in the FB condition. There was a significant negative correlation between subjective hunger ratings and lactate concentration only for the FB condition (r = -0.72, p = 0.028). Full-body resistance exercise induced lower subjective hunger ratings after exercise in relation to UB resistance exercise. The FB also induced higher lactate production and slower recovery of autonomic modulation compared with the UB and LB conditions. Future research is necessary to investigate a mechanistic relationship between lactate concentrations and hunger suppression after resistance exercise.

Postactivation Potentiation Improves Acute Resistance Exercise Performance and Muscular Force in Trained Men.

ABSTRACT: Conrado de Freitas, M, Rossi, FE, Colognesi, LA, de Oliveira, JVNS, Zanchi, NE, Lira, FS, Cholewa, JM, and Gobbo, LA. Postactivation potentiation improves acute resistance exercise performance and muscular force in trained men. J Strength Cond Res 35(5): 1357-1363, 2021-The purpose of this study was to investigate the effects of heavy back squat (90% one repetition maximum [1RM]) postactivation potentiation (PAP) on acute resistance exercise performance and force production in recreationally trained men, and to verify the relationship between maximal strength and the PAP response. Ten resistance-trained men randomly completed 4 experimental trials: (a) back squats without PAP (No-PAP), (b) back squats with PAP, (c) maximum voluntary isometric contraction (MVIC) of the quadriceps without PAP, and (d) MVIC with PAP. Back squats were performed with 4 sets at 70% of 1 RM with 2 minutes of rest interval. The number of squats repetitions performed was recorded for each set, and a total number of repetitions were calculated to analyze performance. Maximum voluntary isometric contraction was measured using electronic dynamometer, and the peak force and mean force were recorded. Blood lactate concentration was analyzed presquat and postsquat exercise. Repetitions performed in the first set was significantly (p < 0.001) greater in the PAP condition (22.00 ± 5.14) compared with No-PAP (15.50 ± 5.10), which resulted in significantly (p = 0.001) more total repetitions performed in the PAP (56.20 ± 17.3) condition compared with No-PAP (48.80 ± 14.5). Maximum voluntary isometric contraction peak was higher in PAP than in No-PAP (PAP = 765.7 ± 147.8 vs. No-PAP = 696.8 ± 131.5 N, p = 0.006). No significant correlations were observed between back squat 1RM relative to body mass and the PAP response in squat and MVIC. There were no significant differences in lactate concentration between conditions. In conclusion, PAP resulting from a heavy load prior back squat exercise improved total volume during resistance exercise. In addition, PAP was effective to increase force production during MVIC, but there was no relationship between relative 1RM values and the PAP response in trained men.

The Effect of Exercise on Gene Expression and Signaling in Mouse Melanoma Tumors.

PURPOSE: To screen for candidate hub genes associated with the effects of exercise on melanoma tumor tissues and to review the potential signaling pathways involved in this process using bioinformatics analysis. METHODS: The GSE62628 expression profile was downloaded from Gene Expression Omnibus database. This data set contains 10 melanoma tumor tissues from two groups of exercise and nonexercise mice. The R software was utilized to identify differentially expressed genes between samples, and functional annotation and pathway analysis were performed. Results were visualized using Cytoscape software. RESULTS: In total, 315 differentially expressed genes were obtained, including 294 upregulated and 21 downregulated genes. The functional analysis showed that these genes were mainly enriched in immune response, inflammatory response, and positive regulation of the ERK1/2 cascade in biological process functional groups. The top 10 candidate hub genes were C3, Kng1, C3ar1, Ptafr, Fgg, Alb, Pf4, Orm1, Aldh3b1, and Apob. The pathway analysis of the most significant module identified from the protein-protein interaction network revealed that the complement and coagulation cascades, Staphylococcus aureus infection, cytokine-cytokine receptor interaction, chemokine signaling pathway and phagosome were mainly involved. C3, C3ar1, Kng1, Ptafr, and Fgg may be the critical genes in the complement and coagulation cascades pathway, and S. aureus in the infection pathway. CONCLUSIONS: Exercise may ameliorate the immune response and inflammatory response in melanoma tissue, and further studies exploring their relationships are warranted.

Short-Time ß-Alanine Supplementation on the Acute Strength Performance after High-Intensity Intermittent Exercise in Recreationally Trained Men.

(1) Background: We investigated the effects of 28 days of beta-alanine (ß-alanine) supplementation on the acute interference effect of high-intensity intermittent exercise (HIIE) on lower-body resistance exercise performance, body composition, and strength when combined with a resistance training program. (2) Methods: Twenty-two males were randomized into: ß-alanine supplementation (6.4 g/day) or placebo (6.4 g/day maltodextrin) during 28 days. Total body water, intracellular and extracellular water, fat-free mass (FFM), and fat mass were assessed using bioelectrical impedance. Participants performed 5000-m HIIE (1:1 effort and rest ratio) followed by resistance exercise (four sets of 80% at 45° leg press until muscular failure) at baseline and after 28 days. The resistance training program consisted of three sets of 10 to 12 RM with 90 s of rest, four days per week. (3) Results: For the post-HIIE leg press volume, higher values were observed post-training than pre-training, but no group x time interaction was observed. There was a non-significant trend for an interaction in the FFM change (ß-alanine = 2.8% versus placebo = 1.0%, p = 0.072). (4) Conclusion: Twenty-eight days of ß-alanine supplementation did not prevent acute strength loss during resistance exercise after high-intensity interval exercise, nor increase strength or hypertrophic adaptations associated with resistance training.

Effects of dietary sports supplements on metabolite accumulation, vasodilation and cellular swelling in relation to muscle hypertrophy: A focus on "secondary" physiological determinants.

Increased blood flow via vasodilation, metabolite production, and venous pooling contribute to the hyperemia and cellular swelling experienced during resistance training. It has been suggested that these effects play a role in hypertrophic adaptations. Over the past 2 decades, sport supplement products have been marketed to promote exercise hyperemia and intracellular fluid storage, thereby enhancing hypertrophy via acute swelling of myocytes. The three main classes of supplements hypothesized to promote exercise-induced hyperemia include vasodilators, such as nitric oxide precursor supplements; anaerobic energy system ergogenic aids that increase metabolite production, such as ß-alanine and creatine; and organic osmolytes, such as creatine and betaine. Previous studies indicated that these dietary supplements are able to improve muscle performance and thus enhance muscle hypertrophy; however, recent evidences also point to these three classes of supplements affecting "secondary" physiological determinants of muscle mass accretion such as vasodilation, metabolite accumulation, and muscle cellular swelling. Although we recognize that the literature is relatively scarce regarding these topics, a better comprehension and discussion of these determinants can lead to increased knowledge and might guide further research regarding the proposed mechanisms of action of the identified compounds. In this case, increased knowledge may contribute to the development of improved efficacy, new products, or direct new research to specifically investigate those secondary effects. The aim of this review was to bring into focus new perspectives associated with secondary physiological effects induced by supplementation and to determine their relevance.

Carbohydrate restriction: Friend or foe of resistance-based exercise performance?

It is commonly accepted that adequate carbohydrate availability is necessary for optimal endurance performance. However, for strength- and physique-based athletes, sports nutrition research and recommendations have focused on protein ingestion, with far less attention given to carbohydrates. Varying resistance exercise protocols, such as differences in intensity, volume, and intraset rest prescriptions between strength-training and physique-training goals elicit different metabolic responses, which may necessitate different carbohydrate needs. The results of several acute and chronic training studies suggest that although severe carbohydrate restriction may not impair strength adaptations during a resistance training program, consuming an adequate amount of carbohydrate in the days leading up to testing may enhance maximal strength and strength-endurance performance. Although several molecular studies demonstrate no additive increases in postexercise mammalian target of rapamycin 1 phosphorylation with carbohydrate and protein compared with protein ingestion alone, the effects of chronic resistance training with carbohydrate restriction on muscle hypertrophy are conflicting and require further research to determine a minimal carbohydrate threshold necessary to optimize muscle hypertrophy. This review summarizes the current knowledge regarding carbohydrate availability and resistance training outcomes and poses new research questions that will better help guide carbohydrate recommendations for strength and physique athletes. In addition, given that success in physique sports is based on subjective appearance, and not objective physical performance, we also review the effects of subchronic carbohydrate ingestion during contest preparation on aesthetic appearance.

The Role of Inflammation and Immune Cells in Blood Flow Restriction Training Adaptation: A Review.

Blood flow restriction (BFR) combined with low-intensity strength training has been shown to increase skeletal muscle mass and strength in a variety of populations. BFR results in a robust metabolic stress which is hypothesized to induce muscle growth via increased recruitment of fast-twitch muscle fibers, a greater endocrine response, and/or enhancing the cellular swelling contribution to the hypertrophic process. Following exercise, neutrophils are the first immune cells to initiate the tissue remodeling process via several mechanisms including an increased production of cytokines and recruitment of monocytes/macrophages, which facilitate the phagocytosis of foreign particles, the differentiation of myoblasts, and the formation of new myotubes. Thus, the purpose of this review was to discuss the mechanisms through which metabolic stress and immune cell recruitment may induce skeletal muscle remodeling following BFR strength training.

Targeting Inflammation and Downstream Protein Metabolism in Sarcopenia: A Brief Up-Dated Description of Concurrent Exercise and Leucine-Based Multimodal Intervention.

Sarcopenia is defined as the progressive loss of muscle mass with age, and poses a serious threat to the physiological and psychological health of the elderly population with consequential economic and social burdens. Chronic low-grade inflammation plays a central role in the development of sarcopenia such that it alters cellular protein metabolism to favor proteolysis over synthesis, and thereby accelerates muscular atrophy. The purpose of this review is to highlight how exercise and nutrition intervention strategies can attenuate or treat sarcopenia. Resistance exercise increases not only muscle mass but also muscle strength, while aerobic exercise is able to ameliorate the age-related metabolic disorders. Concurrent exercise training integrates the advantages of both aerobic and resistance exercise, and may exert a significant synergistic effect in the aging organism. Higher protein intakes rich in the amino acid leucine appear to restore skeletal muscle protein metabolism balance by rescuing protein synthesis in older adults. There is good reason to believe that a multimodal treatment, a combination of exercise and increased leucine consumption in the diet, can combat some of the muscle loss associated with aging. Future research is needed to consolidate these findings to humans, and to further clarify to what extent and by which mechanisms protein metabolism might be directly involved in sarcopenia pathogenesis and the multimodal treatment responses.

Role of metabolic stress for enhancing muscle adaptations: Practical applications.

Metabolic stress is a physiological process that occurs during exercise in response to low energy that leads to metabolite accumulation [lactate, phosphate inorganic (Pi) and ions of hydrogen (H+)] in muscle cells. Traditional exercise protocol (i.e., Resistance training) has an important impact on the increase of metabolite accumulation, which influences hormonal release, hypoxia, reactive oxygen species (ROS) production and cell swelling. Changes in acute exercise routines, such as intensity, volume and rest between sets, are determinants for the magnitude of metabolic stress, furthermore, different types of training, such as low-intensity resistance training plus blood flow restriction and high intensity interval training, could be used to maximize metabolic stress during exercise. Thus, the objective of this review is to describe practical applications that induce metabolic stress and the potential effects of metabolic stress to increase systemic hormonal release, hypoxia, ROS production, cell swelling and muscle adaptations.

Dietary proteins and amino acids in the control of the muscle mass during immobilization and aging: role of the MPS response.

Dietary proteins/essential amino acids (EAAs) are nutrients with anabolic properties that may increase muscle mass or attenuate muscle loss during immobilization and aging via the stimulation of muscle protein synthesis (MPS). An EAA's anabolic threshold, capable to maximize the stimulation of MPS has been hypothesized, but during certain conditions associated with muscle loss, this anabolic threshold seems to increase which reduces the efficacy of dietary EAAs to stimulate MPS. Preliminary studies have demonstrated that acute ingestion of dietary proteins/EAA (with a sufficient amount of leucine) was capable to restore the postprandial MPS during bed rest, immobilization or aging; however, whether these improvements translate into chronic increases (or attenuates loss) of muscle mass is equivocal. For example, although free leucine supplementation acutely increases MPS and muscle mass in some chronic studies, other studies have reported no increases in muscle mass following chronic leucine supplementation. In contrast, chronically increasing leucine intake via the consumption of an overall increase in dietary protein appears to be the most effective dietary intervention toward increasing or attenuating lean mass during aging; however, more research investigating the optimal dose and timing of protein ingestion is necessary. Several studies have demonstrated that decreases in postprandial MPS as a result of increased circulating oxidative and inflammatory are more responsible than muscle protein breakdown for the decreases in muscle mass during disuse and health aging. Therefore, nutritional interventions that reduce oxidation or inflammation in conjunction with higher protein intakes that overcome the anabolic resistance may enhance the MPS response to feeding and either increase muscle mass or attenuate loss. In preliminary studies, antioxidant vitamins and amino acids with antioxidant or anti-inflammatory properties show potential to restore the anabolic response associated with protein ingestion. More research, however, is required to investigate if these nutrients translate to increases in MPS and, ultimately, increased lean mass in aging humans. The purpose of the present review is to discuss the role of protein/EAA intake to enhance postprandial MPS during conditions associated with muscle loss, and bring new perspectives and challenges associated nutritional interventions aimed to optimize the anabolic effects of dietary protein/EAAs ingestion.

Hypertrophy-Promoting Effects of Leucine Supplementation and Moderate Intensity Aerobic Exercise in Pre-Senescent Mice.

Several studies have indicated a positive influence of leucine supplementation and aerobic training on the aging skeletal muscle signaling pathways that control muscle protein balance and muscle remodeling. However, the effect of a combined intervention requires further clarification. Thirteen month old CD-1(®) mice were subjected to moderate aerobic exercise (45 min swimming per day with 3% body weight workload) and fed a chow diet with 5% leucine or 3.4% alanine for 8 weeks. Serum and plasma were prepared for glucose, urea nitrogen, insulin and amino acid profile analysis. The white gastrocnemius muscles were used for determination of muscle size and signaling proteins involved in protein synthesis and degradation. The results show that both 8 weeks of leucine supplementation and aerobic training elevated the activity of mTOR (mammalian target of rapamycin) and its downstream target p70S6K and 4E-BP1, inhibited the ubiquitin-proteasome system, and increased fiber cross-sectional area (CSA) in white gastrocnemius muscle. Moreover, leucine supplementation in combination with exercise demonstrated more significant effects, such as greater CSA, protein content and altered phosphorylation (suggestive of increased activity) of protein synthesis signaling proteins, in addition to lower expression of proteins involved in protein degradation compared to leucine or exercise alone. The current study shows moderate aerobic training combined with 5% leucine supplementation has the potential to increase muscle size in fast-twitch skeletal muscle during aging, potentially through increased protein synthesis and decreased protein breakdown.