Mitigating disuse-induced skeletal muscle atrophy in ageing: Resistance exercise as a critical countermeasure.

The gradual deterioration of physiological systems with ageing makes it difficult to maintain skeletal muscle mass (sarcopenia), at least partly due to the presence of 'anabolic resistance', resulting in muscle loss. Sarcopenia can be transiently but markedly accelerated through periods of muscle disuse-induced (i.e., unloading) atrophy due to reduced physical activity, sickness, immobilisation or hospitalisation. Periods of disuse are detrimental to older adults' overall quality of life and substantially increase their risk of falls, physical and social dependence, and early mortality. Disuse events induce skeletal muscle atrophy through various mechanisms, including anabolic resistance, inflammation, disturbed proteostasis and mitochondrial dysfunction, all of which tip the scales in favour of a negative net protein balance and subsequent muscle loss. Concerningly, recovery from disuse atrophy is more difficult for older adults than their younger counterparts. Resistance training (RT) is a potent anabolic stimulus that can robustly stimulate muscle protein synthesis and mitigate muscle losses in older adults when implemented before, during and following unloading. RT may take the form of traditional weightlifting-focused RT, bodyweight training and lower- and higher-load RT. When combined with sufficient dietary protein, RT can accelerate older adults' recovery from a disuse event, mitigate frailty and improve mobility; however, few older adults regularly participate in RT. A feasible and practical approach to improving the accessibility and acceptability of RT is through the use of resistance bands. Moving forward, RT must be prescribed to older adults to mitigate the negative consequences of disuse atrophy.

Low energy availability reduces myofibrillar and sarcoplasmic muscle protein synthesis in trained females.

Low energy availability (LEA) describes a state where the energy intake is insufficient to cover the energy costs of both exercise energy expenditure and basal physiological body functions. LEA has been associated with various physiological consequences, such as reproductive dysfunction. However, the effect of LEA on skeletal muscle protein synthesis in females performing exercise training is still poorly understood. We conducted a randomized controlled trial to investigate the impact of LEA on daily integrated myofibrillar and sarcoplasmic muscle protein synthesis in trained females. Thirty eumenorrheic females were matched based on training history and randomized to undergo 10 days of LEA (25 kcal · kg fat-free mass (FFM)-1  · day-1 ) or optimal energy availability (OEA, 50 kcal · kg FFM-1  · day-1 ). Before the intervention, both groups underwent a 5-day 'run-in' period with OEA. All foods were provided throughout the experimental period with a protein content of 2.2 g kg lean mass-1  · day-1 . A standardized, supervised combined resistance and cardiovascular exercise training programme was performed over the experimental period. Daily integrated muscle protein synthesis was measured by deuterium oxide (D2 O) consumption along with changes in body composition, resting metabolic rate, blood biomarkers and 24 h nitrogen balance. We found that LEA reduced daily integrated myofibrillar and sarcoplasmic muscle protein synthesis compared with OEA. Concomitant reductions were observed in lean mass, urinary nitrogen balance, free androgen index, thyroid hormone concentrations and resting metabolic rate following LEA. These results highlight that LEA may negatively affect skeletal muscle adaptations in females performing exercise training. KEY POINTS: Low energy availability (LEA) with potential health and performance impairments is widespread among female athletes. We investigated the impact of 10 days of LEA on daily integrated myofibrillar and sarcoplasmic muscle protein synthesis in young, trained females. We show that LEA impairs myofibrillar and sarcoplasmic muscle protein synthesis in trained females performing exercise training. These findings suggest that LEA may have negative consequences for skeletal muscle adaptations and highlight the importance of ensuring adequate energy availability in female athletes.

Disuse-induced skeletal muscle atrophy in disease and nondisease states in humans: mechanisms, prevention, and recovery strategies.

Decreased skeletal muscle contractile activity (disuse) or unloading leads to muscle mass loss, also known as muscle atrophy. The balance between muscle protein synthesis (MPS) and muscle protein breakdown (MPB) is the primary determinant of skeletal muscle mass. A reduced mechanical load on skeletal muscle is one of the main external factors leading to muscle atrophy. However, endocrine and inflammatory factors can act synergistically in catabolic states, amplifying the atrophy process and accelerating its progression. In addition, older individuals display aging-induced anabolic resistance, which can predispose this population to more pronounced effects when exposed to periods of reduced physical activity or mechanical unloading. Different cellular mechanisms contribute to the regulation of muscle protein balance during skeletal muscle atrophy. This review summarizes the effects of muscle disuse on muscle protein balance and the molecular mechanisms involved in muscle atrophy in the absence or presence of disease. Finally, a discussion of the current literature describing efficient strategies to prevent or improve the recovery from muscle atrophy is also presented.

Dairy and Dairy Alternative Supplementation Increase Integrated Myofibrillar Protein Synthesis Rates, and Are Further Increased when Combined with Walking in Healthy Older Women.

BACKGROUND: The stimulation of muscle protein synthesis (MPS) by dietary protein is reduced with age. We hypothesized that twice-daily milk consumption would increase daily rates of MPS in older women relative to a nondairy milk alternative and that MPS would be enhanced by increased physical activity (PA). METHODS: Twenty-two older women were randomly assigned to 1 of 3 experimental groups: whole milk (WM; n = 7, 69 ± 3 y), skim milk (SM; n = 7, 68 ± 3 y), or an almond beverage (AB; n = 8, 63 ± 3 y). From days 1 to 3, participants consumed a standardized diet (0.8 g protein⋅kg-1 ⋅d-1) and performed their habitual PA (Phase 1, Baseline). From days 4 to 6, participants continued to perform habitual PA, but consumed an intervention diet consisting of the standardized diet plus twice-daily beverages (250 mL each) of either WM, SM, or AB (Phase 2, Diet Intervention). Finally, from days 7 to 9, the intervention diet was consumed, and PA via daily steps was increased to ∼150% of habitual daily steps (Phase 3, Intervention Diet + PA). Deuterated water was ingested throughout the study, and muscle biopsies were taken on days 1, 4, 7, and 10 to measure MPS. RESULTS: Daily MPS rates were not differentially affected by the addition of WM, SM, or AB to a standardized diet. There was, however, a significant effect of study phase such that, when collapsed across conditions, MPS was significantly increased from Phase 1 to Phase 2 (+0.133%⋅d-1; 95% CI: 0.035-0.231; P < 0.01) and further increased from Phase 2 to Phase 3 (+0.156%⋅d-1; 95% CI: 0.063-0.250; P < 0.01). CONCLUSIONS: Increasing PA through walking was sufficient to increase daily MPS rates in older women, irrespective of whether dietary protein intake is increased beyond the recommended intake of 0.8 g⋅kg-1 ⋅d-1. The trial was registered at clinicaltrials.gov as NCT04981652.

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

The impact of resistance exercise frequency on muscle protein synthesis rates remains unknown. The aim of this study was to compare daily myofibrillar protein synthesis rates over a 7-day period of low-frequency (LF) versus high-frequency (HF) resistance exercise training. Nine young men (21 ± 2 years) completed a 7-day period of habitual physical activity (BASAL). This was followed by a 7-day exercise period of volume-matched, LF (10 × 10 repetitions at 70% one-repetition maximum, once per week) or HF (2 × 10 repetitions at ∼70% one-repetition maximum, five times per week) resistance exercise training. The participants had one leg randomly allocated to LF and the other to HF. Skeletal muscle biopsies and daily saliva samples were collected to determine myofibrillar protein synthesis rates using 2H2O, with intracellular signaling determined using Western blotting. The myofibrillar protein synthesis rates did not differ between the LF (1.46 ± 0.26%/day) and HF (1.48 ± 0.33%/day) conditions over the 7-day exercise training period (p > .05). There were no significant differences between the LF and HF conditions over the first 2 days (1.45 ± 0.41%/day vs. 1.25 ± 0.46%/day) or last 5 days (1.47 ± 0.30%/day vs. 1.50 ± 0.41%/day) of the exercise training period (p > .05). Daily myofibrillar protein synthesis rates were not different from BASAL at any time point during LF or HF (p > .05). The phosphorylation status and total protein content of selected proteins implicated in skeletal muscle ribosomal biogenesis were not different between conditions (p > .05). Under the conditions of the present study, resistance exercise training frequency did not modulate daily myofibrillar protein synthesis rates in young men.

Immobilization Leads to Alterations in Intracellular Phosphagen and Creatine Transporter Content in Human Skeletal Muscle.

The role of dysregulated intracellular creatine metabolism in disuse atrophy is unknown. In this study, skeletal muscle biopsy samples were obtained after 7-days of unilateral leg immobilization (IMMOB) and the non-immobilized control limb (CTRL) of 15 healthy males (23.1 ± 3.5 yrs). Samples were analyzed for fibre-type cross-sectional area (CSA) and creatine transporter (CreaT) at the cell membrane periphery (MEM) or intracellular (INT) areas, via immunoflouresence microscopy. Creatine kinase (CK) and AMP-activated protein kinase (AMPK) were determined via immunoblot. PCr, Cr and ATP were measured via enzymatic analysis. Body composition and maximal isometric knee extensor strength were assessed before and after disuse. Leg strength and fat-free mass were reduced in IMMOB (~32% and 4%, respectively; P<0.01 for both). Type II fibre CSA was smaller (~12%; P=0.028) and intramuscular PCr lower (~13%; P=0.015) in IMMOB vs. CTRL. CreaT protein was greater in Type I fibres in both limbs (P<0.01). CreaT was greater in IMMOB vs. CTRL (P < 0.01) and inversely associated with PCr concentration in both limbs (P < 0.05). MEM CreaT was greater than the INT CreaT in Type I and II fibres of both limbs (~14% for both; P<0.01 for both). Type I fibre CreaT tended to be greater in IMMOB vs. CTRL (P=0.074). CK was greater, and phospho-to-total AMPKThr172 tended to be greater, in IMMOB vs. CTRL (P=0.013 and 0.051, respectively). These findings suggest that modulation of intracellular creatine metabolism is an adaptive response to immobilisation in young healthy skeletal muscle.

Overload-mediated skeletal muscle hypertrophy is not impaired by loss of myofiber STAT3.

Although the signal pathways mediating muscle protein synthesis and degradation are well characterized, the transcriptional processes modulating skeletal muscle mass and adaptive growth are poorly understood. Recently, studies in mouse models of muscle wasting or acutely exercised human muscle have suggested a potential role for the transcription factor signal transducer and activator of transcription 3 (STAT3), in adaptive growth. Hence, in the present study we sought to define the contribution of STAT3 to skeletal muscle adaptive growth. In contrast to previous work, two different resistance exercise protocols did not change STAT3 phosphorylation in human skeletal muscle. To directly address the role of STAT3 in load-induced (i.e., adaptive) growth, we studied the anabolic effects of 14 days of synergist ablation (SA) in skeletal muscle-specific STAT3 knockout (mKO) mice and their floxed, wild-type (WT) littermates. Plantaris muscle weight and fiber area in the nonoperated leg (control; CON) was comparable between genotypes. As expected, SA significantly increased plantaris weight, muscle fiber cross-sectional area, and anabolic signaling in WT mice, although interestingly, this induction was not impaired in STAT3 mKO mice. Collectively, these data demonstrate that STAT3 is not required for overload-mediated hypertrophy in mouse skeletal muscle.

Short inter-set rest blunts resistance exercise-induced increases in myofibrillar protein synthesis and intracellular signalling in young males.

What is the central question of this study? Does shorter rest between sets of resistance exercise promote a superior circulating hormonal and acute muscle anabolic response compared with longer rest periods? What is the main finding and its importance? We demonstrate that short rest (1 min) between sets of moderate-intensity, high-volume resistance exercise blunts the acute muscle anabolic response compared with a longer rest period (5 min), despite a superior circulating hormonal milieu. These data have important implications for the development of training regimens to maximize muscle hypertrophy. Manipulating the rest-recovery interval between sets of resistance exercise may influence training-induced muscle remodelling. The aim of this study was to determine the acute muscle anabolic response to resistance exercise performed with short or long inter-set rest intervals. In a study with a parallel-group design, 16 males completed four sets of bilateral leg-press and knee-extension exercise at 75% of one-repetition maximum to momentary muscular failure, followed by ingestion of 25 g of whey protein. Resistance exercise sets were interspersed by 1 min (n = 8) or 5 min of passive rest (n = 8). Muscle biopsies were obtained at rest, 0, 4, 24 and 28 h postexercise during a primed continuous infusion of l-[ring-(13) C6 ]phenylalanine to determine myofibrillar protein synthesis and intracellular signalling. We found that the rate of myofibrillar protein synthesis increased above resting values from 0 to 4 h postexercise with 1 (76%; P = 0.047) and 5 min inter-set rest (152%; P < 0.001) and was significantly greater in the 5 min inter-set rest group (P = 0.001). Myofibrillar protein synthesis rates at 24-28 h postexercise remained elevated above resting values (P < 0.05) and were indistinguishable between groups. Postexercise p70S6K(Thr389) and rpS6(Ser240/244) phosphorylation were reduced with 1 compared with 5 min inter-set rest, whereas phosphorylation of eEF2(Thr56) , TSC2(Thr1462) , AMPK(Thr172) and REDD1 protein were greater for 1 compared with 5 min inter-set rest. Serum testosterone was greater at 20-40 min postexercise and plasma lactate greater immediately postexercise for 1 versus 5 min inter-set rest. Resistance exercise with short (1 min) inter-set rest duration attenuated myofibrillar protein synthesis during the early postexercise recovery period compared with longer (5 min) rest duration, potentially through compromised activation of intracellular signalling.

The effects of whey, pea, and collagen protein supplementation beyond the recommended dietary allowance on integrated myofibrillar protein synthetic rates in older males: a randomized controlled trial.

BACKGROUND: Skeletal muscle mass is determined predominantly by feeding-induced and activity-induced fluctuations in muscle protein synthesis (MPS). Older individuals display a diminished MPS response to protein ingestion, referred to as age-related anabolic resistance, which contributes to the progression of age-related muscle loss known as sarcopenia. OBJECTIVES: We aimed to determine the impact of consuming higher-quality compared with lower-quality protein supplements above the recommended dietary allowance (RDA) on integrated MPS rates. We hypothesized that increasing total protein intake above the RDA, regardless of the source, would support higher integrated rates of myofibrillar protein synthesis. METHODS: Thirty-one healthy older males (72 ± 4 y) consumed a controlled diet with protein intake set at the RDA: control phase (days 1-7). In a double-blind, randomized controlled fashion, participants were assigned to consume an additional 50 g (2 × 25g) of whey (n = 10), pea (n = 11), or collagen (n = 10) protein each day (25 g at breakfast and lunch) during the supplemental phase (days 8-15). Deuterated water ingestion and muscle biopsies assessed integrated MPS and acute anabolic signaling. Postprandial blood samples were collected to determine feeding-induced aminoacidemia. RESULTS: Integrated MPS was increased during supplemental with whey (1.59 ± 0.11 %/d; P < 0.001) and pea (1.59 ± 0.14 %/d; P < 0.001) when compared with RDA (1.46 ± 0.09 %/d for the whey group; 1.46 ± 0.10 %/d for the pea group); however, it remained unchanged with collagen. Supplemental protein was sufficient to overcome anabolic signaling deficits (mTORC1 and rpS6), corroborating the greater postprandial aminoacidemia. CONCLUSIONS: Our findings demonstrate that supplemental protein provided at breakfast and lunch over the current RDA enhanced anabolic signaling and integrated MPS in older males; however, the source of additional protein may be an important consideration in overcoming age-related anabolic resistance. This trial was registered clinicaltrials.gov as NCT04026607.

Muscle Protein Synthesis in Response to Plant-Based Protein Isolates With and Without Added Leucine Versus Whey Protein in Young Men and Women.

Background: Plant-based protein supplements often contain lower amounts of leucine and other essential amino acids (EAAs), potentially making them less effective in stimulating muscle protein synthesis (MPS) than animal-based proteins. Combining plant proteins could improve the EAA profile and more effectively support MPS. Objectives: The aim of this study was to determine the effect of a novel plant-based blend protein (PBP), PBP with added leucine (PBP + Leu) to levels equivalent to whey protein isolate (WHEY) on aminoacidemia and MPS responses in young men and women. We hypothesized that PBP + Leu would stimulate MPS equivalent to WHEY, and both would be greater than PBP. Methods: We employed a randomized, double-blind, crossover study consisting of 3 separate study visits to compare PBP, PBP + Leu, and WHEY. To measure MPS response to ingestion of the supplements, a primed continuous infusion of L-[ring13C6] phenylalanine was administered for 8 h at each study visit. Skeletal muscle tissue and blood samples were collected to measure aminoacidemia and MPS. Results: All protein supplements increased mixed MPS above postabsorptive levels (P < 0.001). However, MPS increase following ingestion of PBP was less than that following ingestion of PBP + Leu (P = 0.002) and WHEY (P = 0.046). There were no differences in MPS between PBP + Leu and WHEY (P = 0.052). Conclusions: Consumption of PBP isolate with added leucine stimulated MPS to a similar extent as whey protein in young men and women. PBPs containing higher leucine content promote anabolism to a similar extent as animal-based proteins.This study was registered at clinicaltrials.gov as NCT05139160.

Network-based modelling reveals cell-type enriched patterns of non-coding RNA regulation during human skeletal muscle remodelling.

A majority of human genes produce non-protein-coding RNA (ncRNA), and some have roles in development and disease. Neither ncRNA nor human skeletal muscle is ideally studied using short-read sequencing, so we used a customised RNA pipeline and network modelling to study cell-type specific ncRNA responses during muscle growth at scale. We completed five human resistance-training studies (n=144 subjects), identifying 61% who successfully accrued muscle-mass. We produced 288 transcriptome-wide profiles and found 110 ncRNAs linked to muscle growth in vivo, while a transcriptome-driven network model demonstrated interactions via a number of discrete functional pathways and single-cell types. This analysis included established hypertrophy-related ncRNAs, including CYTOR - which was leukocyte-associated (FDR = 4.9 ×10-7). Novel hypertrophy-linked ncRNAs included PPP1CB-DT (myofibril assembly genes, FDR = 8.15 × 10-8), and EEF1A1P24 and TMSB4XP8 (vascular remodelling and angiogenesis genes, FDR = 2.77 × 10-5). We also discovered that hypertrophy lncRNA MYREM shows a specific myonuclear expression pattern in vivo. Our multi-layered analyses established that single-cell-associated ncRNA are identifiable from bulk muscle transcriptomic data and that hypertrophy-linked ncRNA genes mediate their association with muscle growth via multiple cell types and a set of interacting pathways.

Fortetropin supplementation prevents the rise in circulating myostatin but not disuse-induced muscle atrophy in young men with limb immobilization: A randomized controlled trial.

Supplementation with Fortetropin® (FOR), a naturally occurring component from fertilized egg yolks, reduces circulating myostatin concentration. We hypothesized that FOR would mitigate muscle atrophy during immobilization. We examined the effect of FOR supplementation on muscle size and strength during 2-wk of single-leg immobilization and recovery. Twenty-four healthy young men (22 ± 2 yrs; BMI = 24.3 ± 2.9 kg/m2) were randomly allocated to either a Fortetropin® supplement (FOR-SUPP, n = 12) group consuming 19.8 g/d of FOR or placebo (PLA-SUPP, n = 12) group consuming energy- and macronutrient-matched cheese powder for 6-wk. The 6-wk period consisted of 2-wk run-in, 2-wk single-leg immobilization, and 2-wk recovery phase returning to habitual physical activities. Ultrasonography, dual-energy X-ray absorptiometry, muscle biopsies and isometric peak torque assessments were performed prior to and following each phase (days 1, 14, 28, and 42) to measure vastus lateralis and muscle fiber cross-section area (CSA), leg lean mass (LM), and muscular strength. Blood samples were taken on days 1 and 42 for measurement of plasma myostatin concentration, which increased in PLA-SUPP (4221 ± 541 pg/mL to 6721 ± 864 pg/mL, P = 0.013) but not in FOR-SUPP (5487 ± 489 pg/mL to 5383 ± 781 pg/mL, P = 0.900). After the immobilization phase, vastus lateralis CSA, LM, and isometric peak torque were decreased by 7.9 ± 1.7% (P < 0.001), -1.6 ± 0.6% (P = 0.037), and -18.7 ± 2.7% (P < 0.001) respectively, with no difference between groups. The decreased peak torque was recovered after 2-wk of normal activity (vs. day 1, P = 0.129); however, CSA and LM were not recovered (vs. day 1, P < 0.001 and P = 0.003, respectively), with no differences between groups. Supplementation with FOR prevented the rise in circulating myostatin but not disuse-induced muscle atrophy in young men after 2-wk of single-leg immobilization.

Acute resistance exercise training does not augment mitochondrial remodelling in master athletes or untrained older adults.

Background: Ageing is associated with alterations to skeletal muscle oxidative metabolism that may be influenced by physical activity status, although the mechanisms underlying these changes have not been unraveled. Similarly, the effect of resistance exercise training (RET) on skeletal muscle mitochondrial regulation is unclear. Methods: Seven endurance-trained masters athletes ([MA], 74 ± 3 years) and seven untrained older adults ([OC]. 69 ± 6 years) completed a single session of knee extension RET (6 x 12 repetitions, 75% 1-RM, 120-s intra-set recovery). Vastus lateralis muscle biopsies were collected pre-RET, 1 h post-RET, and 48h post-RET. Skeletal muscle biopsies were analyzed for citrate synthase (CS) enzyme activity, mitochondrial content, and markers of mitochondrial quality control via immunoblotting. Results: Pre-RET CS activity and protein content were ∼45% (p < .001) and ∼74% greater in MA compared with OC (p = .006). There was a significant reduction (∼18%) in CS activity 48 h post-RET (p < .05) in OC, but not MA. Pre-RET abundance of individual and combined mitochondrial electron transport chain (ETC) complexes I-V were significantly greater in MA compared with OC, as were markers of mitochondrial fission and fusion dynamics (p-DRP-1Ser616, p-MFFSer146, OPA-1 & FIS-1, p < .05 for all). Moreover, MA displayed greater expression of p-AMPKThr172, PGC1α, TFAM, and SIRT-3 (p < .05 for all). Notably, RET did not alter the expression of any marker of mitochondrial content, biogenesis, or quality control in both OC and MA. Conclusion: The present data suggest that long-term aerobic exercise training supports superior skeletal muscle mitochondrial density and protein content into later life, which may be regulated by greater mitochondrial quality control mechanisms and supported via superior fission-fusion dynamics. However, a single session of RET is unable to induce mitochondrial remodelling in the acute (1h post-RET) and delayed (48 h post-RET) recovery period in OC and MA.

Increased protein intake derived from leucine-enriched protein enhances the integrated myofibrillar protein synthetic response to short-term resistance training in untrained men and women: a 4-day randomized controlled trial.

Leucine is a critical amino acid stimulating myofibrillar protein synthesis (MyoPS). The consumption of higher leucine-containing drinks stimulates MyoPS, but we know less about higher leucine solid foods. Here, we examined the effect of short-term resistance exercise training (STRT) combined with supplementation of a protein and leucine-enriched bar, compared with STRT alone, on integrated (%/day) rates of MyoPS and anabolic protein signaling. In a nonblinded, randomized crossover trial, eight young adults performed four sessions of STRT without or while consuming the study bar (STRT+Leu, 16 g of protein containing ∼3 g of leucine) for two 4-day phases, separated by 2 days nonexercise (Rest) washout. In combination with serial muscle biopsies, deuterated water permitted the measurement of MyoPS and protein signaling phosphorylation. MyoPS during STRT (1.43 ± 0.06%/day) and STRT+Leu (1.53 ± 0.06%/day) were greater than Rest (1.31 ± 0.05%/day), and MyoPS during STRT+Leu (1.53 ± 0.06%/day) was greater than STRT alone (1.43 ± 0.06%/day). STRT+Leu increased the ratio of phosphorylated to total mechanistic target of rapamycin and 4EBP1 compared to Rest. Engaging in STRT increased integrated MyoPS and protein signaling in young adults and was enhanced with increased protein intake derived from a leucine-enriched protein bar. This study was registered at clinicaltrials.gov as NCT03796897.

Effects of High-Volume Versus High-Load Resistance Training on Skeletal Muscle Growth and Molecular Adaptations.

We evaluated the effects of higher-load (HL) versus (lower-load) higher-volume (HV) resistance training on skeletal muscle hypertrophy, strength, and muscle-level molecular adaptations. Trained men (n = 15, age: 23 ± 3 years; training experience: 7 ± 3 years) performed unilateral lower-body training for 6 weeks (3× weekly), where single legs were randomly assigned to HV and HL paradigms. Vastus lateralis (VL) biopsies were obtained prior to study initiation (PRE) as well as 3 days (POST) and 10 days following the last training bout (POSTPR). Body composition and strength tests were performed at each testing session, and biochemical assays were performed on muscle tissue after study completion. Two-way within-subject repeated measures ANOVAs were performed on most dependent variables, and tracer data were compared using dependent samples t-tests. A significant interaction existed for VL muscle cross-sectional area (assessed via magnetic resonance imaging; interaction p = 0.046), where HV increased this metric from PRE to POST (+3.2%, p = 0.018) whereas HL training did not (-0.1%, p = 0.475). Additionally, HL increased leg extensor strength more so than HV training (interaction p = 0.032; HV < HL at POST and POSTPR, p < 0.025 for each). Six-week integrated non-myofibrillar protein synthesis (iNon-MyoPS) rates were also higher in the HV versus HL condition, while no difference between conditions existed for iMyoPS rates. No interactions existed for other strength, VL morphology variables, or the relative abundances of major muscle proteins. Compared to HL training, 6 weeks of HV training in previously trained men optimizes VL hypertrophy in lieu of enhanced iNon-MyoPS rates, and this warrants future research.

Resistance Exercise, Aging, Disuse, and Muscle Protein Metabolism.

Skeletal muscle is the organ of locomotion, its optimal function is critical for athletic performance, and is also important for health due to its contribution to resting metabolic rate and as a site for glucose uptake and storage. Numerous endogenous and exogenous factors influence muscle mass. Much of what is currently known regarding muscle protein turnover is owed to the development and use of stable isotope tracers. Skeletal muscle mass is determined by the meal- and contraction-induced alterations of muscle protein synthesis and muscle protein breakdown. Increased loading as resistance training is the most potent nonpharmacological strategy by which skeletal muscle mass can be increased. Conversely, aging (sarcopenia) and muscle disuse lead to the development of anabolic resistance and contribute to the loss of skeletal muscle mass. Nascent omics-based technologies have significantly improved our understanding surrounding the regulation of skeletal muscle mass at the gene, transcript, and protein levels. Despite significant advances surrounding the mechanistic intricacies that underpin changes in skeletal muscle mass, these processes are complex, and more work is certainly needed. In this article, we provide an overview of the importance of skeletal muscle, describe the influence that resistance training, aging, and disuse exert on muscle protein turnover and the molecular regulatory processes that contribute to changes in muscle protein abundance. © 2021 American Physiological Society. Compr Physiol 11:2249-2278, 2021.

Enhanced Cycling Time-Trial Performance During Multiday Exercise With Higher-Pressure Compression Garment Wear.

PURPOSE: Compression garments are widely used as a tool to accelerate recovery from intense exercise and have also gained traction as a performance aid, particularly during periods of limited recovery. This study tested the hypothesis that increased pressure levels applied via high-pressure compression garments would enhance "multiday" exercise performance. METHODS: A single-blind crossover design, incorporating 3 experimental conditions-loose-fitting gym attire (CON), low-compression (LC), and high-compression (HC) garments-was adopted. A total of 10 trained male cyclists reported to the laboratory on 6 occasions, collated into 3 blocks of 2 consecutive visits. Each "block" consisted of 3 parts, an initial high-intensity protocol, a 24-hour period of controlled rest while wearing the applied condition/garment (CON, LC, and HC), and a subsequent 8-km cycling time trial, while wearing the respective garment. Subjective discomfort questionnaires and blood pressure were assessed prior to each exercise bout. Power output, oxygen consumption, and heart rate were continuously measured throughout exercise, with plasma lactate, creatine kinase, and myoglobin concentrations assessed at baseline and the end of exercise, as well as 30 and 60 minutes postexercise. RESULTS: Time-trial performance was significantly improved during HC compared with both CON and LC (HC = 277 [83], CON = 266 [89], and LC = 265 [77] W; P < .05). In addition, plasma lactate was significantly lower at 30 and 60 minutes postexercise on day 1 in HC compared with CON. No significant differences were observed for oxygen consumption, heart rate, creatine kinase, or subjective markers of discomfort. CONCLUSION: The pressure levels exerted via lower-limb compression garments influence their effectiveness for cycling performance, particularly in the face of limited recovery.