Periods Of Muscle Disuse Research Articles

The role of muscle disuse in muscular and cardiovascular fitness: A systematic review and meta-regression.

We aimed to assess the effects of muscle disuse on muscle strength (MS), muscle mass (MM) and cardiovascular fitness. Databases were scrutinized to identify human studies assessing the effects of muscle disuse on both (1) MM and (2) maximal oxygen uptake (VO2max) and/or MS. Random-effects meta-analysis and meta-regression with initial physical fitness and length of the protocol as a priori determined moderators were performed. We quantitatively analyzed 51 different studies, and the level of significance was set at p<0.05. Data from the participants in 14 studies showed a decline in both VO2max (SMD: -0.93; 95% CI: -1.27 to -0.58) and MM (SMD: -0.34; 95% CI: -0.57 to -0.10). Data from 47 studies showed a decline in strength (-0.88; 95% CI: -1.04 to -0.73) and mass (SMD: -0.47; 95% CI: -0.58 to -0.36). MS loss was twice as high as MM loss, but differences existed between anatomical regions. Notably, meta-regression analysis revealed that initial MS was inversely associated with MS decline. VO2max and MS decline to a higher extent than MM during muscle disuse. We reported a more profound strength loss in subjects with high muscular strength. This is physiologically relevant for athletes because their required muscular strength can profoundly decline during a period of muscle disuse. It should however be noted that a period of muscle disuse can have devastating consequences in old subjects with low muscular strength.

Lipid Transfer Protein Genes Are Differently Expressed in Rat Soleus Muscle at Early and Later Periods of Muscle Disuse

Lipid Transfer Protein Genes Are Differently Expressed in Rat Soleus Muscle at Early and Later Periods of Muscle Disuse

The effect of protein or amino acid provision on immobilization-induced muscle atrophy in healthy adults: A systematic review and meta-analysis.

Bed rest and limb immobilization are models of muscle disuse associated with skeletal muscle atrophy and reduced strength. The purpose of this systematic review was to examine the impact of protein or amino acid provision before and/or during a period of muscle disuse on muscle atrophy (primary outcome), strength and muscle protein synthesis (secondary outcomes) following a disuse period. We performed a systematic review of Embase, MEDLINE, Web of Science, PubMed and Clinical Trials in December 2022. Eligible studies were randomized controlled trials that combined a dietary protein or amino acid intervention versus control during an experimental model of disuse (bed rest or unilateral limb immobilization) in healthy individuals aged ≥18 years. Nine articles from eight independent trials were identified and rated for risk of bias by two authors. A meta-analysis of muscle mass data revealed no effect (standardized mean difference: 0.2; 95% confidence interval: -0.18 to 0.57, P=0.31) of protein/amino acid intervention in preventing disuse-induced muscle atrophy. Although the meta-analysis was not conducted on strength or muscle protein synthesis data, there was insufficient evidence in the reviewed articles to support the use of protein/amino acid provision in mitigating the disuse-induced decline in either outcome measurement. Additional high-quality studies, including the reporting of randomization procedures and blinding procedures and the provision of statistical analysis plans, might be required to determine whether protein or amino acid provision serves as an effective strategy to attenuate muscle atrophy during periods of disuse.

An Updated Panorama of Blood-Flow-Restriction Methods.

Exercise with blood-flow restriction (BFR) is being increasingly used by practitioners working with athletic and clinical populations alike. Most early research combined BFR with low-load resistance training andconsistently reported increased muscle size and strength without requiring the heavier loads that are traditionally used for unrestricted resistance training. However, this field has evolved with several different active and passive BFR methods emerging in recent research. This commentary aims to synthesize the evolving BFR methods for cohorts ranging from healthy athletes to clinical or load-compromised populations. In addition, real-world considerations for practitioners are highlighted, along with areas requiring further research. The BFR literature now incorporates several active and passive methods, reflecting a growing implementation of BFR in sport and allied health fields. In addition to low-load resistance training, BFR is being combined with high-load resistance exercise, aerobic and anaerobic energy systems training of varying intensities, and sport-specific activities. BFR is also being applied passively in the absence of physical activity during periods of muscle disuse or rehabilitation or prior to exercise as a preconditioning or performance-enhancement technique. These various methods have been reported to improve muscular development; cardiorespiratory fitness; functional capacities; tendon, bone, andvascular adaptations; and physical and sport-specific performance and to reduce pain sensations. However, in emerging BFR fields, many unanswered questions remain to refine best practice.

Effect of High-Protein Diets on Integrated Myofibrillar Protein Synthesis before Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Pilot Study.

Increasing dietary protein intake during periods of muscle disuse may mitigate the resulting decline in muscle protein synthesis (MPS). The purpose of this randomized pilot study was to determine the effect of increased protein intake during periods of disuse before anterior cruciate ligament (ACL) reconstruction on myofibrillar protein synthesis (MyoPS), and proteolytic and myogenic gene expression. Six healthy, young males (30 ± 9 y) were randomized to consume a high-quality, optimal protein diet (OP; 1.9 g·kg−1·d−1) or adequate protein diet (AP; 1.2 g·kg−1·d−1) for two weeks before ACL reconstruction. Muscle biopsies collected during surgery were used to measure integrated MyoPS during the intervention (via daily deuterium oxide ingestion) and gene expression at the time of surgery. MyoPS tended to be higher, with a large effect size in OP compared to AP (0.71 ± 0.1 and 0.54 ± 0.1%·d−1; p = 0.076; g = 1.56). Markers of proteolysis and myogenesis were not different between groups (p > 0.05); however, participants with greater MyoPS exhibited lower levels of MuRF1 gene expression compared to those with lower MyoPS (r = −0.82, p = 0.047). The data from this pilot study reveal a potential stimulatory effect of increased daily protein intake on MyoPS during injury-mediated disuse conditions that warrants further investigation.

The Influence of Omega-3 Fatty Acids on Skeletal Muscle Protein Turnover in Health, Disuse, and Disease.

Ingestion of omega-3 fatty acids is known to exert favorable health effects on a number of biological processes such as improved immune profile, enhanced cognition, and optimized neuromuscular function. Recently, data have emerged demonstrating a positive influence of omega-3 fatty acid intake on skeletal muscle. For instance, there are reports of clinically-relevant gains in muscle size and strength in healthy older persons with omega-3 fatty acid intake as well as evidence that omega-3 fatty acid ingestion alleviates the loss of muscle mass and prevents decrements in mitochondrial respiration during periods of muscle-disuse. Cancer cachexia that is characterized by a rapid involuntary loss of lean mass may also be attenuated by omega-3 fatty acid provision. The primary means by which omega-3 fatty acids positively impact skeletal muscle mass is via incorporation of eicosapentaenoic acid (EPA; 20:5n−3) and docosahexaenoic acid (DHA; 22:6n−3) into membrane phospholipids of the sarcolemma and intracellular organelles. Enrichment of EPA and DHA in these membrane phospholipids is linked to enhanced rates of muscle protein synthesis, decreased expression of factors that regulate muscle protein breakdown, and improved mitochondrial respiration kinetics. However, exactly how incorporation of EPA and DHA into phospholipid membranes alters these processes remains unknown. In this review, we discuss the interaction between omega-3 fatty acid ingestion and skeletal muscle protein turnover in response to nutrient provision in younger and older adults. Additionally, we examine the role of omega-3 fatty acid supplementation in protecting muscle loss during muscle-disuse and in cancer cachexia, and critically evaluate the molecular mechanisms that underpin the phenotypic changes observed in skeletal muscle with omega-3 fatty acid intake.

Disuse-induced nuclear accumulation of histone deacetylase 4 in rat skeletal muscle

Skeletal muscle wasting induced by prolonged periods of muscle disuse due to immobilization, chronic bed rest, physical inactivity, or spaceflight causes dramatic muscle atrophy via multiple signaling pathways. However, the molecular mechanisms of muscle wasting are not completely understood. Histone deacetylase (HDAC) 4 is a central component of muscle transcriptional reprogramming upon denervation. We recently examined the changes in the nuclear expression of HDAC4 and its downstream targets in immobilization-induced rat skeletal muscle atrophy. Nuclear abundance of HDAC4 was found to enhance the transcription of myogenin and MyoD , muscle-specific transcriptional regulators, and induce the expression of atrogin-1, a central component of muscle atrophy. These data demonstrated that the cellular localization of HDAC4 and downstream proteins may play an important role in disuse-induced rat skeletal muscle atrophy.

One Week of Bed Rest Leads to Substantial Muscle Atrophy and Induces Whole-Body Insulin Resistance in the Absence of Skeletal Muscle Lipid Accumulation.

Short (<10 days) periods of muscle disuse, often necessary for recovery from illness or injury, lead to various negative health consequences. The current study investigated mechanisms underlying disuse-induced insulin resistance, taking into account muscle atrophy. Ten healthy, young males (age: 23 ± 1 years; BMI: 23.0 ± 0.9 kg · m(-2)) were subjected to 1 week of strict bed rest. Prior to and after bed rest, lean body mass (dual-energy X-ray absorptiometry) and quadriceps cross-sectional area (CSA; computed tomography) were assessed, and peak oxygen uptake (VO2peak) and leg strength were determined. Whole-body insulin sensitivity was measured using a hyperinsulinemic-euglycemic clamp. Additionally, muscle biopsies were collected to assess muscle lipid (fraction) content and various markers of mitochondrial and vascular content. Bed rest resulted in 1.4 ± 0.2 kg lean tissue loss and a 3.2 ± 0.9% decline in quadriceps CSA (both P < 0.01). VO2peak and one-repetition maximum declined by 6.4 ± 2.3 (P < 0.05) and 6.9 ± 1.4% (P < 0.01), respectively. Bed rest induced a 29 ± 5% decrease in whole-body insulin sensitivity (P < 0.01). This was accompanied by a decline in muscle oxidative capacity, without alterations in skeletal muscle lipid content or saturation level, markers of oxidative stress, or capillary density. In conclusion, 1 week of bed rest substantially reduces skeletal muscle mass and lowers whole-body insulin sensitivity, without affecting mechanisms implicated in high-fat diet-induced insulin resistance.

Loss of the Inducible Hsp70 Delays the Inflammatory Response to Skeletal Muscle Injury and Severely Impairs Muscle Regeneration

Skeletal muscle regeneration following injury is a highly coordinated process that involves transient muscle inflammation, removal of necrotic cellular debris and subsequent replacement of damaged myofibers through secondary myogenesis. However, the molecular mechanisms which coordinate these events are only beginning to be defined. In the current study we demonstrate that Heat shock protein 70 (Hsp70) is increased following muscle injury, and is necessary for the normal sequence of events following severe injury induced by cardiotoxin, and physiological injury induced by modified muscle use. Indeed, Hsp70 ablated mice showed a significantly delayed inflammatory response to muscle injury induced by cardiotoxin, with nearly undetected levels of both neutrophil and macrophage markers 24 hours post-injury. At later time points, Hsp70 ablated mice showed sustained muscle inflammation and necrosis, calcium deposition and impaired fiber regeneration that persisted several weeks post-injury. Through rescue experiments reintroducing Hsp70 intracellular expression plasmids into muscles of Hsp70 ablated mice either prior to injury or post-injury, we confirm that Hsp70 optimally promotes muscle regeneration when expressed during both the inflammatory phase that predominates in the first four days following severe injury and the regenerative phase that predominates thereafter. Additional rescue experiments reintroducing Hsp70 protein into the extracellular microenvironment of injured muscles at the onset of injury provides further evidence that Hsp70 released from damaged muscle may drive the early inflammatory response to injury. Importantly, following induction of physiological injury through muscle reloading following a period of muscle disuse, reduced inflammation in 3-day reloaded muscles of Hsp70 ablated mice was associated with preservation of myofibers, and increased muscle force production at later time points compared to WT. Collectively our findings indicate that depending on the nature and severity of muscle injury, therapeutics which differentially target both intracellular and extracellular localized Hsp70 may optimally preserve muscle tissue and promote muscle functional recovery.

Two Weeks of Reduced Activity Decreases Leg Lean Mass and Induces “Anabolic Resistance” of Myofibrillar Protein Synthesis in Healthy Elderly

Alterations in muscle protein metabolism underlie age-related muscle atrophy. During periods of muscle disuse, muscle protein synthesis is blunted, and muscle atrophy occurs in young and old. The impact of a short reduction in physical activity on muscle protein metabolism in older adults is unknown. The aim of this study was to investigate the impact of 14 days of reduced daily steps on fasted and fed-state rates of myofibrillar protein synthesis (MPS) to provide insight into the mechanisms for changes in muscle mass and markers of metabolic health. Before and after 14 days of reduced daily step-count, 10 healthy older adults (age, 72 ± 1 y) underwent measures of insulin sensitivity, muscle strength, physical function, and body composition. Using a primed constant infusion of L-[ring-(13)C6]phenylalanine with serial muscle biopsies, basal, postabsorptive, and postprandial rates of MPS were determined before and after the 14-day intervention. Daily step-count was reduced by approximately 76% to 1413 ± 110 steps per day. Leg fat-free mass was reduced by approximately 3.9% (P < .001). Postabsorptive insulin resistance was increased by approximately 12%, and postprandial insulin sensitivity was reduced by approximately 43% after step reduction (P < .005). Concentrations of TNF-α and C-reactive protein were increased by approximately 12 and 25%, respectively, after step reduction (P < .05). Postprandial rates of MPS were reduced by approximately 26% after the intervention (P = .028), with no difference in postabsorptive rates. The present study demonstrates that 14 days of reduced steps in older adults induces small but measurable reductions in muscle mass that appear to be underpinned by reductions in postprandial MPS and are accompanied by impairments in insulin sensitivity and systemic inflammatory markers and postprandial MPS.

Contributions to the understanding of the anabolic properties of different dietary proteins

Contributions to the understanding of the anabolic properties of different dietary proteins

Neuromuscular electrical stimulation increases muscle protein synthesis rates in type 2 diabetic men

A loss of skeletal muscle proteins ultimately lowers the capacity for blood glucose disposal. Thus, the development of paradigms that can increase muscle protein accretion will have implications for the treatment of type 2 diabetes at a more advanced age. We aimed to determine the effect of neuromuscular electrical stimulation (NMES) on mixed muscle protein synthesis rates in type 2 diabetic men. Six sedentary, type 2 diabetic men (Age: 70±1 y, BMI: 26.5±1.0 kg·m−2) received a primed, constant infusion of L‐[ring‐13C6]phenylalanine and 60 min of one legged NMES. Biopsies of the vastus lateralis were obtained at 0, 2, and 4 h after NMES to measure mixed muscle protein synthesis rates in the unstimulated (CON) and stimulated (STIM) leg. The electrical current of the NMES protocol consisted of a pulse duration of 500 μs, pulse frequency of 60 Hz, and a 3 sec contraction – 3 sec relaxation time. Muscle protein synthesis rates were increased by 21% and 64% above CON at 0–2 h and 2–4 h in the STIM leg, respectively (P&lt;0.05). Similarly, the cumulative MPS response (0–4 h) was greater in the STIM (0.049±0.008 %·h−1) compared with the CON leg (0.039±0.008 %·h−1). Our data demonstrate that NMES stimulates mixed muscle protein synthesis rates in vivo in humans. This work lends credence to the use of NMES to attenuate muscle protein loss during periods of muscle disuse or to support an increase in skeletal muscle hypertrophy.

Chromium supplement inhibits skeletal muscle atrophy in hindlimb-suspended mice

Skeletal muscle atrophy and whole-body glucose intolerance are consequences of muscle disuse associated with conditions leading to prolonged bed rest. Nutritional supplementation with chromium has been shown to prevent weight loss and improve glucose tolerance in malnourished subjects on long-term total parenteral nutrition. The objective of this study was to evaluate the effect of oral supplementation with a novel chromium complex, chromium ( d-phenylalanine) 3 [Cr( d-phe) 3] at 45 μg/kg/day for 5 weeks, on skeletal muscle atrophy and glucose intolerance in a hindlimb suspension mouse model. Hindlimb-suspended mice exhibited reduced skeletal muscle fiber size and enhanced whole-body glucose intolerance, both of which were reversed by chromium treatment. The inhibition of skeletal muscle atrophy by chromium was associated with reductions in the ubiquitination ligase atrogin-1/muscle atrophy F-box, which is elevated in hindlimb-suspended mice. Neither hindlimb suspension nor chromium treatment altered the protein levels of the myostatin, phospho-Forkhead box O-1 and mammalian target of rapamycin. Chromium-treated animals exhibited elevated Akt ( Homo sapiens v-akt murine thymoma viral oncogene homolog) phosphorylation in their skeletal muscle, with no change observed in the levels of activated JNK (c-Jun N-terminal kinase). Thus, these data suggest that nutritional supplementation with chromium may have potential therapeutic benefits in minimizing skeletal muscle atrophy associated with long periods of muscle disuse.