Search

Chronic sleep loss is a potent catabolic stressor, increasing the risk of metabolic dysfunction and loss of muscle mass and function. To provide mechanistic insight into these clinical outcomes, we sought to determine if acute sleep deprivation blunts skeletal muscle protein synthesis and promotes a catabolic environment. Healthy young adults (N = 13; seven male, six female) were subjected to one night of total sleep deprivation (DEP) and normal sleep (CON) in a randomized cross-over design. Anabolic and catabolic hormonal profiles were assessed across the following day. Postprandial muscle protein fractional synthesis rate (FSR) was assessed between 13:00 and 15:00 and gene markers of muscle protein degradation were assessed at 13:00. Acute sleep deprivation reduced muscle protein synthesis by 18% (CON: 0.072 ± 0.015% vs. DEP: 0.059 ± 0.014%·h-1, p = .040). In addition, sleep deprivation increased plasma cortisol by 21% (p = .030) and decreased plasma testosterone by 24% (p = .029). No difference was found in the markers of protein degradation. A single night of total sleep deprivation is sufficient to induce anabolic resistance and a procatabolic environment. These acute changes may represent mechanistic precursors driving the metabolic dysfunction and body composition changes associated with chronic sleep deprivation. [ABSTRACT FROM AUTHOR]

Background: Emerging research suggests that redistributing total protein intake from 1 high-protein meal/d to multiple moderately high-protein meals improves 24-h muscle protein synthesis. Over time, this may promote positive changes in body composition. Objective: We sought to assess the effects of within-day protein intake distribution on changes in body composition during dietary energy restriction and resistance training. Design: In a randomized parallel-design study, 41 men and women [mean ± SEM age: 35 ± 2 y; body mass index (in kg/m²): 31.5 ± 0.5] consumed an energy-restricted diet (750 kcal/d below the requirement) for 16 wk while performing resistance training 3 d/wk. Subjects consumed 90 g protein/d (1.0 ± 0.03 g ⋅ kg-1 ⋅ d-1, 125% of the Recommended Dietary Allowance, at intervention week 1) in either a skewed (10 g at breakfast, 20 g at lunch, and 60 g at dinner; n = 20) or even (30 g each at breakfast, lunch, and dinner; n = 21) distribution pattern. Body composition was measured pre- and postintervention. Results: Over time, whole-body mass (least-squares mean ± SE: -7.9 ± 0.6 kg), whole-body lean mass ( - 1.0 ± 0.2 kg), whole-body fat mass (-6.9 ± 0.5 kg), appendicular lean mass (-0.7 ± 0.1 kg), and appendicular fat mass (-2.6 ± 0.2 kg) each decreased. The midthigh muscle area (0 ± 1 cm²) did not change over time, whereas the midcalf muscle area decreased (-3 ± 1 cm²). Within-day protein distribution did not differentially affect these body-composition responses. Conclusion: The effectiveness of dietary energy restriction combined with resistance training to improve body composition is not influenced by the within-day distribution of protein when adequate total protein is consumed. This trial was registered at clinicaltrials. gov as NCT02066948. [ABSTRACT FROM AUTHOR]

In recent years, considerable scientific interest has been devoted to amino acid supplementation and its role in regulating skeletal muscle metabolism in health, ageing and disease. This interest has, in part, stemmed from clinical evidence that traditional nutritional supplementation in patients is largely ineffective. In particular, this knowledge has prompted extensive research into the mechanisms responsible for amino acid stimulation of muscle protein metabolism in older adults with sarcopenia. It is well established that ageing diminishes muscle strength and size, contributing to a number of serious health problems such as an increased risk of falls and fractures. Although the reasons behind age-related sarcopenia are multifactorial and involve a complex interplay of hormonal and metabolic stimuli, it is clear that inadequate nutrition and inactivity are strong causative factors. Recently, the idea that elderly muscle is perhaps less anabolically sensitive to amino acids has been put forward as an additional causative factor. In light of this recent evidence, and the further suggestion that the effects of essential amino acids on skeletal muscle are independent of changes in insulin, newer studies are focusing on tailoring the optimal amount and proportion of amino acids needed to stimulate muscle protein synthesis most efficiently in ageing populations. Understanding the mechanisms of amino acid stimulation of muscle protein synthesis may also provide insight into the metabolic regulation of anabolism in skeletal muscle by key hormones such as growth hormone. In this article, we summarize current research concerning amino acids and skeletal muscle, particularly with regard to ageing and inactivity. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Inactivity-mediated protein catabolism occurs in many circumstances ranging from catastrophic events such as severe illness or injury, to unique environments such as spaceflight/microgravity, to more insidious causes such as physical frailty and the progression of aging. Nevertheless, regardless of the etiology, the consequences of inactivity are readily observable and debilitating. Mechanistically, the loss of lean body mass during inactivity is the result of a chronic imbalance between muscle protein synthesis and breakdown. When inactivity is accompanied by the stress of trauma or disease, the rate of muscle protein catabolism can increase several fold. Bed rest studies in healthy volunteers provide a unique opportunity to examine the mechanisms contributing to muscle loss and evaluate strategies for intervention that may slow muscle catabolism and promote anabolism. The prerequisite for muscle protein synthesis and the most readily adaptable stimulus is dietary-derived amino acids. This review focuses on the role of amino acid supplementation in the maintenance of skeletal muscle mass during age-related and clinically mandated inactivity. [ABSTRACT FROM AUTHOR]

Abstract: To counteract the debilitating progression of sarcopenia, a protein supplement should provide an energetically efficient anabolic stimulus. We quantified net muscle protein synthesis in healthy elderly individuals (65–79 yrs) following ingestion of an isocaloric intact whey protein supplement (WY; n=8) or an essential amino acid supplement (EAA; n=7). Femoral arterio-venous blood samples and vastus lateralis muscle biopsy samples were obtained during a primed, constant infusion of L-[ring-2H5]phenylalanine. Net phenylalanine uptake and mixed muscle fractional synthetic rate (FSR) were calculated during the post-absorptive period and for 3.5h following ingestion of 15g EAA or 15g whey. After accounting for the residual increase in the intracellular phenylalanine pool, net post-prandial phenylalanine uptake was 53.4±9.7mg pheleg−1 (EAA) and 21.7±4.6mgpheleg−1 (WY), (P<0.05). Postabsorptive FSR values were 0.056±0.004%h−1 (EAA) and 0.049±0.006%h−1 (WY), (P>0.05). Both supplements stimulated FSR (P<0.05), but the increase was greatest in the EAA group with values of 0.088±0.011%h−1 (EAA) and 0.066±0.004%h−1 (WY), (P<0.05). While both EAA and WY supplements stimulated muscle protein synthesis, EAAs may provide a more energetically efficient nutritional supplement for elderly individuals. [Copyright &y& Elsevier]

Muscular inactivity is inherent in many circumstances, including convalescence from serious illness or injury, spaceflight, and the progression of aging. Inactivity in a healthy individual leads to a decrease in whole-body protein turnover composed primarily of a decrease in muscle protein synthesis. The decrease in muscle protein synthesis leads to a substantial loss of lean body mass. We have demonstrated that this loss of lean mass is greater when inactivity is accompanied by stress, specifically hypercortisolemia. During convalescence from trauma or injury, the anabolic stimulus provided by nutrient ingestion represents a primary means of ameliorating the loss of muscle protein. We have previously demonstrated that ingestion of essential amino acids (EAAs), formulated to mimic the proportion of EAAs in muscle, provides a potent anabolic stimulus for muscle protein. Recently, we demonstrated that EM supplementation throughout 28 d of bed rest stimulated net muscle protein synthesis. The repeated stimulation translated to maintenance of lean body mass and an amelioration of functional decrement compared to a placebo treatment. We have also demonstrated that this EAA supplement stimulates net protein synthesis during acute hypercortisolemia and are currently testing the effects during prolonged inactivity. Although EAAs promote muscle anabolism during hypercortisolemia it is unlikely that a nutritional intervention alone would be effective in maintaining lean body mass during severe stress. It may be necessary to concomitantly reduce the catabolic influence of cortisol or provide another anabolic stimulus. [ABSTRACT FROM AUTHOR]

We recently demonstrated that muscle protein synthesis was stimulated to a similar extent in young and elderly subjects during a 3-h amino acid infusion. We sought to determine if a more practical bolus oral ingestion would also produce a similar response in young (34 ± 4 yr) and elderly (67 ± 2 yr) individuals. Arteriovenous blood samples and muscle biopsies were obtained during a primed (2.0 µmol/kg) constant infusion (0.05 µmol·kg-1·min-1 of L-[ring-²H5]phenylalanine. Muscle protein kinetics and mixed muscle fractional synthetic rate (FSR) were calculated before and after the bolus ingestion of 15 g of essential amino acids (EAA) in young (n = 6) and elderly (n = 7) subjects. After EAA ingestion, the rate of increase in femoral artery phenylalanine concentration was slower in elderly subjects but remained elevated for a longer period. EAA ingestion increased FSR in both age groups by ∼0.04%/h (P < 0.05). However, muscle intracellular (IC) phenylalanine concentration remained significantly higher in elderly subjects at the completion of the study (young: 115.6 ± 5.4 nmol/ml; elderly: 150.2 ± 19.4 nmol/ml). Correction for the free phenylalanine retained in the muscle IC pool resulted in similar net phenylalanine uptake values in the young and elderly. EAA ingestion increased plasma insulin levels in young (6.1 ± 1.2 to 21.3 ± 3.1 µIU/ml) but not in elderly subjects (3.0 ± 0.6 to 4.3 ± 0.4 µIU/ml). Despite differences in the time course of plasma phenylalanine kinetics and a greater residual IC phenylalanine concentration, amino acid supplementation acutely stimulated muscle protein synthesis in both young and elderly individuals. [ABSTRACT FROM AUTHOR]

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 < 30 kg·m − 2 ) young (18–40 y; 74 men, 52 women) and older (60–87 y; 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. [ABSTRACT FROM AUTHOR]

Abstract: Ingestion of sufficient dietary protein is a fundamental prerequisite for muscle protein synthesis and maintenance of muscle mass and function. Elderly people are often at increased risk for protein-energy malnutrition, sarcopenia, and a diminished quality of life. This study sought to compare changes in muscle protein synthesis and anabolic efficiency in response to a single moderate serving (113 g; 220 kcal; 30 g protein) or large serving (340 g; 660 kcal; 90 g protein) of 90% lean beef. Venous blood and vastus lateralis muscle biopsy samples were obtained during a primed, constant infusion (0.08 μmol/kg/min) of L-[ring-13C6] phenylalanine in healthy young (n=17; 34±3 years) and elderly (n=17; 68±2 years) individuals. Mixed muscle fractional synthesis rate was calculated during a 3-hour postabsorptive period and for 5 hours after meal ingestion. Data were analyzed using a two-way repeated measures analysis of variance with Tukey''s pairwise comparisons. A 113-g serving of lean beef increased muscle protein synthesis by approximately 50% in both young and older volunteers. Despite a threefold increase in protein and energy content, there was no further increase in protein synthesis after ingestion of 340 g lean beef in either age group. Ingestion of more than 30 g protein in a single meal does not further enhance the stimulation of muscle protein synthesis in young and elderly. [Copyright &y& Elsevier]