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PURPOSE: Electric bikes (EB) are a form of active transportation with demonstrated health benefits. The purpose of this study was to determine the influence of riding an EB for one week on indices of cardiometabolic health in middle-aged adults. METHODS: Adults (n = 22; age = 57.1 ± 11.3 year; BMI = 27.7 ± 4.9) participated in a 2 week study. During Week 1, participants were instructed to continue regular activities. Starting Week 2 participants were provided an EB to ride at least 3 days for a minimum of 30 min·day-1. Physical activity (PA) and glucose were measured continuously. Body composition, blood lipids, glucose, insulin, hemoglobin A1c (HbA1c), plasma endothelin-1 (ET-1), and carotid-femoral pulse wave velocity (cf-PWV) were measured on days 1 and 14.Data and Statistical analyses or Statistics. Each participant served as their own control. Paired t-tests compared dependent variables between week 1 (without EB) and week 2 (with EB). RESULTS: When provided an EB for one week, moderate to vigorous PA increased by 6-9 min·day-1 (P < 0.05) and sedentary time decreased by ~ 77 min·day-1 (P < 0.05). Data from 24 h continuous glucose monitoring showed the percentage of time in healthy range (70-120 mg·dl-1 glucose) increased (P < 0.05) from week 1 to week 2. Compared to day 1, cf-PWV was lower at day 14 (P < 0.05) following one week of riding an EB. CONCLUSION: Moderately-active, middleaged adults showed improved continuous glucose regulation and lower central arterial stiffness following one week of riding an EB.

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BACKGROUND: Ambulation using standard axillary crutches (SACs) is associated with increased energy expenditure (EE) and decreased ability to perform activities of daily living (ADLs). Using a hands-free crutch (HFC) displays potential for easier completion of ADLs and reduction in energy requirements. OBJECTIVES: To determine if a HFC elicits lower EE and heart rate (HR), improvement in performance of ADLs, and decreased rating of perceived exertion (RPE) compared to common ambulatory devices. DESIGN: A randomized crossover-controlled trial. SETTING: University community. PARTICIPANTS: Twenty healthy college students. MAIN OUTCOME MEASURES: Participants completed a 6-minute walk test at 50 m/min, an ADLs course, and a two-flight stair climb with SACs, HFC, knee scooter (KS), and unassisted ambulation (UA). The order of trial conditions was randomized. EE, HR, time to complete ADLs course and stair climb, and RPE during each condition were obtained. One-way analyses of variance were performed to compare EE, HR response, and RPE between the assistive devices and UA. RESULTS: In all outcomes UA resulted in lower EE, HR, and RPE compared to all the assistive devices (p < .05). For the ADLs course, EE was the same for the three assistive devices, whereas HR was significantly lower for HFC compared to SACs and KS (p < .05). RPE for HFC and KS was lower than SACs (p < .05). For the 6MWT, each device significantly differed from the other devices for EE, HR, and RPE, with KS eliciting the lowest values, followed by HFC. For the stair climbing task, HFC elicited lower EE, HR, and RPE than SACs. Fourteen participants indicated their overall preference for HFCs. CONCLUSIONS: In individuals prescribed weight-bearing restrictions, using a HFC may offer an easier and more preferred alternative to more commonly used SACs during ambulation, stair climbing, and other ADLs.

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

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BACKGROUND: Obesity in older adults contributes to increasing comorbidities and decreased quality of life. There is limited research that includes older adults' perspectives on weight loss. OBJECTIVE: The purpose of this qualitative study was to gain a better understanding of older adults' perceptions and experiences related to weight loss immediately after a 6-month weight loss intervention. DESIGN: A qualitative research design using semi-structured interviews conducted as part of a larger research study exploring weight loss and/or aerobic exercise on muscle inflammation. PARTICIPANTS/SETTING: A sample of community-based older adults (n = 11) in Southwestern Ohio were recruited from September 2018 through August 2019 after completion of a 6-month weight loss intervention. Eligible participants were older than 58 years, with a body mass index (calculated as kg/m2) >27, and sedentary with no cognitive deficits. Exclusions included cancer, heart disease, diabetes, and tobacco use. ANALYSIS: Interviews were recorded, transcribed verbatim, and analyzed using thematic analysis. Descriptive statistics were used for demographic data. RESULTS: Three emergent themes included barriers and challenges to weight loss, which included caregiving roles, challenges with increasing protein intake, and ambivalence to change; personal strategies for success (eg, portion control and meal flexibility); and external strategies for success (eg, visual graphs as feedback measures, alternate measures of success, and social support). CONCLUSIONS: The results of this qualitative study provide insight into older adults' experiences with weight loss, which may be considered when designing weight management interventions. However, more research is needed to examine strategies to address the challenges identified by participants in this research study. Future qualitative research should also focus on weight loss perspectives of older adults in other racial and ethnic groups.

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Reduced flow-mediated dilation (FMD) and elevated plasma endothelin-1 (ET-1) levels may contribute to the higher incidence of adverse cardiovascular events observed in the morning hours. A single bout of intermittent exercise abolishes the diurnal variation in FMD. Studies examining the effects of exercise on vascular and plasma ET-1 responses at different times of day are lacking. We determined the effects of time of day and intermittent aerobic exercise on brachial artery FMD and plasma ET-1 levels in healthy adults. We hypothesized that lower brachial artery FMD in the morning (compared to the afternoon) will be accompanied by higher plasma ET-1 levels. Additionally, we hypothesized that the diurnal variation in brachial artery FMD and plasma ET-1 will be abolished by performing a single bout of intermittent aerobic exercise. Utilizing a randomized, cross-over design, healthy adults [n = 12; 22 ± 4 y; 25.2 ± 2.7 kg/m2] completed two separate trials: morning (08:00 h) and afternoon (16:00 h). Brachial artery FMD and plasma ET-1 were measured prior to and immediately following a bout of intermittent cycling performed at 70% peak Watts. Brachial artery FMD was lower (P < .05) at 08:00 h (4.4 ± 3.4%) compared to 16:00 h (6.3 ± 3.7%), but was unaffected by exercise (4.8 ± 3.9% and 5.7 ± 2.2% for 08:00 h and 16:00 h, respectively). Plasma ET-1 was unaffected by time of day. Compared to pre-exercise, plasma ET-1 decreased (P < .01) at both times of day. Our data indicate that circulating ET-1 levels do not explain the lower morning FMD in healthy adults. Further, a bout of intermittent exercise did not affect brachial artery FMD but decreased plasma ET-1 levels.

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BACKGROUND: Endogenous antioxidants are critical to limiting cellular oxidative damage. METHODS: The authors determined if habitual physical activity (PA) and cardiorespiratory fitness were associated with skeletal muscle expression of endogenous antioxidants (superoxide dismutase, catalase, and glutathione peroxidase) and circulating oxidative stress markers (serum 8-hydroxy-2'-deoxyguanosine [8-OHdG]; oxidized low-density lipoprotein [LDL]) in older adults. Moderate to vigorous PA (MVPA) was estimated using a validated PA questionnaire in 26 older adults (mean [SD]; M/F = 9/17, age = 68 [4] y, body mass index = 26 [3] kg·m-2). Maximal oxygen consumption was estimated using the YMCA submaximal cycle test. Skeletal muscle endogenous antioxidants and serum 8-OHdG and oxidized LDL were measured. Bivariate and partial correlations (controlling for body mass index) were utilized to determine associations among variables. RESULTS: MVPA (1640 [1176] kcal·wk-1) was correlated with superoxide dismutase 2 (r = .55), catalase (r = .55), glutathione peroxidase 1 (r = .48), and 8-OHdG (r = -.41) (all Ps < .05), but not oxidized LDL. MVPA and 8-OHdG were not significantly correlated when controlling for body mass index (r = -.29). Estimated maximal oxygen consumption was correlated with glutathione peroxidase 1 (r = .48; P < .05). CONCLUSIONS: These data show that skeletal muscle endogenous antioxidant expression and circulating oxidative damage are associated with habitual MVPA in older adults. Thus, MVPA in older adults may be protective against reactive oxygen species damage due to higher expression of endogenous antioxidants.

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INTRODUCTION: Postprandial hyperglycemia (PPH) impairs vascular endothelial function (VEF). A single bout of aerobic exercise (AE) attenuates PPH-induced decreases in brachial artery flow-mediated dilation (FMD), a non-invasive measure of VEF, in healthy adults for up to 17 h post-exercise. Studies examining the effects of resistance exercise (RE) on postprandial FMD responses are lacking. PURPOSE: We hypothesized that a single bout of exercise performed the prior evening would attenuate PPH-induced decreases in FMD, independent of exercise modality. METHODS: In a randomized, cross-over design, overweight/obese adults [n = 11 (8 women); 22 ± 4 years; 32.3 ± 5.8 kg m-2] completed 3 separate trials: control (seated rest), AE (30 min at ~ 60% VO2max), or whole-body RE (30 min, 6 exercises, 3 × 10-repetition maximum). Each trial occurred 14-17 h prior to an oral glucose tolerance test (OGTT). Brachial artery FMD and plasma glucose and insulin were measured prior to and at 30-min intervals for 2 h following the OGTT. Repeated-measures ANOVA and Bonferroni post hoc tests were used to evaluate differences within and between trials. RESULTS: Trials occurred 15.3 ± 1.0 h prior to the OGTT. Relative to baseline, FMD transiently decreased (P < 0.05) at 30-60 min post-ingestion, plasma glucose increased (P < 0.01) at 30-90 min post-ingestion, and plasma insulin increased (P < 0.01) at 30-120 min post-ingestion. No between trial differences were observed for FMD, glucose, or insulin. CONCLUSIONS: Aerobic or resistance exercise performed the evening prior to an OGTT does not attenuate postprandial decreases in brachial artery FMD in overweight/obese adults.

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BACKGROUND: Essential amino acids (EAA) and aerobic exercise (AE) acutely and independently stimulate skeletal muscle protein anabolism in older adults. OBJECTIVE: In this Phase 1, double-blind, placebo-controlled, randomized clinical trial, we determined if chronic EAA supplementation, AE training, or a combination of the two interventions could improve muscle mass and function by stimulating muscle protein synthesis. METHODS: We phone-screened 971, enrolled 109, and randomized 50 independent, low-active, nonfrail, and nondiabetic older adults (age 72 ± 1 years). We used a 2 × 2 factorial design. The interventions were: daily nutritional supplementation (15 g EAA or placebo) and physical activity (supervised AE training 3 days/week or monitored habitual activity) for 24 weeks. Muscle strength, physical function, body composition, and muscle protein synthesis were measured before and after the 24-week intervention. RESULTS: Forty-five subjects completed the 24-week intervention. VO2peak and walking speed increased (p < .05) in both AE groups, irrespective of supplementation type, but muscle strength increased only in the EAA + AE group (p < .05). EAA supplementation acutely increased (p < .05) muscle protein synthesis from basal both before and after the intervention, with a larger increase in the EAA + AE group after the intervention. Total and regional lean body mass did not change significantly with any intervention. CONCLUSIONS: In nonfrail, independent, healthy older adults AE training increased walking speed and aerobic fitness, and, when combined with EAA supplementation, it also increased muscle strength and EAA-stimulated muscle protein synthesis. These increases occurred without improvements in muscle mass.

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This study determined if varying physical activity (PA) the day prior to an oral glucose tolerance test (OGTT) differentially influenced postprandial glucose and insulin kinetics. Fifteen healthy, young adults participated in three OGTT trials the morning after performing 50% (LOW), 100% (HABITUAL), or 150% (HIGH) of their habitual PA (determined by 7-day pedometry). Trials were randomized and separated by at least 1-wk. For each OGTT trial, blood glucose and insulin were measured after an overnight fast and at 30-min intervals for 2 h following ingestion of the glucose beverage. Between-trial differences were analyzed using a general linear model with repeated measures. Subjects successfully achieved the desired percentage of habitual steps prior to each trial: LOW: 51±5%, HABITUAL: 99±6%, and HIGH: 149±9%. Fasting blood glucose and glucose total area under the curve (AUC) did not differ between trials. Serum insulin AUC was lower (p<0.05) following the HIGH (34,158±8,786 pmol·min·L-1) compared to the LOW (40,738±9,276 pmol·min·L-1) trial. No differences were observed when the LOW and HIGH trials were compared to HABITUAL. These data suggest that varying the PA level (from 50 to 150% of habitual PA) the day prior to an OGTT influences the insulin (but not blood glucose) response to an OGTT.

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INTRODUCTION: Acute aerobic exercise prevents sitting-induced impairment of flow-mediated dilation (FMD). Further, evidence suggests that sitting-induced impairment of FMD occurs via an oxidative stress-dependent mechanism that disrupts endothelial function. PURPOSE: We hypothesized that acute aerobic exercise would prevent impairment of femoral artery FMD by limiting oxidative stress responses that increase endothelin-1 (ET-1) levels and disrupt nitric oxide (NO) status. METHODS: In a randomized, cross-over study, healthy men (n = 11; 21.2 ± 1.9 years) completed two 3 h sitting trials that were preceded by 45 min of either quiet rest (REST) or a single bout of continuous treadmill exercise (65% maximal oxygen consumption) (EX). Superficial femoral artery FMD, plasma glucose, malondialdehyde (MDA), ET-1, arginine (ARG) and its related metabolites [homoarginine (HA), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA)] were assessed at baseline, 1 h following EX (or REST) (0 h), and at 1 h intervals during 3 h of uninterrupted sitting. Data were analyzed using repeated measures ANOVA. RESULTS: During REST, femoral artery FMD declined from baseline (2.6 ± 1.8%) at 1, 2, and 3 h of sitting and resting shear rate decreased at 3 h. In contrast, when sitting was preceded by EX, femoral artery FMD (2.7 ± 2.0%) and resting shear rate responses were unaffected. No between trial differences were detected for plasma glucose, MDA, ET-1, ARG, HA, ADMA, or SDMA. CONCLUSION: Prior aerobic exercise prevented the decline in femoral artery FMD that is otherwise induced by prolonged sitting independent of changes in oxidative stress, ET-1, and NO status.

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Elevated skeletal muscle expression of toll-like receptor 4 (TLR4) has been linked to increased inflammation in clinical populations. TNFα converting enzyme (TACE), which cleaves membrane-bound TNFα (mTNFα) to its soluble (sTNFα) and more bioactive form, has been linked to chronic disease. In contrast, higher physical activity level is associated with decreased chronic disease risk and inflammation. The purpose of the present study was to examine the relationship between physical activity and skeletal muscle TLR4, TACE, and TNFα in older adults. In 26 older adults (age = 68 ± 4 years, body mass index = 26 ± 3 kg·m(-2)), self-reported physical activity (kcal·week(-1)), estimated maximal oxygen consumption, and body composition (air plethysmography) were measured. TLR4, TACE, mTNFα, and sTNFα were measured in skeletal muscle biopsies (vastus lateralis) using western blot analyses. Pearson product-moment correlations were run between variables. Significance was set at p < 0.05. Skeletal muscle TACE was directly associated with sTNFα (r = 0.53, p < 0.01). Linear regression modeling showed that mTNFα and TACE expression were predictive of sTNFα expression. No correlations were observed between physical activity and TLR4, TACE, or sTNFα. Percent body fat was directly associated with skeletal muscle TLR4 (r = 0.52, p < 0.01) and TACE (r = 0.50, p < 0.01), whereas fasting blood glucose was directly associated with TACE and sTNFα. In conclusion, we found that percent body fat was directly associated with TLR4 and TACE expression in skeletal muscle of older adults. These findings suggest that elevated skeletal muscle expression of TLR4 and TACE may contribute to the augmented inflammation and chronic disease risk observed with increased adiposity.

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

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INTRODUCTION: In healthy individuals, strenuous exercise typically results in a transient increase in the inflammatory cytokine, interleukin-6 (IL-6). This increase in IL-6 is reported to have pleiotropic effects including increased glucose uptake, increased fat oxidation, and anti-inflammatory actions. PURPOSE: The purpose of this study was to determine if patients with a traumatic brain injury (TBI) have a differential cytokine response to exercise compared to healthy control subjects (CON). METHODS: Eight patients with a TBI and eight age- and sex-matched controls completed an exercise test to volitional exhaustion. Metabolic data were collected continuously, and blood was collected at baseline, immediately post-exercise, and every 10 min for an hour post-exercise. Serum was analyzed for IL-6, tumor necrosis factor-alpha, interleukin-10 (IL-10), and cortisol. RESULTS: Peak oxygen consumption (CON 33 ± 2 ml kg(-1) min(-1); TBI 29 ± 2 ml kg(-1) min(-1)) and respiratory exchange ratio during exercise were equivalent between groups. There were no baseline differences between groups for cytokine or cortisol concentrations. Exercise did not increase IL-6 in TBI, whereas IL-6 was elevated from baseline in CON at 0, 40, and 50 min post-exercise (p < 0.05). IL-10 and cortisol increased from baseline in CON at 40 min post-exercise (p < 0.05). CONCLUSIONS: These data indicate that patients recovering from TBI have blunted IL-6, IL-10, and cortisol responses following a peak exercise test compared to non-TBI controls. This lack of an exercise response may represent impaired hypothalamic-pituitary-adrenal axis function.

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The purpose of this study was to observe exercise training-induced effects on adiponectin, leptin, and ghrelin. Twenty-nine older, healthy participants were classified as physically active (comparison group: N = 15, 70.9 ± 1.2 years) or physically inactive (exercise group: N = 14, 70.5 ± 1.4 years). Exercise group participants completed 12 weeks of combined aerobic and resistance exercise training, whereas comparison group participants maintained their current level of exercise and served as a physically active comparison group. Monocyte phenotype, as well as serum ghrelin, leptin, adiponectin, and soluble tumor necrosis factor receptor II were analyzed prior to and following the 12-week period. Ghrelin and adiponectin increased 47% and 55%, respectively, in exercise group participants following exercise training. Percent change in ghrelin (post and pre) was negatively correlated with the percent change in CD14+CD16+ monocytes (post and pre) in exercise group participants. Despite no changes in body mass, these data contribute to evidence for the anti-inflammatory effects of exercise.

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Bed rest induces significant loss of leg lean mass in older adults. Systemic and tissue inflammation also accelerates skeletal muscle loss, but it is unknown whether inflammation is associated to inactivity-induced muscle atrophy in healthy older adults. We determined if short-term bed rest increases toll-like receptor 4 (TLR4) signaling and pro-inflammatory markers in older adult skeletal muscle biopsy samples. Six healthy, older adults underwent seven consecutive days of bed rest. Muscle biopsies (vastus lateralis) were taken after an overnight fast before and at the end of bed rest. Serum cytokine expression was measured before and during bed rest. TLR4 signaling and cytokine mRNAs associated with pro- and anti-inflammation and anabolism were measured in muscle biopsy samples using Western blot analysis and qPCR. Participants lost ∼4% leg lean mass with bed rest. We found that after bed rest, muscle levels of TLR4 protein expression and interleukin-6 (IL-6), nuclear factor-κB1, interleukin-10, and 15 mRNA expression were increased after bed rest (P < 0.05). Additionally, the cytokines interferon-γ, and macrophage inflammatory protein-1ß, were elevated in serum samples following bed rest (P < 0.05). We conclude that short-term bed rest in older adults modestly increased some pro- and anti-inflammatory cytokines in muscle samples while systemic changes in pro-inflammatory cytokines were mostly absent. Upregulation of TLR4 protein content suggests that bed rest in older adults increases the capacity to mount an exaggerated, and perhaps unnecessary, inflammatory response in the presence of specific TLR4 ligands, e.g., during acute illness.

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High-quality proteins such as soy, whey, and casein are all capable of promoting muscle protein synthesis postexercise by activating the mammalian target of rapamycin (mTORC1) signaling pathway. We hypothesized that a protein blend of soy and dairy proteins would capitalize on the unique properties of each individual protein and allow for optimal delivery of amino acids to prolong the fractional synthetic rate (FSR) following resistance exercise (RE). In this double-blind, randomized, clinical trial, 19 young adults were studied before and after ingestion of ∼19 g of protein blend (PB) or ∼18 g whey protein (WP) consumed 1 h after high-intensity leg RE. We examined mixed-muscle protein FSR by stable isotopic methods and mTORC1 signaling with western blotting. Muscle biopsies from the vastus lateralis were collected at rest (before RE) and at 3 postexercise time points during an early (0-2 h) and late (2-4 h) postingestion period. WP ingestion resulted in higher and earlier amplitude of blood branched-chain amino acid (BCAA) concentrations. PB ingestion created a lower initial rise in blood BCAA but sustained elevated levels of blood amino acids later into recovery (P < 0.05). Postexercise FSR increased equivalently in both groups during the early period (WP, 0.078 ± 0.009%; PB, 0.088 ± 0.007%); however, FSR remained elevated only in the PB group during the late period (WP, 0.074 ± 0.010%; PB, 0.087 ± 0.003%) (P < 0.05). mTORC1 signaling similarly increased between groups, except for no increase in S6K1 phosphorylation in the WP group at 5 h postexercise (P < 0.05). We conclude that a soy-dairy PB ingested following exercise is capable of prolonging blood aminoacidemia, mTORC1 signaling, and protein synthesis in human skeletal muscle and is an effective postexercise nutritional supplement.

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In humans, essential amino acids (EAAs) stimulate muscle protein synthesis (MPS) with no effect on muscle protein breakdown (MPB). Insulin can stimulate MPS, and carbohydrates (CHOs) and insulin decrease MPB. Net protein balance (NB; indicator of overall anabolism) is greatest when MPS is maximized and MPB is minimized. To determine whether adding CHO or a gluconeogenic amino acid to EAAs would improve NB compared with EAA alone, young men and women (n = 21) ingested 10 g EAA alone, with 30 g sucrose (EAA+CHO), or with 30 g alanine (EAA+ALA). The fractional synthetic rate and phenylalanine kinetics (MPS, MPB, NB) were assessed by stable isotopic methods on muscle biopsies at baseline and 60 and 180 min following nutrient ingestion. Insulin increased 30 min postingestion in all groups and remained elevated in the EAA+CHO and EAA+ALA groups for 60 and 120 min, respectively. The fractional synthetic rate increased from baseline at 60 min in all groups (P < 0.05; EAA = 0.053 ± 0.018 to 0.090 ± 0.039% · h(-1); EAA+ALA = 0.051 ± 0.005 to 0.087 ± 0.015% · h(-1); EAA+CHO = 0.049 ± 0.006 to 0.115 ± 0.024% · h(-1)). MPS and NB peaked at 30 min in the EAA and EAA+CHO groups but at 60 min in the EAA+ALA group and NB was elevated above baseline longer in the EAA+ALA group than in the EAA group (P < 0.05). Although responses were more robust in the EAA+CHO group and prolonged in the EAA+ALA group, AUCs were similar among all groups for fractional synthetic rate, MPS, MPB, and NB. Because the overall muscle protein anabolic response was not improved in either the EAA+ALA or EAA+CHO group compared with EAA, we conclude that protein nutritional interventions to enhance muscle protein anabolism do not require such additional energy.

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UNLABELLED: Administration of the mTORC1 inhibitor, rapamycin, to humans blocks the increase in skeletal muscle protein synthesis in response to resistance exercise or amino acid ingestion. OBJECTIVE: To determine whether rapamycin administration influences basal post-absorptive protein synthesis or breakdown in human skeletal muscle. MATERIALS/METHODS: Six young (26±2 years) subjects were studied during two separate trials, in which each trial was divided into two consecutive 2 h basal periods. The trials were identical except during one trial a single oral dose (16 mg) of rapamycin was administered immediately prior to the second basal period. Muscle biopsies were obtained from the vastus lateralis at 0, 2, and 4 h to examine protein synthesis, mTORC1 signaling, and markers of autophagy (LC3B-I and LC3B-II protein) associated with each 2 h basal period. RESULTS: During the Control trial, muscle protein synthesis, whole body protein breakdown (phenylalanine Ra), mTORC1 signaling, and markers of autophagy were similar between both basal periods (p>0.05). During the Rapamycin trial, these variables were similar to the Control trial (p>0.05) and were unaltered by rapamycin administration (p>0.05). Thus, post-absorptive muscle protein metabolism and mTORC1 signaling were not affected by rapamycin administration. CONCLUSIONS: Short-term rapamycin administration may only impair protein synthesis in human skeletal muscle when combined with a stimulus such as resistance exercise or increased amino acid availability.

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BACKGROUND: The loss of skeletal muscle mass and strength during aging, sarcopenia, increases the risk for falls and dependency. Resistance exercise (RE) training is effective at improving muscle mass and strength in older adults; however, aging is associated with reduced training-induced hypertrophy. Recent research has illustrated an impaired muscle protein synthetic response following an acute bout of RE in older adults but much less is known regarding the effect of acute RE on muscle protein breakdown (MPB). We hypothesize that the ubiquitin proteasome system and the autophagosomal-lysosomal system may regulate the overall rate of MPB during postexercise recovery. METHODS: Muscle biopsies of the vastus lateralis were sampled from 16 older (age = 70±2 years) and 16 younger (age = 27±2 years) participants at baseline and at 3, 6, and 24 hours following an acute bout of RE. In conjunction with stable isotopic techniques to measure MPB, we utilized immunoblotting and RT-PCR to examine protein and mRNA expression for key signaling molecules in both the ubiquitin proteasome system and the autophagosomal-lysosomal system. RESULTS: MuRF1 mRNA expression increased, whereas GABARAP mRNA decreased after RE in both younger and older adults (p < .05). The LC3B-II/LC3B-I protein ratio decreased in both groups after RE (p < .05), but MPB was not different 24 hour post-RE in either group (p > .05). CONCLUSIONS: Aging does not influence skeletal MPB, autophagy, or the ubiquitin proteasome system following an acute bout of RE. Therefore, targeting the muscle protein synthesis response to exercise may hold more promise in the prevention of sarcopenia.

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INTRODUCTION: Resistance exercise (RE) stimulates a muscle protein anabolic response partially through enhanced satellite cell (SC) activity, however, age- and gender-related changes in SC content over a 24-h time course are not known. METHODS: Ten young (27 ± 2 years) men and women and 11 older (70 ± 2 years) men and women performed an acute bout of RE. Myofiber and SC characteristics were determined from muscle biopsies of the vastus lateralis using immunohistochemistry. Immunoblotting was used to determine phosphorylation of cyclin-dependent kinase-2 and protein expression of p27(Kip1) and cyclin D1. RESULTS: Pax7+ SC were significantly increased in young men 24 h following RE. Percent SC were significantly increased in older women at 6 and 24 h following RE. Aging decreased myonuclear domain and increased protein expression of p27(Kip1) . CONCLUSIONS: An acute bout of RE increases SC content in young men at 24 h and older women at 6 and 24 h.

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