Marlou L. Dirks

Protein supplementation increases muscle mass gain during prolonged resistance-type exercise training in frail elderly people: a randomized, double-blind, placebo-controlled trial.

OBJECTIVES Protein supplementation has been proposed as an effective dietary strategy to augment the skeletal muscle adaptive response to prolonged resistance-type exercise training in elderly people. Our objective was to assess the impact of protein supplementation on muscle mass, strength, and physical performance during prolonged resistance-type exercise training in frail elderly men and women. DESIGN/SETTING/PARTICIPANTS A randomized, double-blind, placebo-controlled trial with 2 arms in parallel among 62 frail elderly subjects (78 ± 1 year). These elderly subjects participated in a progressive resistance-type exercise training program (2 sessions per week for 24 weeks) during which they were supplemented twice daily with either protein (2 * 15 g) or a placebo. MEASUREMENTS Lean body mass (DXA), strength (1-RM), and physical performance (SPPB) were assessed at baseline, and after 12 and 24 weeks of intervention. RESULTS Lean body mass increased from 47.2 kg (95% CI, 43.5-50.9) to 48.5 kg (95% CI, 44.8-52.1) in the protein group and did not change in the placebo group (from 45.7 kg, 95% CI, 42.1-49.2 to 45.4 kg, 95% CI, 41.8-48.9) following the intervention (P value for treatment × time interaction = .006). Strength and physical performance improved significantly in both groups (P = .000) with no interaction effect of dietary protein supplementation. CONCLUSIONS Prolonged resistance-type exercise training represents an effective strategy to improve strength and physical performance in frail elderly people. Dietary protein supplementation is required to allow muscle mass gain during exercise training in frail elderly people. TRIAL REGISTRATION clinicaltrials.gov identifier: NCT01110369.

Protein supplementation improves physical performance in frail elderly people: a randomized, double-blind, placebo-controlled trial.

OBJECTIVES Protein supplementation has been proposed as an effective dietary strategy to increase skeletal muscle mass and improve physical performance in frail elderly people. Our objective was to assess the impact of 24 weeks of dietary protein supplementation on muscle mass, strength, and physical performance in frail elderly people. DESIGN/SETTING/PARTICIPANTS A total of 65 frail elderly subjects were included and randomly allocated to either daily protein or placebo supplementation (15 g protein at breakfast and lunch). MEASUREMENTS Skeletal muscle mass (DXA), muscle fiber size (muscle biopsy), strength (1-RM), and physical performance (SPPB) were assessed at baseline, and after 12 and 24 weeks of dietary intervention. RESULTS Skeletal muscle mass did not change in the protein- (from 45.8 ± 1.7 to 45.8 ± 1.7 kg) or placebo-supplemented group (from 46.7 ± 1.7 to 46.6 ± 1.7 kg) following 24 weeks of intervention (P > .05). In accordance, type I and II muscle fiber size did not change over time (P > .05). Muscle strength increased significantly in both groups (P < .01), with leg extension strength tending to increase to a greater extent in the protein (57 ± 5 to 68 ± 5 kg) compared with the placebo group (57 ± 5 to 63 ± 5 kg) (treatment × time interaction effect: P = .059). Physical performance improved significantly from 8.9 ± 0.6 to 10.0 ± 0.6 points in the protein group and did not change in the placebo group (from 7.8 ± 0.6 to 7.9 ± 0.6 points) (treatment × time interaction effect: P = .02). CONCLUSION Dietary protein supplementation improves physical performance, but does not increase skeletal muscle mass in frail elderly people.

Skeletal muscle atrophy during short-term disuse: Implications for age-related sarcopenia

Situations such as the recovery from injury and illness can lead to enforced periods of muscle disuse or unloading. Such circumstances lead to rapid skeletal muscle atrophy, loss of functional strength and a multitude of related negative health consequences. The elderly population is particularly vulnerable to the acute challenges of muscle disuse atrophy. Any loss of skeletal muscle mass must be underpinned by a chronic imbalance between muscle protein synthesis and breakdown rates. It is recognized that muscle atrophy during prolonged (>10 days) disuse is brought about primarily by declines in post-absorptive and post-prandial muscle protein synthesis rates, without a clear contribution from changes in muscle protein breakdown. Few data are available on the impact of short-term disuse (<10 days) on muscle protein turnover in humans. However, indirect evidence indicates that considerable muscle atrophy occurs during this early phase, and is likely attributed to a rapid increase in muscle protein breakdown accompanied by the characteristic decline in muscle protein synthesis. Short-term disuse atrophy is of particular relevance in the development of sarcopenia, as it has been suggested that successive short periods of muscle disuse, due to sickness or injury, accumulate throughout an individuals lifespan and contributes considerably to the net muscle loss observed with aging. Research is warranted to elucidate the physiological and molecular basis for rapid muscle loss during short periods of disuse. Such mechanistic insight will allow the characterization of nutritional, exercise and/or pharmacological interventions to prevent or attenuate muscle loss during periods of disuse and therefore aid in the treatment of age-related sarcopenia.

There Are No Nonresponders to Resistance-Type Exercise Training in Older Men and Women.

OBJECTIVE To assess the proposed prevalence of unresponsiveness of older men and women to augment lean body mass, muscle fiber size, muscle strength, and/or physical function following prolonged resistance-type exercise training. DESIGN/SETTING/PARTICIPANTS A retrospective analysis of the adaptive response to 12 (n = 110) and 24 (n = 85) weeks of supervised resistance-type exercise training in older (>65 years) men and women. MEASUREMENTS Lean body mass (DXA), type I and type II muscle fiber size (biopsy), leg strength (1-RM on leg press and leg extension), and physical function (chair-rise time) were assessed at baseline, and after 12 and 24 weeks of resistance-type exercise training. RESULTS Lean body mass increased by 0.9 ± 0.1 kg (range: -3.3 to +5.4 kg; P < .001) from 0 to 12 weeks of training. From 0 to 24 weeks, lean body mass increased by 1.1 ± 0.2 kg (range: -1.8 to +9.2 kg; P < .001). Type I and II muscle fiber size increased by 324 ± 137 μm(2) (range: -4458 to +3386 μm(2); P = .021), and 701 ± 137 μm(2) (range: -4041 to +3904 μm(2); P < .001) from 0 to 12 weeks. From 0 to 24 weeks, type I and II muscle fiber size increased by 360 ± 157 μm(2) (range: -3531 to +3426 μm(2); P = .026) and 779 ± 161 μm(2) (range: -2728 to +3815 μm(2); P < .001). The 1-RM strength on the leg press and leg extension increased by 33 ± 2 kg (range: -36 to +87 kg; P < .001) and 20 ± 1 kg (range: -22 to +56 kg; P < .001) from 0 to 12 weeks. From 0 to 24 weeks, leg press and leg extension 1-RM increased by 50 ± 3 kg (range: -28 to +145 kg; P < .001) and 29 ± 2 kg (range: -19 to +60 kg; P < .001). Chair-rise time decreased by 1.3 ± 0.4 seconds (range: +21.6 to -12.5 seconds; P = .003) from 0 to 12 weeks. From 0 to 24 weeks, chair-rise time decreased by 2.3 ± 0.4 seconds (range: +10.5 to -23.0 seconds; P < .001). Nonresponsiveness was not apparent in any subject, as a positive adaptive response on at least one training outcome was apparent in every subject. CONCLUSIONS A large heterogeneity was apparent in the adaptive response to prolonged resistance-type exercise training when changes in lean body mass, muscle fiber size, strength, and physical function were assessed in older men and women. The level of responsiveness was strongly affected by the duration of the exercise intervention, with more positive responses following more prolonged exercise training. We conclude that there are no nonresponders to the benefits of resistance-type exercise training on lean body mass, fiber size, strength, or function in the older population. Consequently, resistance-type exercise should be promoted without restriction to support healthy aging in the older population.

Substantial skeletal muscle loss occurs during only 5 days of disuse.

The impact of disuse on the loss of skeletal muscle mass and strength has been well documented. Given that most studies have investigated muscle atrophy after more than 2 weeks of disuse, few data are available on the impact of shorter periods of disuse. We assessed the impact of 5 and 14 days of disuse on skeletal muscle mass, strength and associated intramuscular molecular signalling responses.

Neuromuscular electrical stimulation prevents muscle disuse atrophy during leg immobilization in humans

Short periods of muscle disuse, due to illness or injury, result in substantial skeletal muscle atrophy. Recently, we have shown that a single session of neuromuscular electrical stimulation (NMES) increases muscle protein synthesis rates. The aim was to investigate the capacity for daily NMES to attenuate muscle atrophy during short‐term muscle disuse.

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.

Reduced satellite cell numbers with spinal cord injury and aging in humans.

INTRODUCTION Both sarcopenia and spinal cord injury (SCI) are characterized by the loss of skeletal muscle mass and function. Despite obvious similarities in atrophy between both models, differences in muscle fiber size and satellite cell content may exist on a muscle fiber type-specific level. METHODS In the present study, we compared skeletal muscle fiber characteristics between wheelchair-dependent young males with SCI (n = 8, 32 ± 4 yr), healthy elderly males (n = 8, 75 ± 2 yr), and young controls (n = 8, 31 ± 3 yr). Muscle biopsies were collected to determine skeletal muscle fiber type composition, fiber size, and satellite cell content. RESULTS Severe atrophy and a shift toward approximately 90% Type II muscle fibers were observed in muscle obtained from males with SCI. Muscle fiber size was substantially smaller in both the SCI (Types I and II fibers) and elderly subjects (Type II fibers) when compared with the controls. Satellite cell content was substantially lower in the wheelchair-dependent SCI subjects in both the Types I and II muscle fibers (0.049 ± 0.019 and 0.050 ± 0.005 satellite cells per fiber, respectively) when compared with the young controls (0.104 ± 0.011 and 0.117 ± 0.009 satellite cells per fiber, respectively). In the elderly, the number of satellite cells was lower in the Type II muscle fibers only (0.042 ± 0.005 vs 0.117 ± 0.009 satellite cells per fiber in the elderly vs young controls, respectively). CONCLUSION This is the first study to show that muscle fiber atrophy as observed with SCI (Types I and II fibers) and aging (Type II fibers) is accompanied by a muscle fiber type-specific reduction in satellite cell content in humans.

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

Physical activity is required to attenuate the loss of skeletal muscle mass with aging. Short periods of muscle disuse, due to sickness or hospitalization, reduce muscle protein synthesis rates, resulting in rapid muscle loss. The present study investigates the capacity of neuromuscular electrical stimulation (NMES) to increase in vivo skeletal muscle protein synthesis rates in older type 2 diabetes patients. Six elderly type 2 diabetic men (70 ± 2 yr) were subjected to 60 min of one-legged NMES. Continuous infusions with L-[ring-¹³C₆]phenylalanine were applied, with blood and muscle samples being collected regularly to assess muscle protein synthesis rates in both the stimulated (STIM) and nonstimulated control (CON) leg during 4 h of recovery after NMES. Furthermore, mRNA expression of key genes implicated in the regulation of muscle mass were measured over time in the STIM and CON leg. Muscle protein synthesis rates were greater in the STIM compared with the CON leg during recovery from NMES (0.057 ± 0.008 vs. 0.045 ± 0.008%/h, respectively, P < 0.01). Skeletal muscle myostatin mRNA expression in the STIM leg tended to increase immediately following NMES compared with the CON leg (1.63- vs. 1.00-fold, respectively, P = 0.07) but strongly declined after 2 and 4 h of recovery in the STIM leg only. In conclusion, this is the first study to show that NMES directly stimulates skeletal muscle protein synthesis rates in vivo in humans. NMES likely represents an effective interventional strategy to attenuate muscle loss in elderly individuals during bed rest and/or in other disuse states.

Neuromuscular electrical stimulation prevents muscle wasting in critically ill comatose patients

Fully sedated patients, being treated in the intensive care unit (ICU), experience substantial skeletal muscle loss. Consequently, survival rate is reduced and full recovery after awakening is compromised. Neuromuscular electrical stimulation (NMES) represents an effective method to stimulate muscle protein synthesis and alleviate muscle disuse atrophy in healthy subjects. We investigated the efficacy of twice-daily NMES to alleviate muscle loss in six fully sedated ICU patients admitted for acute critical illness [n=3 males, n=3 females; age 63 ± 6 y; APACHE II (Acute Physiology and Chronic Health Evaluation II) disease-severity-score: 29 ± 2]. One leg was subjected to twice-daily NMES of the quadriceps muscle for a period of 7 ± 1 day whereas the other leg acted as a non-stimulated control (CON). Directly before the first and on the morning after the final NMES session, quadriceps muscle biopsies were collected from both legs to assess muscle fibre-type-specific cross-sectional area (CSA). Furthermore, phosphorylation status of the key proteins involved in the regulation of muscle protein synthesis was assessed and mRNA expression of selected genes was measured. In the CON leg, type 1 and type 2 muscle-fibre-CSA decreased by 16 ± 9% and 24 ± 7% respectively (P<0.05). No muscle atrophy was observed in the stimulated leg. NMES increased mammalian target of rapamycin (mTOR) phosphorylation by 19 ± 5% when compared with baseline (P<0.05), with no changes in the CON leg. Furthermore, mRNA expression of key genes involved in muscle protein breakdown either declined [forkhead box protein O1 (FOXO1); P<0.05] or remained unchanged [muscle atrophy F-box (MAFBx) and muscle RING-finger protein-1 (MuRF1)], with no differences between the legs. In conclusion, NMES represents an effective and feasible interventional strategy to prevent skeletal muscle atrophy in critically ill comatose patients.