Lex B. Verdijk

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.

Skeletal Muscle Hypertrophy Following Resistance Training Is Accompanied by a Fiber Type–Specific Increase in Satellite Cell Content in Elderly Men

We determined muscle fiber type-specific hypertrophy and changes in satellite cell (SC) content following a 12-week resistance training program in 13 healthy, elderly men (72 +/- 2 years). Leg strength and body composition (dual-energy X-ray absorptiometry and computed tomography) were assessed, and muscle biopsy samples were collected. Leg strength increased 25%-30% after training (p < .001). Leg lean mass and quadriceps cross-sectional area increased 6%-9% (p < .001). At baseline, mean fiber area and SC content were smaller in the Type II versus Type I muscle fibers (p < .01). Following training, Type II muscle fiber area increased from 5,438 +/- 319 to 6,982 +/- 503 microm(2) (p < .01). Type II muscle fiber SC content increased from 0.048 +/- 0.003 to 0.084 +/- 0.008 SCs per fiber (p < .001). No changes were observed in the Type I muscle fibers. In older adults, skeletal muscle tissue is still capable of inducing SC proliferation and differentiation, resulting in Type II muscle fiber hypertrophy.

Protein supplementation before and after exercise does not further augment skeletal muscle hypertrophy after resistance training in elderly men

BACKGROUND Considerable discrepancy exists in the literature on the proposed benefits of protein supplementation on the adaptive response of skeletal muscle to resistance-type exercise training in the elderly. OBJECTIVE The objective was to assess the benefits of timed protein supplementation on the increase in muscle mass and strength during prolonged resistance-type exercise training in healthy elderly men who habitually consume adequate amounts of dietary protein. DESIGN Healthy elderly men (n = 26) aged 72 +/- 2 y were randomly assigned to a progressive, 12-wk resistance-type exercise training program with (protein group) or without (placebo group) protein provided before and immediately after each exercise session (3 sessions/wk, 20 g protein/session). One-repetition maximum (1RM) tests were performed regularly to ensure a progressive workload during the intervention. Muscle hypertrophy was assessed at the whole-body (dual-energy X-ray absorptiometry), limb (computed tomography), and muscle fiber (biopsy) level. RESULTS The 1RM strength increased approximately 25-35% in both groups (P < 0.001). Dual-energy X-ray absorptiometry and computed tomography scans showed similar increases in leg muscle mass (6 +/- 1% in both groups; P < 0.001) and in the quadriceps (9 +/- 1% in both groups), from 75.9 +/- 3.7 and 73.8 +/- 3.2 to 82.4 +/- 3.9 and 80.0 +/- 3.0 cm2 in the placebo and protein groups, respectively (P < 0.001). Muscle fiber hypertrophy was greater in type II (placebo: 28 +/- 6%; protein: 29 +/- 4%) than in type I (placebo: 5 +/- 4%; protein: 13 +/- 6%) fibers, but the difference between groups was not significant. CONCLUSION Timed protein supplementation immediately before and after exercise does not further augment the increase in skeletal muscle mass and strength after prolonged resistance-type exercise training in healthy elderly men who habitually consume adequate amounts of dietary protein. This trial was registered at clinicaltrials.gov as NCT00744094.

The decline in skeletal muscle mass with aging is mainly attributed to a reduction in type II muscle fiber size

BACKGROUND The loss of skeletal muscle mass with aging has been attributed to a decline in muscle fiber number and muscle fiber size. OBJECTIVE To define to what extent differences in leg muscle cross-sectional area (CSA) between young and elderly men are attributed to differences in muscle fiber size. METHODS Quadriceps muscle CSA and type I and type II muscle fiber size were measured in healthy young (n=25; 23 ± 1 y) and older (n=26; 71 ± 1 y) men. Subsequently, the older subjects performed 6 months of resistance type exercise training, after which measurements were repeated. Differences in quadriceps muscle CSA were compared with differences in type I and type II muscle fiber size. RESULTS Quadriceps CSA was substantially smaller in older versus young men (68 ± 2 vs 80 ± 2 cm(2), respectively; P<0.001). Type II muscle fiber size was substantially smaller in the elderly vs the young (29%; P<0.001), with a tendency of smaller type I muscle fibers (P=0.052). Differences in type II muscle fiber size fully explained differences in quadriceps CSA between groups. Prolonged resistance type exercise training in the elderly increased type II muscle fiber size by 24 ± 8% (P<0.01), explaining 100 ± 3% of the increase in quadriceps muscle CSA (from 68 ± 2 to 74 ± 2 cm(2)). CONCLUSION Reduced muscle mass with aging is mainly attributed to smaller type II muscle fiber size and, as such, is unlikely accompanied by substantial muscle fiber loss. In line, the increase in muscle mass following prolonged resistance type exercise training can be attributed entirely to specific type II muscle fiber hypertrophy.

Long-term leucine supplementation does not increase muscle mass or strength in healthy elderly men

BACKGROUND It has been reported that the blunted muscle protein synthetic response to food intake in the elderly can be normalized by increasing the leucine content of a meal. OBJECTIVE The objective was to assess the effect of 3 mo of leucine supplementation on muscle mass and strength in healthy elderly men. DESIGN Thirty healthy elderly men with a mean (+/-SEM) age of 71 +/- 4 y and body mass index (BMI; in kg/m(2)) of 26.1 +/- 0.5 were randomly assigned to either a placebo-supplemented (n = 15) or leucine-supplemented (n = 15) group. Leucine or placebo (2.5 g) was administered with each main meal during a 3-mo intervention period. Whole-body insulin sensitivity, muscle strength (one-repetition maximum), muscle mass (measured by computed tomography and dual-energy X-ray absorptiometry), myosin heavy chain isoform distribution, and plasma amino acid and lipid profiles were assessed before, during, and/or after the intervention period. RESULTS No changes in skeletal muscle mass or strength were observed over time in either the leucine- or placebo-supplemented group. No improvements in indexes of whole-body insulin sensitivity (oral glucose insulin sensitivity index and the homeostasis model assessment of insulin resistance), blood glycated hemoglobin content, or the plasma lipid profile were observed. CONCLUSION Long-term leucine supplementation (7.5 g/d) does not augment skeletal muscle mass or strength and does not improve glycemic control or the blood lipid profile in healthy elderly men. This trial was registered at clinicaltrials.gov as NCT00807508.

The impact of sarcopenia and exercise training on skeletal muscle satellite cells.

It has been well-established that the age-related loss of muscle mass and strength, or sarcopenia, impairs skeletal muscle function and reduces functional performance at a more advanced age. Skeletal muscle satellite cells (SC), as precursors of new myonuclei, have been suggested to be involved in the development of sarcopenia. In accordance with the type II muscle fiber atrophy observed in the elderly, recent studies report a concomitant fiber type specific reduction in SC content. Resistance type exercise interventions have proven effective to augment skeletal muscle mass and improve muscle function in the elderly. In accordance, recent work shows that resistance type exercise training can augment type II muscle fiber size and reverse the age-related decline in SC content. The latter is supported by an increase in SC activation and proliferation factors that generally appear following exercise training. Present findings strongly suggest that the skeletal muscle SC control myogenesis and have an important, but yet unresolved, function in the loss of muscle mass with aging. This review discusses the contribution of skeletal muscle SC in the age-related loss of muscle mass and the efficacy of exercise training as a means to attenuate and/or reverse this process.

Patients with type 2 diabetes show a greater decline in muscle mass, muscle strength, and functional capacity with aging.

BACKGROUND The loss of muscle mass with aging reduces muscle strength, impairs functional capacity, and increases the risk of developing chronic metabolic disease. It has been suggested that the development of type 2 diabetes results in a more rapid decline in muscle mass, strength, and functional capacity. OBJECTIVE To investigate the impact of type 2 diabetes on muscle mass, strength, and functional capacity in an older population. METHODS Muscle mass (DXA and muscle biopsies), strength (1-repetition maximum), functional capacity (sit-to-stand test and handgrip strength), and reaction time performance (computer task) were compared between 60 older men with type 2 diabetes (71 ± 1 years) and 32 age-matched normoglycemic controls (70 ± 1 years). Data were analyzed using ANCOVA to adjust for several potential confounders. RESULTS Leg lean mass and appendicular skeletal muscle mass were significantly lower in older men with type 2 diabetes (19.1 ± 0.3 and 25.9 ± 0.4 kg, respectively) compared with normoglycemic controls (19.7 ± 0.3 and 26.7 ± 0.5 kg, respectively). Additionally, leg extension strength was significantly lower in the group with type 2 diabetes (84 ± 2 vs 91 ± 2 kg, respectively). In agreement, functional performance was impaired in the men with type 2 diabetes, with longer sit-to-stand time (9.1 ± 0.4 vs 7.8 ± 0.3 seconds) and lower handgrip strength (39.5 ± 5.8 vs 44.6 ± 6.1 kg) when compared with normoglycemic controls. However, muscle fiber size and reaction time performance did not differ between groups. CONCLUSION Older patients with type 2 diabetes show an accelerated decline in leg lean mass, muscle strength, and functional capacity when compared with normoglycemic controls. Exercise intervention programs should be individualized to specifically target muscle mass, strength, and functional capacity in the older population with type 2 diabetes.

Elderly Men and Women Benefit Equally From Prolonged Resistance-Type Exercise Training

This study compares the effects of 6 months resistance-type exercise training (three times per week) between healthy elderly women (n = 24; 71±1 years) and men (n = 29; 70±1 years). Muscle mass (dual-energy x-ray absorptiometry-computed tomography), strength (one-repetition maximum), functional capacity (sit-to-stand time), muscle fiber characteristics (muscle biopsies), and metabolic profile (blood samples) were assessed. Leg lean mass (3% ± 1%) and quadriceps cross-sectional area (9% ± 1%) increased similarly in both groups. One-repetition maximum leg extension strength increased by 42% ± 3% (women) and 43% ± 3% (men). Following training, type II muscle fiber size had increased, and a type II muscle fiber specific increase in myonuclear and satellite cell content was observed with no differences between genders. Sit-to-stand time decreased similarly in both groups. Glycemic control and blood lipid profiles improved to a similar extent in both women and men. A generic resistance-type exercise training program can be applied for both women and men to effectively counteract the loss of muscle mass and strength with aging.

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.

Leucine co-ingestion improves post-prandial muscle protein accretion in elderly men

BACKGROUND & AIMS It has been speculated that the amount of leucine in a meal largely determines the post-prandial muscle protein synthetic response to food intake. The present study investigates the impact of leucine co-ingestion on subsequent post-prandial muscle protein accretion following the ingestion of a single bolus of dietary protein in elderly males. METHODS Twenty-four elderly men (74.3±1.0 y) were randomly assigned to ingest 20 g intrinsically L-[1-(13)C]phenylalanine-labeled casein protein with (PRO+LEU) or without (PRO) 2.5 g crystalline leucine. Ingestion of specifically produced intrinsically labeled protein allowed us to create a plasma phenylalanine enrichment pattern similar to the absorption pattern of phenylalanine from the ingested protein and assess the subsequent post-prandial incorporation of L-[1-(13)C] phenylalanine into muscle protein. RESULTS Plasma amino acid concentrations increased rapidly following protein ingestion in both groups, with higher leucine concentrations observed in the PRO+LEU compared with the PRO group (P<0.01). Plasma L-[1-(13)C]phenylalanine enrichments increased rapidly and to a similar extent in both groups following protein ingestion. Muscle protein-bound L-[1-(13)C]phenylalanine enrichments were significantly greater after PRO+LEU when compared with PRO at 2 h (72%; 0.0078±0.0010 vs. 0.0046±0.00100 MPE, respectively; P<0.05) and 6 h (25%; 0.0232±0.0015 vs. 0.0185±0.0010 MPE, respectively; P<0.05) following protein ingestion. The latter translated into a greater muscle protein synthetic rate following PRO+LEU compared with PRO over the entire 6 h post-prandial period (22%; 0.049±0.003 vs. 0.040±0.003% h(-1), respectively; P<0.05). CONCLUSION Leucine co-ingestion with a bolus of pure dietary protein further stimulates post-prandial muscle protein synthesis rates in elderly men.