Tim Snijders

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.

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.

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.

Characteristics of muscle fiber type are predictive of skeletal muscle mass and strength in elderly men.

OBJECTIVES: To investigate the relationship between skeletal muscle fiber type‐specific characteristics, circulating hormone concentrations, and skeletal muscle mass and strength in older men.

Skeletal muscle capillary density and microvascular function are compromised with aging and type 2 diabetes

Adequate muscle perfusion is required for the maintenance of skeletal muscle mass. Impairments in microvascular structure and/or function with aging and type 2 diabetes have been associated with the progressive loss of skeletal muscle mass. Our objective was to compare muscle fiber type specific capillary density and endothelial function between healthy young men, healthy older men, and age-matched type 2 diabetes patients. Fifteen healthy young men (24 ± 1 yr), 15 healthy older men (70 ± 2 yr), and 15 age-matched type 2 diabetes patients (70 ± 1 yr) were selected to participate in the present study. Whole body insulin sensitivity, muscle fiber type specific capillary density, sublingual microvascular density, and dimension of the erythrocyte-perfused boundary region were assessed to evaluate the impact of aging and/or type 2 diabetes on microvascular structure and function. Whole body insulin sensitivity was significantly lower at a more advanced age, with lowest values reported in the type 2 diabetic patients. In line, skeletal muscle capillary contacts were much lower in the older and older type 2 diabetic patients when compared with the young. Sidestream darkfield imaging showed a significantly greater thickness of the erythrocyte perfused boundary region in the type 2 diabetic patients compared with the young. Skeletal muscle capillary density is reduced with aging and type 2 diabetes and accompanied by impairments in endothelial glycocalyx function, which is indicative of compromised vascular function.

Satellite cells in human skeletal muscle plasticity

Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodeling. Our knowledge of the role of satellite cells in muscle fiber adaptation has traditionally relied on in vitro cell and in vivo animal models. Over the past decade, a genuine effort has been made to translate these results to humans under physiological conditions. Findings from in vivo human studies suggest that satellite cells play a key role in skeletal muscle fiber repair/remodeling in response to exercise. Mounting evidence indicates that aging has a profound impact on the regulation of satellite cells in human skeletal muscle. Yet, the precise role of satellite cells in the development of muscle fiber atrophy with age remains unresolved. This review seeks to integrate recent results from in vivo human studies on satellite cell function in muscle fiber repair/remodeling in the wider context of satellite cell biology whose literature is largely based on animal and cell models.

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.

Resistance training‐induced changes in integrated myofibrillar protein synthesis are related to hypertrophy only after attenuation of muscle damage

Skeletal muscle hypertrophy is one of the main outcomes from resistance training (RT), but how it is modulated throughout training is still unknown. We show that changes in myofibrillar protein synthesis (MyoPS) after an initial resistance exercise (RE) bout in the first week of RT (T1) were greater than those seen post‐RE at the third (T2) and tenth week (T3) of RT, with values being similar at T2 and T3. Muscle damage (Z‐band streaming) was the highest during post‐RE recovery at T1, lower at T2 and minimal at T3. When muscle damage was the highest, so was the integrated MyoPS (at T1), but neither were related to hypertrophy; however, integrated MyoPS at T2 and T3 were correlated with hypertrophy. We conclude that muscle hypertrophy is the result of accumulated intermittent increases in MyoPS mainly after a progressive attenuation of muscle damage.

Disuse Impairs the Muscle Protein Synthetic Response to Protein Ingestion in Healthy Men

BACKGROUND Disuse leads to rapid skeletal muscle atrophy, which brings about numerous negative health consequences. Muscle disuse atrophy is, at least in part, attributed to a decline in basal (postabsorptive) muscle protein synthesis rates. However, it remains to be determined whether muscle disuse also impairs the muscle protein synthetic response to dietary protein ingestion. PURPOSE We assessed muscle protein synthesis rates after protein ingestion before and after a period of disuse in humans. METHODS Twelve healthy young (24 ± 1 year) men underwent a 14-day period of one-legged knee immobilization by way of a full leg cast. Before and after the immobilization period, quadriceps cross-sectional area, muscle strength, skeletal muscle protein synthesis rates, and associated im (intramuscular) molecular signaling were assessed. Continuous infusions of l-[ring-²H₅]phenylalanine were applied to assess mixed-muscle protein fractional synthetic rates after the ingestion of 20 g dietary protein. RESULTS Immobilization led to an 8.4% ± 2.8% (P < .001) and 22.9% ± 2.6% (P < .001) decrease in quadriceps muscle cross-sectional area and strength, respectively. Immobilization resulted in a 31% ± 12% reduction in postprandial muscle protein synthesis rates (from 0.046% ± 0.004% to 0.032% ± 0.006% per hour; P < .05). These findings were observed without any discernible changes in the skeletal muscle phosphorylation status of mammalian target of rapamycin or p70 ribosomal protein S6 kinase. CONCLUSIONS A short period of muscle disuse impairs the muscle protein synthetic response to dietary protein intake in vivo in healthy young men. Thus, anabolic resistance to protein ingestion contributes significantly to the loss of muscle mass that is observed during disuse.

Eccentric exercise increases satellite cell content in type II muscle fibers.

INTRODUCTION Satellite cells (SCs) are of key importance in skeletal muscle tissue growth, repair, and regeneration. A single bout of high-force eccentric exercise has been demonstrated to increase mixed muscle SC content after 1-7 d of postexercise recovery. However, little is known about fiber type-specific changes in SC content and their activation status within 24 h of postexercise recovery. METHODS Nine recreationally active young men (23 ± 1 yr) performed 300 eccentric actions of the knee extensors on an isokinetic dynamometer. Skeletal muscle biopsies from the vastus lateralis were collected preexercise and 24 h postexercise. Muscle fiber type-specific SC content and the number of activated SCs were determined by immunohistochemical analyses. RESULTS There was no difference between Type I and Type II muscle fiber SC content before exercise. SC content significantly increased 24 h postexercise in Type II muscle fibers (from 0.085 ± 0.012 to 0.133 ± 0.016 SCs per fiber, respectively; P < 0.05), whereas there was no change in Type I fibers. In accordance, activation status increased from preexercise to 24 h postexercise as demonstrated by the increase in the number of DLK1+ SCs in Type II muscle fibers (from 0.027 ± 0.008 to 0.070 ± 0.017 SCs per muscle fiber P < 0.05). Although no significant changes were observed in the number of Ki-67+ SCs, we did observe an increase in the number of proliferating cell nuclear antigen-positive SCs after 24 h of postexercise recovery. CONCLUSION A single bout of high-force eccentric exercise increases muscle fiber SC content and activation status in Type II but not Type I muscle fibers.