Physiologic and molecular bases of muscle hypertrophy and atrophy: impact of resistance exercise on human skeletal muscle (protein and exercise dose effects)This paper is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.

Normally, skeletal muscle mass is unchanged, beyond periods of growth, but it begins to decline in the fourth or fifth decade of life. The mass of skeletal muscle is maintained by ingestion of protein-containing meals. With feeding, muscle protein synthesis (MPS) is stimulated and a small suppression of muscle protein breakdown (MPB) occurs, such that protein balance becomes positive (MPS > MPB). As the postprandial period subsides and a transition toward fasting occurs, the balance of muscle protein turnover becomes negative again (MPB > MPS). Thus, during maintenance of skeletal muscle mass, the long-term net result is that MPS is balanced by MPB. Acutely, however, it is of interest to determine what regulates feeding-induced increases in MPS, since it appears that, in a number of scenarios (for example aging, disuse, and wasting diseases), a suppression of MPS in response to feeding is a common finding. In fact, recent findings point to the fact that loss of skeletal muscle mass with disuse and aging is due not chronic changes in MPS or MPB, but to a blunted feeding-induced rise in MPS. Resistance exercise is a potent stimulator of MPS and appears to synergistically enhance the gains stimulated by feeding. As such, resistance exercise is an important countermeasure to disuse atrophy and to age-related declines in skeletal muscle mass. What is less well understood is how the intensity and volume of the resistance exercise stimulus is sufficient to result in rises in MPS. Recent advances in this area are discussed here, with a focus on human in vivo data.

Download Full-text

Aging, exercise, and muscle protein metabolism

Journal of Applied Physiology ◽

10.1152/japplphysiol.91551.2008 ◽

2009 ◽

Vol 106 (6) ◽

pp. 2040-2048 ◽

Cited By ~ 197

Author(s):

René Koopman ◽

Luc J. C. van Loon

Keyword(s):

Physical Activity ◽

Skeletal Muscle ◽

Protein Synthesis ◽

Food Intake ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

The Elderly ◽

Age Related

Aging is accompanied by a progressive loss of skeletal muscle mass and strength, leading to the loss of functional capacity and an increased risk of developing chronic metabolic disease. The age-related loss of skeletal muscle mass is attributed to a disruption in the regulation of skeletal muscle protein turnover, resulting in an imbalance between muscle protein synthesis and degradation. As basal (fasting) muscle protein synthesis rates do not seem to differ substantially between the young and elderly, many research groups have started to focus on the muscle protein synthetic response to the main anabolic stimuli, i.e., food intake and physical activity. Recent studies suggest that the muscle protein synthetic response to food intake is blunted in the elderly. The latter is now believed to represent a key factor responsible for the age-related decline in skeletal muscle mass. Physical activity and/or exercise stimulate postexercise muscle protein accretion in both the young and elderly. However, the latter largely depends on the timed administration of amino acids and/or protein before, during, and/or after exercise. Prolonged resistance type exercise training represents an effective therapeutic strategy to augment skeletal muscle mass and improve functional performance in the elderly. The latter shows that the ability of the muscle protein synthetic machinery to respond to anabolic stimuli is preserved up to very old age. Research is warranted to elucidate the interaction between nutrition, exercise, and the skeletal muscle adaptive response. The latter is needed to define more effective strategies that will maximize the therapeutic benefits of lifestyle intervention in the elderly.

Download Full-text

Dietary protein and exercise training in ageing

Proceedings of The Nutrition Society ◽

10.1017/s0029665110003927 ◽

2010 ◽

Vol 70 (1) ◽

pp. 104-113 ◽

Cited By ~ 28

Author(s):

René Koopman

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Exercise Training ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Human Subjects ◽

The Elderly ◽

Age Related

Ageing is accompanied by a progressive loss of skeletal muscle mass and strength, leading to the loss of functional capacity and an increased risk for developing chronic metabolic diseases such as diabetes. The age-related loss of skeletal muscle mass results from a chronic disruption in the balance between muscle protein synthesis and degradation. As basal muscle protein synthesis rates are likely not different between healthy young and elderly human subjects, it was proposed that muscles from older adults lack the ability to regulate the protein synthetic response to anabolic stimuli, such as food intake and physical activity. Indeed, the dose–response relationship between myofibrillar protein synthesis and the availability of essential amino acids and/or resistance exercise intensity is shifted down and to the right in elderly human subjects. This so-called ‘anabolic resistance’ represents a key factor responsible for the age-related decline in skeletal muscle mass. Interestingly, long-term resistance exercise training is effective as a therapeutic intervention to augment skeletal muscle mass, and improves functional performance in the elderly. The consumption of different types of proteins, i.e. protein hydrolysates, can have different stimulatory effects on muscle protein synthesis in the elderly, which may be due to their higher rate of digestion and absorption. Current research aims to elucidate the interactions between nutrition, exercise and the skeletal muscle adaptive response that will define more effective strategies to maximise the therapeutic benefits of lifestyle interventions in the elderly.

Download Full-text

The mechanistic and ergogenic effects of phosphatidic acid in skeletal muscle

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2015-0350 ◽

2015 ◽

Vol 40 (12) ◽

pp. 1233-1241 ◽

Cited By ~ 15

Author(s):

Brandon James Shad ◽

Benoit Smeuninx ◽

Philip James Atherton ◽

Leigh Breen

Keyword(s):

Skeletal Muscle ◽

Phosphatidic Acid ◽

Resistance Exercise ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Food Sources ◽

Whole Body ◽

Skeletal Muscle Protein

Skeletal muscle mass plays a vital role in locomotion, whole-body metabolic health, and is a positive predictor of longevity. It is well established the mammalian target of rapamycin (mTOR) is a central regulator of skeletal muscle protein turnover. The pursuit to find novel nutrient compounds or functional food sources that possess the ability to activate mTOR and promote skeletal muscle protein accretion has been on going. Over the last decade, a key role has been proposed for the phospholipid phosphatidic acid (PA) in mTOR activation. Mechanical load-induced (i.e., resistance exercise) intramuscular PA can directly bind to and activate mTOR. In addition, PA provided exogenously in cell culture heightens mTOR activity, albeit indirectly. Thus, endogenously generated PA and exogenous provision of PA appear to act through distinct mechanisms that converge on mTOR and, potentially, may amplify muscle protein synthesis. In support of this notion, limited evidence from humans suggests that resistance exercise training combined with oral supplemental PA enhances strength gains and muscle hypertrophy. However, the precise mechanisms underpinning the augmented muscle remodelling response with supplemental PA remain elusive. In this review, we will critically examine available evidence from cell cultures and animal and human experimental models to provide an overview of the mechanisms through which endogenous and exogenous PA may act to promote muscle anabolism, and discuss the potential for PA as a therapeutic tool to maintain or restore skeletal muscle mass in the context of ageing and disease.

Download Full-text

Higher skeletal muscle protein synthesis and lower breakdown after chemotherapy in cachectic mice

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2001.281.1.r133 ◽

2001 ◽

Vol 281 (1) ◽

pp. R133-R139 ◽

Cited By ~ 20

Author(s):

S. E. Samuels ◽

A. L. Knowles ◽

T. Tilignac ◽

E. Debiton ◽

J. C. Madelmont ◽

...

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Cancer Cachexia ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Human Condition ◽

Skeletal Muscle Protein ◽

Tumor Bearing

The influence of cancer cachexia and chemotherapy and subsequent recovery of skeletal muscle protein mass and turnover was investigated in mice. Cancer cachexia was induced using colon 26 adenocarcinoma, which is characteristic of the human condition, and can be cured with 100% efficacy using an experimental nitrosourea, cystemustine (C6H12CIN3O4S). Reduced food intake was not a factor in these studies. Three days after cachexia began, healthy and tumor-bearing mice were given a single intraperitoneal injection of cystemustine (20 mg/kg). Skeletal muscle mass in tumor-bearing mice was 41% lower ( P < 0.05) than in healthy mice 2 wk after cachexia began. Skeletal muscle wasting was mediated initially by decreased protein synthesis (−38%; P < 0.05) and increased degradation (+131%; P < 0.05); later wasting resulted solely from decreased synthesis (∼−54 to −69%; P < 0.05). Acute cytotoxicity of chemotherapy did not appear to have an important effect on skeletal muscle protein metabolism in either healthy or tumor-bearing mice. Recovery began 2 days after treatment; skeletal muscle mass was only 11% lower than in healthy mice 11 days after chemotherapy. Recovery of skeletal muscle mass was affected initially by decreased protein degradation (−80%; P < 0.05) and later by increased protein synthesis (+46 to +73%; P < 0.05) in cured compared with healthy mice. This study showed that skeletal muscle wasted from cancer cachexia and after chemotherapeutic treatment is able to generate a strong anabolic response by making powerful changes to protein synthesis and degradation.

Download Full-text

The anabolic role of plant-based proteins in response to chronic resistance exercise

REVISTA CIÊNCIAS EM SAÚDE ◽

10.21876/rcshci.v11i3.1135 ◽

2021 ◽

Vol 11 (3) ◽

pp. 14-23

Author(s):

Carina Sousa Santos ◽

Eudes Souza Oliveira Júnior ◽

Marcus James Lopes de Sá ◽

Elizabethe Adriana Esteves

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Resistance Exercise ◽

Muscle Mass ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

The Elderly ◽

Food Sources ◽

Dietary Adequacy ◽

The Face

Proper maintenance of skeletal muscle mass is essential to prevent sarcopenia and ensure health and quality of life as aging progress. The two determinants of muscle protein synthesis are the increased load on skeletal muscle through resistance exercise and protein intake. For an effective result of maintaining or increasing muscle mass, it is relevant to consider the quantitative and adequate intake of protein, and the dietary source of protein since the plant-based protein has differences in comparison to animals that limit its anabolic capacity. Given the increase in vegetarianism and the elderly population, which consumes fewer food sources of animal protein, the importance of understanding how protein of plant-based protein can sustain muscle protein synthesis in the long term when associated with resistance exercise is justified, as well as the possibilities of dietary adequacy in the face of this demand.

Download Full-text

Combined in vivo muscle mass, muscle protein synthesis and muscle protein breakdown measurement: a ‘Combined Oral Stable Isotope Assessment of Muscle (COSIAM)’ approach

GeroScience ◽

10.1007/s11357-021-00386-2 ◽

2021 ◽

Author(s):

Jessica Cegielski ◽

Daniel J. Wilkinson ◽

Matthew S. Brook ◽

Catherine Boereboom ◽

Bethan E. Phillips ◽

...

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Stable Isotope ◽

Muscle Mass ◽

Protein Turnover ◽

Skeletal Muscle Mass ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Protein Breakdown ◽

Muscle Protein Breakdown

AbstractOptimising approaches for measuring skeletal muscle mass and turnover that are widely applicable, minimally invasive and cost effective is crucial in furthering research into sarcopenia and cachexia. Traditional approaches for measurement of muscle protein turnover require infusion of expensive, sterile, isotopically labelled tracers which limits the applicability of these approaches in certain populations (e.g. clinical, frail elderly). To concurrently quantify skeletal muscle mass and muscle protein turnover i.e. muscle protein synthesis (MPS) and muscle protein breakdown (MPB), in elderly human volunteers using stable-isotope labelled tracers i.e. Methyl-[D3]-creatine (D3-Cr), deuterium oxide (D2O), and Methyl-[D3]-3-methylhistidine (D3-3MH), to measure muscle mass, MPS and MPB, respectively. We recruited 10 older males (71 ± 4 y, BMI: 25 ± 4 kg.m2, mean ± SD) into a 4-day study, with DXA and consumption of D2O and D3-Cr tracers on day 1. D3-3MH was consumed on day 3, 24 h prior to returning to the lab. From urine, saliva and blood samples, and a single muscle biopsy (vastus lateralis), we determined muscle mass, MPS and MPB. D3-Cr derived muscle mass was positively correlated to appendicular fat-free mass (AFFM) estimated by DXA (r = 0.69, P = 0.027). Rates of cumulative myofibrillar MPS over 3 days were 0.072%/h (95% CI, 0.064 to 0.081%/h). Whole-body MPB over 6 h was 0.052 (95% CI, 0.038 to 0.067). These rates were similar to previous literature. We demonstrate the potential for D3-Cr to be used alongside D2O and D3-3MH for concurrent measurement of muscle mass, MPS, and MPB using a minimally invasive design, applicable for clinical and frail populations.

Download Full-text

Characterising the muscle anabolic potential of dairy, meat and plant-based protein sources in older adults

Proceedings of The Nutrition Society ◽

10.1017/s002966511700194x ◽

2017 ◽

Vol 77 (1) ◽

pp. 20-31 ◽

Cited By ~ 48

Author(s):

Stefan H. M. Gorissen ◽

Oliver C. Witard

Keyword(s):

Older Adults ◽

Skeletal Muscle ◽

Amino Acid ◽

Muscle Mass ◽

Dietary Protein ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Amino Acid Profile ◽

Protein Sources ◽

Age Related

The age-related loss of skeletal muscle mass and function is caused, at least in part, by a reduced muscle protein synthetic response to protein ingestion. The magnitude and duration of the postprandial muscle protein synthetic response to ingested protein is dependent on the quantity and quality of the protein consumed. This review characterises the anabolic properties of animal-derived and plant-based dietary protein sources in older adults. While approximately 60 % of dietary protein consumed worldwide is derived from plant sources, plant-based proteins generally exhibit lower digestibility, lower leucine content and deficiencies in certain essential amino acids such as lysine and methionine, which compromise the availability of a complete amino acid profile required for muscle protein synthesis. Based on currently available scientific evidence, animal-derived proteins may be considered more anabolic than plant-based protein sources. However, the production and consumption of animal-derived protein sources is associated with higher greenhouse gas emissions, while plant-based protein sources may be considered more environmentally sustainable. Theoretically, the lower anabolic capacity of plant-based proteins can be compensated for by ingesting a greater dose of protein or by combining various plant-based proteins to provide a more favourable amino acid profile. In addition, leucine co-ingestion can further augment the postprandial muscle protein synthetic response. Finally, prior exercise or n-3 fatty acid supplementation have been shown to sensitise skeletal muscle to the anabolic properties of dietary protein. Applying one or more of these strategies may support the maintenance of muscle mass with ageing when diets rich in plant-based protein are consumed.

Download Full-text

Molecular regulation of human skeletal muscle protein synthesis in response to exercise and nutrients: a compass for overcoming age-related anabolic resistance

AJP Cell Physiology ◽

10.1152/ajpcell.00209.2019 ◽

2019 ◽

Vol 317 (6) ◽

pp. C1061-C1078 ◽

Cited By ~ 9

Author(s):

Nathan Hodson ◽

Daniel W. D. West ◽

Andrew Philp ◽

Nicholas A. Burd ◽

Daniel R. Moore

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Muscle Mass ◽

Human Skeletal Muscle ◽

Molecular Mechanisms ◽

Negative Impact ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Anabolic Resistance ◽

Age Related

Skeletal muscle mass, a strong predictor of longevity and health in humans, is determined by the balance of two cellular processes, muscle protein synthesis (MPS) and muscle protein breakdown. MPS seems to be particularly sensitive to changes in mechanical load and/or nutritional status; therefore, much research has focused on understanding the molecular mechanisms that underpin this cellular process. Furthermore, older individuals display an attenuated MPS response to anabolic stimuli, termed anabolic resistance, which has a negative impact on muscle mass and function, as well as quality of life. Therefore, an understanding of which, if any, molecular mechanisms contribute to anabolic resistance of MPS is of vital importance in formulation of therapeutic interventions for such populations. This review summarizes the current knowledge of the mechanisms that underpin MPS, which are broadly divided into mechanistic target of rapamycin complex 1 (mTORC1)-dependent, mTORC1-independent, and ribosomal biogenesis-related, and describes the evidence that shows how they are regulated by anabolic stimuli (exercise and/or nutrition) in healthy human skeletal muscle. This review also summarizes evidence regarding which of these mechanisms may be implicated in age-related skeletal muscle anabolic resistance and provides recommendations for future avenues of research that can expand our knowledge of this area.

Download Full-text

Interventional strategies to combat muscle disuse atrophy in humans: focus on neuromuscular electrical stimulation and dietary protein

Journal of Applied Physiology ◽

10.1152/japplphysiol.00985.2016 ◽

2018 ◽

Vol 125 (3) ◽

pp. 850-861 ◽

Cited By ~ 12

Author(s):

Marlou L. Dirks ◽

Benjamin T. Wall ◽

Luc J. C. van Loon

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Dietary Protein ◽

Nutritional Support ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Neuromuscular Electrical Stimulation ◽

Muscle Loss ◽

Disuse Atrophy ◽

Muscle Disuse

Numerous situations, such as the recovery from illness or rehabilitation after injury, necessitate a period of muscle disuse in otherwise healthy individuals. Even a few days of immobilization or bed rest can lead to substantial loss of skeletal muscle tissue and compromise metabolic health. The decline in muscle mass is attributed largely to a decline in postabsorptive and postprandial muscle protein synthesis rates. Reintroduction of some level of muscle contraction by the application of neuromuscular electrical stimulation (NMES) can augment both postabsorptive and postprandial muscle protein synthesis rates and, as such, prevent or attenuate muscle loss during short-term disuse in various clinical populations. Whereas maintenance of habitual dietary protein consumption is a prerequisite for muscle mass maintenance, supplementing dietary protein above habitual intake levels does not prevent muscle loss during disuse in otherwise healthy humans. Combining the anabolic properties of physical activity (or surrogates) with appropriate nutritional support likely further increases the capacity to preserve skeletal muscle mass during a period of disuse. Therefore, effective interventional strategies to prevent or alleviate muscle disuse atrophy should include both exercise (mimetics) and appropriate nutritional support.

Download Full-text