The Role of mTORC1 in Regulating Protein Synthesis and Skeletal Muscle Mass in Response to Various Mechanical Stimuli

2013 ◽  
pp. 43-95 ◽  
Author(s):  
Craig A. Goodman
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Mechanical Stimuli

scholarly journals Role of mTORC1 in mechanically induced increases in translation and skeletal muscle mass

2019 ◽  
Vol 127 (2) ◽  
pp. 581-590 ◽  
Author(s):  
Craig A. Goodman
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Mrna Translation ◽  
Current Evidence ◽  
Mechanical Stimuli ◽  
Serine Threonine Kinase ◽  
Mtor Complex 1

Skeletal muscle mass is, in part, regulated by the rate of mRNA translation (i.e., protein synthesis). The conserved serine/threonine kinase, mTOR (the mammalian/mechanistic target of rapamycin), found in the multiprotein complex, mTOR complex 1 (mTORC1), is a major positive regulator of protein synthesis. The purpose of this review is to describe some of the critical steps in translation initiation, mTORC1 and its potential direct and indirect roles in regulating translation, and evidence that mTORC1 regulates protein synthesis and muscle mass, with a particular focus on basal conditions and the response to mechanical stimuli. Current evidence suggests that for acute contraction models of mechanical stimuli, there is an emerging pattern suggesting that there is an early increase in protein synthesis governed by a rapamycin-sensitive mTORC1-dependent mechanism, while at later poststimulation time points, the mechanism may change to a rapamycin-insensitive mTORC1-dependent or even an mTORC1-independent mechanism. Furthermore, evidence suggests that mTORC1 appears to be absolutely necessary for muscle fiber hypertrophy induced by chronic mechanical loading but may only play a partial role in the hypertrophy induced by more intermittent types of acute resistance exercise, with the possibility of mTORC1-independent mechanisms also playing a role. Despite the progress that has been made, many questions about the activation of mTORC1, and its downstream targets, remain to be answered. Further research will hopefully provide novel insights into the regulation of skeletal muscle mTORC1 that may eventually be translated into novel exercise programing and/or targeted pharmacological therapies aimed at preventing muscle wasting and/or increasing muscle mass.

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

2001 ◽  
Vol 281 (1) ◽  
pp. R133-R139 ◽  
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.

scholarly journals Expression Levels of Long Non-Coding RNAs Change in Models of Altered Muscle Activity and Muscle Mass

2020 ◽  
Vol 21 (5) ◽  
pp. 1628 ◽  
Author(s):  
Keisuke Hitachi ◽  
Masashi Nakatani ◽  
Shiori Funasaki ◽  
Ikumi Hijikata ◽  
Mizuki Maekawa ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Skeletal Muscle Mass ◽  
Muscle Size ◽  
Skeletal Muscle Atrophy ◽  
Myostatin Gene ◽  
Expression Levels ◽  
Non Coding Rnas

Skeletal muscle is a highly plastic organ that is necessary for homeostasis and health of the human body. The size of skeletal muscle changes in response to intrinsic and extrinsic stimuli. Although protein-coding RNAs including myostatin, NF-κβ, and insulin-like growth factor-1 (IGF-1), have pivotal roles in determining the skeletal muscle mass, the role of long non-coding RNAs (lncRNAs) in the regulation of skeletal muscle mass remains to be elucidated. Here, we performed expression profiling of nine skeletal muscle differentiation-related lncRNAs (DRR, DUM1, linc-MD1, linc-YY1, LncMyod, Neat1, Myoparr, Malat1, and SRA) and three genomic imprinting-related lncRNAs (Gtl2, H19, and IG-DMR) in mouse skeletal muscle. The expression levels of these lncRNAs were examined by quantitative RT-PCR in six skeletal muscle atrophy models (denervation, casting, tail suspension, dexamethasone-administration, cancer cachexia, and fasting) and two skeletal muscle hypertrophy models (mechanical overload and deficiency of the myostatin gene). Cluster analyses of these lncRNA expression levels were successfully used to categorize the muscle atrophy models into two sub-groups. In addition, the expression of Gtl2, IG-DMR, and DUM1 was altered along with changes in the skeletal muscle size. The overview of the expression levels of lncRNAs in multiple muscle atrophy and hypertrophy models provides a novel insight into the role of lncRNAs in determining the skeletal muscle mass.

scholarly journals Longevity and skeletal muscle mass: the role of IGF signalling, the sirtuins, dietary restriction and protein intake

Aging Cell ◽  
2015 ◽  
Vol 14 (4) ◽  
pp. 511-523 ◽  
Author(s):  
Adam P. Sharples ◽  
David C. Hughes ◽  
Colleen S. Deane ◽  
Amarjit Saini ◽  
Colin Selman ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Dietary Restriction ◽  
Protein Intake ◽  
Skeletal Muscle Mass

scholarly journals Preservation of Liver Protein Synthesis during Dietary Leucine Deprivation Occurs at the Expense of Skeletal Muscle Mass in Mice Deleted for eIF2 Kinase GCN2

2004 ◽  
Vol 279 (35) ◽  
pp. 36553-36561 ◽  
Author(s):  
Tracy G. Anthony ◽  
Brent J. McDaniel ◽  
Rachel L. Byerley ◽  
Barbara C. McGrath ◽  
Douglas R. Cavener ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Liver Protein

Aging, exercise, and muscle protein metabolism

2009 ◽  
Vol 106 (6) ◽  
pp. 2040-2048 ◽  
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.

scholarly journals LINCing Nuclear Mechanobiology With Skeletal Muscle Mass and Function

2021 ◽  
Vol 9 ◽  
Author(s):  
Maria J. A. van Ingen ◽  
Tyler J. Kirby
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Striated Muscle ◽  
Genetic Diseases ◽  
Mechanical Stimuli ◽  
Muscle Adaptation ◽  
Cellular Environment ◽  
Additional Level ◽  
And Function

Skeletal muscle demonstrates a high degree of adaptability in response to changes in mechanical input. The phenotypic transformation in response to mechanical cues includes changes in muscle mass and force generating capabilities, yet the molecular pathways that govern skeletal muscle adaptation are still incompletely understood. While there is strong evidence that mechanotransduction pathways that stimulate protein synthesis play a key role in regulation of muscle mass, there are likely additional mechano-sensitive mechanisms important for controlling functional muscle adaptation. There is emerging evidence that the cell nucleus can directly respond to mechanical signals (i.e., nuclear mechanotransduction), providing a potential additional level of cellular regulation for controlling skeletal muscle mass. The importance of nuclear mechanotransduction in cellular function is evident by the various genetic diseases that arise from mutations in proteins crucial to the transmission of force between the cytoskeleton and the nucleus. Intriguingly, these diseases preferentially affect cardiac and skeletal muscle, suggesting that nuclear mechanotransduction is critically important for striated muscle homeostasis. Here we discuss our current understanding for how the nucleus acts as a mechanosensor, describe the main cytoskeletal and nuclear proteins involved in the process, and propose how similar mechanoresponsive mechanisms could occur in the unique cellular environment of a myofiber. In addition, we examine how nuclear mechanotransduction fits into our current framework for how mechanical stimuli regulates skeletal muscle mass.

scholarly journals Impact of Sarcopenia as a Prognostic Biomarker of Bladder Cancer

2018 ◽  
Author(s):  
Hiroshi Fukushima ◽  
Kosuke Takemura ◽  
Hiroaki Suzuki ◽  
Fumitaka Koga
Keyword(s):  
Skeletal Muscle ◽  
Bladder Cancer ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Prognostic Biomarker ◽  
Inflammatory Diseases ◽  
Poor Nutritional Status ◽  
Lack Of Exercise ◽  
Worse Prognosis

Sarcopenia, the degenerative and systemic loss of skeletal muscle mass, indicates patient frailty and impaired physical function. Sarcopenia can be caused by multiple factors, including advanced age, lack of exercise, poor nutritional status, inflammatory diseases, endocrine diseases, and malignancies. Recently, growing evidence has indicated the importance of sarcopenia in the management of patients with various cancers. Sarcopenia is associated with not only higher rates of treatment-related complications but also worse prognosis in cancer-bearing patients. In this article, we conducted a systematic literature review regarding the significance of sarcopenia as a prognostic biomarker of bladder cancer. We also reviewed recent studies focusing on the prognostic role of changes in skeletal muscle mass during the course of treatment in bladder cancer patients.

scholarly journals WITHDRAWN (By Publisher): Letter to the Editor: Protective Role of Skeletal Muscle Mass Against Progression From Metabolically Healthy to Unhealthy Phenotype

2019 ◽  
Vol 104 (8) ◽  
pp. W1-W3
Author(s):  
Jean-Christophe Lagacé ◽  
Dominic Tremblay ◽  
Jasmine Paquin ◽  
Alexis Marcotte-Chénard ◽  
Eléonor Riesco ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Protective Role ◽  
Letter To The Editor ◽  
Metabolically Healthy
Sign in / Sign up

Export Citation Format

Share Document