Lipoprotein subfractions in patients with sarcopenia and their relevance to skeletal muscle mass and function

Sarcopenia was originally conceptualized as the age-related loss of skeletal muscle mass. Over the ensuing decades, the conceptual definition of sarcopenia has changed to represent a condition in older adults that is characterized by declining muscle mass and function, with “function” most commonly conceived as muscle weakness and/or impaired physical performance (e.g., slow gait speed). Findings over the past 15-years, however, have demonstrated that changes in grip and leg extensor strength are not primarily due to muscle atrophy per se, and that to a large extent, are reflective of declines in the integrity of the nervous system. This article briefly summarizes findings relating to the complex neuromuscular mechanisms that contribute to reductions in muscle function associated with advancing age, and the implications of these findings on the development of effective therapies.

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Sarcopenia in women with hip fracture: A comparison of hormonal biomarkers and their relationship to skeletal muscle mass and function

Osteoporosis and Sarcopenia ◽

10.1016/j.afos.2020.06.001 ◽

2020 ◽

Vol 6 (3) ◽

pp. 139-145

Author(s):

Ming Li Yee ◽

Raphael Hau ◽

Alison Taylor ◽

Mark Guerra ◽

Peter Guerra ◽

...

Keyword(s):

Skeletal Muscle ◽

Hip Fracture ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

And Function

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Skeletal Muscle Mass Regulation in Critical Illness

10.1093/med/9780199653461.003.0035 ◽

2014 ◽

Author(s):

Zudin Puthucheary ◽

Hugh Montgomery ◽

Nicholas Hart ◽

Stephen Harridge

Keyword(s):

Skeletal Muscle ◽

Critical Illness ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Bed Rest ◽

Protein Homeostasis ◽

Highly Sensitive ◽

And Function ◽

Inadequate Nutrition

Muscle is a dynamic, plastic, and malleable tissue that is highly sensitive to mechanical and metabolic signals. Muscle mass is regulated by protein homeostasis, with protein being continually turned over, reflecting a balance between synthesis and breakdown. This chapter discusses the effect of critical illness on skeletal muscle mass, protein homeostasis, and the intracellular signalling driving anabolism and catabolism. The focus will be on the unique challenges to which the skeletal muscle are exposed, such as inflammation, sepsis, sedation, and inadequate nutrition, which, in combination with the disuse signals of immobilization and bed rest, engender dramatic changes in muscle structure and function. The mechanisms regulating muscle loss during critical illness are being unravelled, but many questions remain unanswered. Detailed understanding of these mechanisms will help drive strategies to minimize or prevent intensive care-acquired muscle weakness and the long-term consequences experienced by ICU survivors.

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Clinical impact of sarcopenia assessment in patients with hepatocellular carcinoma undergoing treatments

Journal of Gastroenterology ◽

10.1007/s00535-020-01711-w ◽

2020 ◽

Vol 55 (10) ◽

pp. 927-943 ◽

Cited By ~ 2

Author(s):

Giovanni Marasco ◽

Matteo Serenari ◽

Matteo Renzulli ◽

Luigina Vanessa Alemanni ◽

Benedetta Rossini ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Skeletal Muscle ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Appropriate Treatment ◽

Risk Of Mortality ◽

Short And Long Term ◽

Poor Outcomes ◽

And Function

Abstract Changes in body composition are associated with poor outcomes in cancer patients including hepatocellular carcinoma (HCC). Sarcopenia, defined as the loss of skeletal muscle mass, quality and function, has been associated with a higher rate of complications and recurrences in patients with cirrhosis and HCC. The assessment of patient general status before HCC treatment, including the presence of sarcopenia, is a key-point for achieving therapy tolerability and to avoid short- and long-term complications leading to poor patients’ survival. Thus, we aimed to review the current literature evaluating the role of sarcopenia assessment related to HCC treatments and to critically provide the clinicians with the most recent and valuable evidence. As a result, sarcopenia can be predictive of poor outcomes in patients undergoing liver resection, transplantation and systemic therapies, offering the chance to clinicians to improve the muscular status of these patients, especially those with high-grade sarcopenia at high risk of mortality. Further studies are needed to clarify the predictive value of sarcopenia in other HCC treatment settings and to evaluate its role as an additional staging tool for identifying the most appropriate treatment. Besides, interventional studies aiming at increasing the skeletal muscle mass for reducing complications and increasing the survival in patients with HCC are needed.

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The gut microbiota influences skeletal muscle mass and function in mice

Science Translational Medicine ◽

10.1126/scitranslmed.aan5662 ◽

2019 ◽

Vol 11 (502) ◽

pp. eaan5662 ◽

Cited By ~ 37

Author(s):

Shawon Lahiri ◽

Hyejin Kim ◽

Isabel Garcia-Perez ◽

Musarrat Maisha Reza ◽

Katherine A. Martin ◽

...

Keyword(s):

Skeletal Muscle ◽

Neuromuscular Junction ◽

Gut Microbiota ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Neuromuscular Junctions ◽

Short Chain Fatty Acids ◽

Germ Free ◽

Mouse Skeletal Muscle ◽

And Function

The functional interactions between the gut microbiota and the host are important for host physiology, homeostasis, and sustained health. We compared the skeletal muscle of germ-free mice that lacked a gut microbiota to the skeletal muscle of pathogen-free mice that had a gut microbiota. Compared to pathogen-free mouse skeletal muscle, germ-free mouse skeletal muscle showed atrophy, decreased expression of insulin-like growth factor 1, and reduced transcription of genes associated with skeletal muscle growth and mitochondrial function. Nuclear magnetic resonance spectrometry analysis of skeletal muscle, liver, and serum from germ-free mice revealed multiple changes in the amounts of amino acids, including glycine and alanine, compared to pathogen-free mice. Germ-free mice also showed reduced serum choline, the precursor of acetylcholine, the key neurotransmitter that signals between muscle and nerve at neuromuscular junctions. Reduced expression of genes encoding Rapsyn and Lrp4, two proteins important for neuromuscular junction assembly and function, was also observed in skeletal muscle from germ-free mice compared to pathogen-free mice. Transplanting the gut microbiota from pathogen-free mice into germ-free mice resulted in an increase in skeletal muscle mass, a reduction in muscle atrophy markers, improved oxidative metabolic capacity of the muscle, and elevated expression of the neuromuscular junction assembly genes Rapsyn and Lrp4. Treating germ-free mice with short-chain fatty acids (microbial metabolites) partly reversed skeletal muscle impairments. Our results suggest a role for the gut microbiota in regulating skeletal muscle mass and function in mice.

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Growth differentiation factor 15 (GDF-15) inhibition to increase muscle mass and function in cancer cachexia.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e15633 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e15633-e15633

Author(s):

Matthew Peloquin ◽

Brianna LaCarubba ◽

Stephanie Joaqium ◽

Gregory Weber ◽

John Stansfield ◽

...

Keyword(s):

Skeletal Muscle ◽

Body Weight ◽

Muscle Mass ◽

Muscle Function ◽

Skeletal Muscle Mass ◽

Cancer Cachexia ◽

Tumor Model ◽

Growth Differentiation Factor 15 ◽

Myostatin Inhibition ◽

And Function

e15633 Background: Almost half of cancer deaths are attributed to cancers most frequently associated with cachexia. Cachexia is a complex metabolic disease characterized by anorexia and unintentional weight loss. Skeletal muscle depletion has been recognized as a key feature of the disease, however muscle anabolic therapies have not been successful, suggesting that treatments that target multiple aspects of the disease will be most effective. Growth differentiation factor 15 (GDF-15) is a cytokine that induces anorexia and weight loss and is associated with cachexia in cancer patients. In preclinical cancer cachexia models, GDF-15 inhibition is sufficient to normalize food intake and body weight, including skeletal muscle mass. However, it remains to be determined whether the increased skeletal muscle mass also results in restoration of muscle function. Therefore, we examined the effect of GDF-15 inhibition on muscle mass and function in mouse models of cancer cachexia in comparison with myostatin inhibition, an established muscle anabolic pathway. Methods: Cachectic mouse tumor models were established with subcutaneous implantation of tumor cell lines reported to be GDF-15-dependent; mouse renal cell carcinoma (RENCA) and human ovarian cancer (TOV-21G) cell lines. Mice were treated with anti-GDF-15 (mAB2) or anti-myostatin (RK35) monoclonal antibodies and skeletal muscle function was assessed in vivo via maximum force, maximum rate of contraction and half relax time. In the RENCA tumor model, GDF-15 inhibition fully restored body weight and skeletal muscle mass whereas myostatin inhibition showed only a modest effect. Results: Consistent with the muscle mass improvement, GDF-15 inhibition dramatically increased functional muscle endpoints compared to the partial effect of myostatin inhibition. Interestingly, in the TOV-21G tumor model GDF-15 inhibition only partially restored body weight, however skeletal muscle mass and muscle function were completely normalized. Consistent with the functional assessment, GDF-15 inhibition in the RENCA tumor model decreased the expression of several catabolic genes (i.e. Trim63, Fbxo32, Myh7 and Myh2). The GDF-15 effect is likely to be secondary to the reversal of anorexia since wildtype mice pair-fed to Fc-GDF-15-treated mice demonstrated equivalent muscle mass loss. Conclusions: Taken together these data suggest that GDF-15 inhibition holds potential as an effective therapeutic approach to alleviate multiple aspects of cachexia.

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Markers of oxidative stress, skeletal muscle mass and function, and their responses to resistance exercise training in older adults

Experimental Gerontology ◽

10.1016/j.exger.2017.12.024 ◽

2018 ◽

Vol 103 ◽

pp. 101-106 ◽

Cited By ~ 5

Author(s):

Ciriaco Carru ◽

Mariasole Da Boit ◽

Panagiotis Paliogiannis ◽

Angelo Zinellu ◽

Salvatore Sotgia ◽

...

Keyword(s):

Oxidative Stress ◽

Older Adults ◽

Skeletal Muscle ◽

Exercise Training ◽

Resistance Exercise ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Resistance Exercise Training ◽

Markers Of Oxidative Stress ◽

And Function

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l-Carnitine Supplementation in Older Women. A Pilot Study on Aging Skeletal Muscle Mass and Function

Nutrients ◽

10.3390/nu10020255 ◽

2018 ◽

Vol 10 (2) ◽

pp. 255 ◽

Cited By ~ 10

Author(s):

Angelika Sawicka ◽

Dace Hartmane ◽

Patrycja Lipinska ◽

Ewa Wojtowicz ◽

Wieslawa Lysiak-Szydlowska ◽

...

Keyword(s):

Skeletal Muscle ◽

Pilot Study ◽

Older Women ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Carnitine Supplementation ◽

And Function

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LINCing Nuclear Mechanobiology With Skeletal Muscle Mass and Function

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.690577 ◽

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.

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