Long‐term administration of the mitochondria‐targeted antioxidant mitoquinone mesylate fails to attenuate age‐related oxidative damage or rescue the loss of muscle mass and function associated with aging of skeletal muscle

For decades the biomedical community has documented the accelerated loss of muscle mass that occurs with advancing aging, termed sarcopenia. The timely review article (“Attenuation of Adverse Effects of Aging on Skeletal Muscle by Regular Exercise and Nutritional Support”) by Arthur Leon presents our current state of knowledge on the biological processes responsible for age-induced loss of muscle mass and function. This loss of skeletal muscle has critical health implications as it can negatively affect morbidity and mortality. A significant theme throughout the review is that a lifelong commitment to regular physical activity and good dietary habits is extremely important to combat age related reductions in muscle mass and function. However, multi-targeted therapeutic approaches, in conjunction with nutrition and exercise, may be beneficial to prevent or treat sarcopenia. Additionally, while significant progress has been made in our understanding of the molecular and biochemical contributors to sarcopenia, further research using well-controlled clinical trials are needed to determine the long-term benefit of exercise and nutrition on aging skeletal muscle.

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NEUROMUSCULAR CHANGES WITH AGING AND SARCOPENIA

Journal of Frailty & Aging ◽

10.14283/jfa.2018.35 ◽

2018 ◽

pp. 1-3

Author(s):

B.C. Clark

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Muscle Function ◽

Skeletal Muscle Mass ◽

The Past ◽

Conceptual Definition ◽

Age Related ◽

Per Se ◽

Definition Of ◽

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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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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An investigation of p53 in skeletal muscle aging

Journal of Applied Physiology ◽

10.1152/japplphysiol.00363.2019 ◽

2019 ◽

Vol 127 (4) ◽

pp. 1075-1084 ◽

Cited By ~ 2

Author(s):

Scott M. Ebert ◽

Jason M. Dierdorff ◽

David K. Meyerholz ◽

Steven A. Bullard ◽

Asma Al-Zougbi ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Muscle Fibers ◽

Skeletal Muscle Atrophy ◽

P53 Expression ◽

Skeletal Muscle Fibers ◽

Age Related ◽

Skeletal Muscle Aging ◽

And Function

Age-related skeletal muscle atrophy is a very common and serious condition that remains poorly understood at the molecular level. Several lines of evidence have suggested that the tumor suppressor p53 may play a central, causative role in skeletal muscle aging, whereas other, apparently contradictory lines of evidence have suggested that p53 may be critical for normal skeletal muscle function. To help address these issues, we performed an aging study in male muscle-specific p53-knockout mice (p53 mKO mice), which have a lifelong absence of p53 expression in skeletal muscle fibers. We found that the absence of p53 expression in skeletal muscle fibers had no apparent deleterious or beneficial effects on skeletal muscle mass or function under basal conditions up to 6 mo of age, when mice are fully grown and exhibit peak muscle mass and function. Furthermore, at 22 and 25 mo of age, when age-related muscle weakness and atrophy are clearly evident in mice, p53 mKO mice demonstrated no improvement or worsening of skeletal muscle mass or function relative to littermate control mice. At advanced ages, p53 mKO mice began to die prematurely and had an increased incidence of osteosarcoma, precluding analyses of muscle mass and function in very old p53 mKO mice. In light of these results, we conclude that p53 expression in skeletal muscle fibers has minimal if any direct, cell autonomous effect on basal or age-related changes in skeletal muscle mass and function up to at least 22 mo of age. NEW & NOTEWORTHY Previous studies implicated the transcriptional regulator p53 as a potential mediator of age-related skeletal muscle weakness and atrophy. We tested this hypothesis by investigating the effect of aging in muscle-specific p53-knockout mice. Our results strongly suggest that p53 activity within skeletal muscle fibers is not required for age-related skeletal muscle atrophy or weakness.

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The age-related loss of skeletal muscle mass and function: Measurement and physiology of muscle fibre atrophy and muscle fibre loss in humans

Ageing Research Reviews ◽

10.1016/j.arr.2018.07.005 ◽

2018 ◽

Vol 47 ◽

pp. 123-132 ◽

Cited By ~ 71

Author(s):

D.J. Wilkinson ◽

M. Piasecki ◽

P.J. Atherton

Keyword(s):

Skeletal Muscle ◽

Muscle Fibre ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Function Measurement ◽

Age Related ◽

And Function ◽

Fibre Loss ◽

Fibre Atrophy

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Role of IGF-1 in Age-Related Loss of Skeletal Muscle Mass and Function

Sarcopenia – Age-Related Muscle Wasting and Weakness ◽

10.1007/978-90-481-9713-2_17 ◽

2010 ◽

pp. 393-418 ◽

Cited By ~ 3

Author(s):

Chris D. McMahon ◽

Thea Shavlakadze ◽

Miranda D. Grounds

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Age Related ◽

And Function

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Nutrition and microRNAs: Novel Insights to Fight Sarcopenia

Antioxidants ◽

10.3390/antiox9100951 ◽

2020 ◽

Vol 9 (10) ◽

pp. 951

Author(s):

Alessandra Barbiera ◽

Laura Pelosi ◽

Gigliola Sica ◽

Bianca Maria Scicchitano

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Molecular Mechanisms ◽

Muscle Protein ◽

Low Grade ◽

Protein Homeostasis ◽

Dietary Interventions ◽

Physiological Processes ◽

Age Related ◽

And Function

Sarcopenia is a progressive age-related loss of skeletal muscle mass and strength, which may result in increased physical frailty and a higher risk of adverse events. Low-grade systemic inflammation, loss of muscle protein homeostasis, mitochondrial dysfunction, and reduced number and function of satellite cells seem to be the key points for the induction of muscle wasting, contributing to the pathophysiological mechanisms of sarcopenia. While a range of genetic, hormonal, and environmental factors has been reported to contribute to the onset of sarcopenia, dietary interventions targeting protein or antioxidant intake may have a positive effect in increasing muscle mass and strength, regulating protein homeostasis, oxidative reaction, and cell autophagy, thus providing a cellular lifespan extension. MicroRNAs (miRNAs) are endogenous small non-coding RNAs, which control gene expression in different tissues. In skeletal muscle, a range of miRNAs, named myomiRNAs, are involved in many physiological processes, such as growth, development, and maintenance of muscle mass and function. This review aims to present and to discuss some of the most relevant molecular mechanisms related to the pathophysiological effect of sarcopenia. Besides, we explored the role of nutrition as a possible way to counteract the loss of muscle mass and function associated with ageing, with special attention paid to nutrient-dependent miRNAs regulation. This review will provide important information to better understand sarcopenia and, thus, to facilitate research and therapeutic strategies to counteract the pathophysiological effect of ageing.

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Recent advances and future avenues in understanding the role of adipose tissue cross talk in mediating skeletal muscle mass and function with ageing

GeroScience ◽

10.1007/s11357-021-00322-4 ◽

2021 ◽

Author(s):

Andrew Wilhelmsen ◽

Kostas Tsintzas ◽

Simon W. Jones

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

Muscle Mass ◽

Extracellular Vesicles ◽

Cross Talk ◽

Skeletal Muscle Mass ◽

Activity Level ◽

Age Related ◽

And Function

AbstractSarcopenia, broadly defined as the age-related decline in skeletal muscle mass, quality, and function, is associated with chronic low-grade inflammation and an increased likelihood of adverse health outcomes. The regulation of skeletal muscle mass with ageing is complex and necessitates a delicate balance between muscle protein synthesis and degradation. The secretion and transfer of cytokines, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), both discretely and within extracellular vesicles, have emerged as important communication channels between tissues. Some of these factors have been implicated in regulating skeletal muscle mass, function, and pathologies and may be perturbed by excessive adiposity. Indeed, adipose tissue participates in a broad spectrum of inter-organ communication and obesity promotes the accumulation of macrophages, cellular senescence, and the production and secretion of pro-inflammatory factors. Pertinently, age-related sarcopenia has been reported to be more prevalent in obesity; however, such effects are confounded by comorbidities and physical activity level. In this review, we provide evidence that adiposity may exacerbate age-related sarcopenia and outline some emerging concepts of adipose-skeletal muscle communication including the secretion and processing of novel myokines and adipokines and the role of extracellular vesicles in mediating inter-tissue cross talk via lncRNAs and miRNAs in the context of sarcopenia, ageing, and obesity. Further research using advances in proteomics, transcriptomics, and techniques to investigate extracellular vesicles, with an emphasis on translational, longitudinal human studies, is required to better understand the physiological significance of these factors, the impact of obesity upon them, and their potential as therapeutic targets in combating muscle wasting.

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(−)-Epicatechin-Enriched Extract from Camellia sinensis Improves Regulation of Muscle Mass and Function: Results from a Randomized Controlled Trial

Antioxidants ◽

10.3390/antiox10071026 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1026

Author(s):

Hyeyeong Seo ◽

Seok-Hee Lee ◽

Yooheon Park ◽

Hee-Seok Lee ◽

Jeong Sup Hong ◽

...

Keyword(s):

Skeletal Muscle ◽

Treatment Group ◽

Muscle Mass ◽

Green Tea ◽

Green Tea Extract ◽

Control Group ◽

Therapeutic Benefits ◽

Age Related ◽

Tea Extract ◽

And Function

Loss of skeletal muscle mass and function with age represents an important source of frailty and functional decline in the elderly. Antioxidants from botanical extracts have been shown to enhance the development, mass, and strength of skeletal muscle by influencing age-related cellular and molecular processes. Tannase-treated green tea extract contains high levels of the antioxidants (−)-epicatechin (EC) and gallic acid that may have therapeutic benefits for age-related muscle decline. The aim of this study was to investigate the effect of tannase-treated green tea extract on various muscle-related parameters, without concomitant exercise, in a single-center, randomized, double-blind, placebo-controlled study. Administration of tannase-treated green tea extract (600 mg/day) for 12 weeks significantly increased isokinetic flexor muscle and handgrip strength in the treatment group compared with those in the placebo (control) group. In addition, the control group showed a significant decrease in arm muscle mass after 12 weeks, whereas no significant change was observed in the treatment group. Blood serum levels of follistatin, myostatin, high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, IL-8, insulin-like growth factor-1 (IGF-1), and cortisol were analyzed, and the decrease in myostatin resulting from the administration of tannase-treated green tea extract was found to be related to the change in muscle mass and strength. In summary, oral administration of tannase-treated green tea extract containing antioxidants without concomitant exercise can improve muscle mass and strength and may have therapeutic benefits in age-related muscle function decline.

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