scholarly journals NEUROMUSCULAR CHANGES WITH AGING AND SARCOPENIA

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.

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

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.

scholarly journals An investigation of p53 in skeletal muscle aging

2019 ◽  
Vol 127 (4) ◽  
pp. 1075-1084 ◽  
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.

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

GeroScience ◽  
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.

scholarly journals Association Between Fish Consumption and Muscle Mass and Function in Middle-Age and Older Adults

2021 ◽  
Vol 8 ◽  
Author(s):  
Maha H. Alhussain ◽  
Moodi Mathel ALshammari
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Muscle Mass ◽  
Fish Consumption ◽  
Repeated Measures ◽  
Skeletal Muscle Mass ◽  
Middle Age ◽  
Statistical Significance ◽  
Age Related ◽  
And Function

Background: Sarcopenia, the age-related loss of skeletal muscle mass and function, represents a crucial risk factor for disability and mortality. Increasing intake of some nutrients, particularly protein and omega-3 fatty acids seems to be a promising strategy to augment muscle mass and function.Objective: The purpose of this study was to assess the beneficial effects of fish consumption on muscle mass and function among middle-age and older adults.Methods: Twenty-two adults aged 50–85 years participated in this study. Participants were asked to consume 150–170-g of fish for lunch twice a week for a 10-week period. During that period, participants were asked to maintain their normal diet and physical activity. Outcome measures included anthropometry, muscle mass, and muscle function. All these measures were assessed at baseline, week 5, and week 10. Repeated-measures analysis of variance was used to analyze statistical significance.Results: Consuming fish twice a week for 10 weeks significantly increased the skeletal muscle mass and appendicular lean mass divided by height squared (ALM/h2) (p < 0.01). Handgrip strength and gait speed <0.8 m/s were also improved (p < 0.01) at week 10 compared with that at baseline.Discussion: Consuming fish seems to improve muscle mass and function and may slow sarcopenia progression in middle-age and older adults.

scholarly journals Lactobacillus plantarum HY7715 Ameliorates Sarcopenia by Improving Skeletal Muscle Mass and Function in Aged Balb/c Mice

2021 ◽  
Vol 22 (18) ◽  
pp. 10023
Author(s):  
Kippeum Lee ◽  
Jisoo Kim ◽  
Soo-Dong Park ◽  
Jae-Jung Shim ◽  
Jung-Lyoul Lee
Keyword(s):  
Skeletal Muscle ◽  
Lactobacillus Plantarum ◽  
Muscle Mass ◽  
Physical Performance ◽  
Muscle Function ◽  
Skeletal Muscle Mass ◽  
Myoblast Differentiation ◽  
Microbiome Composition ◽  
And Function

Sarcopenia is a loss of muscle mass and function in elderly people and can lead to physical frailty and fall-related injuries. Sarcopenia is an inevitable event of the aging process that substantially impacts a person’s quality of life. Recent studies to improve muscle function through the intake of various functional food materials are attracting attention. However, it is not yet known whether probiotics can improve muscle mass and muscle strength and affect physical performance. Lactobacillus plantarum HY7715 (HY7715) is a lactic acid bacteria isolated from kimchi. The present research shows that L. plantarum HY7715 increases physical performance and skeletal muscle mass in 80-week-old aged Balb/c male mice. HY7715 not only induces myoblast differentiation and mitochondrial biogenesis but also inhibits the sarcopenic process in skeletal muscle. In addition, HY7715 recovers the microbiome composition and beta-diversity shift. Therefore, HY7715 has promise as a functional probiotic supplement to improve the degeneration of muscle function that is associated with aging.

scholarly journals Association of Diet Quality with Low Muscle Mass-Function in Korean Elderly

2019 ◽  
Vol 16 (15) ◽  
pp. 2733 ◽  
Author(s):  
Mikyeong Jung ◽  
Saejong Park ◽  
Hyesook Kim ◽  
Oran Kwon
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Diet Quality ◽  
Skeletal Muscle Mass ◽  
Mass Function ◽  
Elderly Men ◽  
Age Related ◽  
European Working ◽  
And Function ◽  
Korean Elderly

There is a growing body of evidence that links nutrition to muscle mass and function in the elderly, suggesting that it has an important role to play both in the prevention and management of age-related sarcopenia. Some nutrients have been studied, but less is known about the influence of overall diet quality on the loss of skeletal muscle mass and function. This study investigated the interrelationship between the recommended food score (RFS), as an indicator of overall diet quality, and muscle mass function among the Korean elderly. The sample consisted of 521 participants (263 men and 258 women), aged >65 years, who participated in the 2014–2015 National Fitness Award project. Appendicular skeletal muscle mass (ASM) was assessed by bioelectrical impedance analysis. Low muscle mass was defined as having an ASM corrected for height lower than the cutoff value established by the European Working Group on Sarcopenia in Older People. Muscle function, assessed by handgrip strength (HGS), was defined as low if it was below the 20th percentile of elderly men and women. Low muscle mass-function, defined as low muscle mass with low muscle strength (HGS), was found in 29 men (11.0%) and 22 women (8.5%). In elderly men, the low muscle mass-function group had significantly lower RFS values than the normal group after adjustments for age, body fat percentage, drinking, smoking, education, and physical activity (p = 0.019). However, there was no association between RFS and muscle mass-function in elderly women. Our findings suggest that better diet quality may be associated with higher muscle mass in elderly Korean men.

scholarly journals Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Eugenia Migliavacca ◽  
Stacey K. H. Tay ◽  
Harnish P. Patel ◽  
Tanja Sonntag ◽  
Gabriele Civiletto ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Oxidative Capacity ◽  
Molecular Profile ◽  
Transcriptional Signature ◽  
Age Related ◽  
Transcriptional Changes ◽  
Physical Autonomy ◽  
And Function

AbstractThe causes of impaired skeletal muscle mass and strength during aging are well-studied in healthy populations. Less is known on pathological age-related muscle wasting and weakness termed sarcopenia, which directly impacts physical autonomy and survival. Here, we compare genome-wide transcriptional changes of sarcopenia versus age-matched controls in muscle biopsies from 119 older men from Singapore, Hertfordshire UK and Jamaica. Individuals with sarcopenia reproducibly demonstrate a prominent transcriptional signature of mitochondrial bioenergetic dysfunction in skeletal muscle, with low PGC-1α/ERRα signalling, and downregulation of oxidative phosphorylation and mitochondrial proteostasis genes. These changes translate functionally into fewer mitochondria, reduced mitochondrial respiratory complex expression and activity, and low NAD+ levels through perturbed NAD+ biosynthesis and salvage in sarcopenic muscle. We provide an integrated molecular profile of human sarcopenia across ethnicities, demonstrating a fundamental role of altered mitochondrial metabolism in the pathological loss of skeletal muscle mass and function in older people.

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