Age-related Loss Of Skeletal Muscle Research Articles

3D Mitochondrial Structure in Aging Human Skeletal Muscle: Insights into MFN-2 Mediated Changes.

Age-related atrophy of skeletal muscle, is characterized by loss of mass, strength, endurance, and oxidative capacity during aging. Notably, bioenergetics and protein turnover studies have shown that mitochondria mediate this decline in function. Although exercise has been the only therapy to mitigate sarcopenia, the mechanisms that govern how exercise serves to promote healthy muscle aging are unclear. Mitochondrial aging is associated with decreased mitochondrial capacity, so we sought to investigate how aging affects mitochondrial structure and potential age-related regulators. Specifically, the three-dimensional (3D) mitochondrial structure associated with morphological changes in skeletal muscle during aging requires further elucidation. We hypothesized that aging causes structural remodeling of mitochondrial 3D architecture representative of dysfunction, and this effect is mitigated by exercise. We used serial block-face scanning electron microscopy to image human skeletal tissue samples, followed by manual contour tracing using Amira software for 3D reconstruction and subsequent analysis of mitochondria. We then applied a rigorous in vitro and in vivo exercise regimen during aging. Across 5 human cohorts, we correlate differences in magnetic resonance imaging, mitochondria 3D structure, exercise parameters, and plasma immune markers between young (under 50 years) and old (over 50 years) individuals. We found that mitochondria we less spherical and more complex, indicating age-related declines in contact site capacity. Additionally, aged samples showed a larger volume phenotype in both female and male humans, indicating potential mitochondrial swelling. Concomitantly, muscle area, exercise capacity, and mitochondrial dynamic proteins showed age-related losses. Exercise stimulation restored mitofusin 2 (MFN2), one such of these mitochondrial dynamic proteins, which we show is required for the integrity of mitochondrial structure. Furthermore, we show that this pathway is evolutionarily conserved as Marf, the MFN2 ortholog in Drosophila, knockdown alters mitochondrial morphology and leads to the downregulation of genes regulating mitochondrial processes. Our results define age-related structural changes in mitochondria and further suggest that exercise may mitigate age-related structural decline through modulation of mitofusin 2.

Biophysical and nutritional combination treatment for myosteatosis in patients with sarcopenia: a study protocol for single-blinded randomised controlled trial

IntroductionSarcopenia is characterised by age-related loss of skeletal muscle and function and is associated with risks of adverse outcomes. The prevalence of sarcopenia increases due to ageing population and effective...

Age-Related Loss of Skeletal Muscle and Associated Risk Factors in Middle-Aged Men: A Comprehensive Study

Age-Related Loss of Skeletal Muscle and Associated Risk Factors in Middle-Aged Men: A Comprehensive Study

Physical exercise attenuates age-related muscle atrophy and exhibits anti-ageing effects via the adiponectin receptor 1 signalling.

Although the adiponectin signalling exerts exercise-mimicking effects, whether this pathway contributes to the anti-ageing benefits of physical exercise has not been established yet. Swim exercise training and wheel running were used to measure lifespan in the nematode Caenorhabditis elegans and skeletal muscle quality in mice, respectively. Muscle weight, muscle fibre cross-sectional area (CSA) and myonuclei number were used to evaluate muscle mass. RNA sequencing (RNA-Seq) analysis of skeletal muscle in exercised mice was used to study the underlying mechanisms. Western blot and immunofluorescence were performed to explore autophagy- and senescence-related markers. The C.elegans adiponectin receptor PAQR-1/AdipoR1, but not PAQR-2/AdipoR2, was activated (3.55-fold and 3.48-fold increases in p-AMPK on Days 1 and 6, respectively, P<0.001), which was involved in lifespan extension in exercised worms. Exercise training increased skeletal muscle mass index (1.29-fold, P<0.01), muscle weight (1.75-fold, P<0.001), myonuclei number (1.33-fold, P<0.05), muscle fibre CSA (1.39-fold, P<0.05) and capillary abundance (2.19-fold, P<0.001 for capillary density; 1.58-fold, P<0.01 for capillary number) in aged mice. Physical exercise reduced protein (2.94-fold, P<0.001) and mRNA levels (1.70-fold, P<0.001) of p16INK4a , a marker for cellular senescence, in skeletal muscle of aged mice. These beneficial effects of exercise on skeletal muscle of mice were dependent on AdipoR1. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis for differentially expressed genes in skeletal muscle between exercised mice with and without AdipoR1 knockdown by RNA-Seq analysis revealed that several KEGG pathways, such as 'AMPK signalling pathway' (P<0.001), 'FOXO signalling pathway' (P<0.001) and 'autophagy' (P<0.001) were overrepresented. Knockdown of FoxO3a inhibited exercise-mediated beneficial effects on skeletal muscle quality of mice by inhibiting autophagy/mitophagy (3.81-fold reduction in LC3-II protein, P<0.001; 1.53-fold reduction in BNIP3 protein, P<0.05). Knockdown of daf-16, the FoxO homologue in C.elegans, reduced autophagy (2.77-fold and 2.06-fold reduction in GFP::LGG-1 puncta in seam cells and the intestine, respectively, P<0.05) and blocked lifespan extension by exercise in worms. Our findings provide insights into how the AdipoR1 pathway has an impact on the anti-ageing benefits of exercise and implicate that activation of the AdipoR1 signalling may represent a potential therapeutic strategy for reducing age-related loss of skeletal muscle.

Effects of Turmeric Extract on Age-Related Skeletal Muscle Atrophy in Senescence-Accelerated Mice.

Muscle atrophy is one of the main causes of sarcopenia-the age-related loss of skeletal muscle. In this study, we investigated the effect of turmeric (Curcuma longa) extract (TE) supplementation on age-related muscle atrophy in a senescence-accelerated mouse model and explored the underlying mechanisms. Twenty-six-week-old male, senescence-accelerated mouse resistant (SAMR) mice received the AIN-93G basal diet, while twenty-six-week-old male, senescence-accelerated mouse prone 8 (SAMP8) mice received the AIN-93G basal diet or a 2% TE powder-supplemented diet for ten weeks. Our findings revealed that TE supplementation showed certain effects on ameliorating the decrease in body weight, tibialis anterior weight, and mesenteric fat tissue weight in SAMP8 mice. TE improved gene expression in the glucocorticoid receptor-FoxO signaling pathway in skeletal muscle, including redd1, klf15, foxo1, murf1, and mafbx. Furthermore, TE might have the certain potential on improving the dynamic balance between anabolic and catabolic processes by inhibiting the binding of glucocorticoid receptor or FoxO1 to the glucocorticoid response element or FoxO-binding element in the MuRF1 promoter in skeletal muscle, thereby promoting muscle mass and strength, and preventing muscle atrophy and sarcopenia prevention. Moreover, TE may have reduced mitochondrial damage and maintained cell growth and division by downregulating the mRNA expression of the genes mfn2 and tsc2. Thus, the results indicated TE's potential for preventing age-related muscle atrophy and sarcopenia.

Is dexamethasone-induced muscle atrophy an alternative model for naturally aged sarcopenia model?

Primary sarcopenia is usually known as age-related skeletal muscle loss; however, other factors like endocrine, lifestyle and inflammation can also cause muscle loss, known as secondary sarcopenia. Although many studies have used different sarcopenia animal models for exploring the underlying mechanism and therapeutic approaches for sarcopenia, limited study has provided evidence of the relevance of these animal models. This study aims to investigate the similarity and difference in muscle qualities between primary and secondary sarcopenia mice models, using naturally aged mice and dexamethasone-induced mice. 21-month-old mice were used as naturally aged primary sarcopenia mice and 3-month-old mice received daily intraperitoneal injection of dexamethasone (20 mg/ kg body weight) for 10 days were used as secondary sarcopenia model. This study provided measurements for muscle mass and functions, including Dual-energy X-ray absorptiometry (DXA) scanning, handgrip strength test and treadmill running to exhaustion test. Besides, muscle contraction, muscle fibre type measurements and gene expression were also performed to provide additional information on muscle qualities. The results suggest two sarcopenia animal models shared a comparable decrease in forelimb lean mass, muscle fibre size, grip strength and muscle contraction ability. Besides, the upregulation of protein degradation genes was also observed in two sarcopenia animal models. However, only primary sarcopenia mice were identified with an early stage of mtDNA deletion. Collectively, this study evaluated that the dexamethasone-induced mouse model could be served as an alternative model for primary sarcopenia, according to the comparable muscle mass and functional changes. However, whether dexamethasone-induced mice can be used as an animal model when studying the molecular mechanisms of sarcopenia needs to be carefully evaluated. The purpose of sarcopenia research is to investigate appropriate treatments for reversing the loss of skeletal muscle mass and functions. Using animal models for the preclinical study could predict the safety and efficacy of the treatments. This study compared the typical age-related sarcopenia mice model and dexamethasone-induced secondary sarcopenia mice to provide evidence of the pathological and functional changes in the mice models.

Skeletal Muscle and Fat Mass Reflect Chronic Pain in Older Adult.

Objectives: The prevalence of chronic pain increases with age. It has been reported that chronic pain is associated with sarcopenia and obesity. Age-related skeletal muscle loss and fat gain are known to occur due to chronic inflammation. The aim of this study was to analyze how skeletal muscle and fat, caused by chronic inflammation due to aging, regulate the development of geriatric chronic pain. Methods: The results of skeletal muscle and fat mass, 412 participants aged ≥65 years with non-specific chronic pain lasting ≥6 months, including low back, neck, and knee pain, was compared with the control without chronic pain. Body composition threshold regulating chronic pain was calculated. Results: A significantly lower skeletal muscle mass index and higher body fat percentage were observed in patients with chronic pain than that in the control. The muscle fat ratio (MFR) was significantly lower in the chronic pain group than in the control group. When the MFR threshold related to chronic pain was calculated by sex, it was 2.984 for men and 1.867 for women. Conclusions: Evaluation of the body composition of elderly patients with non-specific chronic pain revealed that the MFR was useful as an index related to chronic pain.

Free Fatty Acid Species Differentially Modulate the Inflammatory Gene Response in Primary Human Skeletal Myoblasts.

Simple SummaryEpidemiological studies show that obesity increases the risk of muscle mass loss with age, a syndrome called sarcopenic obesity. Obesity leads to increased free fatty acids (FFAs) and excessive fat deposits, which impair the integrity of skeletal muscles by unknown mechanisms. This report indicates that FFAs directly affect human skeletal muscle cell replication and inflammatory gene expression. The structural characteristics of FFAs play a decisive role in triggering both processes. Thus, the characterization of abundant FFA species in the skeletal muscle of obese individuals may become a useful tool to predict the progression of sarcopenic obesity.Age-related loss of skeletal muscle is associated with obesity and inflammation. In animal models, intramuscular fat deposits compromise muscle integrity; however, the relevant fat components that mediate muscular inflammation are not known. Previously, we hypothesized that free fatty acids (FFAs) may directly induce inflammatory gene expression in skeletal muscle cells of obese rats. Here, we examined this hypothesis in primary human skeletal myoblasts (SkMs) using multiplex expression analysis of 39 inflammatory proteins in response to different FFA species. Multiplex mRNA quantification confirmed that the IL6, IL1RA, IL4, LIF, CXCL8, CXCL1, CXCL12 and CCL2 genes were differentially regulated by saturated and unsaturated C16 or C18 FFAs. Fluorescence staining revealed that only saturated C16 and C18 strongly interfere with myoblast replication independent of desmin expression, mitochondrial abundance and oxidative activity. Furthermore, we addressed the possible implications of 71 human receptor tyrosine kinases (RTKs) in FFA-mediated effects. Phosphorylated EphB6 and TNK2 were associated with impaired myoblast replication by saturated C16 and C18 FFAs. Our data suggest that abundant FFA species in human skeletal muscle tissue may play a decisive role in the progression of sarcopenic obesity by affecting inflammatory signals or myoblast replication.

Association Between Sarcopenia and Adverse Events Following Transcatheter Aortic Valve Implantation

BackgroundSarcopenia, the age-related loss of skeletal muscle mass/function, has been identified as a marker of frailty. We examined the association between sarcopenia and adverse events following transcatheter aortic valve implantation (TAVI). MethodsA retrospective cohort study was conducted at Toronto General Hospital. All patients who underwent TAVI in the time period 2007-2017 with preoperative computed tomography were included. Skeletal muscle index (SMI) was calculated radiographically using psoas muscle area at the L3 vertebral level, divided by height. Various measures of sarcopenia, including mean SMI, SMI below the sex-specific median, and SMI in the lowest sex-specific quartile were calculated. The primary outcome was postoperative adverse events, defined as a composite of in-hospital mortality and morbidity including cardiovascular, pulmonary, neurologic, access-related, and gastrointestinal complications. Univariate and multivariate logistic regression were performed to determine the association between sarcopenia and adverse events. ResultsA total of 468 patients (mean age: 80.7 years) were included. Baseline comorbidity burden was high, particularly congestive heart failure (93.4%). Postoperative adverse events occurred in 62 patients (13.2%). Univariate logistic regression demonstrated that postoperative adverse events were correlated with mean SMI (odds ratio [OR] 0.81, 95% confidence interal [CI] 0.66-0.97), events were less than the SMI (OR 2.16, 95% CI 1.24-3.84), and SMI in the sex-specific lowest quartile (OR 2.34, 95% CI 1.33-4.07). On multivariate analysis, SMI in the sex-specific lowest quartile was an independent predictor of adverse events (OR 2.53, 95% CI 1.41-4.50). ConclusionsSarcopenia defined by radiologic psoas muscle measurements was independently associated with in-hospital mortality and morbidity following TAVI.

SY2-5 The need for rehabilitation–rethinking the rehabilitation of older cancer patients

Age-related skeletal muscle loss and weakness in older cancer patients is manifested by conditions such as sarcopenia and frailty. In oncology settings, sarcopenia and frailty have been associated with a variety of adverse health outcomes and may affect treatment outcomes. In 2010, the European Working Group on Sarcopenia in Older People (EWGSOP) proposed sarcopenia. Later, the Asian Working Group for Sarcopenia (AWGS) proposed a new set of diagnostic criteria for the Asian population. Recently, it has been shown that both exercise and nutritional interventions are useful in Japan, as well as screening for sarcopenia. The number of studies that combine exercise and nutrition interventions is increasing. On the other hand, I think the pre-sarcopenia and dynapenia conditions are important, but I get the impression that they are being left behind. In this presentation, I will present the latest findings on these conditions for the elderly and skeletal muscles, and summarize the information necessary for the rehabilitation of elderly cancer patients.

Sarcopenia and Neuroscience: Learning to Communicate.

In the 1990s and early 2000s, the common definition for sarcopenia was age-related loss of skeletal muscle, and low levels of muscle mass were central to sarcopenia diagnosis. In more recent consensus definitions, however, low muscle strength displaces low muscle mass as a defining feature of sarcopenia. The change stems from growing evidence that muscle weakness is a better predictor of adverse health outcomes (eg, mobility limitations) than muscle mass. This evidence accompanies an emerging recognition that central neural mechanisms are critical determinants of age-related changes in strength and mobility that can occur independently of variations in muscle mass. However, strikingly little practical attention is typically given to the potential role of the central nervous system in the etiology or remediation of sarcopenia (ie, low muscle function). In this article, we provide an overview of some mechanisms that mediate neural regulation of muscle contraction and control, and highlight the specific contributions of neural hypoexcitability, dopaminergic dysfunction, and degradation of functional and structural brain connectivity in relation to sarcopenia. We aim to enhance the lines of communication between the domains of sarcopenia and neuroscience. We believe that appreciation of the neural regulation of muscle contraction and control is fundamental to understanding sarcopenia and to developing targeted therapeutic strategies for its treatment.

Rehabilitation Nutrition and Exercise Therapy for Sarcopenia.

Sarcopenia is an age-related loss of skeletal muscle associated with adverse outcomes such as falls, fractures, disability, and increased mortality in older people and hospitalized patients. About half of older male nursing home residents have sarcopenia. The diagnostic criteria by the European Working Group on Sarcopenia in Older People (EWGSOP) and the Asian Working Group for Sarcopenia (AWGS) have led to increased interest in sarcopenia. Exercise and nutritional management are crucial for the prevention and treatment of sarcopenia. Nutritional therapy for sarcopenia that includes 20 g of whey protein and 800 IU of vitamin D twice a day improves lower limb strength. Exercise therapy for sarcopenia, such as resistance training and 6 months of home exercises, improves muscle strength and physical function. Combination therapy that includes both nutritional and exercise therapy improves gait speed and knee extension strength more than either exercise alone or nutrition therapy alone. Excessive bedrest and mismanagement of nutrition in medical facilities can lead to iatrogenic sarcopenia. Iatrogenic sarcopenia is sarcopenia caused by the activities of health care workers in health care facilities. Appropriate nutritional management and exercise programs through rehabilitation nutrition are important for prevention and treatment of iatrogenic sarcopenia. Nutritional and exercise therapy should be started very early after admission and adjusted to the level of inflammation and disease status. Repeated assessment, diagnosis, goal setting, interventions, and monitoring using the rehabilitation nutrition care process is important to maximize treatment effectiveness and improve patients' functional recovery and quality of life.

Association between Reproductive Span and Sarcopenia.

Sarcopenia is defined as an age-related loss of skeletal muscle and is associated with several health disorders. Causes of sarcopenia, which included physical inactivity, alcohol, dietary habits, and smoking, have been researched. The present study was undertaken to examine the association between reproductive span and sarcopenia in Korean women. Data obtained from 2008 to 2011 Korea National Health and Nutrition Examination Surveys (KNHANES) were analyzed. We defined sarcopenia based on the cut-off values of the Foundation for the National Institutes of Health (FNIH) sarcopenia project criteria: ASM/BMI < 0.512 for women. Reproductive span was defined as years from menarche to menopause, and we divided the 3970 study subjects into three groups by reproductive span tertile. Multivariate logistic regression analysis was used to determine adjusted ORs for the relation between reproductive span and sarcopenia. The prevalence of sarcopenia in the study was 17.7% (704 of 3970). Multiple logistic regression analysis was performed using weighted populations. After adjusting for covariates, reproductive span was found to be inversely associated with the risk of sarcopenia [Tertile 1 = 1 (reference); Tertile 2, odds ratio (OR) = 0.927, 95% confidence interval (CI) = 0.863–0.995; Tertile 3, OR = 0.854, 95% CI = 0.793–0.915].

Advance in Drug Delivery for Ageing Skeletal Muscle.

The age-related loss of skeletal muscle, sarcopenia, is characterized by progressive loss of muscle mass, reduction in muscle strength, and dysfunction of physical performance. It has become a global health problem leading to several adverse outcomes in the ageing population. Research on skeletal muscle loss prevention and treatment is developing quickly. However, the current clinical approaches to sarcopenia are limited. Recently, novel drug delivery systems offer new possibilities for treating aged muscle loss. Herein, we briefly recapitulate the potential therapeutic targets of aged skeletal muscle and provide a concise advance in the drug delivery systems, mainly focus on the use of nano-carriers. Furthermore, we elaborately discuss the prospect of aged skeletal muscle treatment by nanotechnology approaches.

Potential Importance of Immune System Response to Exercise on Aging Muscle and Bone.

The age-related loss of skeletal muscle and bone tissue decreases functionality and increases the risk for falls and injuries. One contributing factor of muscle and bone loss over time is chronic low-grade inflammation. Exercise training is an effective countermeasure for decreasing the loss of muscle and bone tissue, possibly by enhancing immune system response. Herein, we discuss key interactions between the immune system, muscle, and bone in relation to exercise perturbations, and we identify that there is substantial "cross-talk" between muscle and bone and the immune system in response to exercise. Recent advances in our understanding of the "cross-talk" between muscle and bone and the immune system indicate that exercise is likely to mediate many of the beneficial effects on muscle and bone via their interactions with the immune system. The age-related loss of muscle and bone tissue may be partially explained by an impaired immune system via chronic low-grade inflammation. Exercise training has a beneficial effect on immune system function and aging muscle and bone. Theoretically, the "cross-talk" between the immune system, muscle, and bone in response to exercise enhances aging musculoskeletal health.

Effects of Exercise Training on Growth and Differentiation Factor 11 Expression in Aged Mice.

Exercise training is considered an effective way to prevent age-related skeletal muscle loss. However, the molecular mechanism has not been clarified. Growth and differentiation factor 11 (GDF11) has been controversially considered a regulator of skeletal muscle aging. In this study, we examined whether GDF11 is associated with skeletal muscle aging and the effects of exercise training on age-related skeletal muscle loss. First, we observed that Gdf11 mRNA and protein expression levels in young (5-month-old, n = 6) and aged (22-to 26-month-old, n = 5) mice were not significantly different. Aged mice were then divided into sedentary (n = 5) and exercise (n = 6) groups. The exercise group performed moderate-intensity treadmill running for 6 weeks. Treadmill exercise training increased Gdf11 mRNA expression in the soleus muscle, but its protein expression was not altered. In contrast, the GDF11 level in the plantaris muscle was not changed at either the mRNA or protein level. Collectively, our data demonstrate that GDF11 levels do not change during aging, and that treadmill exercise training increased Gdf11 mRNA expression in a predominantly slow-twitch muscle.

The PNPLA3 rs738409 C>G variant influences the association between low skeletal muscle mass and NAFLD: the Shanghai Changfeng Study.

Age-related skeletal muscle loss and patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphisms are both associated with increased liver steatosis and fibrosis in the absence of obesity. To investigate the influence of PNPLA3 polymorphism on the relationship between skeletal muscle loss and non-alcoholic fatty liver disease (NAFLD). Liver fat content was measured using a quantitative ultrasound method, and liver fibrosis was assessed by NAFLD fibrosis, BARD and FIB-4 scores in 3969 Chinese adults. The degree of sarcopenia was measured by weight-adjusted appendicular skeletal muscle mass (ASM%=appendicular skeletal muscle mass(kg)/body weight(kg)100%). The NAFLD proportion increased from 19.9% to 41.2% in men and 26.3% to 42.3% in women with decreasing ASM% quartiles (P<0.001). Low ASM% was inversely associated with NAFLD in PNPLA3 CC (odds ratio [OR]: men, 0.735 [0.610-0.885] and women, 0.812 [0.718-0.918], both P=0.001) and CG (OR: men, 0.673 [0.573-0.790] and women, 0.798 [0.713-0.893], both P<0.001) but not GG genotype carriers. The association remained significant after adjustment for age, cigarette smoking, fat mass, interaction between fat mass and ASM%, obesity, diabetes and all components of metabolic syndrome. Subgroup analyses found that PNPLA3 GG gene variant did not increase the risk for NAFLD in individuals with low ASM% regardless of obesity status. Low ASM% also increased risk for liver fibrosis (all P<0.05), which became insignificant after multiple adjustments. Low ASM% is associated with NAFLD and liver fibrosis. Dissociation of sarcopenia and NAFLD was found in PNPLA3 GG genotype carriers. A stratification based on PNPLA3 genotypes might facilitate personalised treatment for NAFLD.

Aging and metalloproteinases expression in mussels extracellular matrix

Abstract Emerging traits of cachexia in the elderly are usually attributed to disease, reduced physical activity, reduced appetite, reduced metabolic rate, and reduced energy demand. Lower physical activity and malnutrition lead to sarcopenia, understood as age-related skeletal muscle loss, often associated with reductions in strength, speed of contraction, and muscle power. In addition, the loss of muscle mass observed in old age may be due to changes in the nervous and endocrine systems, changes in muscle metabolism, decreased cell proliferation capacity, chronic age-related inflammation and oxidative stress, chronic disease conditions, and use of pharmaceuticals. Many diseases of muscle are accompanied by increased expression and activity of matrix metalloproteinases (MMP) from the zinc-dependent endopeptidase family, which are involved in the matrix remodeling process that accompanies muscle regeneration. Disorders of collagen accumulation resulting from changes in MMP expression may lead to pathological processes of muscle fibrosis. With the exception of the membrane-type matrix metalloproteinases (MT-MMP), MMP are synthesized in cells and secreted into the extracellular matrix (ECM). Secretory MMP can aggregate on cell surfaces by binding to MT-MMP, along with molecules responsible for cell adhesion, integrins or proteoglycans. To date, over 20 subtypes of metalloproteinases have been classified, each coded by different genes. MMP–induced degradation of structural matrix components (such as collagen, laminin, fibronectin) creates space for suitable cells and facilitates cell migration through the matrix. These enzymes are also involved in the regulation of cell activ ity and take part in inflammatory reactions. Many of the peptides released during partial ECM proteolysis may also act as signaling molecules with autocrine or paracrine action. MMPs also participate in cell-cell communication. Under physiological conditions, MMP are expressed at a very low level in tissues. Induction of expression occurs only in times of ECM reconstruction. Due to their protease activity, these enzymes remain under strict multi-level regulation, i.e. at the level of transcription, post-translational processing, secretion, activation, and degradation. Active MMPs are regulated by tissue inhibitors of metalloproteinases and by numerous cytokines and growth factors.

Castration induces satellite cell activation that contributes to skeletal muscle maintenance

Sarcopenia, the age-related loss of skeletal muscle, is a side effect of androgen deprivation therapy (ADT) for prostate cancer patients. Resident stem cells of skeletal muscle, satellite cells (SCs), are an essential source of progenitors for the growth and regeneration of skeletal muscle. Decreased androgen signaling and deficits in the number and function of SCs are features of aging. Although androgen signaling is known to regulate skeletal muscle, the cellular basis for ADT-induced exacerbation of sarcopenia is unknown. Furthermore, the consequences of androgen deprivation on SC fate in adult skeletal muscle remain largely unexplored. We examined SC fate in an androgen-deprived environment using immunofluorescence and fluorescence-activated cell sorting (FACS) with SC-specific markers in young castrated mice. To study the effects of androgen deprivation on SC function and skeletal muscle regenerative capacity, young castrated mice were subjected to experimental regenerative paradigms. SC-derived-cell contributions to skeletal muscle maintenance were examined in castrated Pax7CreER/+; ROSA26mTmG/+ mice. SCs were depleted in Pax7CreER/+; ROSA26DTA/+ mice to ascertain the consequences of SC ablation in sham and castrated skeletal muscles. Confocal immunofluorescence analysis of neuromuscular junctions (NMJs), and assessment of skeletal muscle physiology, contractile properties, and integrity were conducted. Castration led to SC activation, however this did not result in a decline in SC function or skeletal muscle regenerative capacity. Surprisingly, castration induced SC-dependent maintenance of young skeletal muscle. The functional dependence of skeletal muscles on SCs in young castrated mice was demonstrated by an increase in SC-derived-cell fusion within skeletal muscle fibers. SC depletion was associated with further atrophy and functional decline, as well as the induction of partial innervation and the loss of NMJ-associated myonuclei in skeletal muscles from castrated mice. The maintenance of skeletal muscles in young castrated mice relies on the cellular contributions of SCs. Considering the well-described age-related decline in SCs, the results in this study highlight the need to devise strategies that promote SC maintenance and activity to attenuate or reverse the progression of sarcopenia in elderly androgen-deprived individuals.

Association between hand muscle thickness and whole-body skeletal muscle mass in healthy adults: a pilot study.

[Purpose] Handgrip strength is a surrogate indicator for assessing disease-related and age-related skeletal muscle loss. Clinical utility as such a surrogate can be at least partially explained by the close relationship between handgrip strength and whole-body skeletal muscle mass. The handgrip strength is related to hand muscle size. Thus, the present study examined whether hand muscle thickness is associated with whole-body skeletal muscle mass. [Subjects and Methods] Thirty healthy male adults participated in this study. All subjects were right-hand dominant. Two muscle thicknesses (lumbrical and interosseous muscles) in the right hand were measured using ultrasonography. Whole-body and appendicular skeletal muscle masses were assessed using dual-energy X-ray absorptiometry. [Results] Although lumbrical muscle thickness was not correlated with whole-body skeletal muscle mass, there was a significant correlation with appendicular skeletal muscle mass. Furthermore, interosseous muscle thickness was significantly correlated with both whole-body and appendicular skeletal muscle masses. [Conclusion] The present findings suggest that two muscle thicknesses in the hand are related to whole-body and/or appendicular skeletal muscle mass in healthy adults. Therefore, we propose that despite being smaller than other limb muscles, hand muscle thickness may be useful as surrogate indicator for assessing disease-related and age-related skeletal muscle loss.