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The age-related loss of skeletal muscle mass and function that is associated with sarcopenia can result in ultimate consequences such as decreased quality of life. The causes of sarcopenia are multifactorial and include environmental and biological factors. The purpose of this review is to synthesize what the literature reveals in regards to the ce...
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... this point, telomere length reaches a critical length and the chromosome may become un- capped. This in turn may result in disruption of chromosome integrity because uncapped telomeres activate signaling pathways that correlate with DNA damage and apoptosis (Figure 1) (124). ...
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... re- sults suggest that the microenvironment of aged skeletal muscle suppresses myogenic capability. However, positioning aged skeletal muscle in a young muscle tissue environmental milieu accelerates its repair (9, 13, 139, 145, 169, 170, 172, 173). Hetero- chronic transplantation studies and parabiotically paired mice demonstrate that in the presence of young environment, both aged and young satellite cells are able to fully activate and the muscle is com- pletely repaired (13,173,174). ...
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Background:
Endometrial cancer is the sixth most frequent type of cancer among women worldwide. Type I adenocarcinomas account for 80-85% of endometrial cancer cases and sometimes require more aggressive treatment than the remaining part of this group. Therefore, molecular markers to stratify adenocarcinomas are needed.
Materials and methods:
In...
Citations
... Low muscle mass is influenced by various factors, including aging, genetic predisposition, levels of physical activity, dietary habits, and diseases (8,9). Studies indicate that muscle mass and physical function decline with age, even in highly active older individuals, as muscle mass and strength remain significantly lower than in younger counterparts, highlighting the close relationship between low muscle mass and aging (10)(11)(12). ...
Objective
Muscle mass gradually declines with advancing age, and as an anti-aging protein, klotho may be associated with muscle mass. This study aims to explore the relationship between klotho levels and muscle mass in the middle-aged population.
Methods
Utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2011 to 2018, we conducted a cross-sectional analysis on a cohort of individuals aged 40–59. Weighted multivariable analysis was employed to assess the correlation between klotho and low muscle mass, with stratified and Restricted Cubic Spline (RCS) analyses.
Results
The cross-sectional investigation revealed a significant negative correlation between klotho levels and the risk of low muscle mass (Model 3: OR = 0.807, 95% CI: 0.712–0.915). A notable interaction between klotho and sex was observed, with a significant interaction effect (P for interaction = 0.01). The risk association was notably higher in females. The risk association was notably higher in females. Additionally, RCS analysis unveiled a significant linear relationship between klotho and low muscle mass (P for nonlinear = 0.9495, P for overall<0.0001).
Conclusion
Our observational analysis revealed a noteworthy inverse relationship between klotho and low muscle mass, particularly prominent among female participants. This discovery provides crucial insights for the development of more effective intervention strategies and offers a new direction for enhancing muscle quality in the middle-aged population.
... [1] Although sarcopenia is typically correlated with the aging process, lifestyle factors and chronic diseases are also implicated in its occurrence and progression. [2,3] The prevalence of sarcopenia exhibits substantial global variability, ranging from 10% to 27%. [4][5][6] Given the globally expanding aging population, the prevalence of sarcopenia has substantially increased. ...
Background
Previous studies on the association between serum uric acid (UA) levels and sarcopenia have yielded contradictory results. This meta-analysis and literature review assessed the association between serum UA levels and sarcopenia. Moreover, we conducted a comparative analysis of the differences in serum UA concentrations between individuals with and without sarcopenia.
Methods
A systematic search was conducted across various medical databases, namely PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, and Wanfang (from the start to August 20, 2023). This search focused on published studies that investigated the relationship between serum UA levels and sarcopenia. The relationship between serum UA concentration and the occurrence of sarcopenia was analyzed, and the differences in serum UA concentrations between individuals with sarcopenia and control groups were reviewed. Statistical analysis was performed using STATA 11.0 and R 4.1.3.
Results
Sixteen studies were considered for our analysis. The results indicated a significant association between low serum UA concentration and a higher sarcopenia risk, particularly among male patients (adjusted odds ratio = 0.65, 95% confidence interval [CI] = 0.49, 0.87, P = .004, I² = 0%). Individuals with sarcopenia exhibited decreased serum UA concentrations compared with those of the control group (mmol/L: weighted mean difference = −28.25, 95% CI = −40.45, −16.05, P < .001; mg/dL: weighted mean difference = −0.82, 95% CI = −1.05, −0.58, P < .001). Additionally, serum UA concentration was positively correlated with skeletal muscle mass index and handgrip strength (skeletal muscle index: correlation coefficient = 0.17, 95% CI = 0.11, 0.22, P < .001; handgrip strength: common odds ratios = 0.10, 95% CI = 0.06, 0.14, P < .001).
Conclusion
Individuals with sarcopenia have relatively low serum UA concentrations. A notable correlation between serum UA concentration and sarcopenia was observed. Hence, monitoring UA levels could aid in the early detection and treatment of sarcopenia, enabling timely intervention to preserve muscle mass and strength.
... The Forelimb grip strength test assessed skeletal falls, compromised functionality, weakness, and, in extreme cases, mortality (Cruz-Jentoft and Sayer 2019). It has been documented that the content of human muscle tissue progressively diminishes starting from the age of 35, exhibiting a decline of up to 30% in individuals between the ages of 50 and 80 (Arthur and Cooley 2012). Sarcopenia impacts virtually all elderly individuals. ...
Abstact
With advancing age, the incidence of sarcopenia increases, eventually leading to a cascade of adverse events. However, there is currently a lack of effective pharmacological treatment for sarcopenia. Sodium-glucose co-transporter 2 inhibitor (SGLT2i) empagliflozin demonstrates anti-fibrotic capabilities in various organs. This study aims to determine whether empagliflozin can improve skeletal muscle fibrosis induced by sarcopenia in naturally aging mice. A natural aging model was established by feeding male mice from 13 months of age to 19 months of age. A fibrosis model was created by stimulating skeletal muscle fibroblasts with TGF-β1. The Forelimb grip strength test assessed skeletal muscle function, and expression levels of COL1A1, COL3A1, and α-SMA were analyzed by western blot, qPCR, and immunohistochemistry. Additionally, levels of AMPKα/MMP9/TGFβ1/Smad signaling pathways were examined. In naturally aging mice, skeletal muscle function declines, expression of muscle fibrosis markers increases, AMPKα expression is downregulated, and MMP9/TGFβ1/Smad signaling pathways are upregulated. However, treatment with empagliflozin reverses this phenomenon. At the cellular level, empagliflozin exhibits similar anti-fibrotic effects, and these effects are attenuated by Compound C and siAMPKα. Empagliflozin exhibits anti-fibrotic effects, possibly associated with the AMPK/MMP9/TGFβ1/Smad signaling pathways.
... Karim et al. (2022) Wnt signaling plays an essential role in myogenesis, muscle repair, and stem cell regeneration. Arthur and Cooley, (2012). ...
Introduction: A noteworthy correlation was seen between changes in the gut microbiome and sarcopenia in older adults. Along with increasing research on probiotic supplementation for various medical problems, we aimed to obtain evidence and summarize the effect of probiotic supplementation on sarcopenic indices among older adults.
Methods: We utilized PubMed, EBSCO, and Proquest, in addition to manual search using synonyms and variation for ‘probiotic,’ ‘sarcopenia,’ and ‘older adults.’ Randomized controlled trials investigated the utilization of probiotics or probiotic-containing products in older adults with sarcopenic indices including muscle mass and strength. The random-effects model was applied to the meta-analysis process.
Results: Seven studies were obtained with 733 pooled older adults. Probiotic supplementation resulted in a significant increase of muscle mass with adjusted SMD (Standardized Mean Difference) of 0.962 (95% CI: 0.288 to 1.635, p = 0.049) using till and trim analysis and muscle strength with SMD of 1.037 (95% CI: 0.077 to 1.996, p = 0.03). However, both outcomes were associated with significantly high heterogeneity (I ² = 89.5% and I ² = 89.9%, respectively).
Conclusion: When opposed to a placebo, the probiotic treatment improved the amount of muscle and its endurance based on recent evidence, however, further studies should be done with larger samples and targeted populations.
... In skeletal muscle, where both AXIN1 and AXIN2 are expressed, AXIN2 plays a more prominent role, particularly in myogenesis [158][159][160]. In this context, AXIN2 can functionally replace AXIN1 in regulating AMPactivated protein kinase (AMPK). ...
AXIN1, has been initially identified as a prominent antagonist within the WNT/β-catenin signaling pathway, and subsequently unveiled its integral involvement across a diverse spectrum of signaling cascades. These encompass the WNT/β-catenin, Hippo, TGFβ, AMPK, mTOR, MAPK, and antioxidant signaling pathways. The versatile engagement of AXIN1 underscores its pivotal role in the modulation of developmental biological signaling, maintenance of metabolic homeostasis, and coordination of cellular stress responses. The multifaceted functionalities of AXIN1 render it as a compelling candidate for targeted intervention in the realms of degenerative pathologies, systemic metabolic disorders, cancer therapeutics, and anti-aging strategies. This review provides an intricate exploration of the mechanisms governing mammalian AXIN1 gene expression and protein turnover since its initial discovery, while also elucidating its significance in the regulation of signaling pathways, tissue development, and carcinogenesis. Furthermore, we have introduced the innovative concept of the AXIN1-Associated Phosphokinase Complex (AAPC), where the scaffold protein AXIN1 assumes a pivotal role in orchestrating site-specific phosphorylation modifications through interactions with various phosphokinases and their respective substrates.
... 26 Being involved in muscle repair, Wnt signalling activation resulted impaired in the aged skeletal muscle; particularly, the imbalance of Wnt and Notch signalling pathways leads to the age-related decrease in muscle regenerative capacity. 27 Wnt pathway is also strictly connected to cadherin signalling pathway: In C2C12 cell line, it was demonstrated that M-cadherin regulates β-catenin phosphorylation and, consequently, the Wnt cascade and, thus, affects myogenesis. 28 FGF signalling pathway is essential for skeletal muscle stem cells and its deregulation could lead to decrease of stem cell self-renewal and, consequently, muscle wasting. ...
Background
Skeletal muscle mass wasting almost invariably accompanies bone loss in elderly, and the coexistence of these two conditions depends on the tight endocrine crosstalk existing between the two organs, other than the biomechanical coupling. Since the current diagnostics limitation in this field, and given the progressive population aging, more effective tools are needed. The aim of this study was to identify circulating microRNAs (miRNAs) as potential biomarkers for muscle mass wasting in post‐menopausal osteoporotic women.
Methods
One hundred seventy‐nine miRNAs were assayed by quantitative real‐time polymerase chain reaction in plasma samples from 28 otherwise healthy post‐menopausal osteoporotic women (73.4 ± 6.6 years old). The cohort was divided in tertiles based on appendicular skeletal muscle mass index (ASMMI) to better highlight the differences on skeletal muscle mass (first tertile: n = 9, ASMMI = 4.88 ± 0.40 kg·m ⁻² ; second tertile: n = 10, ASMMI = 5.73 ± 0.23 kg·m ⁻² ; third tertile: n = 9, ASMMI = 6.40 ± 0.22 kg·m ⁻² ). Receiver operating characteristic (ROC) curves were calculated to estimate the diagnostic potential of miRNAs. miRNAs displaying a statistically significant fold change ≥ ±1.5 and area under the curve (AUC) > 0.800 ( P < 0.05) between the first and third tertiles were considered. A linear regression model was applied to estimate the association between miRNA expression and ASMMI in the whole population, adjusting for body mass index, age, total fat (measured by total‐body dual‐energy X‐ray absorptiometry [DXA]) and bone mineral density (measured by femur DXA). Circulating levels of adipo‐myokines were evaluated by bead‐based immunofluorescent assays and enzyme‐linked immunosorbent assays.
Results
Five miRNAs (hsa‐miR‐221‐3p, hsa‐miR‐374b‐5p, hsa‐miR‐146a‐5p, hsa‐miR‐126‐5p and hsa‐miR‐425‐5p) resulted down‐regulated and two miRNAs (hsa‐miR‐145‐5p and hsa‐miR‐25‐3p) were up‐regulated in the first tertile (relative‐low ASMMI) compared with the third tertile (relative‐high ASMMI) (fold change ≥ ±1.5; P ‐value < 0.05). All the corresponding ROC curves had AUC > 0.8 ( P < 0.05). Two signatures hsa‐miR‐126‐5p, hsa‐miR‐146a‐5p and hsa‐miR‐425‐5p; and hsa‐miR‐126‐5p, hsa‐miR‐146a‐5p, hsa‐miR‐145‐5p and hsa‐miR‐25‐3p showed the highest AUC, 0.914 (sensitivity = 77.78%; specificity = 100.00%) and 0.901 (sensitivity = 88.89%; specificity = 100.00%), respectively.
Conclusions
In this study, we identified, for the first time, two miRNA signatures, hsa‐miR‐126‐5p, hsa‐miR‐146a‐5p and hsa‐miR‐425‐5p; and hsa‐miR‐126‐5p, hsa‐miR‐146a‐5p, hsa‐miR‐145‐5p and hsa‐miR‐25‐3p, specifically associated with muscle mass wasting in post‐menopausal osteoporotic women.
... Second, we could not identify the potential circRNA/miRNA/mRNA molecular mechanisms of these two circRNAs. Considering that the progression of sarcopenia is related to the activation of the Wnt/β-catenin signaling pathway, additional molecular studies may reveal a link between sarcopenia and the two circRNAs which inhibit the Wnt/β-catenin signaling pathway [10,33]. However, the association between the two hsa_circRNAs and sarcopenia was insignificant in the current study. ...
The clinical significance of hsa_circ_0004018 and hsa_circ_0003570 in patients with hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) is unclear. We aimed to explore the clinical significance and prognostic utility of these two circular RNAs (circRNAs) in patients with HBV-HCC. Based on 86 paired tissue samples of HCC and adjacent non-HCC, the relative expression profiles of hsa_circ_0004018 and hsa_circ_0003570 were determined using quantitative real-time polymerase chain reactions. The cut-off values were the median expression of each of the two circRNAs in 86 patients with HBV-HCC. The combination group comprised patients with high levels of the two circRNAs. Clinicopathological features, body composition profiles at the L3 level, and survival rates were investigated. The expression of hsa_circ_0004018 and hsa_circ_0003570 was downregulated in HCC tissues compared with non-HCC tissues. High expression levels of hsa_circ_0003570 (hazard ratio (HR), 0.437; p = 0.009) and hsa_circ_0004018 (HR, 0.435; p = 0.005) were inversely independent risk factors for overall and progression-free survival in patients with HBV-HCC, whereas the combination group was also an inversely independent risk factor for overall (HR, 0.399; p = 0.005) and progression-free survival (HR, 0.422; p = 0.003) in patients with HBV-HCC. The combination of hsa_circ_0003570 and hsa_circ_0004018 may be a potential prognostic biomarker for HBV-HCC.
... Once received, these signals are passed into host cells to modulate cell growth and renewal. Notable examples of such transmembrane structures include connexins [47], pannexins [48], notch [49,50], and low-density lipoprotein receptor-related proteins 5/6 (Lrp5/6) [51][52][53]. ...
Physical activity is well-established as an important protective factor against degenerative conditions and a promoter of tissue growth and renewal. The discovery of Fibronectin domain-containing protein 5 (FNDC5) as the precursor of Irisin in 2012 sparked significant interest in its potential as a diagnostic biomarker and a therapeutic agent for various diseases. Clinical studies have examined the correlation between plasma Irisin levels and pathological conditions using a range of assays, but the lack of reliable measurements for endogenous Irisin has led to uncertainty about its prognostic/diagnostic potential as an exercise surrogate. Animal and tissue-engineering models have shown the protective effects of Irisin treatment in reversing functional impairment and potentially permanent damage, but dosage ambiguities remain unresolved. This review provides a comprehensive examination of the clinical and basic studies of Irisin in the context of degenerative conditions and explores its potential as a therapeutic approach in the physiological processes involved in tissue repair/regeneration.
... Muscle mass, strength and function are progressively lost with aging [1]. A loss or reduction in skeletal muscle function often leads to increased morbidity and mortality either directly, or indirectly, via the development of secondary diseases such as diabetes, obesity and cardiovascular disease [1,2]. Maintaining skeletal muscle function throughout the lifespan into old age is essential for independent living and good health. ...
Blue whiting (BW) represents an underutilised fish species containing a high-quality protein and amino acid (AA) profile with numerous potentially bioactive peptide sequences, making BW an economic and sustainable alternative source of protein. This study investigated the impact of three different BW protein hydrolysates (BWPH-X, Y and Z) on growth, proliferation and muscle protein synthesis (MPS) in skeletal muscle (C2C12) myotubes. BWPHs were hydrolysed using different enzymatic and heat exposures and underwent simulated gastrointestinal digestion (SGID), each resulting in a high degree of hydrolysis (33.41–37.29%) and high quantities of low molecular mass peptides (86.17–97.12% <1 kDa). C2C12 myotubes were treated with 1 mg protein equivalent/mL of SGID-BWPHs for 4 h. Muscle growth and myotube thickness were analysed using an xCelligence™ platform. Anabolic signalling (phosphorylation of mTOR, rpS6 and 4E-BP1) and MPS measured by puromycin incorporation were assessed using immunoblotting. BWPH-X significantly increased muscle growth (p < 0.01) and myotube thickness (p < 0.0001) compared to the negative control (amino acid and serum free media). Muscle protein synthesis (MPS), as measured by puromycin incorporation, was significantly higher after incubation with BWPH-X compared with the negative control, but did not significantly change in response to BWPH-Y and Z treatments. Taken together, these preliminary findings demonstrate the anabolic potential of some but not all BWPHs on muscle enhancement, thus providing justification for human dietary intervention studies to confirm and translate the results of such investigations to dietary recommendations and practices.
... 250 It has been reported that Notch signaling is impaired in regenerating aged skeletal muscle, which can be restored by physiological stimuli of exercise. [251][252][253] Therefore, further researches should be carried out to demonstrate the underlying mechanisms of mechanotransduction mediated tissue regeneration with different exercise types, which may provide the novel targets for clinical interventions (Fig. 2). ...
Physical activity has been known as an essential element to promote human health for centuries. Thus, exercise intervention is encouraged to battle against sedentary lifestyle. Recent rapid advances in molecular biotechnology have demonstrated that both endurance and resistance exercise training, two traditional types of exercise, trigger a series of physiological responses, unraveling the mechanisms of exercise regulating on the human body. Therefore, exercise has been expected as a candidate approach of alleviating a wide range of diseases, such as metabolic diseases, neurodegenerative disorders, tumors, and cardiovascular diseases. In particular, the capacity of exercise to promote tissue regeneration has attracted the attention of many researchers in recent decades. Since most adult human organs have a weak regenerative capacity, it is currently a key challenge in regenerative medicine to improve the efficiency of tissue regeneration. As research progresses, exercise-induced tissue regeneration seems to provide a novel approach for fighting against injury or senescence, establishing strong theoretical basis for more and more “exercise mimetics.” These drugs are acting as the pharmaceutical alternatives of those individuals who cannot experience the benefits of exercise. Here, we comprehensively provide a description of the benefits of exercise on tissue regeneration in diverse organs, mainly focusing on musculoskeletal system, cardiovascular system, and nervous system. We also discuss the underlying molecular mechanisms associated with the regenerative effects of exercise and emerging therapeutic exercise mimetics for regeneration, as well as the associated opportunities and challenges. We aim to describe an integrated perspective on the current advances of distinct physiological mechanisms associated with exercise-induced tissue regeneration on various organs and facilitate the development of drugs that mimics the benefits of exercise.
