BACKGROUND

Sarcopenia is highly prevalent in patients with liver cirrhosis and contributes to decreased quality of life, increased morbidity, and mortality. The role of myostatin in cirrhosis-related sarcopenia remains controversial but may represent a potential therapeutic target.

This study aimed to investigate the association between serum myostatin levels and sarcopenia in patients with liver cirrhosis.

A cross-sectional study was conducted with 80 patients diagnosed with liver cirrhosis at Prof. Dr. I.G.N.G. Ngoerah General Hospital, Denpasar, Bali, Indonesia. Serum myostatin levels (ng/L) were measured using an ELISA technique. Sarcopenia was diagnosed based on the 2019 Asian Working Group for Sarcopenia (AWGS) consensus. Elevated myostatin levels were defined as values above the median. Bivariate and multivariate analyses were performed to assess associations between myostatin, cirrhosis severity, and sarcopenia.

The severity of cirrhosis (CTP B and C) was associated with elevated myostatin levels (PR = 2.046; 95% CI: 1.310–3.193; p = 0.002). Bivariate analysis demonstrated that elevated myostatin (PR = 2.178; 95% CI: 1.370–3.461; p < 0.001), CTP B and C (PR = 1.818; 95% CI: 1.223–2.701; p = 0.004), ascites (PR = 1.606; 95% CI: 1.110–2.324; p = 0.034), and malnutrition (PR = 1.806; 95% CI: 1.242–2.626; p = 0.004) were associated with sarcopenia. In multivariate analysis, only elevated serum myostatin remained significantly associated with sarcopenia (AOR = 4.273; 95% CI: 1.557–11.724; p = 0.005).

Elevated serum myostatin levels are strongly associated with sarcopenia in patients with liver cirrhosis. Cirrhosis severity is also linked to higher myostatin levels, suggesting a potential role for myostatin-targeted interventions in sarcopenia management.

Aging is typically associated with decreased musculoskeletal function, leading to reduced mobility and increased frailty. As a hallmark of aging, cellular senescence plays a crucial role in various age-related musculoskeletal diseases, including osteoporosis, osteoarthritis, intervertebral disc degeneration, and sarcopenia. The detrimental effects of senescence are primarily due to impaired regenerative capacity of stem cells and the pro-inflammatory environment created by accumulated senescent cells. The secreted senescence-associated secretory phenotype (SASP) can induce senescence in neighboring cells, further amplifying senescent signals. Although the removal of senescent cells and the suppression of SASP factors have shown promise in alleviating disease progression and restoring musculoskeletal health in mouse models, clinical trials have yet to demonstrate significant efficacy. This review summarizes the mechanisms of cellular senescence in age-related musculoskeletal diseases and discusses potential therapeutic strategies targeting cellular senescence.
Humans ; Cellular Senescence/physiology* ; Musculoskeletal Diseases/pathology* ; Aging/pathology* ; Animals ; Senescence-Associated Secretory Phenotype/physiology* ; Sarcopenia ; Osteoporosis

INTRODUCTION: The diagnosis of sarcopenia relies on key indicators such as handgrip strength, walking speed and muscle mass. Developing a composite index that integrates these measures could enhance clinical evaluation in older adults. This study aimed to standardise and combine these metrics to establish a z score for the sarcopenia composite index (ZoSCI) tailored for the ageing population. Additionally, we explore the risk factors associated with ZoSCI to provide insights into early prevention and intervention strategies. METHOD: This retrospective study analysed data between January 2017 and December 2021 from an elderly health programme in Taiwan, applying the Asian Working Group for Sarcopenia criteria to assess sarcopenia. ZoSCI was developed by standardising handgrip strength, walking speed and muscle mass into z scores and integrating them into a composite index. Receiver operating characteristic (ROC) curve analysis was used to determine optimal cut-off values, and multiple regression analysis identified factors influencing ZoSCI. RESULTS: Among the 5047 participants, the prevalence of sarcopenia was 3.7%, lower than the reported global prevalence of 3.9-15.4%. ROC curve analysis established optimal cut-off points for distinguishing sarcopenia in ZoSCI: -1.85 (sensitivity 0.91, specificity 0.88) for males and -1.97 (sensitivity 0.93, specificity 0.88) for females. Factors associated with lower ZoSCI included advanced age, lower education levels, reduced exercise frequency, lower body mass index and creatinine levels. CONCLUSION This study introduces ZoSCI, a new compo-site quantitative indicator for identifying sarcopenia in older adults. The findings highlight specific risk factors that can inform early intervention. Future studies should validate ZoSCI globally, with international collaborations to ensure broader applicability.
Humans ; Sarcopenia/physiopathology* ; Male ; Aged ; Female ; Retrospective Studies ; Hand Strength ; Taiwan/epidemiology* ; ROC Curve ; Aged, 80 and over ; Risk Factors ; Walking Speed ; Geriatric Assessment/methods* ; Prevalence ; Muscle, Skeletal ; Middle Aged

The increasing prevalence of aging has led to a rising incidence of comorbidity of sarcopenia and obesity, posing significant burdens on socioeconomic and public health. Current research has systematically explored the pathogenesis of each condition; however, the mechanisms underlying their comorbidity remain unclear. This study reviews the current literature on sarcopenia and obesity in the aging population, focusing on their shared biological mechanisms, which include loss of autophagy, abnormal macrophage function, mitochondrial dysfunction, and reduced sex hormone secretion. It also identifies metabolic mechanisms such as insulin resistance, vitamin D metabolism abnormalities, dysregulation of iron metabolism, decreased levels of nicotinamide adenine dinucleotide, and gut microbiota imbalances. Additionally, this study also explores the important role of genetic factors, such as alleles and microRNAs, in the co-occurrence of sarcopenia and obesity. A better understanding of these mechanisms is vital for developing clinical interventions and preventive strategies.
Humans ; Sarcopenia/physiopathology* ; Obesity/physiopathology* ; Aging/physiology* ; Autophagy/physiology* ; Insulin Resistance ; Comorbidity ; Vitamin D/metabolism* ; Gonadal Steroid Hormones/metabolism* ; Gastrointestinal Microbiome ; Mitochondria ; MicroRNAs

OBJECTIVE: This study aimed to evaluate the relationships of white blood cell (WBC) count, platelet (PLT) count, and PLT-to-WBC ratio (PWR) with muscle mass in Chinese older adults. METHODS: This cross-sectional analysis involved 4,033 Chinese older adults aged ≥ 65 years from the Healthy Ageing and Biomarkers Cohort Study. Muscle mass and total skeletal muscle mass index (TSMI) were measured by bioelectric impedance analysis. WBC, PLT, and PWR were measured using standard methods. Multivariate linear regression was used to examine the associations of WBC count, PLT count, and PWR with TSMI. RESULTS: High WBC count, PLT count, and PWR were associated with low TSMI, with coefficients of -0.0091 (95% confidence interval [ CI]: -0.0142 to -0.0041), -0.0119 (95% CI: -0.0170 to -0.0068), and -0.0051 (95% CI: -0.0102 to -0.0001). The associations between the three inflammatory indices and TSMI were linear. Stratified analyses indicated that the relationship between inflammatory markers and TSMI was more evident in male participants and in individuals aged < 80 years than in their counterparts. CONCLUSION Elevated WBC count, PLT count, and PWR correlated with muscle mass loss. This study highlights the importance of regular monitoring of inflammatory markers as a potential strategy for the screening and management of sarcopenia in older adults.
Humans ; Aged ; Male ; Female ; China ; Leukocyte Count ; Cross-Sectional Studies ; Platelet Count ; Aged, 80 and over ; Muscle, Skeletal/anatomy & histology* ; Independent Living ; Blood Platelets ; Leukocytes ; Sarcopenia

BACKGROUND AND AIM: The association between physical activity (PA) and sarcopenia has mostly been investigated in older people, with few studies focused on earlier life stages. The present study aimed to determine whether higher PA levels are associated with a lower sarcopenia risk in middle-aged and early older people. METHODS: This was an 8-year follow-up study. Participants were 6,500 community-dwelling adults aged 40-74 years who participated in the baseline questionnaire survey conducted in 2011-2014 in Japan. Levels of total and leisure-time PAs at baseline were assessed using validated metabolic equivalent scores. Multi-frequency bioelectrical impedance analysis and handgrip strength measurement were performed in 2021-2022, and participants with low height-adjusted appendicular lean mass (<20th percentile) and low grip strength were diagnosed as having sarcopenia (outcome). Covariates were demographics, body size, lifestyle, and disease history at baseline. RESULTS: The prevalence of sarcopenia was 137/2926 (4.7%) for men and 127/3574 (3.6%) for women. Higher total PA levels were associated with lower odds of sarcopenia (P for trend = 0.0278), with the second highest group having a significantly lower OR (0.51) than the lowest group (reference) in women, but not in men. Regarding leisure-time PA, those engaged in leisure-time vigorous PA had a lower OR of sarcopenia than those who did not (OR = 0.67, P = 0.0625). CONCLUSION Higher levels of total PA are associated with a lower risk of sarcopenia in women but not in men, suggesting a sex difference in this association. In addition, high levels of vigorous leisure-time PA may be effective for preventing sarcopenia.
Humans ; Sarcopenia/epidemiology* ; Japan/epidemiology* ; Male ; Female ; Middle Aged ; Aged ; Follow-Up Studies ; Independent Living/statistics & numerical data* ; Exercise ; Adult ; Prevalence ; Risk Factors ; Hand Strength ; East Asian People

BACKGROUND: Cardiovascular disease (CVD) is the predominant cause of mortality in China. However, the mechanisms linking sarcopenia to CVD remain poorly understood, particularly in normal-weight populations. Individuals with the absence of overweight or obesity may tend to experience missed opportunities for timely intervention. This study aimed to investigate the longitudinal association between sarcopenia and incidence of new-onset CVD in a normal-weight population, and to examine the mediating effect of functional limitation in this relationship. METHODS: We conducted a closed-cohort analysis using a nationwide sample of 4,147 middle-aged and older adults with normal weight in China. We performed Cox proportional hazards regression analysis to explore the associations of baseline sarcopenia with incident CVD. The difference method was applied to estimate the mediation proportion of functional limitation in this association. RESULTS: Over a mean follow-up period of 7.62 years, CVD occurred in 835 participants. In the multivariable-adjusted Cox model, individuals with sarcopenia exhibited a significantly higher likelihood of developing incident CVD compared to those without sarcopenia (adjusted hazard ratio [aHR] = 1.45, 95% confidence interval [CI]: 1.21-1.73, P < 0.001). Similar associations were observed for the incidence of heart disease and stroke. Functional limitation accounted for approximately 15.0% of the total effect of sarcopenia on incident CVD (P < 0.001). CONCLUSIONS Sarcopenia exerts both direct and indirect effects on incident CVD among middle-aged and older adults who are normal weight, with functional limitation serving as a significant mediator. Interventions targeting both sarcopenia and functional limitation may offer a promising strategy for enhancing cardiovascular health in this population.
Humans ; Sarcopenia/complications* ; China/epidemiology* ; Male ; Female ; Middle Aged ; Cardiovascular Diseases/etiology* ; Aged ; Incidence ; Cohort Studies ; Proportional Hazards Models ; Risk Factors ; Aged, 80 and over ; Longitudinal Studies

BACKGROUND: Exposure to air pollution and adherence to a healthy lifestyle have been identified to be related to sarcopenia. However, the interactive effects between these two factors remain insufficiently elucidated. The present study was designed to investigate the potential interaction exposure to air pollution with healthy lifestyle on the risk of developing sarcopenia. METHODS: In the retrospective cohort study, all data was extracted from China Health and Retirement Longitudinal Study. Household air pollution was assessed based on the utilization of solid fuels for cooking and heating. A lifestyle score was constructed comprising information on physical activity, smoking, drinking and sleeping time. Multivariate logistic regression model was used to assess the effects of household air pollution and healthy lifestyle score on sarcopenia, separately. We further explored the additive interaction between household air pollution and healthy lifestyle score to sarcopenia using the interaction table developed by T Anderson. Relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI) were used to evaluate the additive interactive effect. RESULTS: 2,114 participants were included in this study. The result indicated that exposed to household air pollution [adjusted relative risk (RR) = 1.80, 95% confidence interval (CI): 1.15-2.94] and unhealthy lifestyle (adjusted RR = 1.46, 95%CI: 1.04-2.03) were both significantly associated with increased risk of sarcopenia. Furthermore, participants exposed to both household air pollution and an unhealthy lifestyle exhibited a significantly higher risk of sarcopenia relative to those without household air pollution exposure and maintaining a healthy lifestyle (adjusted RR = 2.44). But RERI, AP, and SI suggested that there is no statistically significant additive interaction between household air pollution exposure and healthy lifestyle factors in relation to sarcopenia risk. CONCLUSION Household air pollution in conjunction with an unhealthy lifestyle confers a significantly higher risk of sarcopenia compared to either factor in isolation, with no evidence of a significant additive interaction between these two risk factors.
Humans ; China/epidemiology* ; Male ; Sarcopenia/etiology* ; Female ; Longitudinal Studies ; Middle Aged ; Aged ; Air Pollution, Indoor/adverse effects* ; Retrospective Studies ; Healthy Lifestyle ; Risk Factors ; Environmental Exposure/adverse effects* ; Cooking ; Aged, 80 and over

OBJECTIVES: Osteoarthritis (OA) and sarcopenia are significant health concerns in the elderly, substantially impacting their daily activities and quality of life. However, the relationship between them remains poorly understood. This study aims to uncover common biomarkers and pathways associated with both OA and sarcopenia. METHODS: Gene expression profiles related to OA and sarcopenia were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between disease and control groups were identified using R software. Common DEGs were extracted via Venn diagram analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to identify biological processes and pathways associated with shared DEGs. Protein-protein interaction (PPI) networks were constructed, and candidate hub genes were ranked using the maximal clique centrality (MCC) algorithm. Further validation of hub gene expression was performed using 2 independent datasets. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of key genes for OA and sarcopenia. Mouse models of OA and sarcopenia were established. Hematoxylin-eosin and Safranin O/Fast Green staining were used to validate the OA model. The sarcopenia model was validated via rotarod testing and quadriceps muscle mass measurement. Real-time reverse transcription PCR (real-time RT-PCR) was employed to assess the mRNA expression levels of candidate key genes in both models. Gene set enrichment analysis (GSEA) was conducted to identify pathways associated with the selected shared key genes in both diseases. RESULTS: A total of 89 common DEGs were identified in the gene expression profiles of OA and sarcopenia, including 76 upregulated and 13 downregulated genes. These 89 DEGs were significantly enriched in protein digestion and absorption, the PI3K-Akt signaling pathway, and extracellular matrix-receptor interaction. PPI network analysis and MCC algorithm analysis of the 89 common DEGs identified the top 17 candidate hub genes. Based on the differential expression analysis of these 17 candidate hub genes in the validation datasets, AEBP1 and COL8A2 were ultimately selected as the common key genes for both diseases, both of which showed a significant upregulation trend in the disease groups (all P<0.05). The value of area under the curve (AUC) for AEBP1 and COL8A2 in the OA and sarcopenia datasets were all greater than 0.7, indicating that both genes have potential value in predicting OA and sarcopenia. Real-time RT-PCR results showed that the mRNA expression levels of AEBP1 and COL8A2 were significantly upregulated in the disease groups (all P<0.05), consistent with the results observed in the bioinformatics analysis. GSEA revealed that AEBP1 and COL8A2 were closely related to extracellular matrix-receptor interaction, ribosome, and oxidative phosphorylation in OA and sarcopenia. CONCLUSIONS AEBP1 and COL8A2 have the potential to serve as common biomarkers for OA and sarcopenia. The extracellular matrix-receptor interaction pathway may represent a potential target for the prevention and treatment of both OA and sarcopenia.
Sarcopenia/genetics* ; Osteoarthritis/genetics* ; Computational Biology/methods* ; Humans ; Protein Interaction Maps/genetics* ; Animals ; Mice ; Gene Expression Profiling ; Gene Ontology ; Transcriptome ; Male ; Signal Transduction/genetics* ; Gene Regulatory Networks

Multimorbidity of chronic diseases is one of the most common health issues among older adults, and the resulting demand for long-term medical care and management imposes a considerable burden on healthcare systems. Muscle strength, a core indicator of overall health status, is closely associated with the risk of developing multimorbidity of chronic diseases in older adults. Decline in muscle strength not only increases the risk of multimorbidity of chronic diseases but also interacts with it to exacerbate disease burden. In older adults with existing multimorbidity of chronic diseases, muscle strength decline can impair physical function and quality of life, leading to a vicious cycle of disease progression and physical disability. Strength training can help prevent multimorbidity, with potential mechanisms including the promotion of anti-inflammatory effects and enhancement of mitochondrial energy metabolism. This review summarizes the impact of muscle strength decline on multimorbidity of chronic diseases in older adults and the effectiveness and potential mechanisms of exercise interventions, providing evidence to delay muscle strength decline, prevent the occurrence and progression of multimorbidity of chronic diseases, and improve quality of life in older adults.
Humans ; Aged ; Chronic Disease/prevention & control* ; Muscle Strength/physiology* ; Multimorbidity ; Quality of Life ; Resistance Training ; Exercise Therapy ; Exercise ; Sarcopenia