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Low-load resistance training with blood flow restriction (LRT-BFR) has shown potential to improve muscle strength and mass in different populations; however, there remains limited evidence in sarcopenic people diagnosed with sarcopenia criteria. This study systematically compared the effectiveness of LRT-BFR and conventional high-intensity resistance training (CRT) on clinical muscle outcomes (muscle mass, strength and performance), cardiovascular disease (CVD) risk factors and sarcopenia-related biomarkers of older people with sarcopenia. Twenty-one older individuals (aged 65 years and older) diagnosed with sarcopenia were randomly assigned to the LRT-BFR (20%-30% one-repetition maximum (1RM), n = 10) or CRT (60%-70% 1RM, n = 11) group. Both groups underwent a supervised exercise program three times a week for 12 weeks. The primary outcome was knee extensor strength (KES), and the secondary outcomes included body composition (body mass, body mass index and body fat percentage), muscle mass [appendicular skeletal muscle mass index (ASMI)], handgrip strength, physical performance [short physical performance battery (SPPB) and 6-m walk], CVD risk factors [hemodynamic parameters (systolic and diastolic blood pressure and heart rate (SBP, DBP and HR)) and lipid parameters (total cholesterol, triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein)], sarcopenia-related blood biomarkers [inflammatory biomarkers, hormones (growth hormone (GH) and insulin-like growth factor 1) and growth factors (myostatin and follistatin)] and quality of life [Short Form 36 Health Survey (SF-36)]. Both interventions remarkably improved the body composition, KES, 6-m walk, SBP, HDL, TG, GH, FST and SF-36 scores. CRT significantly improved the ASMI (p < 0.05) and SPPB (p < 0.05). A significant improvement in HR was observed only after LRT-BFR. No significant between-group differences were found before and after the interventions. This study suggested that LRT-BFR and CRT are beneficial to the clinical muscle outcomes, CVD risk factors and certain sarcopenia-related biomarkers of older people with sarcopenia. By comparison, CRT seems more effective in improving muscle mass, while LRT-BFR may be more beneficial for improving cardiovascular health in this population. Therefore, LRT-BFR is a potential alternative to CRT for aging sarcopenia., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The aim of this study was to investigate the relationship between red blood cell distribution width and albumin ratio (RAR) levels and mortality in adult patients with sarcopenic obesity in the United States. The study included 1,361 adult patients with sarcopenic obesity from the National Health and Nutrition Examination Survey (1999-2006). The X-tile was used to determine the optimal subgroup thresholds for RAR values, and propensity score matching (PSM) was employed to reduce baseline bias. Cox regression analysis, Kaplan-Meier survival curves, and restricted cubic spline analysis were utilized to assess the relationship between RAR levels and all-cause and cardiovascular mortality. Subgroup analysis and the Subpopulation Treatment Effect Pattern Plot were employed to determine survival advantages across different subgroups. Time-dependent ROC analysis to evaluate the accuracy of RAR level in predicting survival outcomes at different time points. Post-PSM multifactorial Cox regression analyses revealed that RAR was a significant independent predictor of all-cause mortality (HR 1.487, 95% CI: 1.259-1.756) and an independent risk factor for cardiovascular mortality (HR 1.487, 95% CI: 1.260-1.758) in patients with sarcopenic obesity. The survival advantage was consistent across subgroups. Restricted cubic spline analysis indicated an approximate S-shaped association between RAR levels and mortality. Time-dependent ROC curves demonstrate that the areas under the all-cause mortality curves at the RAR level for 1-year, 3-year, 5-year, and 10-year are 0.79, 0.66, 0.64, and 0.63, respectively. The areas under the cardiovascular mortality curve are 0.80, 0.70, 0.66, and 0.61, respectively. Moreover, in comparison to the baseline model lacking covariates, the AUC values of the joint model exhibited heightened levels at various time points. Therefore, We demonstrated that the RAR level is an independent prognostic factor for mortality risk in the American population with sarcopenic obesity, and it is reasonable to consider the RAR level as a simple and effective risk prediction tool., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Sarcopenic obesity (SO) and osteoarthritis (OA) are highly prevalent musculoskeletal conditions that significantly impair health-related quality of life., Aim: This study investigated the association between SO and OA, and explored the potential mediating role of insulin resistance in this relationship. We utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018., Methods: This cross-sectional analysis employs NHANES data collected from 1999 to 2018, including participants aged 18 years and older. SO was assessed using dual-energy X-ray absorptiometry (DXA) measurements. Insulin resistance was estimated using the triglyceride-glucose (TyG) index. OA status was based on self-reported physician diagnosis. Statistical analyses included weighted logistic regression, restricted cubic spline (RCS) interaction analysis, mediation analysis using structural equation modeling (SEM), and receiver operating characteristic (ROC) curve analysis. Subgroup analyses were conducted based on age, sex, and diabetes status., Results: The sarcopenic obese group demonstrated the highest prevalence of OA (23.4 %), hypertension (47.8 %), and diabetes (12.0 %). Additionally, they exhibited elevated levels of triglycerides, cholesterol, glucose, blood urea nitrogen (BUN), creatinine, and uric acid. Logistic regression revealed significant positive associations between sarcopenic obesity, the TyG index, and OA risk. RCS analysis identified significant non-linear relationships and interactions of the TyG index with age, sex, and diabetes status on OA risk. Mediation analysis indicated that the TyG index mediated approximately 4.9 % of the effect of sarcopenic obesity on OA risk. ROC curve analysis demonstrated moderate diagnostic accuracy for the TyG index (AUC = 0.65), which improved when incorporated into the multivariate model (AUC = 0.78). Subgroup analyses confirmed significant associations between the TyG index and sarcopenic obesity with OA risk across different age, sex, and diabetes status categories., Conclusion: Our findings suggest a significant correlation between insulin resistance, as measured by the TyG index, and elevated OA risk in individuals with sarcopenic obesity. Targeting insulin resistance through future research may be a promising avenue to lower OA risk in this population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Small non-coding RNAs (ncRNAs) have recently emerged as potential biomarkers of sarcopenia. However, previous studies have rarely explored the association of small ncRNAs with sarcopenic components, especially muscle strength and physical performance. We aimed to examine circulating small ncRNA profiles to detect low muscle strength and physical performance in older adults., Methods: Ninety-eight older adults were randomly selected from Korean Frailty and Aging Cohort Study and classified into the "Normal," "Low muscle strength (MS) only," "Low physical performance (PP) only," and "Low MS and PP" groups by Asian Working Group for Sarcopenia 2019 criteria. We used high-throughput sequencing to delineate small ncRNA profiles in plasma. Differentially expressed small ncRNAs were analyzed to reveal distinct patterns based on muscle strength and physical performance status., Results: In "Low MS and PP" group, 119 miRNAs, 86 piRNAs, 92 snoRNAs, 106 snRNAs, and 15 tRNAs were differentially expressed compared to "Normal" group (p < 0.05). After Benjamini-Hochberg adjustment, 39 miRNAs, 2 piRNAs, 75 snoRNAs, 48 snRNAs, and 15 tRNAs showed differential expression in "Low MS and PP" group compared to than "Normal" group (adjusted p < 0.05). No significant differences were observed in comparisons between the other groups (adjusted p > 0.05)., Conclusion: The expression of circulating small ncRNAs were comprehensively characterized, revealing distinct signatures in older adults with both low muscle strength and physical performance compared to normal individuals. Although preliminary, this characterization can advance small ncRNA research on age-related declines in muscle strength and physical performance by providing foundational data for further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Sarcopenia is a known risk factor for adverse outcomes across multiple disease states, including severe trauma. Factors such as age, hyperinflammation, prolonged immobilization, and critical illness may not only exacerbate progression of this disease but may also contribute to the development of induced sarcopenia, or sarcopenia secondary to hospitalization. This study seeks to (1) determine the effects of severe traumatic injury on changes in skeletal muscle mass in older adults; (2) test whether changes in skeletal muscle mass are associated with clinical frailty, physical performance, and health-related quality of life; and (3) examine trauma-induced frailty and temporal changes in myokine and chemokine profiles., Methods: A prospective, longitudinal cohort study of 47 critically ill, older (≥45 years) adults presenting after severe blunt trauma was conducted. Repeated measures of computed tomography-based skeletal muscle index, frailty, and quality of life were obtained in addition to selected plasma biomarkers over 6 months., Results: Severe trauma was associated with significant losses in skeletal muscle mass and increased incidence of sarcopenia from 36% at baseline to 60% at 6 months. Severe trauma also was associated with a transient worsening of induced frailty and reduced quality of life irrespective of sarcopenia status, which returned to baseline by 6 months after injury. Admission biomarker levels were not associated with skeletal muscle index at the time points studied but demonstrated distinct temporal changes across our entire cohort., Conclusions: Severe blunt trauma in older adults is associated with increased incidence of induced sarcopenia and reversible induced frailty. Despite muscle wasting, functional decline is transient, with a return to baseline by 6 months, suggesting a need for holistic definitions of sarcopenia and further investigation into long-term functional outcomes in this population., Competing Interests: Conflicts of Interest/Disclosure The authors have no related conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose of Review: Serum creatinine reflects both muscle mass and kidney function. Serum cystatin C has recently been recommended as an additional marker for estimating kidney function, and use of both markers together may provide an index of muscle mass. This review aims to describe the biological basis for and recent research examining the relationship of these markers to muscle mass in a range of adult populations and settings., Recent Findings: This review identified 67 studies, 50 of which had direct measures of muscle mass, and almost all found relationships between serum creatinine and cystatin C and muscle mass and related outcomes. Most studies have been performed in older adults, but similar associations were found in general populations as well as in subgroups with cancer, chronic kidney disease (CKD), and other morbid conditions. Creatinine to cystatin C ratio was the measure examined the most often, but other measures showed similar associations across studies., Summary: Measures of serum creatinine and cystatin C together can be an index of muscle mass. They are simple and reliable measures that can be used in clinical practice and research. Further study is needed to determine actionable threshold values for each measure and clinical utility of testing and intervention., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Sex steroids play a key role on male bone homeostasis and body composition (BC), their role in men living with HIV (MLWH) is less recognized. This study aimed at investigating the prevalence of low BMD, sarcopenia, and sarcopenic obesity (SO) and their relationship with sex steroids in MLWH aged < 50., Methods: Prospective, cross-sectional, observational study on MLWH younger than 50 (median age 47.0 years). BC and BMD were evaluated with DXA. Two different definitions of sarcopenia were applied: appendicular lean mass/height 2 (ALMI) < 7.26 kg/m 2 or appendicular lean mass/body weight (ALM/W) < 28.27%. Low BMD was defined for Z-score < -2.0. Sarcopenia coupled with obesity identified SO. Serum total testosterone (T) and estradiol (E2) were measured by LC-MS/MS; free testosterone (cFT) was calculated by Vermeulen equation., Results: Sarcopenia was detected in 107 (34.9%) and 44 (14.3%) out of 307 MLWH according to ALMI and ALM/W, respectively. The prevalence of SO was similar by using both ALMI (11.4%) and ALM/W (12.4%). Sarcopenic and SO MLWH had lower total T and cFT in both the definition for sarcopenia. BMD was reduced in 43/307 (14.0%). Serum E2 < 18 pg/mL was an independent contributing factor for sarcopenia, SO, and low BMD., Conclusions: T and E2 are important determinants of BC even in MLWH. This is among the first studies investigating the distribution of obesity phenotypes and the prevalence of SO among MLWH showing that SO is present in 11-12% of enrolled MLWH regardless of the definition used. However, deep differences emerged using two different diagnostic definitions., (© 2024. The Author(s).)

Fall is common in the elderly, and chronic kidney disease is considered a major risk factor. Serum creatinine (Cre) and cystatin C (Cys C) are commonly used biomarkers for renal function, while the ratio of Cre to Cys C, known as the sarcopenia index (SI), provides insights into muscle health. This study investigates the relationships between Cre, Cys C, estimated glomerular filtration rates (eGFR), SI, and self-reported falls using National Health and Nutrition Examination Survey (NHANES) data. We included 4,272 older adults with eGFR > 30mL/min/1.73m 2 from NHANES (1999 to 2004) and divided them into the fall and non-fall groups based on the questionnaires. Correlations were assessed using restricted cubic spline, weighted generalized linear regression models. Multi-factor logistic regression analysis identified serum Cys C as significantly associated with falls (all participants: OR 1.16, 95% CI: 1.09 to 1.23, p < 0.001; participants with eGFR > 75 mL/min/1.73m 2 : OR 1.17, 95% CI: 1.05 to 1.30, p < 0.001,). In contrast, Cre and eGFR were not significant after adjustments; SI showed marginal significance (p = 0.045). Cys C is significantly associated with fall risk in older adults, demonstrating a positive linear relationship with self-reported falls., (© 2024. The Author(s).)

The triglyceride glucose (TyG) related index, a metric used to evaluate assessing insulin resistance (IR), has received limited attention in its association with sarcopenia. Our study aims to explore the predictive potential of the TyG index for sarcopenia. This study utilized data from the China Health and Retirement Longitudinal Study, a nationally representative, community-based cohort study, including a sample size of 10,537 participants aged 45 years and older. Associations between TyG related index and sacopenia was explored using multivariate logistic regression. Analysis of the predictive value of TyG related index for sarcopenia using receiver-operating characteristic curve (ROC). We evaluated the correlation between the TyG related index and the risk of sarcopenia using Cox proportional hazards models. Additionally, we utilized restricted cubic spline (RCS) regression analyses to explore the connections between the TyG-related index and sarcopenia. Logistic regression analysis showed an association between TyG (OR 0.961[0.955,0.968], P < 0.001), TyG-body mass index (TyG-BMI) (OR 0.872[0.867,0.878], P < 0.001), TyG- waist circumference (TyG-WC) (OR 0.896[0.890,0.902], P < 0.001) and sarcopenia. The results of the ROC analysis indicated that the area under the curve values for TyG, TyG-BMI, and TyG-WC were 0.659, 0.903, and 0.819, respectively. Compared to those without sarcopenia, patients with sarcopenia had a 37.7% (HR 0.623[0.502,0.774], P < 0.001), 4.8% (HR 0.952[0.947,0.958], P < 0.001), and 0.4% (HR 0.996[0.995,0.996], P < 0.001) lower risk with increasing TyG, TyG-BMI, and TyG-WC, respectively. RCS results show nonlinear relationship between TyG-BMI (P < 0.001) and TyG-WC (P < 0.001) and risk of sarcopenia. We observed a correlation between the TyG-related index and sarcopenia, with the TyG-BMI index demonstrating strong predictive capability for sarcopenia., (© 2024. The Author(s).)

Background: The relationship between serum lipids and sarcopenia remains unclear due to conflicting results in previous studies., Objective: To explore the associations and potential causality between serum lipids, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and total cholesterol (TC), and sarcopenia., Methods: Data from the National Health and Nutrition Examination Survey (NHANES) were analysed using multivariable regression and restricted cubic splines (RCSs) to assess the associations between serum lipids and sarcopenia. Bidirectional Mendelian randomization (MR) was employed to investigate the causal relationships with sarcopenia-related traits such as appendicular lean mass (ALM), hand grip strength, and usual walking pace., Results: Serum HDL-C and TG levels were inversely associated with ALMBMI, with each 1-unit increase linked to a 0.13 % and 1.32 % decrease, respectively. Elevated TG, but not HDL-C, LDL-C, or TC levels, was significantly associated with an increased risk of sarcopenia (P for trend = 0.001). RCS analysis revealed a log-shaped dose-response relationship between TG and sarcopenia risk (P overall <0.001, P non-linear <0.001), with a cutoff value of 92.75 mg/dL. Genetically predicted HDL-C, LDL-C, and TG were associated with ALM. Conversely, ALM showed an inverse causal relationship with all four serum lipids. Additionally, genetically predicted usual walking pace influenced HDL-C and TG levels (P < 0.001)., Conclusion: The study reveals a nonlinear association between TG levels and sarcopenia risk, and a bidirectional association between lipid profiles and muscle mass, underscoring the need for further research to elucidate these mechanisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: This study aims to investigate how the impact of preoperative sarcopenia and inflammatory markers for laryngeal cancer patients and develop a new scoring system to predict their prognosis., Materials and Methods: Patients who underwent laryngectomy for laryngeal cancer (LC) from December 2015 to December 2020 at the Second Affiliated Hospital of Fujian Medical University were included. Independent prognostic factors were determined using univariate and multivariate analyses. A new scoring system (SFAR) was established based on FAR and preoperative sarcopenia, and statistically analyzed., Results: 198 cases included in this study that met the admission criteria. Multivariate analysis shown that preoperative sarcopenia, pTNM stage, and FAR were independent prognostic factors for laryngeal cancer. Based on these three indicators, we developed the SFAR scoring system. Multivariate analysis showed that SFAR was an independent predictor of laryngeal cancer (p < 0.001). SFAR was then incorporated into a prognostic model that included T-stage and N-stage, and a column-line graph was generated to accurately predict its survival., Conclusion: Systemic inflammation and sarcopenia are significantly associated with postoperative prognosis in laryngeal cancer. A new scoring system (SFAR) had implications for improving the prognosis of patients undergoing surgery for laryngeal cancer., (© 2024. The Author(s).)

Background: Recent studies have demonstrated that very high high-density lipoprotein cholesterol (HDL-C) level was paradoxically linked with higher risk of cardiovascular mortality, all-cause mortality, and several age-related diseases. However, whether very high HDL-C level is associated with a higher risk of sarcopenia in older adults remains unclear. We aimed to investigate the association between HDL-C level and the risk of developing sarcopenia and low grip strength over time in older adults., Methods: Participants were from the ongoing China Health and Retirement Longitudinal Study (CHARLS), which includes a nationally representative sample of adults aged ≥45 years and was performed from 2011 to 2020 with follow-ups every two to three years. The current study included 4031 participants aged ≥60 years. Muscle health-related data were collected in waves 2011, 2013, and 2015. Based on HDL-C level at baseline, participants were categorized into five groups: <35 mg/dl, 35-40 mg/dl, 40-60 mg/dl, 60-70 mg/dl and >70 mg/dl. The main outcomes were incident sarcopenia and incident low grip strength over follow-up. Low grip strength and sarcopenia were defined according to the 2019 Consensus by the Asian Working Group for Sarcopenia. Cox proportional-hazard regression was performed to investigate the association between HDL-C level and the risk of developing sarcopenia and low grip strength in older adults., Results: The mean age of study sample was 67.3 (SD 6.1) years, and 49.6% were male. During an average 3.7-year follow-up, 409 (10.1%) participants developed sarcopenia and 771 (21.1%) developed low grip strength. Non-linear association was observed between HDL-C level and the hazard of developing sarcopenia and low grip strength. The multivariable model showed that compared to the reference group (40-60 mg/dl), older adults with very high HDL-C level (>70 mg/dl) had a significantly higher risk of developing sarcopenia (HR 1.69, 95% CI 1.28-2.23) and low grip strength (HR 1.23 95% CI 1.00-1.51). Stratified analyses by sex revealed similar association., Conclusions: We present the first longitudinal evidence that very high HDL-C level was associated with a significantly higher risk of muscle strength decline and developing sarcopenia in older adults. It is essential to monitor the muscle health of older adults with very high HDL-C level in clinical practice., Competing Interests: Conflict of interest There is no conflict of interest to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Sarcopenia, the gradual and generalized loss of muscle mass and function with ageing, is one of the major health problems in older adults, given its high prevalence and substantial socioeconomic implications. Despite the extensive efforts to reach consensus on definition and diagnostic tests and cut-offs for sarcopenia, there is an urgent and unmet need for non-invasive, specific and sensitive biomarkers for the disease. Extracellular vesicles (EVs) are present in different biofluids including plasma, whose cargo reflects cellular physiology. This work analysed EV proteome in sarcopenia and robust patients in the search for differentially contained proteins that can be used to diagnose the disease., Methods: Plasma small EVs (sEVs) from a total of 29 robust controls (aged 73.4 ± 5.6 years; 11 men and 18 women) and 49 sarcopenic patients (aged 82.3 ± 5.4 years; 15 men and 34 women) aged 65 years and older were isolated and their cargo was analysed by proteomics. Proteins whose concentration in sEVs was different between sarcopenic and robust patients were further validated using ELISA. The concentration of these candidates was correlated to the EWGSOP2 sarcopenia tests for low muscle strength and low physical performance, and receiver operating characteristic (ROC) curve analyses were carried out to evaluate their diagnostic power, sensitivity and specificity., Results: Proteomic analysis identified 157 sEVs proteins in both sarcopenic and robust samples. Among them, 48 proteins had never been reported in the ExoCarta nor Vesiclepedia databases. Statistical analysis revealed eight proteins whose concentration was significantly different between groups: PF4 (log2 FC = 4.806), OIT3 (log2 FC = -1.161), MMRN1 (log2 FC = -1.982), MASP1 (log2 FC = -0.627), C1R (log2 FC = 1.830), SVEP1 (log2 FC = 1.295), VCAN (FC = 0.937) and SPTB (log2 FC = 1.243). Among them, platelet factor 4 (PF4) showed the lowest concentration while Complement C1r subcomponent (C1R) increased the most in sarcopenic patients, being these results confirmed by ELISA (P = 1.07E-09 and P = 0.001287, respectively). The concentrations of candidate proteins significantly correlated with EWGSOP2 tests currently used. ROC curve analysis showed an area under the curve of 0.8921 and 0.7476 for PF4 and C1R, respectively. Choosing the optimal for PF4, 80% sensitivity and 85.71% specificity was reached while the optimal cut-off value of C1R would allow sarcopenia diagnosis with 75% sensitivity and 66.67% specificity., Conclusions: Our results support the determination of EV PF4 and C1R as plasma diagnostic biomarkers in sarcopenia and open the door to investigate the role of the content of these vesicles in the pathogeny of the disease., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background: The pathophysiology of sarcopenia is complex and multifactorial and has not been fully elucidated. The impact of resistance training and nutritional support (RTNS) on metabolomics and lipodomics in older adults with sarcopenia remains uncertain. This study aimed to explore potential biomarkers of sarcopenia and clinical indicators of RTNS in older sarcopenic adults., Methods: Older individuals diagnosed with sarcopenia through routine health checkups at a community hospital were recruited for a 12-week randomized controlled trial focusing on RTNS. Plasma metabolomic and lipidomic profiles of 45 patients with sarcopenia and 47 matched controls were analysed using 1 H-nuclear magnetic resonance ( 1 H-NMR) and liquid chromatography-mass spectrometer (LC-MS)., Results: At baseline, the patient and control groups had similar age, sex, and height distribution. The patient group had significantly lower weight, BMI, grip strength, gait speed, skeletal muscle index, lean mass of both the upper and lower limbs, and lower limb bone mass. There was a significant difference in 12 metabolites between the control and patient groups. They are isoleucine (patient/control fold change [FC] = 0.86 ± 0.04, P = 0.0005), carnitine (FC = 1.05 ± 0.01, P = 0.0110), 1-methylhistamine/3-methylhistamine (FC = 1.24 ± 0.14, P = 0.0039), creatinine (FC = 0.71 ± 0.04, P < 0.0001), carnosine (FC = 0.71 ± 0.04, P = 0.0007), ureidopropionic acid (FC = 0.61 ± 0.10, P = 0.0107), uric acid (FC = 0.88 ± 0.03, P = 0.0083), PC (18:2/20:0) (FC = 0.69 ± 0.03, P = 0.0010), PC (20:2/18:0) (FC = 0.70 ± 0.06, P = 0.0014), PC (18:1/20:1) (FC = 0.74 ± 0.05, P = 0.0015), PI 32:1 (FC = 4.72 ± 0.17, P = 0.0006), and PI 34:3 (FC = 1.88 ± 0.13, P = 0.0003). Among them, carnitine, 1-methylhistamine/3-methylhistamine, creatinine, ureidopropionic acid, uric acid, PI 32:1, and PI 34:3 were first identified. Notably, PI 32:1 had highest diagnostic accuracy (0.938) for sarcopenia. 1-Methylhistamine/3-methylhistamine, carnosine, PC (18:2/20:0), PI 32:1, and PI 34:3 levels were not different from the control group after RTNS. These metabolites are involved in amino acid metabolism, lipid metabolism, and the PI3K-AKT/mTOR signalling pathway through the ingenuity pathway analysis., Conclusions: These findings provide information on metabolic changes, lipid perturbations, and the role of RTNS in patients with sarcopenia. They reveal new insights into its pathological mechanisms and potential therapies., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

The aim of this study is to evaluate the relationship between serum TLR (Toll Like Receptor) 4, 9 and Resolvin E1 levels and primary sarcopenia in geriatric patients and to compare the diagnostic accuracy of these biomarkers with the SARC-F score. A total of 88 patients aged 65 years and older were evaluated in the study. Comorbidities and geriatric syndromes were identified and patients with secondary sarcopenia were excluded. EWGSOP2 criteria were used as diagnostic criteria for sarcopenia and SARC-F questionnaire was used to find individuals at risk for sarcopenia. Serum TLR 4, 9 and Resolvin E1 levels were analyzed by ELISA. There were no significant differences between the two groups in terms of age and gender (p = 0.654 and p = 1.000, respectively). SARC-F, serum TLR 9 and Resolvin E1 were significantly higher in the sarcopenia group compared to the non-sarcopenia group (p < 0.001, p < 0.001 and p = 0.040, respectively). Statistically significant parameters were evaluated by multiple regression analysis. TLR 9 and SARC-F score were both found to be associated with sarcopenia in multivariate logistic regression analysis [Odds ratio (OR) 3145, (95%) confidence interval (CI) 5.9-1,652,888.3, p = 0.012; OR 4.788, (95%) CI 2.148-10.672, p < 0.001, respectively]. ROC curve analysis showed that the area under the ROC curve (AUC) for TLR 9 and SARC-F was 0.896 (p < 0.001) and 0.943 (p < 0.001), respectively. Although this study supports the use of the SARC-F questionnaire in daily practice, serum TLR 9 levels may be an alternative to SARC-F in cases where SARC-F is not feasible., (© 2024. The Author(s).)

Background & Aims: There is an emerging and urgent need to identify biomarkers of sarcopenia. A novel sarcopenia index (SI), based on serum creatinine and cystatin C, has emerged as a potential biomarker for use. The SI can predict clinical outcomes and discriminate between the presence of sarcopenia in a range of chronic and acute conditions. However, the SI has not yet been tested in a large real-world general population dataset. This study aimed to investigate the accuracy of the SI in the identification of sarcopenia in a large prospective general population cohort., Methods: Data were taken from UK Biobank, a large prospective epidemiological study in the United Kingdom (UK). Serum creatinine and cystatin C values were used to calculate the SI [creatinine (mg/dl)/cystatin C (mg/dl) × 100]. Probable sarcopenia was defined by maximum handgrip strength (HGS). Muscle mass was assessed using bioelectrical impedance analysis. Low muscle mass was defined as an appendicular lean mass (ALM) index below prespecified thresholds. Confirmed sarcopenia was defined as both low HGS and low muscle mass. Pearson correlation coefficients and logistic regression were used to explore the association between various sarcopenia traits (probable sarcopenia, low ALM index, and confirmed sarcopenia) and the SI. The diagnostic value of the SI was investigated using the area under the receiver operating characteristic curve (area under the curve, AUC)., Results: 458,702 participants were included in the analysis (46.4% males, mean age, males: 68.7 (±8.2) years; females: 68.2 (±8.0) years)). Probable sarcopenia was observed in 4.5% of males and 6.1% of females; low ALM index in 2.8% of males and 0.7% of females; confirmed sarcopenia in 0.3% of males and 0.1% of females. SI was significantly lower in individuals with confirmed sarcopenia (males: 86.3 ± 16.6 vs. 99.5 ± 15.3, p < .01; females: 73.6 ± 13.7 vs. 84.6 ± 14.0, p < .01). For every 1-unit increase in the SI, the odds of confirmed sarcopenia were reduced by 5% in males (odds ratio (OR): 0.95, p < 0.001) and 7% in females (OR: 0.923, p < 0.001). The AUC showed acceptable discriminative ability of confirmed sarcopenia (males: AUC = 0.731; females: AUC = 0.711)., Conclusions: Using a large real-world dataset of almost half a million people, our study indicated the SI has acceptable diagnostic accuracy when identifying those with sarcopenia and may be a useful biomarker to aid the stratification of those at risk and in need of intervention., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The authors declare that they have no competing interests. T.Y. reports grants from NIHR during the conduct of the study., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Sarcopenia, a group of muscle-related disorders, leads to the gradual decline and weakening of skeletal muscle over time. Recognizing the pivotal role of gastrointestinal conditions in maintaining metabolic homeostasis within skeletal muscle, we hypothesize that the effectiveness of the myogenic programme is influenced by the levels of gastrointestinal hormones in the bloodstream, and this connection is associated with the onset of sarcopenia., Methods: We first categorized 145 individuals from the Emergency Room of Taipei Veterans General Hospital into sarcopenia and non-sarcopenia groups, following the criteria established by the Asian Working Group for Sarcopenia. A thorough examination of specific gastrointestinal hormone levels in plasma was conducted to identify the one most closely associated with sarcopenia. Techniques, including immunofluorescence, western blotting, glucose uptake assays, seahorse real-time cell metabolic analysis, flow cytometry analysis, kinesin-1 activity assays and qPCR analysis, were applied to investigate its impacts and mechanisms on myogenic differentiation., Results: Individuals in the sarcopenia group exhibited elevated plasma levels of glucagon-like peptide 1 (GLP-1) at 1021.5 ± 313.5 pg/mL, in contrast to non-sarcopenic individuals with levels at 351.1 ± 39.0 pg/mL (P < 0.05). Although it is typical for GLP-1 levels to rise post-meal and subsequently drop naturally, detecting higher GLP-1 levels in starving individuals with sarcopenia raised the possibility of GLP-1 influencing myogenic differentiation in skeletal muscle. Further investigation using a cell model revealed that GLP-1 (1, 10 and 100 ng/mL) dose-dependently suppressed the expression of the myogenic marker, impeding myocyte fusion and the formation of polarized myotubes during differentiation. GLP-1 significantly inhibited the activity of the microtubule motor kinesin-1, interfering with the translocation of glucose transporter 4 (GLUT4) to the cell membrane and the dispersion of mitochondria. These impairments subsequently led to a reduction in glucose uptake to 0.81 ± 0.04 fold (P < 0.01) and mitochondrial adenosine triphosphate (ATP) production from 25.24 ± 1.57 pmol/min to 18.83 ± 1.11 pmol/min (P < 0.05). Continuous exposure to GLP-1, even under insulin induction, attenuated the elevated glucose uptake., Conclusions: The elevated GLP-1 levels observed in individuals with sarcopenia are associated with a reduction in myogenic differentiation. The impact of GLP-1 on both the membrane translocation of GLUT4 and the dispersion of mitochondria significantly hinders glucose uptake and the production of mitochondrial ATP necessary for the myogenic programme. These findings point us towards strategies to establish the muscle-gut axis, particularly in the context of sarcopenia. Additionally, these results present the potential of identifying relevant diagnostic biomarkers., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background: Osteo-sarcopenia (OS) has become a global public health problem and a frontier research problem, as a combination of sarcopenia (SP) and osteoporosis (OP) diseases. The clinical performances include muscle weakness, systemic bone pain, standing difficulty, even falls and fractures, etc., which seriously affect the patient's life and work. The pathological mechanism of the OS may be the abnormal metabolism which disrupts the equilibrium stability of the musculoskeletal system. Therefore, this study combined vitamin D (Vit. D) and whole-body vibration training (WBVT) to intervene in subjects of OS, aiming to evaluate the effectiveness and safety of the diagnosis and treatment protocol and to explore the efficacy mechanism., Methods: We propose a multicenter, parallel-group clinical trial to evaluate the efficacy and safety of Vit. D combined with WBVT intervention in OS. Subjects who met the inclusion or exclusion criteria and signed the informed consent form would be randomly assigned to the WBVT group, Vit. D group, or WBVT+ Vit. D group. All subjects will be treated for 1 month and followed up after 3 and 6 months. The primary outcomes are lumbar bone mineral density (BMD) and appendicular skeletal muscle mass (ASM) measured by dual-energy X-ray absorptiometry (DXA) and handgrip strength measured by grip strength meter. Secondary outcomes include serum markers of myostatin (MSTN), irisin and bone turnover markers (BTM), SARC-CalF questionnaire, 1-min test question of osteoporosis risk, patient health status (evaluated by the SF-36 health survey), physical performance measurement that includes 5-time chair stand test, 6-m walk, and the short physical performance battery (SPPB)., Discussion: If Vit. D combined with WBVT can well relieve OS symptoms without adverse effects, this protocol may be a new treatment strategy for OS. After therapeutic intervention, if the serum marker MSTN/irisin is significant, both have the potential to become sensitive indicators for screening OS effective drugs and treatments, which also indicates that WBVT combined with Vit. D plays a role in improving OS by regulating MSTN/irisin., Trial Registration: Chinese Clinical Trial Registry ChiCTR2400082269 . Registered on March 26, 2024., (© 2024. The Author(s).)

Background: A newly developed technique, the Triglyceride-glucose (TyG) index, supplies a more straightforward method to identify IR than the HOMA-IR (Homeostasis Model Assessment of Insulin Resistance). Yet no methodical analysis has looked into the link involving the TyG index and low muscle mass (LMM), low muscle strength (LMS), and sarcopenia within the US. Thus, this study intended to find any connection concerning the TyG index and LMM, LMS, and sarcopenia., Methods: Between 2011 to 2014, data from the NHANES were used to conduct a nationally representative study involving 2,504 participants. LMM, LMS, and sarcopenia were the outcome variables. Moreover, this positive correlation persists irrespective of age and gender., Results: The TyG index revealed a significant correlation with the prevalence of developing LMM (OR = 1.63(1.26-2.11), p =0.001), LMS (OR = 1.61(1.36-1.91), p <0.001) and sarcopenia (OR = 1.59 (1.23-2.07), p <0.001), after correcting for all variables. Utilizing smooth curve fitting alongside two-piecewise linear regression models, an inverted U-shaped correlation between the TyG index and the prevalence of LMM, LMS, and sarcopenia. Finally, subgroup analysis revealed that the association between the TyG index and LMM, LMS, and sarcopenia was particularly evident in all gender, age subgroups, and individuals with a normal BMI of 25., Conclusion: Sarcopenia and the TyG index reveal an essential positive link. It highlights the potential utility of the TyG index as a screening tool for identifying individuals at risk of sarcopenia earlier., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wei and Liu.)

Background: Epidemiological and experimental evidence suggests that chronic inflammation plays an important role in the onset and progression of sarcopenia. However, there is inconsistent data on the inflammatory cytokines involved in the pathogenesis of sarcopenia. Therefore, we performed a two-sample Mendelian randomization (MR) analysis to explore the causal relationship between circulating cytokines and sarcopenia-related traits., Methods: The MR analysis utilized genetic data from genome-wide association study that included genetic variations in 41 circulating cytokines and genetic variant data for appendicular lean mass (ALM), hand grip strength, and usual walking pace. Causal associations were primarily explored using the inverse variance-weighted (IVW) method, supplemented by MR-Egger, simple mode, weighted median, and weighted mode analyses. Additionally, sensitivity analyses were also performed to ensure the reliability and stability of the results., Results: Three cytokines [hepatocyte growth factor (HGF), interferon gamma-induced protein 10 (IP-10), and macrophage colony-stimulating factor (M-CSF)] were positively associated with ALM (β: 0.0221, 95% confidence interval (CI): 0.0071, 0.0372, P = 0.0039 for HGF; β: 0.0096, 95%CI: 4e-04, 0.0189, P = 0.0419 for IP-10; and β: 0.0100, 95%CI: 0.0035, 0.0165, P = 0.0025 for M-CSF). Conversely, higher levels of interleukin-7 (IL-7), monocyte chemotactic protein 3 (MCP-3), and regulated on activation, normal T cell expressed and secreted (RANTES) were associated with decreased hand grip strength (β: -0.0071, 95%CI: -0.0127, -0.0014, P = 0.0140 for IL-7; β: -0.0064, 95%CI: -0.0123, -6e-04, P = 0.0313 for MCP-3; and β: -0.0082, 95%CI: -0.0164, -1e-04, P = 0.0480 for RANTES). Similarly, interleukin 1 receptor antagonist (IL-1RA) was negatively correlated with usual walking pace (β: -0.0104, 95%CI: -0.0195, -0.0013, P = 0.0254). Sensitivity analysis confirmed the robustness of these findings., Conclusions: Our study provides additional insights into the pivotal role of specific inflammatory cytokines in the pathogenesis of sarcopenia. Further research is required to determine whether these cytokines can be used as targets for the prevention and treatment of sarcopenia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Sun, Shi, Song, Wu, Wu and Lin.)

Background: Cholinesterase is a classical nutritional and inflammatory marker. The aim of the present study was to evaluate the value of cholinesterase as a predictive marker for postoperative skeletal muscle loss after gastrectomy for gastric cancer., Methods: The study comprised 68 patients who had undergone gastrectomy for gastric cancer. Skeletal muscle mass was evaluated using skeletal mass index, and major skeletal muscle loss was defined as less than or equal to the median change rate (1-year postoperative/preoperative) of skeletal mass index in all patients. We explored the relationship between postoperative major skeletal muscle loss and disease-free survival and overall survival. Then we investigated the relationship between change rate of skeletal muscle index and serum cholinesterase levels after gastrectomy., Results: The median value of change rate of skeletal mass index was 0.93. Postoperative major skeletal muscle loss was significantly associated with disease-free survival after gastrectomy (P = 0.003). Although major skeletal muscle loss had worse overall survival, it was not significant (P = 0.058). The change rate of skeletal mass index and cholinesterase had a stronger positive correlation compared with other nutritional indices according to Spearman's rank correlation coefficient (r = 0.438, P ≤ 0.001)., Conclusion: Evaluation of serum cholinesterase levels may be valuable for predicting postoperative skeletal muscle loss after gastrectomy, suggesting the importance of cholinesterase in postoperative nutritional management of patients with gastric cancer., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: As populations live longer, there is a progressive increase in chronic degenerative diseases, particularly those related to the musculoskeletal system. Sarcopenia is characterized by loss of skeletal muscle mass, muscle strength, and loss of physical function. It is a common disease in older adults associated with various adverse health outcomes. There is a lack of bioindicators to screen for sarcopenia. Albumin and lymphocyte counts are commonly used to assess the degree of malnutrition, and blood routine, lipids, and thyroid function are relatively easy to obtain as part of a routine physical examination. Therefore, finding blood markers that can screen for sarcopenia is essential. Our primary aim was to explore whether the bioindicators of body composition, lymphocytes, albumin, lipids, and thyroid hormones are associated with sarcopenia, and a secondary aim was to investigate changes in these indicators after an intensive lifestyle intervention preliminarily., Methods: 60 subjects were selected from Runda and Bailian community health centers in Suzhou, China. They underwent body composition analysis and tested lymphocyte, albumin, lipid, and thyroid hormone levels. The 30 sarcopenia subjects underwent a 3-month intensive lifestyle intervention program. At the end of the intervention, we rechecked the bioindicators. Statistical analyses were performed in IBM SPSS v26.0., Results: The blood indices of sarcopenia subjects were generally lower in albumin, non-high-density lipoprotein cholesterol (non-HDL-C), and free triiodothyronine (FT3). Body mass index (BMI)(r = 0.6266, p < 0.0001), fat-free mass (r = 0.8110, p < 0.0001), basal metabolism (r = 0.7782, p < 0.0001), and fat mass (r = 0.3916, p = 0.0020) were positively correlated with appendicular skeletal muscle index (ASMI). Higher BMI and FT3 were associated with lower odds of sarcopenia, while higher fat mass was associated with higher odds of sarcopenia. After a 3-month intensive intervention, sarcopenia subjects had a significant increase in BMI, ASMI, lymphocyte, and albumin levels, and an increase in FT3, but with a non-significant difference (p = 0.342)., Conclusions: Low BMI, FT3, and high fat mass were associated with sarcopenia. Intensive lifestyle intervention can significantly improve ASMI, BMI, lymphocytes, albumin, and FT3 in sarcopenia subjects, which is favorable for delaying the progression of sarcopenia., Trial Registration: This study was retrospectively registered on ClinicalTrials.gov, registration number NCT06128577, date of registration: 07/11/2023., (© 2024. The Author(s).)

Background: Sarcopenia is a complication that occurs after liver transplantation (LT), and it is a poor prognostic factor., Methods: A total of 23 healthy controls and 131 LT patients (18 - 76 weeks of age) were enrolled in the study. Pa-tients were grouped according to the North American Working Group on Sarcopenia in Liver Transplantation by performing pre- and post-transplant CT scans of the third lumbar (L3). The serum C-reactive protein (CRP) was analyzed and the liver frailty index (LFI) was assessed. Their associations with postoperative sarcopenia, skeletal muscle index (SMI), and poor outcomes were examined., Results: Before LT, the serum CRP was increased in patients with LT, compared with the healthy subjects, and had the highest levels in patients with sarcopenia. There were seventy-nine patients with sarcopenia after LT, including 48 who had been diagnosed with sarcopenia preoperatively and 31 who had a new onset of sarcopenia after LT. There was a moderate-strength negative correlation between the preoperative and postoperative rates of change in CRP and L3 SMI. Patients assessed as frail preoperatively (LFI ≥ 4.5) were associated with postoperative sarcopenia, and 19 of the new postoperative sarcopenia cases occurred in patients assessed as frail preoperatively. The serum CRP levels and LFI were significantly higher in patients who experienced a prolonged hospitalization and early infections postoperatively than in patients without significant adverse events. CRP (post-LT) > 2.575 pg/mL (OR = 1.16, 95% CI: 1.06 - 2.39, p = 0.026) as well as frailty (OR = 1.36, 95% CI: 1.20 - 2.60, p = 0.001) were independent predictors of sarcopenia after LT in patients., Conclusions: Serum CRP levels and LFI may be effective for an early detection of sarcopenia in patients with LT.

Objective: To evaluate the impact of the serum creatinine- and cystatin C-based new sarcopenia index (SI) on renal outcomes in non-dialysis-dependent patients with chronic kidney disease (CKD)., Methods: In this observational Korean Cohort Study for Outcome in Patients With CKD (KNOW-CKD), 1957 patients with CKD stage 1 to stage 4 were analyzed from 2011 to 2019. Men and women were separately assigned to quartile groups according to their SI. The primary outcome was a composite renal outcome consisting of 50% reduction in estimated glomerular filtration rate or end-stage kidney disease. With use of Fine and Gray subdistribution hazard models, the association between the SI and the primary outcome was analyzed., Results: During a median follow-up of 6.0 (4.2 to 7.7) years, the primary composite renal outcome occurred in 528 (28.6%) patients within a median of 3.0 (1.8 to 5.0) years. In unadjusted and adjusted models, lower SI groups had a poor primary outcome compared with the highest group (quartile 4). The hazard ratios for quartiles 1, 2, and 3 compared with quartile 4 in the fully adjusted model were 4.47 (95% CI, 3.05 to 6.56; P<.001), 3.08 (95% CI, 2.13 to 4.48; P<.001), and 2.09 (95% CI, 1.45 to 3.01; P<.001), respectively. Restricted cubic spline regression analyses found a relatively inverse linear relationship between the SI and the composite renal outcome., Conclusion: The new SI is an independent predictor of renal outcomes. A low SI is associated with poor renal outcome., (Copyright © 2024 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Sarcopenia is frequent in hemodialysis patients and associated with an increased likelihood of adverse outcomes. Early identification of the risk of sarcopenia and effective intervention are of great importance for dialysis patients. However, little research has been carried out on potential biomarkers of sarcopenia in hemodialysis patients. The aim of this study was to investigate whether serum carnitine or acylcarnitine levels are biomarkers of sarcopenia in hemodialysis patients, and whether these are prognostic factors for occurrence of complications., Methods: This prospective clinical pilot study enrolled patients (n = 259) who were treated in the Blood Purification Center from May 2021 to July 2022, all participants were followed-up for 1- year. Serum carnintine and acylcarnitine (AC) were measured using our previously reported targeted liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The correlations between carnitine or acylcarnitine levels with sarcopenia and prognosis in patients were analysed., Results: The C0 (Free carnitine, FC) and total carnitine (TC) levels were significantly lower in the sarcopenia group than in the nonsarcopenia group [nonsarcopenia vs. sarcopenia: 20.97 (16.96, 25.83) vs. 17.77 (14.30, 22.78); p = 0.002] and [nonsarcopenia vs. sarcopenia: 30.12 (24.76, 36.62) vs. 26.03 (21.30, 32.01); p = 0.003]. Besides, significant difference between the groups were noted in low free carnitine (C0 < 20 μmol/L) patients (nonsarcopenia vs. sarcopenia: 72 (42.4%) vs. 56 (62.9%); p = 0.002) and high C2/C0 ratio (>0.4) patients (nonsarcopenia vs. sarcopenia: 36 (21.2%) vs. 30 (33.7%); p = 0.028). By multivariable analysis, the disturbed CM defined as C0 deficient and/or C2/C0 carnitine ratio abnormal rise was independently and significantly correlated with the prevalence of sarcopenia after adjusting for some confounding factors, such as age, gender and dialysis duration (P values for trend <0.05). Hemodialysis patients with sarcopenia [OR: 3.214 (1.307,7.904)] and disturbed CM [OR: 3.217 (1.112,9.305)] both had a 3-fold increased risk of falling and fracture after one year follow up. In addition, age and sarcopenia [OR: 2.883 (1.321, 6.289)] were independently and positively associated with incidence of Cardio- and cerebro-vascular events., Conclusion: Disturbed carnitine metabolism is independently correlated with sarcopenia and prognosis in patients with hemodialysis. Serum carnitine level and C0/C2 ratio has the potential to be a simple, objective, and quick test for sarcopenia assessment whether such an intervention should be carried out for dialysis patients., Competing Interests: Conflict of interest There are no conflicts of interest/competing interests to declare., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Aim: Vitamin D (VD) affects skeletal muscles. The high prevalence of VD deficiency in Japan may lead to decreased skeletal muscle mass and strength, increasing the prevalence of sarcopenia. Therefore, we aimed to investigate the association between serum VD levels and skeletal muscle indices in a Japanese community-dwelling older population., Methods: We extracted data from the Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians (SONIC) study. We analyzed the data for participants in the 70s and 90s age groups. Skeletal mass index (SMI) using bioimpedance analysis, grip strength, walking speed, and serum VD levels using 25-hydroxyvitamin D [25(OH)D] were measured., Results: We analyzed the data of 310 participants in their 70s and 48 in their 90s. Mean serum 25(OH)D levels were 21.6 ± 5.0 ng/mL in the 70s group and 23.4 ± 9.1 ng/mL in the 90s group. In the 70s group, serum 25(OH)D levels correlated with SMI (r = 0.21, P < 0.0001) and grip strength (r = 0.30, P < 0.0001). Serum 25(OH)D levels were independently associated with SMI after adjusting for sex, body mass index, and serum albumin levels. In the 90s group, serum 25(OH)D levels were correlated with SMI (r = 0.29, P = 0.049) and grip strength (r = 0.34, P = 0.018). However, the multivariate analysis showed no independent association between SMI, grip strength, and serum 25(OH)D levels., Conclusion: In a cross-sectional analysis of an older population, serum VD levels were associated with SMI and grip strength, and this association was more pronounced in the 70s group than in the 90s group. Our results suggest that serum VD levels maintain skeletal muscle mass and grip strength. Geriatr Gerontol Int 2024; 24: 898-903., (© 2024 The Author(s). Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Background: Patients with idiopathic pulmonary fibrosis (IPF) often experience sarcopenia and malnutrition. However, this has not been fully examined through longitudinal surveys. This study investigated whether sarcopenia and malnutrition were associated with 1-year outcomes in IPF., Methods: We evaluated sarcopenia and nutritional status in 64 outpatients with IPF. We assessed the time-to-event for respiratory-related hospitalizations or deaths 12 months after enrollment. Sarcopenia was diagnosed by the criteria of the Asian Working Group for Sarcopenia, 2019. Nutritional status was assessed by serum transthyretin and the Geriatric Nutritional Risk Index (GNRI)., Results: The average age was 73.6 ± 7.9 years, and the percent predicted forced vital capacity (FVC) was 81.9 ± 15.7%. Of the 64 patients, 24 (37.5%) had sarcopenia. The median serum transthyretin level and mean GNRI were 23.8 mg/dL and 102, respectively. Eleven patients (17.2%) experienced respiratory-related hospitalization or death within the first year. Cox regression analysis showed that the % predicted diffusion capacity for carbon monoxide, lowest oxygen saturation in the 6-min walk test, serum transthyretin level, and GNRI were significant predictors of 1-year outcomes. The Kaplan-Meier method, which divided the patients into two groups based on a transthyretin level of 22.6 mg/dL, showed a significant difference (P < 0.001, log-rank test). Sarcopenia and the percent predicted FVC did not predict the 1-year outcomes., Conclusions: This pilot study represents the first longitudinal survey assessing patients with IPF for sarcopenia and malnutrition. Serum transthyretin levels may predict respiratory-related hospitalization or death within 1 year in patients with IPF., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Objectives: Plasma C-terminal agrin-fragment-22 (CAF22), a breakdown product of neuromuscular junction, is a potential biomarker of muscle loss. However, its levels from adolescence to octogenarians are unknown., Methods: We evaluated young (18-34 years, n = 203), middle-aged (35-59 years, n = 163), and old men (60-87 years, n = 143) for CAF22, handgrip strength (HGS), appendicular skeletal-mass index (ASMI), and gait speed., Results: We found an age-associated increase in CAF22 from young (100.9 ± 29 pmol) to middle-aged (128.3 ± 38.7 pmol) and older men (171.5 ± 35.5 pmol) (all p<0.05). This was accompanied by a gradual reduction in HGS (37.7 ± 6.1 kg, 30.2 ± 5.2 kg, and 26.6 ± 4.7 kg, for young, middle-aged, and old men, respectively), ASMI (8.02 ± 1.02 kg/m 2 , 7.65 ± 0.92 kg/m 2 , 6.87 ± 0.93 kg/m 2 , for young, middle-aged, and old men, respectively), and gait speed (1.29 ± 0.24 m/s, 1.05 ± 0.16 m/s, and 0.81 ± 0.13 m/s, for young, middle-aged, and old men, respectively). After adjustment for age, we found negative regressions of CAF22 with HGS (- 0.0574, p < 0.001) and gait speed (- 0.0162, p < 0.001) in the cumulative cohort. The receiver operating characteristics analysis revealed significant efficacy of plasma CAF22 in diagnosing muscle weakness (HGS < 27 kg) (middle-aged men; AUC = 0.731, 95% CI = 0.629-0.831, p < 0.001, Older men; AUC = 0.816, 95% CI = 0.761-0.833, p < 0.001), and low gait speed (0.8 m/s) (middle-aged men; AUC = 0.737, 95% CI = 0.602-0.871, p < 0.001, older men; AUC = 0.829, 95% CI = 0.772-0.886, p < 0.001), and a modest efficacy in diagnosing sarcopenia (middle-aged men; AUC = 0.701, 95% CI = 0.536-0.865, p = 0.032, older men; AUC = 0.822, 95% CI = 0.759-0.884, p < 0.001) in middle-aged and older men., Conclusion: Altogether, CAF22 increases with advancing age and may be a reliable marker of muscle weakness and low gait speed., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: To assess the ability of dual-energy X-ray absorptiometry (DXA) and hand-grip dynamometer to measure damage in inflammatory myopathies (IM)., Methods: Forty adult IM patients with a disease duration ≥12 months, low or no disease activity for ≥6 months, were prospectively enrolled. Thirty healthy age and sex-matched volunteers were enrolled as controls. Whole-body DXA and hand-grip dynamometer were used to measure muscle mass, grip strength and diagnose sarcopenia (EWGSOP2 criteria). Relationships between the results of strength in 12 muscles, functional tests, patient-reported disability, IMACS damage score, and history of the disease were assessed. The serum levels of potential molecular actors in the damage were measured., Results: DXA and grip strength measurements took ≤20 min. Both muscle mass and grip strength were decreased in IM patients vs volunteers (-10% and -30%, respectively) with a dispersion that varied widely (interquartile range -24.3% to +7.8% and -51.3% to -18.9%, respectively). Muscle mass and grip strength were non-redundantly correlated (r up to 0.6, P = 0.0001) with strength in 14 muscles (manual muscle test and hand-held dynamometer), functions (of limbs, respiratory and deglutition muscles), patient-reported disability, damage (extension and severity in muscular and extra-muscular domains) and blood levels of several myokines. Seven IM patients (17.5%) were sarcopenic. They had the worst damage, impaired functions, disability and history of severe myopathy. Decreased irisin and osteonectin levels were associated with sarcopenia (area under the curve 0.71 and 0.80, respectively)., Conclusion: DXA and hand-grip dynamometer are useful tools to assess damage in IM. Irisin and osteonectin may play a role in IM damage pathogenesis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This study analyzed 22 randomized controlled trials involving 959 participants to determine the impact of resistance training (RT) on body composition, muscle strength, and biomarkers in sarcopenic older adults. Regarding body composition, RT had a small effect size on relative muscle mass (RMM, SMD = 0.25[0.06,0.45]) and absolute muscle mass (AMM, SMD = 0.28[0.06,0.50]) but no effect on reducing body fat percentage (BF%). Meta-regression analysis pinpointed key predictors (p < 0.05): training period, number of sets, contraction speed, and average age. Subgroup analysis revealed that 3 sets over an 8-12 weeks training period, with slower muscle contraction speed at a 60-70 % 1-repetition maximum (1RM) training intensity, produced the most significant effects on reducing BF% and increasing RMM, respectively. Regarding muscle strength, RT had a large effect size on handgrip strength (HS, SMD = 0.83[0.43,1.23]), knee extension strength (KES, SMD = 0.90[0.50,1.30]), but no effect on chair stand test. Meta-regression analysis pinpointed key predictors (p < 0.05): training intensity, number of sets, body mass index, and sample size. Subgroup analysis revealed that the number of sets ≥ 3 and training intensity >70 % 1RM produced the most significant effect of RT on HS. Regarding biomarkers, RT had a medium effect size on insulin-like growth factor-1 (SMD = 0.70[0.10,1.30]), interleukin-10 (SMD = 0.61[0.09,1.13]), follistatin (SMD = 0.56[0.16,0.96]), but no effect on interleukin-6, tumor necrosis factor-alpha, and myostatin. It concludes that RT is an effective way to improve muscle strength and the level of synthetic hormones and anti-inflammatory factors in sarcopenic older adults, with a slight impact on body composition and no impact on pro-inflammatory factors., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare for this study., (Copyright © 2024. Published by Elsevier B.V.)

Background: Observational studies have documented increased serum IL-6 levels in elderly individuals afflicted with sarcopenia. Nevertheless, the relationship between serum IL-6 concentrations and sarcopenia prevalence in the aging population is yet to be defined., Methods: We executed a systematic review and meta-analysis of cross-sectional studies that scrutinized serum IL-6 levels in older adults with and without sarcopenia. Relevant studies were sourced from PubMed, Scopus, Embase, Cochrane Library, and Web of Science from inception until 10 September 2023. The standard mean differences (SMDs) in serum IL-6 levels between studies were synthesized using a random-effects model. To examine the influence of demographic and clinical factors on these outcomes, we performed subgroup analyses and meta-regression, focusing on variables such as sex, age, and body mass index (BMI). We also assessed the relationship between serum IL-6 levels and the defining components of sarcopenia: muscle mass, muscle strength, and physical performance. We used Fisher's Z transformation to standardize the interpretation of effect sizes from these relationships. The transformed values were then converted to summary correlation coefficients (r) for a clear and unified summary of the results., Results: We included twenty-one cross-sectional studies involving 3,902 participants. Meta-analysis revealed significantly elevated serum IL-6 levels in older adults with sarcopenia compared with those without sarcopenia (SMD = 0.31; 95% CI 0.18, 0.44). The difference was highly pronounced in the subgroups of male and those with female percentage below 50% or a mean BMI below 24 kg/m 2 . Serum IL-6 levels were inversely correlated with muscle mass (summary r = -0.18; 95% CI -0.30, -0.06), but not with handgrip strength (summary r = -0.10; 95%CI: -0.25, 0.05) or gait speed (summary r = -0.09; 95%CI: -0.24, 0.07)., Conclusions: This meta-analysis establishes a link between increased serum IL-6 levels and sarcopenia in the elderly, particularly in relation to decreased muscle mass.

Background: The ratio between non-high-density lipoprotein cholesterol and high-density lipoprotein cholesterol (NHHR) is a reliable marker for assessing the risk linked to lipid metabolism disorders. Sarcopenia, characterized by age-related loss of muscle mass and strength/function, includes the assessment of muscle mass, muscle strength, and muscle-specific strength. However, research into NHHR's relationship with low muscle mass risk remains unexplored., Methods: Our study utilized a cross-sectional approach, examining data derived from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. Through multivariable linear and logistic regression, we investigated the relationships of the NHHR with muscle mass and low muscle mass. We visualized the results using smoothing curves and assessed threshold effects. We also performed various subgroup and sensitivity analyses., Results: This research encompassed 9,012 participants and demonstrated significant nonlinear associations between NHHR and ALM BMI or low muscle mass risk in a generalized additive model (GAM), pinpointing critical NHHR values (3.328 and 3.367) where changes in NHHR significantly impacted ALM BMI and low muscle mass risk., Conclusions: The NHHR demonstrates a significant association with an increased risk of low muscle mass among middle-aged Americans. This ratio has potential as a predictive marker for low muscle mass. Further exploration of NHHR is expected to aid in advancing preventive and therapeutic measures for this condition., (© 2024. The Author(s).)

Background: The role of C-reactive protein (CRP), an inflammatory marker, in the development of sarcopenia remains uncertain., Methods: This cross-sectional research involved the enrollment of 207 patients, classified into two groups: 74 patients with sarcopenia and 133 patients without sarcopenia. Clinical data of the participants, including hand grip strength, walking speed, appendicular lean mass (ALM), and calf circumference, were collected and recorded. We evaluated the extent to which CRP levels are associated with the risk of sarcopenia using both univariate and multivariate logistic regression models. Besides, the correlation between CRP levels, hand grip strength, ALM, and walking speed was examined using the Spearman rank correlation test. Moreover, we have employed the Mendelian randomization (MR) analysis technique to explore the causal relationship between CRP levels and the occurrence of sarcopenia., Results: The sarcopenia group showed a higher proportion of older women, with significant differences in anemia prevalence, calf circumference, gait speed, ALM, hand grip strength, and elevated CRP levels compared to the control group. Logistic regression analyses identified CRP as an independent risk factor for sarcopenia (OR: 1.151, 95% CI:1.070-1.238, and P < 0.001). Correlation analysis results revealed a noteworthy inverse association with hand grip strength ( R  = -0.454 and P < 0.001), ALM ( R  = -0.426 and P < 0.001), and walking speed ( R  = -0.431 and P < 0.001). MR analysis provided further evidence of a significant detrimental link between genetically predicted CRP levels and essential sarcopenia characteristics, with consistent results across various statistical models., Conclusions: Our study uncovered strong evidence supporting a noteworthy inverse association and causality between CRP concentrations and sarcopenia, indicating that CRP has the potential to serve as a biomarker for sarcopenia., Competing Interests: The authors emphasize that the study was conducted impartially, with no involvement in any business or financial associations that could create conflicts of interest., (Copyright © 2024 Shangjin Lin et al.)

Background: The relationship between atherogenic index of plasma (AIP) and triglyceride glucose-body mass index (TyG-BMI) and sarcopenia has not been studied in the United States (US) population., Methods: This research included 4,835 people from the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2018. The relationship between sarcopenia and TyG-BMI, as well as the AIP index, was examined through the utilization of restricted cubic spline (RCS) analysis, subgroup analysis, and multivariate logistic regression analysis. Diagnostic value of AIP and TyG-BMI for sarcopenia was compared by receiver operating characteristic (ROC) curves., Results: In this research, 428 people with sarcopenia were identified among the 4,835 subjects that were included in the experiment. AIP and sarcopenia were positively associated with an odds ratio (OR) of 1.58 and a 95% confidence interval (CI) of (1.07, 2.34) on fully adjusted multivariate logistic regression analysis. Similarly, TyG-BMI and sarcopenia were positively associated with an OR of 8.83 and a 95% CI of (5.46, 14.26). AIP and sarcopenia had a non-linear positive connection (P-value<0.001, P-Nonlinear=0.010), while TyG-BMI and sarcopenia had a linear positive correlation (P-value<0.001, P-Nonlinear=0.064), according to RCS analysis. Subgroup analyses showed a significant interaction between TyG-BMI and sarcopenia due to gender (P = 0.023). ROC curves showed that TyG-BMI (AUC:0.738, 95% CI: 0.714 - 0.761) was more useful than AIP (AUC:0.648, 95% CI: 0.622 - 0.673) in diagnosing sarcopenia., Conclusion: In US adults aged 20-59 years, our study revealed a correlation between elevated AIP and TyG-BMI levels and heightened sarcopenia risk. Moreover, TyG-BMI has better diagnostic validity than AIP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pan, Wang, Tang and Qian.)

This study aimed to explore the correlation between serum ferritin and additional biomarkers associated with iron metabolism, as well as their connection to muscle atrophy and frailty in the community-dwelling middle-aged and elderly population. The study included 110 middle-aged and elderly participants. Participants were categorized into an iron accumulation group (31 cases) and a normal iron group (79 cases) based on the standard ferritin values for men and women. Based on the criteria of the Asian Working Group on Muscular Dystrophy, participants were classified into a sarcopenia group (31 cases) and a non-sarcopenia group (79 cases). Using the Fried frailty syndrome criteria, participants were categorized into non-frailty (7 cases), pre-frailty (50 cases), and frailty (53 cases) groups. We employed multiple linear regression, binary logistic regression, partial correlation analysis, and ordinal logistic regression to assess the associations between iron metabolism indices and the presence of muscle atrophy and frailty. Compared with the normal iron group, the iron overload group had significantly higher ferritin, weight loss, fatigue, slow gait, and frailty scores (P < .05). Among the 3 models we set, ferritin was not significantly correlated with muscle mass in models 1 and 3 (P > .05), ferritin was positively correlated with muscle mass in model 2 (Pmodel2 = .048), but Transferrin saturation was positively correlated with muscle mass in all 3 models (Pmodel1 = .047, Pmodel2 = .026, Pmodel3 = .024). Ferritin, body mass index and iron overload were the influencing factors of sarcopenia (Pferritin = .027, PBMI < .001, Piron overload = .028). Ferritin was positively correlated with weight loss, fatigue, slow gait, frailty score, and frailty grade (P < .05). Age, gender and ferritin were the influencing factors of frailty classification (P < .05). Disrupted iron metabolism can lead to decreased muscle mass and function among the middle-aged and elderly, increasing frailty risk. It's crucial to prioritize community-based frailty screening and prevention, focusing on iron utilization as well as storage, since accelerating the body's iron metabolism cycle might influence muscle health more significantly than iron reserves., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: The purpose of the present study was to examine the association of oxidative stress markers with sarcopenia in the general United States population under the age of 60., Methods: We used the National Health and Nutrition Examination Survey data from 2011‒2014 and performed Restricted Cubic Spline (RCS) plots, weighted multivariable logistic regression analysis to calculate ratio ratios and 95% Confidence Intervals, and subgroup analysis based on age, sex, hypertension, diabetes mellitus, and body mass index stratification to determine the association of markers of oxidative stress with the prevalence of sarcopenia., Results: The present analysis included a total of 8,782 participants. Firstly, the RCS plots showed a roughly L-shaped curve association of total bilirubin and serum iron with a prevalence of sarcopenia. Secondly, albumin was negatively and linearly associated with the risk of sarcopenia. Finally, with the increase in gamma-glutamyl transferase, the prevalence of sarcopenia showed a trend of first rising and then declining as a result of the iron increase., Conclusions: We demonstrated a nonlinear association between markers of oxidative stress and sarcopenia. The need to focus more on levels of oxidative stress in the body could provide better prevention strategies for sarcopenia., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Aims: Sarcopenia is linked to impaired physical function and exercise tolerance. The aim of this systematic review and meta-analysis was to examine the association of sarcopenia and low appendicular skeletal muscle (ASM) with biomarkers of cardiac function, B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP), in patients with heart failure (HF)., Methods and Results: From inception until May 2023, a systematic literature search of observational studies was undertaken utilizing the PubMed, Web of Science, Scopus, and Cochrane Library databases. A meta-analysis employing a random-effects model was used to compute the pooled effects (CRD42023418465). Overall, 16 studies were included in this systematic review and meta-analysis. Our main analysis showed that sarcopenia in HF was linked to significantly higher levels of BNP (MD: 87.76, 95% CI 20.74-154.78, I 2 = 61%, P = 0.01) and NT-proBNP (MD: 947.45, 95% CI 98.97-1795.93, I 2 = 35%, P = 0.03). Similarly, low ASM was associated with significantly higher levels of BNP (MD: 118.95, 95% CI 46.91-191.00, I 2 = 93%, P < 0.01) and NT-proBNP (MD: 672.01, 95% CI 383.72-960.30, I 2 = 2%, P < 0.01). The quality of the included cohort studies was considered moderate, using the binary AXIS checklist and the Cochrane Tool to Assess the Risk of Bias in Cohort Studies., Conclusions: In patients with HF, sarcopenia and reduced ASM are associated with considerably higher plasma levels of BNP and NT-proBNP. Future research is required to investigate whether sarcopenia may express dysregulated biomarkers of cardiac function., (© 2024. The Author(s).)

Sarcopenia is related to disease severity in chronic kidney disease (CKD) patients; however, its pathophysiology remains poorly known. We investigated the associations of biomarkers of intestinal leak with sarcopenia in various stages of CKD. We recruited 61-76-year-old male controls and patients with various stages of CKD (n = 36-57/group) for measuring plasma lipopolysaccharide-binding protein (LBP) and zonulin (markers of intestinal leak), handgrip strength (HGS), skeletal mass index (SMI), and gait speed (markers of sarcopenia), and short physical performance battery (SPPB; marker of physical capacity). CKD stages 4 and 5 were associated with lower HGS, SMI, gait speed, and cumulative SPPB scores and a higher sarcopenia prevalence than controls and patients with CKD stages 1 and 2 (all p < 0.05). CKD patients (stages 1 and 2) had elevated plasma zonulin and LBP when compared with CKD stages 4 and 5. Plasma zonulin and LBP exhibited significant correlations with renal function, HGS, gait speed, SPPB scores, and oxidative stress markers in CKD stages 4 and 5 (all p < 0.05). However, similar relations were not found in early CKD. Collectively, intestinal leak may be contributing to sarcopenia and physical disability in the advanced stages of CKD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Observational studies have reported that circulating cytokines are associated with sarcopenia. However, the causal relationship between circulating cytokines and sarcopenia has not been elucidated., Objectives: This study aimed to investigate the causal relationship between circulating cytokines and sarcopenia with genetic data using Mendelian randomization (MR)., Methods: Two-sample bidirectional MR analysis was performed to investigate the causal relationship in individuals of European ancestry. The publicly available genome-wide association study statistics were used to select the key eligible single nucleotide polymorphisms significantly associated with circulating cytokines. Multiple MR analysis approaches, including inverse variance weighted (IVW), MR-Egger, weighted median method (WMM), and MR-Pleiotropy residual Sum and Outlier (MR-PRESSO) methods, were used for the analysis. Sarcopenia-related traits were appendicular lean mass (ALM) and grip strength., Results: This study demonstrated the causal effect of genetically predicted circulating interleukin interleukin-16 (IL16) levels on both ALM [odds ratio (OR) = 0.990, 95% confidence interval (CI): 0.980-1.000, P = 0.049] and grip strength (OR = 0.971, 95% CI: 0.948-0.995, P = 0.020]. Additionally, C-X-C motif chemokine ligand 10 (CXCL10), interleukin-1beta (IL1B), and hepatocyte growth factor (HGF) were correlated with ALM, while vascular endothelial growth factor (VEGF), interleukin-12 (IL12), and interleukin-15 (IL15) were correlated with grip strength. The results of MR-Egger, weighted median, weighted mode, and simple mode methods were consistent with the IVW estimates. Sensitivity analysis revealed that horizontal pleiotropy did not bias the causal estimates., Conclusion: These findings indicate that inflammatory cytokines exert a significant causal effect on sarcopenia and provide promising leads for the development of novel therapeutic targets for the disease. By evaluating the role of circulating cytokines in the pathologic condition via a genetic epidemiological approach, our study made contributions to a further investigation of underlying mechanisms of sarcopenia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: Sarcopenia is a serious problem in adults and children. However, limited modalities are available for diagnosing pediatric sarcopenia. The serum creatinine to cystatin C ratio (Cre/CysC ratio) is a promising method for muscle quantification, although its clinical significance in the pediatric population is unknown. This study aimed to evaluate the relationship between the Cre/CysC ratio and physical performance., Methods: This was a single-center retrospective study. Patients aged <15 years who had visited the University of Tokyo Hospital for measurements of serum creatinine and cystatin C levels, body height, and body weight were included. The patients were assigned according to their age (<2 or ≥2 years), and the relationship between the Cre/CysC ratio and physical performance at the time of measurement was analyzed., Results: We included 266 patients, revealing a significant relationship between Cre/CysC ratio and physical performance in children aged ≥2 years (p < 0.001) but not in children aged <2 years (p = 0.42). The repeater-operator curve analysis of Cre/CysC to predict bedridden status showed good performance (the area under the curve was 0.82 (95% CI, 0.75-0.89)) and the cut-off value 0.44 had good accuracy (sensitivity 0.87, specificity 0.61)., Conclusions: The Cre/CysC ratio was a significant marker of impaired physical performance, and a Cre/CysC ratio <0.44 accurately predicted bedridden status in children aged >2 years., Competing Interests: Declaration of competing interest The authors declare there is no conflict of interest related to this study., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The role of interleukins in sarcopenia development has been acknowledged, yet the specifics of their involvement remain to be fully understood. This study aimed to explore alterations in interleukin levels among sarcopenia patients., Methods: Searches were conducted in Embase, Medline, and the Cochrane Library for literature published up to May 2023. Eligible observational studies with a diagnosis of sarcopenia were included. The Newcastle-Ottawa Scale was utilized for quality assessment. For data synthesis, a random-effects model was used, and the Mantel-Haenszel method was used for pooled estimates., Results: Of the 7685 articles screened, 37 met the inclusion criteria. Statistically significant differences in the levels of IL-1β, IL-6 and IL-10 were detected in sarcopenia patients. Specifically, IL-1β (95 % CI: 0.33 [0.12, 0.54], P < 0.05), IL-6 (95 % CI: 0.91 [0.59, 1.24], P < 0.05), and IL-10 (95 % CI: 0.11 [0.07,0.15], P < 0.05) were detected. However, no significant associations were found between serum IL-4 (95 % CI: 0.36 [-0.18, 0.42], P = 0.44), IL-8 (95 % CI: -1.05 [-3.06, 0.95], P = 0.3), IL-12 (95 % CI: -3.92 [-8.32,0.48], P = 0.08) or IL-17 (95 % CI: 0.22 [-2.43, 2.88], P = 0.87) and sarcopenia. Subgroup analysis showed no significant difference in IL-6 (95 % CI: -0.03 [-0.72, 0.66], P = 0.93) and IL-10 (95 % CI: 0.1 [-0.44, 0.64], P = 0.72) among patients with European standard sarcopenia., Conclusions: Inflammation plays a role in sarcopenia, and the serum levels of IL-1β, IL-6, and IL-10 are associated with sarcopenia. Further research is needed to clarify these associations., Clinical Trials Registration Number: CRD42024506656., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Background: Increasing interest surrounds the utility of blood-based biomarkers for diagnosing sarcopenia. C-terminal agrin fragment (CAF), a marker of neuromuscular junction stability, is amongst the most promising candidates; however, a dearth of reference data impedes the incorporation of its use in public health settings. This study aimed to establish reference values for plasma CAF concentrations across adulthood in a large, well-characterized cohort of healthy adults; and comprehensively examine the association between plasma CAF levels and skeletal muscle health., Methods: One thousand people aged between 18 and 87 years took part in this study (mean age = 50.4 years; 51% females). Body composition and muscle strength were examined using DXA and hand dynamometry. Plasma CAF concentrations were measured, in duplicate, using commercially available ELISA kits. Sarcopenia and individual sarcopenia signatures [low skeletal muscle index (SMI) only/low grip strength only] were classified using the EWGSOP2 algorithm., Results: Detailed reference CAF values, according to sex and age, are presented. A significant but modest age-related increase in plasma CAF concentration was observed (P = 0.018). Across adulthood, CAF concentrations were negatively associated with grip strength and SMI (both P < 0.001). In people ≥50 years old, CAF concentrations were 22.6% higher in those with sarcopenia (P < 0.001), 11.3% higher in those with low SMI (P = 0.006) and 9.6% higher in those with low grip strength (P = 0.0034), compared with controls. People in the highest CAF concentration quartile, had 3.25 greater odds for sarcopenia (95% CI = 1.41-7.49, P = 0.005), 2.76 greater odds for low SMI (95% CI = 1.24-5.22, P = 0.012), and 2.56 greater odds for low grip strength (95% CI = 1.07-5.57, P = 0.037), compared with those in the lowest quartile. People with a CAF Z-score ≥2 had 9.52 greater odds for sarcopenia (95% CI = 3.01-30.05, P < 0.001) compared with a Z-score <1. Plasma CAF concentration had an acceptable level of diagnostic accuracy for sarcopenia (AUC = 0.772, 95% CI = 0.733-0.807, P < 0.001)., Conclusions: The reference values presented herein may guide the clinical interpretation of circulating CAF and help identify people at risk of poor skeletal muscle outcomes for inclusion in therapeutic interventions. Our findings add clarity to existing data, demonstrating a robust relationship between circulating CAF and skeletal muscle integrity in the largest adult cohort to date, and support the use of CAF as an accessible, cost-effective screening tool for sarcopenia. However, further research into the prognostic utility of plasma CAF, and the establishment of normative data from other populations, are urgently needed if routine CAF screening is to be embedded into public healthcare settings., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background: Growth differentiation factor-15 (GDF-15) has been associated with senescence, lower muscle strength, and physical performance in healthy older people. Still, it is not clear whether GDF-15 can be utilized as a biomarker of sarcopenia and frailty in the early stages of hospitalization. We investigated the association of plasma GDF-15 with sarcopenia and frailty in older, acutely admitted medical patients., Methods: The present study is based on secondary analyses of cross-sectional data from the Copenhagen PROTECT study, a prospective cohort study including 1071 patients ≥65 years of age admitted to the acute medical ward at Copenhagen University Hospital, Bispebjerg, Denmark. Muscle strength was assessed using handgrip strength, and lean mass was assessed using direct segmental multifrequency bioelectrical impedance analyses and used to clarify the potential presence of sarcopenia defined according to guidelines from the European Working Group on Sarcopenia in Older People. Frailty was evaluated using the Clinical Frailty Scale. Plasma GDF-15 was measured using electrochemiluminescence assays from Meso Scale Discovery (MSD, Rockville, MD, USA)., Results: We included 1036 patients with completed blood samples (mean age 78.9 ± 7.8 years, 53% female). The median concentration of GDF-15 was 2669.3 pg/mL. Systemic GDF-15 was significantly higher in patients with either sarcopenia (P < 0.01) or frailty (P < 0.001) compared with patients without the conditions. Optimum cut-off points of GDF-15 relating to sarcopenia and frailty were 1541 and 2166 pg/mL, respectively., Conclusions: Systemic GDF-15 was higher in acutely admitted older medical patients with sarcopenia and frailty compared with patients without. The present study defined the optimum cut-off for GDF-15, related to the presence of sarcopenia and frailty, respectively. When elevated above the derived cutoffs, GDF-15 was strongly associated with frailty and sarcopenia in both crude and fully adjusted models., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Chronic kidney disease (CKD) is linked to an elevated risk of malnutrition and sarcopenia, contributing to the intricate network of CKD-related metabolic disorders. Adipokines and myokines are markers and effectors of sarcopenia and nutritional status. The aim of this study was to assess whether the adipokine-myokine signature in patients on kidney replacement therapy could help identify malnutrition and sarcopenia. The study involved three groups: 84 hemodialysis (HD) patients, 44 peritoneal dialysis (PD) patients, and 52 kidney transplant recipients (KTR). Mean age was 56.1 ± 16.3 years. Malnutrition was defined using the 7-Point Subjective Global Assessment (SGA) and the Malnutrition-Inflammation Score (MIS). Sarcopenia was diagnosed based on reduced handgrip strength (HGS) and diminished muscle mass. Concentrations of adipokines and myokines were determined using the enzyme-linked immunosorbent assay (ELISA). 32.8% of all study participants were identified as malnourished and 20.6% had sarcopenia. For malnutrition, assessed using the 7-Point SGA, in ROC analysis albumin (area under the curve (AUC) 0.67 was the best single biomarker identified. In dialysis patients, myostatin (AUC 0.79) and IL-6 (AUC 0.67) had a high discrimination value for sarcopenia, and we were able to develop a prediction model for sarcopenia, including age, albumin, adiponectin, and myostatin levels, with an AUC of 0.806 (95% CI: 0.721-0.891). Adipokines and myokines appear to be useful laboratory markers for assessing malnutrition and sarcopenia. The formula we propose could contribute to a better understanding of sarcopenia and potentially lead to more effective interventions and management strategies for dialysis patients.

Background: Despite the known association between chronic inflammation and reduced muscle mass, there is a gap in research regarding the association between the systemic immune-inflammation index (SII) and sarcopenic obesity (SO). This study aims to assess the relationship between SII and SO in middle-aged and elderly adults and the mediating role of triglyceride-glucose index (TyG)., Methods: This cross-sectional study involved 2,719 participants aged 45-90 years who underwent health check-ups. SO was evaluated by combining sarcopenia [assessed by handgrip strength and appendicular skeletal muscle index (ASMI)] with obesity (determined by body fat percentage). Association between SII and SO, sarcopenia, and obesity in middle-aged and elderly individuals was examined using multivariable logistic regression, restricted cubic spline analysis, and subgroup analysis. Bidirectional mediation analysis was conducted to determine the direct and indirect effects through SII and TyG., Results: The study included 2,719 participants, of which 228 had SO (8.4%). SO prevalence increased as the SII quartiles rose (P for trend <0.001). SII (per SD increase) had a significantly positive association with SO in both middle-aged individuals (OR = 1.69, 95% CI: 1.43 ~ 1.99) and older adults (OR = 2.52, 95% CI: 1.68 ~ 3.77). The relationship between SII and SO was found to be non-linear (P nonlinear <0.05). In addition, SII showed a strong negative relationship with both handgrip strength and ASMI across all participants. In subgroup analysis, SII was still shown to significantly increase the risk of SO in all subgroups by gender, body mass index, waist circumference, smoking, drinking, hypertension, diabetes, dyslipidemia. TyG was found to mediate 21.36%, 11.78%, and 9.94% of the associations between SII and SO, sarcopenia, and obesity, respectively. SII had no mediation effect on the association between TyG and SO, sarcopenia, and obesity (P>0.05)., Conclusions: Elevated levels of SII were associated with an increased risk of SO in middle-aged and elderly adults, especially in the elderly population, and elevated TyG levels played a role in this relationship., (© 2024. The Author(s).)

Objectives: This study aimed to investigate the association of cystatin C, serum creatinine and sarcopenia index with cardiovascular and all-cause death in general population., Methods: Data of participants from the National Health and Nutrition Examination Surveys (NHANES) from 1999 to 2004 were used and all participants were followed up regularly until December 31, 2019. Multivariable Cox analysis was used to investigate the association of cystatin C, serum creatinine and sarcopenia index with cardiovascular and all-cause death. Restricted cubic spline was conducted to evaluate the nonlinear association., Results: A total of 9894 participants with a mean age of 45.64 years were enrolled and followed up for a mean duration of 15.62 ± 4.68 years. Approximately 50.3% were male and there were a total of 2681 all-cause deaths and 691 cardiovascular deaths recorded during the follow-up period. In final adjusted model, compared with the first quartile of cystatin C (< 0.659 mg/L), the risk of cardiovascular and all-cause death increased 2.36-fold and 1.71-fold for participants in the fourth quartile (≥ 0.877 mg/L) (HR: 3.36, 95% CI: 2.06-5.46, P < 0.001; HR: 2.71, 95% CI: 2.17-3.38, P < 0.001; respectively). Furthermore, a higher sarcopenia index (< 88.41 vs. ≥125.52) was associated with the reduced risk of cardiovascular death (HR: 0.41, 95% CI: 0.31-0.53, P < 0.001) as well as all-cause death (HR: 0.41, 95% CI: 0.35-0.49, P < 0.001). Additionally, restricted cubic splines showed that there was a nonlinear relationship between sarcopenia index levels and all-cause death while there was a linear relationship between sarcopenia index levels and cardiovascular death., Conclusions: Higher sarcopenia index was associated with the decreased risk of cardiovascular and all-cause death in general population in the United States. Elevated cystatin C was positively associated with cardiovascular and all-cause death., (© 2024. The Author(s).)

Background: The Triglyceride-glucose (TyG) index is a marker of insulin resistance, but its role in sarcopenia is controversial. The purpose of this study was to investigate the association of the TyG index with sarcopenia., Methods: 4030 participants aged 20 years and above were selected from National Health and Nutrition Examination Survey for cross sectional study. Weighted logistic regression model was used to estimate the association between TyG index and sarcopenia. Threshold effect analysis and restricted cubic spline were employed to describe nonlinear link, with interaction tests and subgroup analyses performed., Results: It was found in the fully adjusted model that the TyG index was positively associated with sarcopenia (per 1-unit increase in the TyG index: OR = 1.31, 95%CI: 1.07, 1.60). This association was further highlighted in groups characterized by the absence of MetS or diabetes, as well as the absence of vigorous or moderate work activity. Furthermore, analysis of the curve fitting and threshold effects indicated a nonlinear relationship, which exhibited a turning point at 9.14., Conclusion: The study results indicated that the TyG index was positively associated with sarcopenia. Enhancing the management of insulin resistance could help reduce the risk of developing sarcopenia., (© 2024. The Author(s).)

Introduction: Patients with Cushing's syndrome (CS) in remission show sustained fatigue, myopathy, and an increased prevalence of sarcopenia. The mechanisms that determine these persistent muscle problems are not well known. We aimed to identify circulating microRNAs (miRNAs) with differential expression that could be potential biomarkers for the diagnosis and/or prognosis in CS., Patients and Methods: Thirty-six women in sustained remission for 13 ± 7 years (mean ± SD) from CS, with a median age (IQ range) of 51 (45.2-60) years and mean ± SD BMI of 27 ± 4 Kg/m 2 , and 36 matched healthy controls were investigated. In 7 patients sarcopenia was present according to the European Working Group on Sarcopenia in Older People (EWGSOP) criteria. Small RNA libraries were generated and indexed using a modified Illumina TruSeq small RNA-sequencing protocol. MiRNAs were identified in plasma using bioinformatic analysis, and validation was carried out using RT-qPCR. For the validation, Taqman probes were performed on QuantStudio 5 equipment (Applied Biosystems)., Results: In a first discovery group using RNA-sequencing, plasma samples of 18 CS patients and 18 healthy subjects were investigated; circulating miR-28-5p, miR-495-3p and miR-654-5p were upregulated in CS patients as compared with controls (p<0.05). In a validation study of the 3 upregulated miRNAs in 36 patients and 26 controls, no differences were observed by RT-qPCR; however, the expression of circulating miR-28-5p was upregulated in CS patients with sarcopenia as compared with those without (AUC for fold-change in the ROC analysis, 0.798; p=0.0156). The optimized cut-off value for miR-28-5p to identify CS patients with sarcopenia was 3.80, which yielded a sensitivity of 86% and a specificity of 69%., Conclusion: MiR-28-5p, a muscle-specific microRNA involved in myotube proliferation and differentiation in vivo , may serve as an independent non-invasive biomarker for identifying CS patients at high-risk of sarcopenia despite biochemical remission., Competing Interests: JSI-C was employed by company EpiDisease S.L. JLG-G is a founding partner of EpiDisease SL, a Spin-off from the Center for Biomedical Network Research of Spain. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission., (Copyright © 2024 Seco-Cervera, Ibáñez-Cabellos, Pallardo, García-Giménez, Aulinas, Martel-Duguech, Webb and Valassi.)

Background: Cancer and sarcopenia are both closely related to lipid metabolism, but the relationship between lipid metabolism and patients with cancer and sarcopenia has not been thoroughly studied. The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a reliable measure of lipid metabolism. The purpose of this study was to determine the possible relationship between the NHHR and sarcopenia in individuals with cancer., Methods: Data from the National Health and Nutrition Examination Survey (NHANES) database for individuals with cancer, with and without sarcopenia was analyzed using weighted multiple regression equations, weighted regression cubic spline (RCS) analysis, and weighted subgroup analysis., Results: In total, 1,602 individuals with cancer were included, of whom 17.1% had sarcopenia. In Adjusted Model 2, the occurrence of sarcopenia was found to be significantly associated with a higher NHHR in cancer (95% confidence interval [CI]:1.01-1.39, P = 0.036). Individuals with high a NHHR had a 2.09-fold higher risk of developing sarcopenia in comparison to those with a low NHHR (95% CI:1.12-3.92, P = 0.022). RCS analysis further identified a U-shaped non-linear relationship between females with cancer and the muscle index. Subgroup analysis indicated that sex was a significant stratifying factor, whereas age, race, marital status, smoking and drinking habits, and history of cardiovascular disease, arthritis, hypertension, and diabetes had no significant impact., Conclusion: From the perspective of lipid metabolism, the NHHR may serve as an indicator for monitoring and preventing the occurrence of sarcopenia in individuals with cancer, particularly for females with cancer who appear to have greater sensitivity., (© 2024. The Author(s).)

Background: Sarcopenia has been reported to play an important role in frailty syndrome. The serum creatinine/serum cystatin C ratio (Scr/Cys C ratio) has recently been recognized as a valuable indicator for assessing sarcopenia. However, few studies have examined the association between serum creatinine/serum cystatin C ratio and frailty. The objective of this study is to investigate the relationship between the serum creatinine/serum cystatin C ratio and frailty among older adults residing in the community., Methods and Materials: A Total of 1926 community-dwelling older adults aged ≥ 60 years in the 2011 waves of the China Health and Retirement Longitudinal Study (CHARLS) were included. The participants' frailty status was determined using a 39 item frailty index (FI), which classified individuals as "robust" (FI ≤ 0.1), "pre-frailty" (0.1 < FI < 0.25), or "frailty" (FI ≥ 0.25). The Scr/Cys C ratio was determined by dividing the serum creatinine level (mg/dL) by the cystatin C level (mg/L). The one-way analysis of variance(ANOVA) and Chi-squared test (χ2)were applied to compare the differences between the 3 groups. Both linear regression and logistic regression models were used to further investigate the relationship between Scr/Cys C ratio and frailty., Results: After adjusting for potential confounding factors, the study revealed that participants in the Q1 quartile of Scr/Cys C ratio had increased odds of frailty (Q1vs.Q4: OR = 1.880, 95% CI 1.126-3.139, p = 0.016) compared with those in the Q4 quartile group. In fully adjusted logistic regression models, male participants in the Q2 quartile of Scr/Cys C ratio were significantly correlated with higher odds of pre-frailty (Q2 vs.Q4: OR = 1.693, 95%CI 1.040-2.758, p = 0.034). However, this correlation was not observed in females (OR = 0.984, 95% CI 0.589-1.642, p = 0.950,). Additionally, the study observed an increase in both the frailty index and the incidence of frailty as age increased in both males and females., Conclusion: Among community-dwelling older adults, lower Serum creatinine to cystatin C ratio were found to be associated with increased odds of frailty prevalence in males., (© 2024. The Author(s).)