Human hallmarks of sarcopenia include muscle weakness and a blunted response to exercise. Nicotinamide N-methyltransferase inhibitors (NNMTis) increase strength and promote the regenerative capacity of aged muscle, thus offering a promising treatment for sarcopenia. Since human hallmarks of sarcopenia are recapitulated in aged (24-month-old) mice, we treated mice from 22 to 24 months of age with NNMTi, intensive exercise, or a combination of both, and compared skeletal muscle adaptations, including grip strength, longitudinal running capacity, plantarflexor peak torque, fatigue, and muscle mass, fiber type, cross-sectional area, and intramyocellular lipid (IMCL) content. Exhaustive proteome and metabolome analyses were completed to identify the molecular mechanisms underlying the measured changes in skeletal muscle pathophysiology. Remarkably, NNMTi-treated aged sedentary mice showed ~ 40% greater grip strength than sedentary controls, while aged exercised mice only showed a 20% increase relative to controls. Importantly, the grip strength improvements resulting from NNMTi treatment and exercise were additive, with NNMTi-treated exercised mice developing a 60% increase in grip strength relative to sedentary controls. NNMTi treatment also promoted quantifiable improvements in IMCL content and, in combination with exercise, significantly increased gastrocnemius fiber CSA. Detailed skeletal muscle proteome and metabolome analyses revealed unique molecular mechanisms associated with NNMTi treatment and distinct molecular mechanisms and cellular processes arising from a combination of NNMTi and exercise relative to those given a single intervention. These studies suggest that NNMTi-based drugs, either alone or combined with exercise, will be beneficial in treating sarcopenia and a wide range of age-related myopathies.

OBJECTIVE: To develop and validate a predictive model for sarcopenia.
METHODS: A total of 240 subjects who visited our hospital between August 2021 and May 2023 were randomly divided by time of entry into a training set containing 2/3 of patients and a validation set containing 1/3 of patients. The muscle thickness (MT), echo intensity (EI), and shear wave velocity (SWV) of the medial gastrocnemius muscle were measured. Indicators that were meaningful in the univariate analysis in the training set were included in a binary logistic regression to derive a regression model, and the model was evaluated using a consistency index, calibration plot, and clinical validity curve. Diagnostic efficacy and clinical applicability were compared between the model and unifactorial indicators.
RESULTS: Four meaningful variables, age, body mass index (BMI), MT, and SWV, were screened into the predictive model. The model was Logit Y = 21.292 + 0.065 × Age - 0.411 × BMI - 0.524 × MT - 3.072 × SWV. The model was well differentiated with an internally validated C-index of 0.924 and an external validation C-index of 0.914. The calibration plot predicted probabilities against actual probabilities showed excellent agreement. The specificity, sensitivity, and Youden\'s index of the model were 73.80%, 97.40%, and 71.20%, respectively, when using the diagnostic cut-off value of >0.279 for sarcopenia. The logistic model had higher diagnostic efficacy (p < 0.001) and higher net clinical benefit (p < 0.001) over the same threshold range compared to indicators.
CONCLUSIONS: The logistic model of sarcopenia has been justified to have good discriminatory, calibrated, and clinical validity, and has higher diagnostic value than indicators.

OBJECTIVE: Recent studies have indicated that comorbidities such as sarcopenia and anemia can influence the prognosis of patients with colorectal cancer (CRC). However, the synergistic effects of sarcopenia and anemia on the survival of CRC patients are not yet comprehensively understood. This study aimed to investigate the relationship between anemia and sarcopenia and their synergistic effect on survival in patients with CRC.
METHODS: A total of 1629 patients who underwent colorectal surgery were retrospectively reviewed. Patients were categorized into four hemoglobin-sarcopenia combined classifications (HS grade) according to their hemoglobin and skeletal muscle index (SMI) levels: hemoglobin low/SMI low (HS1), hemoglobin low/SMI high (HS2), hemoglobin high/SMI low (HS3), and hemoglobin high/SMI high (HS4). Association with overall survival (OS) was analyzed using both univariable and multivariable analyses.
RESULTS: In total, 1024 patients with stage I-III CRC were analyzed. Patient allocation according to HS grade was 124 (12.1%) in HS1, 298 (29.1%) in HS2, 135 (13.2%) in HS3, and 467 (45.6%) in HS4. The Kaplan-Meier curves of OS showed statistically significant differences according to anemia and sarcopenia status as well as to HS grade (all P < 0.001). Univariable analysis of factors associated with OS revealed statistical significance in absence of anemia (hazard ratio [HR] 0.550, 95% confidence interval [CI] 0.400-0.756, P < 0.001], absence of sarcopenia (HR 0.560, P < 0.001), and HS grade (HS2, HR 0.515, P = 0.002; HS3, HR 0.468, P = 0.006; HS4, HR 0.325, P < 0.001). Multivariable analysis showed that compared to the HS1 group, the HS2 and HS4 groups showed significantly better OS (HS2, HR 0.527, 95% CI 0.340-0.817, P = 0.004; HS4, HR 0.574, 95% CI 0.361-0.912, P = 0.018).
CONCLUSIONS: Sarcopenia, characterized by a low SMI and the presence of anemia before surgery, was associated with reduced OS among patients with non-metastatic CRC.

OBJECTIVE: 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.

UNASSIGNED: Physical performance is a major contributor of mobility and independence during older life. Despite a progressive decline in musculoskeletal function starts from middle age, several factors acting during the life-course can negatively influence musculoskeletal functional capacities. Lifestyle interventions incorporating nutrition and physical exercise can help maximizing the muscle functional capacities in early life as well as preserving them later in life. Among various dietary compounds, omega-3 polyunsaturated fatty acids (PUFAs) are gaining growing attention for their potential effects on muscle membrane composition and muscle function. Indeed, several pathways are enhanced, such as an attenuation of pro-inflammatory oxidative stress, mitochondrial function, activation of the mammalian target of rapamycin (mTOR) signaling and reduction of insulin resistance.
UNASSIGNED: We performed a narrative review to explore the existing literature on the relationship between omega-3 PUFAs and physical performance across the life-course.
UNASSIGNED: Growing evidence from randomized controlled trials (RCTs) suggests beneficial effects of omega-3 PUFAs on muscle function, including physical performance parameters in mid to later life. On the other hand, despite a direct association in early life is not available in literature, some mechanisms by which omega-3 PUFAs may contribute to improved adult physical performance could be hypothesized.
UNASSIGNED: Omega-3 PUFAs are gaining growing attention for their positive effect on muscle function parameters. The integration of physical function measures in future studies would be of great interest to explore whether omega-3 PUFAs could contribute to improved muscle function, starting from early life and extending throughout the lifespan. However, larger and high-quality RCTs are needed to fully elucidate the beneficial effects of omega-3 PUFAs supplementation on muscle mass and function.

UNASSIGNED: Sarcopenic obesity (SO) is a clinical disorder characterized by increased adiposity and decreased muscle mass and function, commonly observed in older adults. However, most of the studies that investigated SO prevalence rates were not based on current standardized diagnostic methods. Thus, this study aims to estimate the prevalence rates of SO and their level of agreement using different instruments proposed by the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) Consensus, in a sample of hospitalized older adults with severe obesity.
UNASSIGNED: A cross-sectional study with 90 older adults (≥ 60 years) with severe obesity (body mass index ≥ 35 kg/m/²) seeking an in-hospital multidisciplinary body weight reduction program. Skeletal muscle function was assessed using the five-repetition Sit-Stand test (5-SSt) and Handgrip Strength (HGS). Body composition was evaluated by high percentages of fat mass (FM), low appendicular lean mass (ALM/W), and skeletal muscle mass (SMM/W), adjusted to body weight. The stage of SO was assessed on the presence of at least one comorbidity and specific cut-offs were adopted for each step. All analyses were performed according to gender and age range.
UNASSIGNED: The prevalence rates of SO in the total sample were 23.3%, 25.5%, 31.1%, and 40.0% considering altered values of 5-SSt+FM+ALM/W, HGS+FM+ALM/W, 5-SSt+FMSSM/W, and HGS+FM+SSM/W, respectively. Higher prevalence rates were observed among female and old elderly subgroups, regardless of the diagnostic combination. There were weak agreements between the muscle function tests (5-SSt versus HGS) using both muscle mass indexes in the total sample and all subgroups. Moderate agreements were observed between muscle mass indexes (SMM/W versus ALM/W) in the total sample, male and younger older adults (using 5-SSt), and strong agreements for men and younger older adults (using HGS).
UNASSIGNED: The discrepancies observed between the prevalence rates and their levels of agreement reinforce the need for new studies in similar populations aiming for better standardization of SO assessment.

BACKGROUND: While sarcopenia is recognized as a predictor of mortality in cirrhosis, its influence on acute-on-chronic liver failure (ACLF) remains uncertain. Despite multiple studies examining the impact of sarcopenia on short-term mortality in patients with ACLF, the sample size of these studies was limited, and their outcomes were inconsistent. Therefore, this study aimed to explore the impact of sarcopenia on both short- and long-term mortality in patients with ACLF.
METHODS: This retrospective cohort study included 414 patients with ACLF that were treated between January 2016 and September 2022. Sarcopenia was diagnosed based on the measurement of the skeletal muscle index at the third lumbar vertebra (L3-SMI). Subsequently, the patients were divided into sarcopenia and non-sarcopenia groups. We analysed the basic clinical data of the two groups. Multivariate Cox proportional analysis was used to analyse short-term (28 days) and long-term (1 year and overall) mortality rates.
RESULTS: A total of 414 patients were included, with a mean age of 52.88 ± 13.41 years. Among them, 318 (76.8%) were male, and 239 (57.7%) had sarcopenia. A total of 280 (67.6%) patients died during the study period. Among them, 153 patients died within 28 days (37%) and 209 patients died within 1 year (50.5%). We found that the 28-day, 1-year and overall mortality rates in the sarcopenia group were significantly higher than those in the non-sarcopenia group (37% vs. 22.3%, P < 0.01; 50.5% vs. 34.9%, P < 0.01; and 67.6% vs. 53.1%, P < 0.01, respectively). Multivariate Cox regression analysis revealed that sarcopenia was significantly associated with increased mortality. The hazard ratios for sarcopenia were 2.05 (95% confidence interval [CI] 1.41-3.00, P < 0.01) for 28-day mortality, 1.81 (95% CI 1.29-2.54, P < 0.01) for 1-year mortality and 1.82 (95% CI 1.30-2.55, P < 0.01) for overall mortality. In addition, muscle density and international normalized ratio were associated with short- and long-term mortality.
CONCLUSIONS: Sarcopenia is associated with both short- and long-term mortality in patients with ACLF. Therefore, regular monitoring for sarcopenia is important for these patients.

BACKGROUND: The comprehensive impact of prolonged home-based resistance training on individuals grappling with chronic kidney disease (CKD) have yet to be fully elucidated. This study aimed to explore the outcomes of varying exercise durations on physical performance, nutritional status, and kidney function within this specific population, encompassing patients undergoing dialysis and those affected by severe sarcopenia.
METHODS: This was a 1-year observational double cohort study following a 52-week longitudinal design, we enrolled 101 adult CKD outpatients. These participants were divided into two groups: the continuous group, comprising individuals who consistently exercised for over 6 months, and the interrupted group, which included those who did not sustain regular exercise for the same duration. The exercise regimen involved resistance exercises conducted at least 3 to 5 days per week, involving activities like lifting dumbbells and executing weighted wall squats. Physical activity assessments and biochemical blood tests were conducted at weeks 0, 4, 16, 28, 40, and 52 for all participants.
RESULTS: The continuous exercise group exhibited better handgrip strength and sit-to-stand movement compared to the interrupted group. Their estimated glomerular filtration rate stayed steady while the interrupted group was declined. Additionally, those who exercised consistently had better metabolism: higher carbon dioxide levels, increased albumin, better nutritional scores, and lower levels of blood urea nitrogen, creatinine, fasting blood glucose, and body weight. Subsequent adjustments for potential confounding factors continued to show improved physical performance and kidney function over time.
CONCLUSIONS: Our findings indicate the advantageous impact of extended resistance exercise training on overall health of CKD patients, even those on dialysis or with severe sarcopenia. Dedication to this exercise routine could improve kidney function, metabolism, and physical abilities in these patients.

OBJECTIVE: We aimed to investigate the impact of sarcopenia and sarcopenic obesity (SO) on the clinical outcome in older patients with COVID-19 infection and chronic disease.
METHODS: We prospectively collected data from patients admitted to Huadong Hospital for COVID-19 infection between November 1, 2022, and January 31, 2023. These patients were included from a previously established comprehensive geriatric assessment (CGA) cohort. We collected information on their pre-admission condition regarding sarcopenia, SO, and malnutrition, as well as their medical treatment. The primary endpoint was the incidence of intubation, while secondary endpoints included in-hospital mortality rates. We then utilized Kaplan-Meier (K-M) survival curves and the log-rank tests to compare the clinical outcomes related to intubation or death, assessing the impact of sarcopenia and SO on patient clinical outcomes.
RESULTS: A total of 113 patients (age 89.6 ± 7.0 years) were included in the study. Among them, 51 patients had sarcopenia and 39 had SO prior to hospitalization. Intubation was required for 6 patients without sarcopenia (9.7%) and for 18 sarcopenia patients (35.3%), with 16 of these being SO patients (41%). Mortality occurred in 2 patients without sarcopenia (3.3%) and in 13 sarcopenia patients (25.5%), of which 11 were SO patients (28%). Upon further analysis, patients with SO exhibited significantly elevated risks for both intubation (Hazard Ratio [HR] 7.43, 95% Confidence Interval [CI] 1.26-43.90, P < 0.001) and mortality (HR 6.54, 95% CI 1.09-39.38, P < 0.001) after adjusting for confounding factors.
CONCLUSIONS: The prevalence of sarcopenia or SO was high among senior inpatients, and both conditions were found to have a significant negative impact on the clinical outcomes of COVID-19 infection. Therefore, it is essential to regularly assess and intervene in these conditions at the earliest stage possible.

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: 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.
CONCLUSIONS: 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.