Identification of shared gene signatures and pathways for diagnosing osteoporosis with sarcopenia through integrated bioinformatics analysis and machine learning.

BACKGROUND: Prior studies have suggested a potential relationship between osteoporosis and sarcopenia, both of which can present symptoms of compromised mobility. Additionally, fractures among the elderly are often considered a common outcome of both conditions. There is a strong correlation between fractures in the elderly population, decreased muscle mass, weakened muscle strength, heightened risk of falls, and diminished bone density. This study aimed to pinpoint crucial diagnostic candidate genes for osteoporosis patients with concomitant sarcopenia. METHODS: Two osteoporosis datasets and one sarcopenia dataset were obtained from the Gene Expression Omnibus (GEO). Differential expression genes (DEGs) and module genes were identified using Limma and Weighted Gene Co-expression Network Analysis (WGCNA), followed by functional enrichment analysis, construction of protein-protein interaction (PPI) networks, and application of a machine learning algorithm (least absolute shrinkage and selection operator (LASSO) regression) to determine candidate hub genes for diagnosing osteoporosis combined with sarcopenia. Receiver operating characteristic (ROC) curves and column line plots were generated. RESULTS: The merged osteoporosis dataset comprised 2067 DEGs, with 424 module genes filtered in sarcopenia. The intersection of DEGs between osteoporosis and sarcopenia module genes consisted of 60 genes, primarily enriched in viral infection. Through construction of the PPI network, 30 node genes were filtered, and after machine learning, 7 candidate hub genes were selected for column line plot construction and diagnostic value assessment. Both the column line plots and all 7 candidate hub genes exhibited high diagnostic value (area under the curve ranging from 1.00 to 0.93). CONCLUSION: We identified 7 candidate hub genes (PDP1, ALS2CL, VLDLR, PLEKHA6, PPP1CB, MOSPD2, METTL9) and constructed column line plots for osteoporosis combined with sarcopenia. This study provides reference for potential peripheral blood diagnostic candidate genes for sarcopenia in osteoporosis patients.

Impact of sarcopenia and vitamin D levels on the severity of lower urinary tract symptoms in older males.

OBJECTIVES: To assess the impact of sarcopenia and vitamin D levels on the severity of lower urinary tract symptoms (LUTS). METHODS: A total of 193 male patients, aged 60 years and above, who visited the geriatric outpatient clinic at Ibn-i Sina Hospital in Ankara, Turkey, between December 2019 and March 2021, were enrolled. Sarcopenia was diagnosed according to the criteria set by the European Working Group on Sarcopenia in Older People. The presence and severity of lower urinary tract symptoms were assessed using the International Prostate Symptom Score questionnaire, categorizing symptom severity as mild or moderate-to-severe. RESULTS: The median patient age was 71 years (range: 66-77). Sarcopenia affected 24.9% of the population studied. Mild LUTS was observed in 43.5% and moderate-to-severe LUTS was observed in 56.5% of patients. Sarcopenia prevalence was significantly higher in the individuals with moderate-to-severe LUTS compared to those with mild-LUTS (p=0.021). After adjusting for Charlson comorbidity index and age, only vitamin D levels were significantly associated with increased odds of moderate-to-severe LUTS (odds ratio [OR]=0.95, 95% confidence interval [CI]: [0.92-0.98], p=0.002). Sarcopenia was not significantly associated with the severity of LUTS (OR=2.04, 95% CI: [0.94-4.45], p=0.070). An inverse linear trend was observed between quartiles of 25 (OH) vitamin D and LUTS severity. As 25 (OH)vitamin D levels increased, the proportion of patients with moderate-to-severe LUTS decreased (p=0.023). CONCLUSION: Sarcopenia did not significantly impact LUTS severity, but low vitamin D levels were associated with moderate-to-severe LUTS.

The Validity of Muscle Ultrasound in the Diagnostic Workup of Sarcopenia Among Older Adults: A Scoping Review.

Purpose: Muscle ultrasound has emerged as a promising method in the diagnostic work-up of sarcopenia. The objective of this scoping review was to explore the validity of muscle ultrasound against the latest sarcopenia definitions among older adults. Methods: We adhered to the PRISMA guidelines for scoping reviews. A systematic search of databases was performed by two independent reviewers. All articles comparing the performance of ultrasound to an internationally acknowledged sarcopenia definition among older adults (≥60 years) and published between 2019/01/01 (the year updated sarcopenia definitions were introduced) and 2023/11/15 were included. Data were extracted and collated by muscle and muscle parameters. Results: Out of 2290 articles screened, six studies comprising 24 validity tests among a total of 1619 older adults (mean age 74.1 years, 52.2% female) were included. The validity tests investigated the rectus femoris (n = 7), biceps brachii (n = 5), gastrocnemius medialis (n = 4), tibialis anterior (n = 4), soleus (n = 3), and rectus abdominis (n = 1). The parameter muscle thickness (MT) (n = 14) was most commonly measured. The latest European and Asian sarcopenia definitions (EWGSOP2, AWGS2) were applied as reference standards in four validity tests each. None of the studies used the Sarcopenia Definition and Outcome Consortium (SDOC) criteria. The highest area under the curve AUC (0.92, 95% confidence interval [CI] 0.89-0.94) was found for the muscle thickness of the rectus femoris muscle. Due to substantial heterogeneity among the studies, pooling of data using a meta-analytic approach was not feasible. Conclusion: Limited number of studies have examined the validity of muscle ultrasound for diagnosing sarcopenia based on recent definitions among older adults. Thereby, muscle thickness of the rectus femoris showed promising results regarding validity. Further studies are needed to investigate the validity of key muscles and to validate muscle ultrasound among older hospitalized patients.

Progressive sarcopenia and myosteatosis predict prognosis of advanced HCC patients treated with immune checkpoint inhibitors.

Background: Immunotherapy stands as a pivotal modality in the therapeutic landscape for the treatment of advanced hepatocellular carcinoma, yet responses vary among patients. This study delves into the potential impact of sarcopenia, myosteatosis and adiposity indicators, as well as their changes during immunotherapy, on treatment response and prognosis in patients with advanced hepatocellular carcinoma treated with immune checkpoint inhibitors. Methods: In this retrospective analysis, 116 patients with advanced hepatocellular carcinoma receiving immune checkpoint inhibitors were recruited. Skeletal muscle, intramuscular, subcutaneous, and visceral adipose tissue were assessed by computed tomography at the level of the third lumbar vertebrae before and after 3 months of treatment. Sarcopenia and myosteatosis were evaluated by skeletal muscle index and mean muscle density using predefined threshold values. Patients were stratified based on specific baseline values or median values, along with alterations observed during the treatment course. Overall survival (OS) and progression-free survival (PFS) were compared using the log-rank test and a multifactorial Cox proportional risk model. Results: A total of 116 patients were recruited and divided into two cohorts, 81 patients for the training set and 35 patients for the validating set. In the overall cohort, progressive sarcopenia (P=0.021) and progressive myosteatosis (P=0.001) were associated with objective response rates, whereas progressive myosteatosis (P<0.001) was associated with disease control rates. In the training set, baseline sarcopenia, myosteatosis, and subcutaneous and visceral adipose tissue were not significantly associated with PFS and OS. In multivariate analysis adjusting for sex, age, and other factors, progressive sarcopenia(P=0.002) and myosteatosis (P=0.018) remained independent predictors of PFS. Progressive sarcopenia (P=0.005), performance status (P=0.006) and visceral adipose tissue index (P=0.001) were all independent predictors of OS. The predictive models developed in the training set also had good feasibility in the validating set. Conclusion: Progressive sarcopenia and myosteatosis are predictors of poor clinical outcomes in patients with advanced hepatocellular carcinoma receiving immune checkpoint inhibitors, and high baseline visceral adiposity is associated with a poorer survival.

Computed Tomography-Assessed Sarcopenia Predicts Mortality in Kidney Transplant Candidates.

OBJECTIVES: Sarcopenia is common in chronic kidney disease and associated with increased mortality. We investigated the prevalence of sarcopenia, defined as low muscle mass by the psoas muscle index, in endstage renal disease patients on waiting lists for kidney transplant and determined its association with prognostic nutritional index, C-reactive protein-toalbumin ratio, cardiovascular events, and mortality. MATERIALS AND METHODS: Our study included 162 patients with end-stage renal disease and 87 agematched healthy controls. We calculated nutritional status as follows: prognostic nutritional index = (10 × albumin [g/dL]) + (0.005 × total lymphocyte count (×103/µL]) and C-reactive protein-to-albumin ratio. We gathered demographic and laboratory data from medical records. RESULTS: Patients with end-stage renal disease had a mean age of 44.7 ± 14.2 years; follow-up time was 3.37 years (range, 0.35-9.60 y). Although patients with endstage renal disease versus controls had higher prevalence of sarcopenia (16.7% vs 3.4%; P = .002) and C-reactive protein-to-albumin ratio (1.47 [range, 0.12-37.10] vs 0.74 [range, 0.21-10.20]; P < .001), prognostic nutritional index was lower (40 [range, 20.4-52.2] vs 44 [range, 36.1-53.0]; P < .001). In patients with end-stage renal disease with and without sarcopenia, prognostic nutritional index (P = .005) was lower and C-reactive protein-to-albumin ratio (P = .041) was higher in those with versus those without sarcopenia. Among 67 patients on waiting lists who received kidney transplants, those without sarcopenia had better 5-year patient survival posttransplant than those with sarcopenia (P = .001). Multivariate regression analysis showed sarcopenia and low prognostic nutritional index were independentrisk factors for mortality among patients with end-stage renal disease. CONCLUSIONS: Sarcopenia was ~5 times more frequent in patients with end-stage renal disease than in healthy controls and was positively correlated with the prognostic nutritional index. Sarcopenia was an independent risk factor for mortality in patients on transplant waiting lists.

Predictive value of adductor pollicis muscle thickness for ultrasound-based sarcopenia in older adults.

BACKGROUND: The adductor pollicis muscle thickness (APMT) is least affected by subcutaneous adipose tissue and can be measured externally. The aim of this study is to identify the predictive value of APMT for the diagnosis of ultrasonography-based sarcopenia. METHODS: A total of 245 outpatients who were aged ≥65 years (49 with sarcopenia and 196 without sarcopenia) were included in this cross-sectional study. Patients with knee or hip replacement, advanced dementia, cerebrovascular disease, neurodegenerative disease, or decompensated heart failure and those using drugs that affect muscle functions, such as steroids, were excluded. Comprehensive geriatric assessments and anthropometric measurements of the patients were performed. APMT was assessed with a skinfold caliper. The diagnosis of sarcopenia was based on a low Sonographic Thigh Adjustment Ratio (STAR) index (anterior thigh muscle thickness by ultrasonography/body mass index [BMI] ratio, cutoff points are <1.4 for men and <1.0 for women) and low handgrip strength. The predictive ability of APMT for ultrasound-based sarcopenia diagnosis was examined. RESULTS: There was no significant difference in terms of arm and calf circumference and BMI between the sarcopenic and nonsarcopenic groups. APMT, handgrip strength, anterior thigh muscle thickness, and gait speed were significantly lower in the patients with sarcopenia. The best cutoff points of APMT for sarcopenia were ≤16.5 for women and ≤21.5 for men with areas under the curve of 0.70 and 0.66, respectively, and negative predictive values of 91.2 and 94.3, respectively (P < 0.001). CONCLUSION: APMT can be a useful anthropometric marker for ultrasound-based sarcopenia diagnosis.

The clinical significance of sarcopenia in patients with hepatocellular carcinoma treated with lenvatinib and PD-1 inhibitors.

Background and aim: Sarcopenia has gained considerable attention in the context of hepatocellular carcinoma, as it has been correlated with a poorer prognosis among patients undergoing sorafenib or lenvatinib treatment for hepatocellular carcinoma (HCC). The clinical significance of sarcopenia in first-line advanced HCC patients treated with lenvatinib and programmed death-1 (PD-1) inhibitors needs to be clarified. Methods: Sarcopenia was diagnosed using CT (Computed tomography) or MRI (Magnetic Resonance Imaging), with the psoas muscle index (PMI) as the surrogate marker. Patients were grouped based on sarcopenia presences, and a comparative analysis examined characteristics, adverse events, and prognosis. The Cox regression analysis was applied to identify independent prognostic factors for survival, while nomograms were constructed to predict 1-year survival. Results: Among 180 patients, 46 had sarcopenia. Patients with baseline sarcopenia demonstrated significantly inferior median progression-free survival (mPFS) (3.0 vs. 8.3 months) and median overall survival (mOS) (7.3 vs. 21.6 months). The same results for mPFS (3.3 vs. 9.2 months) and mOS (9.4 vs. 24.2 months) were observed in patients who developed sarcopenia after treatment. Furthermore, significantly higher grade 3 or higher adverse events (AEs) (73.91% vs 41.79%, p<0.001) were recorded in the sarcopenia group compared to the non-sarcopenia group. In the multivariate analysis, distant metastasis, elevated PLR and CRP levels, and low PMI remained independent predictive factors for poor OS. Additionally, skeletal muscle loss remained a significant independent risk factor for PFS. We developed a nomogram incorporating these four indicators, which predicted 12-month survival with a C-index of 0.853 (95% CI, 0.791 - 0.915), aligning well with actual observations. Conclusion: The prognosis of patients with HCC and sarcopenia is significantly worse when treated with lenvatinib and PD-1 inhibitors. The combination regimen of lenvatinib plus PD-1 inhibitors should be cautiously recommended due to the inferior prognosis and higher AEs.

Prevalence and clinical characteristics of Sarcopenia in older adult patients with stable chronic obstructive pulmonary disease: a cross-sectional and follow-up study.

BACKGROUND: The relationship between sarcopenia and chronic obstructive pulmonary disease (COPD) has been increasingly reported, and there is some overlap regarding their clinical features and pulmonary rehabilitation (PR) strategies. No Korean study has reported the actual prevalence of sarcopenia in patients with stable COPD who are recommended for pulmonary rehabilitation. This study evaluated the prevalence and clinical features of sarcopenia in older adult outpatients with stable COPD and the changes after 6 months. METHODS: In this cross-sectional and 6-month follow-up study, we recruited 63 males aged ≥ 65 diagnosed with stable COPD. Sarcopenia was diagnosed using the AWGS 2019 criteria, which included hand grip strength testing, bioelectrical impedance analysis, Short Physical Performance Battery administration, and Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falling screening tool administration. A 6-minute walk test (6 MWT) was conducted, forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), maximal inspiratory and expiratory pressures (MIP and MEP, respectively) and peak expiratory flow (PEF) were assessed, and patient-reported questionnaires were administered. RESULTS: At baseline, 14 (22%) patients were diagnosed with possible sarcopenia, and eight (12.6%) were diagnosed with sarcopenia. There were significant differences in the age; body mass index; Body mass index, airflow Obstruction, Dyspnea, and Exercise index; modified Medical Research Council dyspnea scores; and International Physical Activity Questionnaire scores between the normal and sarcopenia groups. Whole-body phase angle, MIP, MEP, PEF, and 6-minute walk distance (6 MWD) also showed significant differences. Over 6 months, the proportion of patients with a reduced FEV1 increased; however, the proportion of patients with sarcopenia did not increase. CONCLUSION: A relatively low prevalence of sarcopenia was observed in older adult outpatients with stable COPD. No significant change in the prevalence of sarcopenia was found during the 6-month follow-up period. TRIAL REGISTRATION: The study was registered with the Clinical Research Information Service (KCT0006720). Registration date: 30/07/2021.

Muscle mass as a modifier of stress response in acute ischemic stroke patients.

Stroke triggers a systemic inflammatory response over the ensuing days after the cerebral insult. The age and comorbidities of the stroke population make them a vulnerable population for low muscle mass and sarcopenia, the latter being another clinical condition that is closely associated with inflammation, as shown by increased levels of pro-inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR). In this study, we evaluated the relationship between post-stroke NLR changes and muscle mass in a prospective cohort of acute ischemic stroke patients (n = 102) enrolled in the Muscle Assessment in Stroke Study Turkey (MASS-TR). Admission lumbar computed tomography images were used to determine the cross-sectional muscle area of skeletal muscles at L3 vertebra level and calculate the skeletal muscle index (SMI). The median (IQR) SMI was 44.7 (39.1-52.5) cm2/m2, and the NLR at admission and follow-up were 4.2 (3.0-10.5) and 9.4 (5.7-16.2), respectively. While there was no relationship between SMI and admission NLR, a significant inverse correlation was observed between SMI and follow-up NLR (r = - 0.26; P = 0.007). Lower SMI remained significantly associated (P = 0.036) with higher follow-up NLR levels in multivariate analysis. Our findings highlight the importance of muscle mass as a novel factor related to the level of post-stroke stress response.

Content validity of SarQoL, a quality of life questionnaire specific to sarcopenia.

BACKGROUND: The Sarcopenia & Quality of Life (SarQoL) questionnaire is a patient-reported outcome measure designed for assessing health-related quality of life in individuals with sarcopenia. Despite its wide acceptance in the scientific literature, its content validity has only been partially demonstrated so far. AIMS: To enhance the evidence supporting the content validity of the SarQoL questionnaire. METHODS: Following COSMIN methodology, semi-structured interviews were conducted with 17 Belgian older adults who met the EWGSOP2 criteria for the diagnosis of sarcopenia and 11 experts in sarcopenia, with clinical or research background. Comprehensiveness, relevance and comprehensibility of SarQoL content were assessed through individual transcripts and were qualitatively analyzed thematically according to the seven dimensions of SarQoL. RESULTS: The majority of the concepts elicited during the semi-structured interviews fitted within existing SarQoL dimensions. Importantly, the different domains of SarQoL were consensually considered as relevant by patients and experts. Some new emergent concepts were identified by the participants. While many of them could be considered as enrichments of existing dimensions or sub-concepts, other new concepts (i.e. self-fulfilment, acceptance of the reduced condition, adaptation/use of strategies, depression) may highlight two potential dimensions not covered by SarQoL, i.e. patient empowerment and depression. Cognitive interviews also highlighted that SarQoL items and instructions were clear and comprehensible. CONCLUSIONS: SarQoL, in its current form, demonstrates good evidence of content validity for assessing health-related quality of life in patients with sarcopenia. We do not recommend adding new items or dimensions to SarQoL. Instead, for researchers or clinicians who aim to specifically address self-empowerment or depression of sarcopenic populations, we suggest completing the assessment of quality of life by concurrently using additional validated scales of patient empowerment or depression.

Sleeping more than 8 h: a silent factor contributing to decreased muscle mass in Chinese community-dwelling older adults.

BACKGROUND: Muscle mass loss is an age-related process that can be exacerbated by lifestyle, environmental and other factors, but can be mitigated by good sleep. The objective of this study was to investigate the correlation between varying time lags of sleep duration and the decline in muscle mass among individuals aged 60 years or older by using real-world health monitoring data obtained from wearable devices and smart home health monitoring devices. METHODS: This study included 86,037 observations from 2,869 participants in the Mobile Support System database. Missing data were supplemented by multiple imputation. The investigation utilized generalized estimating equations and restricted cubic spline curve to examine the relationship between sleep duration and low muscle mass. Various lag structures, including 0, 1, 2, 0-1, 0-2, and 1-2 months, were fitted, and the interaction effect of observation time with sleep duration was estimated for each lag structure. Additionally, subgroup analyses were conducted. The models were adjusted for various covariates, including gender, age, body mass index, footsteps, smoking status, drinking status, marital status, number of chronic diseases, number of medications, diabetes mellitus, hyperlipidemia, coronary artery disease, respiratory disease, and musculoskeletal disease and an interaction term between time and sleep duration. RESULTS: The results of the generalized estimating equation showed a significant correlation (p < 0.001) between sleep duration of 8 h or more and low muscle mass in older adults, using 6-7 h of sleep as a reference. This effect was seen over time and prolonged sleep accumulated over multiple months had a greater effect on muscle mass loss than a single month. The effect of long sleep duration on muscle mass loss was significantly greater in females than in males and greater in the over-75 than in the under-75 age group. Restricted cubic spline plots showed a non-linear relationship between sleep duration and low muscle mass (p < 0.001). CONCLUSIONS: This study found an association between sustained nighttime sleep of more than eight hours and decreased muscle mass in older adults, especially older women.

Serum iron level is independently associated with sarcopenia: a retrospective study.

Sarcopenia greatly reduces the quality of life of the elderly, and iron metabolism plays an important role in muscle loss. This study aimed to investigate the association between iron status and sarcopenia. A total of 286 adult patients hospitalized between 2019 and 2021 were included in this study, of which 117 were diagnosed with sarcopenia. Serum iron, total iron binding capacity (TIBC), transferrin, and transferrin saturation levels were compared between groups with and without sarcopenia and were included in the logistic analyses, with significant variables further included in the logistic regression model for the prediction of sarcopenia. Serum iron, TIBC, and transferrin levels decreased significantly in the sarcopenia group (p < 0.05), and were negatively associated with handgrip strength, relative skeletal muscle index, and multiple test performances (p < 0.05). Multivariate logistic analysis showed that sex, age, body mass index (BMI), and serum iron level were independent risk factors for sarcopenia. In the final logistic regression model, male sex (odds ratio [OR] 3.65, 95% confidence interval [CI] 1.67-7.98), age > 65 years (OR 5.40, 95% CI 2.25-12.95), BMI < 24 kg/m2 (OR 0.17, 95% CI 0.08-0.36), and serum iron < 10.95 µmol/L (OR 0.39, 95% CI 0.16-0.93) were included. Our study supported the impact of iron metabolism on muscle strength and performance.

Association between non-alcoholic fatty liver disease and risk of sarcopenia: a systematic review and meta-analysis.

OBJECTIVES: To determine the association of non-alcoholic fatty liver disease (NAFLD) with the incidence of sarcopenia. DESIGN: Systematic review and meta-analysis of observational clinical studies. SETTING AND PARTICIPANTS: Adults with NAFLD. METHODS: Databases such as PubMed, Embase, Cochrane and Web of Science were searched for eligible studies published from the inception of each database up to 4 April 2023. All cross-sectional studies on the association between NAFLD and sarcopenia were included in this study. The quality of the included studies and risk of bias was assessed using the Agency for Healthcare Research and Quality checklist. STATA V.15.1 software was used for statistical analysis. RESULTS: Of the 1524 retrieved articles, 24 were included in this review, involving 88 609 participants. Our findings showed that the prevalence of sarcopenia was higher in the NAFLD group than in the control group (pooled OR 1.74, 95% CI 1.39 to 2.17). In a subgroup analysis by region, patients with NAFLD showed an increased risk of sarcopenia (pooled OR 1.97, 95% CI 1.54 to 2.51) in the Asian group, whereas patients with NAFLD had no statistically significant association with the risk of sarcopenia in the American and European groups, with a pooled OR of 1.31 (95% CI 0.71 to 2.40) for the American group and a pooled OR of 0.99 (95% CI 0.21 to 4.69) for the European group. Similar results were observed in the sensitivity analysis, and no evidence of publication bias was observed. CONCLUSIONS AND IMPLICATIONS: The current study indicated a significant positive correlation between NAFLD and sarcopenia, which may be affected by regional factors. This study provides the correlation basis for the relationship between NAFLD and sarcopenia and helps to find the quality strategy of sarcopenia targeting NAFLD.

Sarcopenia prevalence using handgrip strength or chair stand performance in adults living with type 2 diabetes mellitus.

BACKGROUND: The updated European Working Group on Sarcopenia in Older People (EWGSOP2) recommends handgrip strength (HGS) and the chair stand test (CST) to assess muscle strength, with the CST being a convenient proxy for lower limb strength. However, adiposity may differentially influence these strength criteria and produce discrepant sarcopenia prevalence. OBJECTIVE: To determine the prevalence of sarcopenia using HGS or the CST, and to investigate the associations between these strength criteria and adiposity in adults with type 2 diabetes mellitus. METHODS: The EWGSOP2 definition was used to assess the prevalence of probable (low muscle strength), confirmed (plus low muscle mass) and severe (plus poor physical performance) sarcopenia. Linear regression models were used to study the association between different measures of muscle strength and adiposity. RESULTS: We used data from 732 adults with type 2 diabetes mellitus (35.7% female, aged 64 ± 8 years, body mass index 30.7 ± 5.0 kg/m2). Using the CST compared with HGS produced a higher prevalence of probable (31.7% vs. 7.1%), confirmed (5.6% vs. 1.6%) and severe (1.0% vs. 0.3%) sarcopenia, with poor agreement between strength criteria to identify probable sarcopenia. CST performance, but not HGS, was significantly associated with all measures of adiposity in unadjusted and adjusted models. CONCLUSIONS: Higher levels of adiposity may impact CST performance, but not HGS, resulting in a higher prevalence of sarcopenia in adults with type 2 diabetes mellitus. Consideration should be paid to the most appropriate measure of muscle function in this population.

Endurance Training Inhibits the JAK2/STAT3 Pathway to Alleviate Sarcopenia.

Aging leads to a decrease in muscle function, mass, and strength in skeletal muscle of animals and humans. The transcriptome identified activation of the JAK/STAT pathway, a pathway that is associated with skeletal muscle atrophy, and endurance training has a significant effect on improving sarcopenia; however, the exact mechanism still requires further study. We investigated the effect of endurance training on sarcopenia. Six-month-old male SAMR1 mice were used as a young control group (group C), and the same month-old male SAMP8 mice were divided into an exercise group (group E) and a model group (group M). A 3-month running exercise intervention was performed on group E, and the other two groups were kept normally. Aging caused significant signs of sarcopenia in the SAMP8 mice, and endurance training effectively improved muscle function, muscle mass, and muscle strength in the SAMP8 mice. The expression of JAK2/STAT3 pathway factor was decreased in group E compared with group M, and the expression of SOCS3, the target gene of STAT3, and NR1D1, an atrophy-related factor, was significantly increased. Endurance training significantly improved the phenotypes associated with sarcopenia, and the JAK2/STAT3 pathway is a possible mechanism for the improvement of sarcopenia by endurance training, while NR1D1 may be its potential target. Keywords: Sarcopenia, Endurance training, Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3), Nuclear receptor subfamily 1, group D member 1 (Nr1d1).

Association of low muscle mass with cognitive function and mortality in USA seniors: results from NHANES 1999-2002.

BACKGROUND: Sarcopenia and cognitive impairment have been linked in prior research, and both are linked to an increased risk of mortality in the general population. Muscle mass is a key factor in the diagnosis of sarcopenia. The relationship between low muscle mass and cognitive function in the aged population, and their combined impact on the risk of death in older adults, is currently unknown. This study aimed to explore the correlation between low muscle mass and cognitive function in the older population, and the relationship between the two and mortality in older people. METHODS: Data were from the National Health and Nutrition Examination Survey 1999-2002. A total of 2540 older adults aged 60 and older with body composition measures were included. Specifically, 17-21 years of follow-up were conducted on every participant. Low muscle mass was defined using the Foundation for the National Institute of Health and the Asian Working Group for Sarcopenia definitions: appendicular lean mass (ALM) (< 19.75 kg for males; <15.02 kg for females); or ALM divided by body mass index (BMI) (ALM: BMI, < 0.789 for males; <0.512 for females); or appendicular skeletal muscle mass index (ASMI) (< 7.0 kg/m2 for males; <5.4 kg/m2 for females). Cognitive functioning was assessed by the Digit Symbol Substitution Test (DSST). The follow-up period was calculated from the NHANES interview date to the date of death or censoring (December 31, 2019). RESULTS: We identified 2540 subjects. The mean age was 70.43 years (43.3% male). Age-related declines in DSST scores were observed. People with low muscle mass showed lower DSST scores than people with normal muscle mass across all age groups, especially in the group with low muscle mass characterized by ALM: BMI (60-69 years: p < 0.001; 70-79 years: p < 0.001; 80 + years: p = 0.009). Low muscle mass was significantly associated with lower DSST scores after adjusting for covariates (ALM: 43.56 ± 18.36 vs. 47.56 ± 17.44, p < 0.001; ALM: BMI: 39.88 ± 17.51 vs. 47.70 ± 17.51, p < 0.001; ASMI: 41.07 ± 17.89 vs. 47.42 ± 17.55, p < 0.001). At a mean long-term follow-up of 157.8 months, those with low muscle mass were associated with higher all-cause mortality (ALM: OR 1.460, 95% CI 1.456-1.463; ALM: BMI: OR 1.452, 95% CI 1.448-1.457); ASMI: OR 3.075, 95% CI 3.063-3.088). In the ALM: BMI and ASMI-defined low muscle mass groups, participants with low muscle mass and lower DSST scores were more likely to incur all-cause mortality ( ALM: BMI: OR 0.972, 95% CI 0.972-0.972; ASMI: OR 0.957, 95% CI 0.956-0.957). CONCLUSIONS: Low muscle mass and cognitive function impairment are significantly correlated in the older population. Additionally, low muscle mass and low DSST score, alone or in combination, could be risk factors for mortality in older adults.

Construction of an Exercise Intervention Program for Patients with Sarcopenic Obesity: A Delphi Method Study.

Purpose: Construct an exercise intervention program for patients with sarcopenic obesity. Material and Methods: Based on the COM-B theoretical model and evidence-based principles, the program was constructed using qualitative methods of literature analysis and Delphi method. The Delphi panel consisted of 15 experts from the fields of clinical medicine, rehabilitation medicine, medical technology, and nursing. Results: Fifteen experts were consulted, and the consultation recovery rate was 100%; the authority coefficient of the 1st round was 0.83, with coefficients of variation ranging from 0.00 to 0.27, and importance scores ranging from (4.13±1.13) to (5±0); the authority coefficient of the 2nd round was 0.82, with coefficients of variation ranging from 0.00 to 0.20, and importance scores ranging from (4.53±0.64) to (5±0); Kendall's harmony coefficient was 0.102, 0.115, respectively, and the differences were statistically significant(P < 0.05). The constructed exercise intervention program for patients with sarcopenic obesity included 4 primary indicators, 12 secondary indicators, and 28 tertiary indicators. Conclusion: The constructed exercise intervention program for patients with sarcopenic obesity is scientific, feasible and generalizable, and can provide useful reference for related personnel to develop exercise programs for patients with sarcopenic obesity.

Effects of Ninjin'yoeito on Patients with Chronic Obstructive Pulmonary Disease and Comorbid Frailty and Sarcopenia: A Preliminary Open-Label Randomized Controlled Trial.

Purpose: To present the preliminarily findings regarding the effects of a herbal medicine, Ninjin'yoeito, on comorbid frailty and sarcopenia in patients with chronic obstructive pulmonary disease (COPD). Patients and Methods: Patients with COPD (GOLD II or higher) and fatigue were randomly assigned to Group A (n = 28; no medication for 12 weeks, followed by 12-week administration) or B (n= 25; 24-week continuous administration). Visual analog scale (VAS) symptoms of fatigue, the COPD assessment test (CAT), and the modified Medical Research Council (mMRC) Dyspnea Scale were examined. Physical indices such asknee extension leg strength and walking speed, skeletal muscle mass index (SMI), and respiratory function test were also measured. Results: VAS fatigue scales in Group B significantly improved after 4, 8, and 12 weeks compared to those in Group A (each p<0.001, respectively). Right and left knee extension leg strength in Group B significantly improved after 12 weeks compared to that in Group A (p=0.042 and p=0.037, respectively). The 1-s walking speed for continued to increase significantly over 24 weeks in Group B (p=0.016, p<0.001, p<0.001, p=0.004, p<0.001, and p<0.001 after 4, 8, 12, 16, 20, and 24 weeks, respectively); it also significantly increased after the administration of Ninjin'yoeito in Group A. In Group B, the SMI significantly increased at 12 weeks in patients with sarcopenia (p=0.025). The CAT scores in Group B significantly improved after 12 weeks compared to those in Group A (p=0.006). The mMRC scores in Group B also significantly improved after 8 and 12 weeks compared to those in Group A (p= 0.045 and p <0.001, respectively). The changes in %FEV1.0 in Group B were significantly improved at 12 and 24 weeks (p=0.039 and p=0.036, respectively). Conclusion: Overall, Ninjin'yoeito significantly improved patients' quality of life, physical activity, muscle mass, and possibly lung function, suggesting that Ninjin'yoeito may improve frailty and sarcopenia in patients with COPD.