Metabolic dysfunction-associated steatotic liver disease (MASLD) is intrinsically linked with widespread metabolic perturbations, including within skeletal muscle. Indeed, MASLD is associated with a range of skeletal muscle abnormalities, including insulin resistance, myosteatosis, and sarcopenia, which all converge on the liver to drive disease progression and adverse patient outcomes. This review explores the mechanistic links between skeletal muscle and MASLD, including the role of abnormal glycemic control, systemic inflammation, and disordered myokine signaling. In turn, we discuss how intrinsic liver pathology can feed back to further exacerbate poor skeletal muscle health. Given the central importance of skeletal muscle in MASLD pathogenesis, it offers clinicians an opportunity to intervene for therapeutic benefit. We, therefore, summarize the role of nutrition and physical activity on skeletal muscle mass, quality, and metabolic function and discuss the knock-on effect this has on the liver. An awareness of these treatment strategies is particularly important in the era of effective pharmacological and surgical weight loss interventions, which can be associated with the development of sarcopenia. Finally, we highlight a number of promising drug agents in the clinical trial pipeline that specifically target skeletal muscle in an attempt to improve metabolic and physical functioning.

The triglyceride-glucose (TyG) index serves as an alternative index for assessing insulin resistance (IR). The relationship between the TyG index and its combined indicators and sarcopenia remains insufficiently explored.

To investigate the association between the TyG index and its combined parameters and sarcopenia.

This cross-sectional study encompassed 792 community-dwelling older adults from the Chongqing Aging and Sarcopenia Evaluation (CHASE) cohort. The multivariate logistic regression model was used to analyze the relationship between the TyG index and its combined parameters, which include the triglyceride glucose-body mass index (TyG-BMI), triglyceride glucose-calf girth (TyG-CG), triglyceride glucose-waist circumference (TyG-WC), and triglyceride glucose-waist-to-hip ratio (TyG-WHR). The receiver operator characteristic (ROC) curve was utilized to assess the diagnostic effect of each index. The integrated discrimination improvement index (IDI) and net reclassification improvement (NRI) were applied to compare the diagnostic efficacy among the indices.

The TyG index and its combined parameters demonstrated a significant correlation with the risk of sarcopenia (P < 0.05). The area under the ROC curve (AUC) for the TyG index in predicting the risk of sarcopenia was 0.623 (95% confidence interval: 0.570-0.675). Notably, composite parameters incorporating the TyG index showed enhanced predictive performance. Specifically, TyG-BMI showing the highest AUC of 0.892 (95% confidence interval: 0.860-0.924), indicating its strong predictive potential. Furthermore, the diagnostic efficacy of TyG-BMI was superior to that of all other indicators in both the IDI and NRI.

The TyG index demonstrates diagnostic potential for sarcopenia identification, with significantly enhanced accuracy when combined with other parameters. Among them, TyG-BMI is a robust sarcopenia risk predictor due to its superior predictive power.

To determine the prevalence and factors associated with sarcopenia in rheumatoid arthritis (RA) patients at a central university hospital in Hanoi, Vietnam.

Patients with RA aged ≥ 18 were enrolled in this cross-sectional study. Dual-energy X-ray absorptiometry was performed to measure appendicular skeletal muscle (ASM). Assessment of muscle function included hand grip strength (HGS) and gait speed (GS). Sarcopenia was defined according to Asian Working Group for Sarcopenia (AWGS) criteria 2019. RA disease activity was evaluated by disease activity score 28 CRP (DAS28-CRP). Medical history and previous medications including steroids, methotrexate, bDMARDs, clinical characteristics, and comorbidities were also documented. Multivariable adjusted regression was used to examine potential factors associated with sarcopenia in patients with RA.

A total of 156 patients with RA were recruited, out of which the prevalence of sarcopenia was 62.82%. Among the participants, 95.16% had a low appendicular lean mass index (ALMI), 91.67% had low hand grip strength, and 36.54% had slow gait speed. Active RA disease was significantly associated with a higher odd ratio of having sarcopenia, low muscle mass, and low hand grip strength. After adjusting for potential factors, male (aOR 6.66), RA disease activity level (aOR 3.07), and hypertension (aOR 4.06) were statistically independent factors associated with sarcopenia.

Effective RA management to achieve clinical remission is essential to mitigate sarcopenia risk. Further studies are essential to better understand sarcopenia and improve management in patients with RA. Key Points • Prevalence: Sarcopenia was present in 62.82% of patients with RA, especially in those with higher disease activity. • Risk Factors: Male gender, active disease, and hypertension were associated with sarcopenia. • Inflammation and disease activity: Active RA and elevated CRP levels were linked to reduced muscle mass and strength.

Metabolic-Associated Fatty Liver Disease (MAFLD) is a public health concern that is constantly expanding, with a fast-growing prevalence, and it affects about a quarter of the world's population. This condition is a significant risk factor for cardiovascular, hepatic, and oncologic diseases, such as hypertension, hepatoma, and atherosclerosis. Sarcopenia was long considered to be an aging-related syndrome, but today, it is acknowledged to be secondarily related to chronic diseases such as metabolic syndrome, cardiovascular conditions, and liver diseases, among other comorbidities associated with insulin resistance and chronic inflammation, besides inactivity and poor nutrition. The physiopathology involving MAFLD and sarcopenia has still not been solved. Inflammation, oxidative stress, mitochondrial dysfunction, and insulin resistance seem to be some of the keys to this relationship since this hormone target is mainly the skeletal muscle. This review aimed to comprehensively discuss the main metabolic and physiological pathways involved in these conditions. MAFLD and sarcopenia are interconnected by a complex network of pathophysiological mechanisms, such as insulin resistance, skeletal muscle tissue production capacity, chronic inflammatory state, oxidative stress, and mitochondrial dysfunction, which are the main contributors to this relationship. In addition, in a clinical analysis, patients with sarcopenia and MAFLD manifest more severe hepatitis fibrosis when compared to patients with only MAFLD. These patients, with both disorders, also present clinical improvement in their MAFLD when treated for sarcopenia, reinforcing the association between them. Lifestyle changes accompanied by non-pharmacological interventions, such as dietary therapy and increased physical activity, undoubtedly improve this scenario.

Background: Muscle loss during sarcopenia and atrophy is also commonly associated with age-related insulin resistance. Interestingly, branched-chain amino acids (BCAA) which are known for stimulating muscle protein synthesis are commonly elevated during insulin resistance and sarcopenic obesity. Objectives: This study investigated the effects of the interplay between atrophy and insulin resistance on insulin sensitivity, mitochondrial metabolism, and BCAA catabolic capacity in a myotube model of skeletal muscle insulin resistance. Methods: C2C12 myotubes were treated with dexamethasone to induce atrophy. Insulin resistance was induced via hyperinsulinemia. Gene and expression were measured using qRT-PCR and Western blot, while mitochondrial and lipid content were assessed using fluorescent staining. Cell metabolism was analyzed via Seahorse metabolic assays. Results: Both dexamethasone-induced atrophy and insulin resistance independently reduced insulin-stimulated pAkt levels, as well as mitochondrial function and content. However, neither treatment affected gene or protein expression associated with mitochondrial biogenesis or content. Although dexamethasone independently reduced insulin sensitivity in otherwise previously insulin-sensitive cells, dexamethasone had no significant effect on extracellular BCAA content. Conclusions: Our findings indicate the metabolic interplay between atrophy and insulin resistance and demonstrate that both can reduce mitochondrial function, though only limited effects were observed on indicators of BCAA catabolism and utilization. This emphasizes the need for future studies to investigate the mechanisms that underlie atrophy and other metabolic disorders to develop new interventions.

Extracellular vesicles (EVs) are membrane-bound structures released by cells carrying diverse biomolecules involved in intercellular communication. Small EVs are abundant in body fluids, playing a key role in cell signaling. Their natural occurrence and therapeutic potential, especially in the context of muscular disorders, make them a significant area of research. Sarcopenia, characterized by progressive muscle fiber loss, represents a pathological state in which EVs could offer therapeutic benefits, reducing morbidity and mortality. Recent studies have proposed an interplay between adipose tissue (AT) and skeletal muscle regarding sarcopenia pathology. AT dysregulation, as seen in obesity, contributes to skeletal muscle loss in a multifactorial way. While AT-derived stem cell (ATDSC) small EVs have been implicated in musculoskeletal homeostasis, their precise action in muscle regeneration remains incompletely understood. In this context, ATDSC-derived small EVs can stimulate skeletal muscle regeneration through improved proliferation and migration of muscle cells, enhancement of muscular perfusion, improvement of tendon and nerve regeneration, stimulation of angiogenesis, and promotion of myogenic differentiation. However, they can also increase skeletal muscle loss. Notably, this is the first comprehensive review to systematically examine the role of ATDSC-derived small EVs in sarcopenia.

Data regarding the risk of incident type 2 diabetes (T2D) and prediabetes among patients with hepatitis C virus (HCV) achieving direct-acting antivirals (DAAs)-induced sustained virologic response (SVR12) remains limited.

A total of 1079 patients, including 589 with normoglycemia and 490 with prediabetes, who underwent biannual fasting glucose and glycosylated haemoglobin (HbA1c) assessment for a median post-SVR12 follow-up of 5.5 years, were enrolled. We reported the crude (cIRs) and age-standardised incidence rates (ASIRs) of T2D and prediabetes. Factors associated with incident T2D and prediabetes were assessed using the Cox proportional hazards models.

The cIRs of T2D and prediabetes were 1.18 and 8.99 per 100 person-years of follow-up (PYFU), respectively. Additionally, the ASIRs of T2D and prediabetes were 1.09 (95% CI: 0.76-1.53) and 8.47 (95% CI: 7.23-9.90) per 100 PYFU. Prediabetes (adjusted hazard ratio [aHR]: 4.71; 95% confidence interval (CI): 2.55-8.70, p < 0.001), body mass index (BMI) per kg/m2 increase (aHR: 1.17; 95% CI: 1.09-1.26, p < 0.001) and liver stiffness measurement (LSM) per kPa increase (aHR: 1.05; 95% CI: 1.02-1.09, p = 0.001) were associated with a higher risk of incident T2D. Age per year increase (aHR: 1.02; 95% CI: 1.01-1.03, p < 0.001) was associated with a higher risk of incident prediabetes.

The incidence rates of T2D and prediabetes remain substantial among patients after HCV eradication. Lifestyle modification, drug therapy and regular monitoring of glycemic status are crucial for patients at risk of developing T2D and prediabetes following HCV clearance.

Background/Objectives: Sarcopenia, abdominal obesity, and sarcopenic obesity are prevalent and clinically significant in older adults, each shaped by diverse biopsychosocial factors. However, integrative analyses using nationally representative data remain limited in Korea. Methods: We analyzed 2118 adults aged ≥65 years from the 2022-2023 Korea National Health and Nutrition Examination Survey (KNHANES). Body composition was classified into sarcopenia, abdominal obesity, and sarcopenic obesity. Guided by Engel's Biopsychosocial Model, we examined biological (e.g., sex, chronic disease, nutrition, exercise), psychological (e.g., stress, sleep, self-rated health), and social (e.g., income, education, living status) variables. Complex-sample multinomial logistic regression identified condition-specific associations. Results: Prevalence rates were 18.2% for sarcopenia, 41.0% for abdominal obesity, and 3.4% for sarcopenic obesity. Eating alone and a lack of resistance exercise were common risk factors across all three conditions. Sarcopenia was associated with male sex, insufficient dietary intake, alcohol consumption, poor self-rated health, and low household income. Abdominal obesity was linked to recent weight gain, hypertension, diabetes, prolonged sedentary time, perceived obesity, and low educational attainment. Sarcopenic obesity was associated with male sex, diabetes, elevated hs-CRP, perceived stress, poor self-rated health, and economic inactivity. Conclusions: Body composition abnormalities among older Korean adults are influenced by complex, condition-specific interactions across biological, psychological, and social domains. These findings emphasize the significance of adopting an integrative perspective that considers physical, psychological, and social health components when addressing age-related body composition issues.

The association between sarcopenia and cardiometabolic index (CMI) among the Chinese elderly adults remains unclear. The present study aimed to examine the association based on a national survey.

Data from China Health and Retirement Longitudinal Study (CHARLS, wave 2011 and 2015) were employed. All subjects met the inclusion criteria were classified by the median of CMI. Four logistic regression models were established to explore the cross-sectional and longitudinal associations between CMI and sarcopenia. Subgroups analysis, tendency analysis, etc. were conducted to testify the robustness of the association. The non-linear relationship was explored using restricted cubic spline (RCS).

5,016 participants were enrolled in this study. The ORs of the longitudinal analysis in the models were 0.42(0.34,0.53), 0.37(0.29,0.46), 0.40(0.31,0.51) and 0.42(0.33,0.53)), respectively. Similar results were also found after propensity score matching (PSM), inverse probability weighting (IPTW) and cross-sectional analysis. Moreover, a non-linear relationship was found between CMI and sarcopenia in the total participants (both p for overall and p for non-linear < 0.001).

A U-shaped relationship between CMI and sarcopenia risk was found in the middle aged and elderly Chinese, with both deficient and excessive CMI levels showing detrimental effects. Maintaining a moderate CMI significantly diminishes the risk of sarcopenia.

Although sarcopenia and insulin resistance are closely related, there is limited evidence regarding how they interact to influence mortality across different population groups. The purpose of this study was to examine the relationship between skeletal muscle mass and insulin resistance and its impact on mortality and cardiovascular disease risk using large-scale national data from Korea and the United States.

We analysed data from the National Health and Nutrition Examination Survey (NHANES) 1999-2006 and 2011-2018 and the Korea National Health and Nutrition Examination Survey (KNHANES) 2008-2011, with mortality follow-up through to 2019. Cox regression models were used to assess the effects of muscle mass (appendicular skeletal mass index, ASMI) and insulin resistance on all-cause and major adverse cardiovascular and cerebrovascular events (MACCE)-related mortality. Mediation analysis was performed to examine direct and indirect effects.

The study included 8036 participants from NHANES and 14 449 from KNHANES. The sarcopenia group demonstrated a lower homeostasis model assessment for insulin resistance and better metabolic indices than the normal group despite having a higher mortality rate. Insulin resistance positively correlated with muscle mass (r = 0.203, p < 0.001 in the NHANES; r = 0.143, p < 0.001 in the KNHANES), and both insulin resistance and sarcopenia were identified as independent risk factors for all-cause and MACCE-related mortality. When the participants were categorized into four groups based on the presence or absence of insulin resistance and sarcopenia, those with both conditions exhibited the highest risk of all-cause mortality (hazard ratio [HR]: 2.30, 95% confidence interval [CI]: 1.72-3.08 in the NHANES; HR: 2.60, 95% CI: 2.14-3.16 in the KNHANES) and MACCE-related mortality among the groups (HR: 3.18, 95% CI: 1.99-5.08 in the NHANES; HR: 2.47, 95% CI: 1.66-3.69 in the KNHANES). Mediation analysis revealed that low muscle mass was associated with decreased insulin resistance but directly increased both all-cause mortality and MACCE-related mortality (NHANES: total natural direct effects [TNDE], HR: 2.08, 95% CI: 1.57-2.76; KNHANES: TNDE, HR: 1.69, 95% CI: 1.28-2.23).

This study found that low ASMI was inversely associated with insulin resistance and positively associated with mortality risk in both cohorts. These findings, consistent across two large national studies, highlight the complex relationships between muscle mass, insulin sensitivity and mortality. Further studies are needed to assess the underlying mechanisms and clinical implications of these associations.

Clinicaltrials.gov ID: NCT05616013.

The link between serum insulin level and low muscle mass among older adults is not yet fully understood. This study seeks to investigate this association using data from a nationally representative large-scale survey.

The study utilized data from two waves of the China Health and Nutrition Survey (CHNS) conducted in 2009 and 2015. Subjects meeting the inclusion criteria were classified according to the Asia Working Group for Sarcopenia 2019 criteria. The study employed ordinary least squares (OLS) regression models to analyze the cross-sectional association between appendicular skeletal muscle mass (ASM) and serum insulin level. Additionally, based on the median insulin level in the population without low muscle mass in 2009, these individuals were divided into high insulin and low insulin groups. Logistic regression models were utilized to examine the longitudinal association between low muscle mass and serum insulin level.

In 2009, a cross-sectional association study enrolled a total of 2329 participants aged over 60 years, with 53.1% women and a median age of 68.00 years. The prevalence of low muscle mass in the study population was 30.83%, with females accounting for 60.03%. In the adjusted OLS regression model based on blood biomarker, serum insulin level was positively associated with ASM (β = 0.075, 95% confidence interval (95% CI): 0.034-0.117, P < 0.01). A total of 944 individuals from the 2009 population without low muscle mass were divided into high insulin and low insulin groups based on the median insulin level, and were followed up until 2015. It was found that there was a significant difference in the incidence of low muscle mass between the two groups. (12.44% vs. 7.45%, P = 0.01). The adjusted logistic regression models indicated that higher serum insulin levels were associated with a reduced incidence of low muscle mass (Hazard ratio = 0.958, 95% CI: 0.925-0.989, P = 0.01).

Adequate serum insulin level could potentially serve as a protective factor in preserving healthy muscle mass among Chinese adults aged 60 and above.

Not applicable.

Postoperative delirium (POD) is generally associated with increased postoperative adverse events. We aimed to investigate whether preoperative quantitative quadriceps muscle ultrasound could predict POD in older patients after gastrointestinal surgery in order to provide more targeted prevention and treatment measures.

We prospectively collected data from elderly patients who underwent elective gastrointestinal surgery from August to December 2023 at a tertiary hospital in China. Intergroup difference analysis and univariate and multivariate logistic regression analyses were used to explore independent risk factors. We calculated and assessed the parameters via sensitivity, specificity, the Youden index, and the area under the receiver operating characteristic curve (AUC), calibration curves and the Hosmer-Lemeshow test. The nomogram was validated internally through bootstrap resampling. The decision curve analysis (DCA) was used to evaluate its clinical validity.

A total of 695 patients who underwent gastrointestinal surgery were analyzed in this investigation, among which 137 patients experienced POD with an incidence rate of 19.7%. After conducting multivariate logistic regression analyses using R software, six independent risk factors associated with POD were identified, including age, quadriceps muscle thickness (Q-MT), quadriceps echo intensity (Q-EI), Charlson Comorbidity Index (CCI), preoperative frailty and preoperative Minimum Mental State Examination (MMSE) scores. The AUC value of the model was 0.966 (95% CI: 0.950-0.982; p < 0.05). The calibration curve revealed that the predicted probability of the nomogram was consistent with the actual probability, and the Hosmer-Lemeshow goodness-of-fit test value was 0.811. DCA revealed that the nomogram has a net benefit for POD.

Quantitative quadriceps ultrasound parameters, including the Q-MT and Q-EI, could predict POD after gastrointestinal surgery in older patients. We have developed a new nomogram for predicting POD in older patients who undergo gastrointestinal surgery.

The trial was registered in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ) on August 3, 2023, with the registration number of ChiCTR2300074304.

This cross-sectional study analyzed National Health and Nutrition Examination Survey data from 2011 to 2018, focusing on individuals aged ≥20 years. The association between metabolic score for insulin resistance (METS-IR) and sarcopenia was examined using weighted multivariable logistic regression, with dose-response relationships characterized by restricted cubic spline analysis. Subgroup and sensitivity analyses were performed, and receiver operating characteristic curve analysis assessed METS-IR's ability to detect sarcopenia, with the area under the curve used for evaluation. The study included 4553 participants (mean age, 40 years; 49.4% male and 50.6% female). In the descriptive analysis, METS-IR levels in sarcopenia (mean, 52.39) were significantly higher than METS-IR levels in nonsarcopenia (mean, 41.94), indicating an association with sarcopenia. A univariate logistic regression analysis showed that sarcopenia and METS-IR were positively correlated. Even after accounting for all variables, METS-IR maintained a stable positive correlation with the prevalence of sarcopenia (odds ratio, 1.06 [95% CI, 1.06-1.08]). The results remained stable when METS-IR was categorized into quartiles. METS-IR was found to positively correlate with sarcopenia prevalence using restricted cubic spline analysis. According to subgroup analysis, there is a consistent and stable positive correlation between the prevalence of sarcopenia and METS-IR. Sensitivity analysis showed that METS-IR and sarcopenia continued to have a significant positive connection even after excluding extreme findings. The area under the curve value of METS-IR in the receiver operating characteristic curve analysis was 0.7217, suggesting that METS-IR could be a useful predictor of sarcopenia.

Sarcopenia refers to the decline in skeletal muscle mass and function. Due to its increased mortality rate and severe disability, the clinical importance of sarcopenia is becoming increasingly prominent. Although the exact cause of sarcopenia is not fully understood, the gut microbiota (GM) plays a crucial role in the pathogenesis of sarcopenia, and increasing evidence suggests that gut dysbiosis may be associated with disease development. In the past few decades, the use of probiotics has surged, few studies have explored their impact on sarcopenia prevention and treatment. Lactobacillus probiotics are commonly used for gut health and immune support, but their mechanism in sarcopenia via the gut-muscle axis remains uncertain. This review highlights the treatment challenges, GM's role in sarcopenia, and the potential of Lactobacillus as an adjunct therapy. In addition, we also discuss the possible mechanisms by which Lactobacillus affect muscle function, such as alleviating inflammatory states, clearing excessive reactive oxygen species (ROS), improving skeletal muscle metabolism, enhancing intestinal barrier function and modulating the gut microbiota and its metabolites. These mechanisms may collectively contribute to the preservation of muscle mass and function, offering a promising avenue for advancing microbial therapies for sarcopenia.

The global burden of liver cancer among adolescents and young adults (AYAs) has often been underestimated, despite significant shifts in its etiology. This study analyzes the disease burden of liver cancer in AYAs from 1990 to 2021 and forecasts trends up to 2040 using data from the Global Burden of Disease Study 2021. Our goal is to provide insights that can inform resource allocation and policy planning.

Incidence, mortality, and disability-adjusted life years (DALYs) data were extracted and estimated annual percentage changes calculated to assess trends. Correlation between age-standardized rates and sociodemographic index (SDI) was analyzed using Spearman correlation, and future trends were predicted using the Bayesian age-period-cohort model.

Globally, there were 24,348 new liver cancer cases and 19,270 deaths among AYAs in 2021, with decreases in age-standardized rates for incidence, mortality, and DALYs from 1990 to 2021. East Asia bears the highest burden, with males experiencing significantly higher rates than females. The burden increases with age, peaking at 35-39 years. Higher SDI is associated with lower incidence, mortality, and DALYs. While HBV remains the leading cause, NASH is the fastest-growing contributor to liver cancer incidence and mortality. Projections indicate a continued decline in liver cancer burden among AYAs, though female cases are expected to rise.

Despite a gradual decline in liver cancer burden among AYAs, NASH is emerging as a significant and rising cause of incidence and mortality. Regional and gender disparities persist, highlighting the need for tailored prevention and healthcare strategies to alleviate the liver cancer AYA's burden globally.

Frailty is the third major complication of older patients with diabetes mellitus. Exercise plays an irreplaceable role in improving the frailty and physical function of older patients with type 2 diabetes (T2DM), but the compliance of exercise is not high. At present, there is little research on the influencing factors of exercise behavior in older diabetes patients with frailty.

The aim of this study is to analyze the obstacles and promoting factors that affect exercise behavior from the perspective of patients, providing a basis for developing personalized exercise intervention strategies.

A semi-structured face-to-face in-depth interview was conducted on older T2DM patients combined with frailty in the endocrinology department of a tertiary hospital using phenomenological research methods. Analyze data and extract topics based on COM-B system and Colaizzi seven step analysis method.

The themes were identified containing: capability (restriction of physical function, exercise psychology, shortage of exercise knowledge); motivation (importance recognition of exercise, exercise self-efficacy, exercise habit); opportunity (multiple external support, prescription and guidance of exercise, environment and social resources). Most sub-themes had the potential as barriers and facilitators, with the exception of capability which were highlighted as barriers.

The factors influencing the exercise behavior of older patients with T2DM combined with frailty are complex and diverse. Healthcare professionals should take targeted measures to develop personalized exercise prescriptions to improve patients' participation in exercise, maximize the benefits of exercise therapy.

The Receptor for Advanced Glycation End Products (RAGE), classically considered a mediator of acute and chronic inflammatory responses, has recently been implicated by genetic knockout studies as a regulator of skeletal muscle physiology during development and following acute injury. Yet, the role of its soluble isoform, soluble RAGE (sRAGE), in muscle regeneration remains relatively unexplored. To address this knowledge gap, Adeno-Associated Virus (AAV) mediated and genetic knockin supplementation strategies were developed to specifically assess the effects of changing levels of sRAGE on muscle regeneration. We evaluated general muscle physiology and histology, including central nucleation, and myofiber size. We found that acute induction of sRAGE in aged and atherosclerotic animals accelerates muscle repair after cryoinjury. Similarly, genetic modification of the endogenous Ager gene locus to favor production of sRAGE over transmembrane RAGE accelerates repair of cryo-damaged skeletal muscle. However, increasing sRAGE via AAV delivery or using our transgenic mouse lines had no impact on muscle repair in aged or diseased mice after barium chloride (BaCl2) injury. Together, these studies identify a unique muscle regulatory activity of sRAGE that is variable across injury models and may be targeted in a context-specific manner to alter the skeletal muscle microenvironment and boost muscle regenerative output.

To assess the associations between the creatinine-to-body weight (Cre/BW) ratio and reversion to normoglycemia mediated by the aspartate aminotransferase-to-alanine aminotransferase (De Ritis) ratio. This retrospective cohort study included 24,884 prediabetic participants from health check-ups in 32 regions across 11 Chinese cities. We employed multivariable Cox regression to assess time-to-event outcomes, smooth curve fitting for trend analysis, and inflection point analysis to determine critical thresholds. Subgroup analyses were performed to explore interactions. Mediation analysis was conducted to clarify the mechanisms linking prediabetes with health outcomes. In the analysis of 24,884 individuals, it was observed that 49.08% of the prediabetic subjects experienced normoglycemic conversion during a follow-up period spanning 73,517.66 person-years. Following full adjustment, the Cre/BW ratio was positively associated with normoglycemic conversion among prediabetic individuals (HR 1.42, 95% CI 1.30-1.55). Multivariate smooth spline analysis revealed a nonlinear relationship between the Cre/BW ratio and glucose status conversion (P for nonlinearity < 0.05), with the curves leveling off when the Cre/BW ratio (×100) reached 1.34. Subgroup analysis and additional sensitivity analyses confirmed that the results between the Cre/BW ratio and glucose status conversion were robust. Additionally, the De Ritis ratio was found to explain 50% of the association between the Cre/BW ratio and the prediabetes-to-normoglycemia transition. A higher Cre/BW ratio was associated with a better chance of controlling blood glucose levels in prediabetic individuals, with the De Ritis ratio playing a key mediating role.

Although appendicular skeletal muscle mass (ASM) has been linked to the severity of hepatic steatosis, investigations of its correlation among younger age groups are lacking. We aimed to elucidate the role of ASM in determining the severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in younger patients.

Retrospective data were collected from patients younger than 35 years who visited the Armed Forces Goyang Hospital between June 2022 and February 2024. Steatosis presence was determined by a controlled attenuation parameter score ≥ 250 dB/m, and significant fibrosis was identified with liver stiffness measurement > 8.0 kPa. ASM was measured using multifrequency bioelectrical impedance analysis (InBody 620).

Of 910 participants, 630 were diagnosed with MASLD. Patients with MASLD had lower ASM/fat mass (ASM/F) (1.02 vs. 1.91; p < 0.001), ASM/body mass index (BMI) (0.91 vs. 1.04/m2; p < 0.001), and ASM/body weight (ASM/W) (29.5% vs. 33.8%; p < 0.001) than non-MASLD patients. Additionally, ASM/F, ASM/BMI, and ASM/W significantly decreased with worsening steatosis severity and were notably lower in patients with significant fibrosis. Among 107 patients with MASLD who underwent two examinations with a median interval of 6.0 months, those with increased ASM/F showed a higher proportion of steatosis regression and a lower proportion of steatosis worsening than those with decreased ASM/F (steatosis regression, 43.1% vs. 22.9%; worsening, 11.1% vs. 28.6%; p = 0.031). All three ASM indices were significant factors in steatosis regression during the study period.

ASM is associated with the severity of steatosis and significant fibrosis in MASLD in young adults < 35 years.

Skeletal muscle is the largest insulin-sensitive tissue in the human body, alteration in muscle mass and strength substantially impact glucose metabolism. This systematic review aims to investigate further the relationship between muscle mass and strength towards type 2 diabetes mellitus (T2DM) incidence.

This systematic review included cohort studies that examinedthe relationship between muscle mass and/or muscle strength on T2DM incidence. A comprehensive search was conducted across PubMed, EBSCO, ProQuest, and Google scholar employing specific Medical Subject Headings (MeSH) and relevant keywords related to or synonymous with "muscle mass", "muscle strength", and "Type 2 Diabetes Mellitus incidence".

Twenty-five cohort studies were included, 11 studies on muscle mass and 16 studies on muscle strength. Participants included were 278,475 for muscle mass and 400,181 for muscle strength. Skeletal muscle mass normalized to body weight (SMM/BW), appendicular skeletal musce mass normalized to body weight (ASM/BW), and handgrip strength normalized to body mass index (HGS/BMI) consistently demonstrate significant inverse association with T2DM even after sex and/or BMI stratification. Handgrip strength normalized to body weight (HGS/BW) demonstrates a strong inverse association with T2DM incidence, however, adiposity should be considered.

Muscle mass and strength demonstrate strong association with T2DM incidence. Adiposity, a key T2DM risk factor, should also be assessed through a simple BMI or a sophisticated technique with BIA or CT-scan. The combination of muscle variables and adiposity could further enhance T2DM risk assessment. However, T2DM risks are multifactorial, with various contributing factors, further large-scale studies are needed to validate these findings.

Acute sarcopenia is sarcopenia lasting less than 6 months, typically following acute illness or injury. It may impact patient recovery and quality of life, advancing to chronic sarcopenia. However, its development and assessment remain poorly understood, particularly during hospitalisation. This systematic review aimed to elucidate the incidence of acute sarcopenia and examine changes in muscle parameters during hospitalisation.

Eighty-eight papers were included in the narrative synthesis; 33 provided data for meta-analyses on the effects of hospitalisation on handgrip strength (HGS), rectus femoris cross-sectional area (RFCSA) and various muscle function tests. Meta-regressions were performed for length of hospital stay (LoS) and age for all meta-analyses; sex was also considered for HGS.

Acute sarcopenia development was assessed in four studies with a pooled incidence of 18% during hospitalisation. Incidence was highest among trauma patients in intensive care (59%), whereas it was lower among medical and surgical patients (15%-20%). Time of development ranged from 4 to 44 days. HGS remained stable during hospitalisation (SMD = 0.05, 95% CI = -0.18:0.28, p = 0.67) as did knee extensor strength. LoS affected HGS performance (θ = 0.04, 95% CI = 0.001:0.09, p = 0.045) but age (p = 0.903) and sex (p = 0.434) did not. RFCSA, reduced by 16.5% over 3-21 days (SMD = -0.67, 95% CI = -0.92:-0.43, p < 0.001); LoS or time between scans did significantly predict the reduction (θ = -0.04, 95% CI = -0.077:-0.011, p = 0.012). Indices of muscle quality also reduced. Muscle function improved when assessed by the short physical performance battery (SMD = 0.86, 95% CI = 0.03:1.69, p = 0.046); there was no change in 6-min walk (p = 0.22), timed up-and-go (p = 0.46) or gait speed tests (p = 0.98). The only significant predictor of timed up-and-go performance was age (θ = -0.11, 95% CI = -0.018:-0.005, p = 0.009).

Assessment and understanding of acute sarcopenia in clinical settings are limited. Incidence varies between clinical conditions, and muscle parameters are affected differently. HGS and muscle function tests may not be sensitive enough to identify acute changes during hospitalisation. Currently, muscle health deterioration may be underdiagnosed impacting recovery, quality of life and overall health following hospitalisation. Further evaluation is necessary to determine the suitability of existing diagnostic criteria of acute sarcopenia. Muscle mass and quality indices might need to become the primary determinants for muscle health assessment in hospitalised populations.

Primary sarcopenia is characterized by a progressive loss of skeletal muscle mass, strength, and physical function that occurs with aging. Despite the related adverse or even serious health outcomes, no medications are currently available for treating primary sarcopenia. Here, we discuss recent advancements in understanding the mechanistic role of gut microbiota-muscle cross-talk in primary sarcopenia, and the therapeutic implications. The mechanistic insights encompass a causal role of gut dysbiosis in primary sarcopenia, potentially mediated through gut microbiota-derived bioactive metabolites, such as short-chain fatty acids (SCFAs), secondary bile acids, and their associated signaling pathways, which may be translated into the development of new microbiome-based treatment and diagnostic approaches. Furthermore, we identify challenges that need addressing in future studies to facilitate the translation into potential novel treatment and differential diagnosis for older individuals with sarcopenia.

The loss of skeletal muscle mass and strength, known as sarcopenia, is prevalent in older adults and linked to an increased risk of disability, frailty, and early mortality. Muscle health is crucial for the functionality and independence of older adults. As the aging population continuously grows, finding cost-effective strategies for preventing and treating sarcopenia is an important public health priority. While nutrition is recognized as a key factor in the development of sarcopenia, its role in preventing and treating the condition is still under investigation. In recent decades, nutritional research has shifted from a focus on individual nutrients or healthy foods to examining the combination of nutrients and foods in dietary patterns, along with their potential synergistic and antagonistic effects. A balanced diet and regular participation in physical activity are essential for maintaining musculoskeletal health. One of the healthy eating patterns with the greatest evidence of multiple health benefits is the Mediterranean diet, which has also been linked to positive effects on muscle function in observational studies. However, there is a lack of intervention studies. This review explores the updated evidence from longitudinal prospective studies on associations between adherence to the Mediterranean diet and sarcopenia in order to promote preventive and intervention strategies for healthy muscle aging.

The objective of this study was to investigate the association between sarcopenia and liver fibrosis in patients aged 18-59 years with metabolic dysfunction-associated steatotic liver disease (MASLD) and to assess the potential of sarcopenia as a risk factor for the progression of liver fibrosis.

The study included 821 patients with MASLD in the US cohort and 3,405 patients with MASLD in the Chinese cohort. Liver controlled attenuation parameters (CAP) and liver stiffness measurements (LSM) were assessed by vibration-controlled transient elastography (VCTE) to evaluate the extent of hepatic steatosis and fibrosis. Sarcopenia was assessed by measuring appendicular skeletal muscle mass (ASM) and calculating ASMI. To analyze the relationship between sarcopenia, ASMI, and liver fibrosis, logistic regression models, multivariate-adjusted models, and restricted cubic spline (RCS) models were employed, with stratification and interaction analyses.

The results demonstrated that patients with sarcopenia exhibited a markedly elevated risk of significant liver fibrosis, advanced liver fibrosis, and cirrhosis compared to those without sarcopenia in both cohorts. After adjusting for confounding variables, sarcopenia was identified as an independent risk factor for the progression of liver fibrosis in patients with MASLD. A significant negative correlation was observed between ASMI and the severity of liver fibrosis, with a progressive reduction in the risk of liver fibrosis associated with increasing ASMI. Additionally, a non-linear feature was evident in some liver fibrosis indicators. Subgroup analysis further corroborated the finding that the harmful effect of sarcopenia on liver fibrosis was consistent across all identified subgroups.

Sarcopenia may be associated with the progression of liver fibrosis in patients with MASLD. Monitoring ASMI may assist in identifying individuals at an elevated risk of liver fibrosis in MASLD patients.

The fibronectin domain-containing protein 5 (FNDC5), or irisin, is an adipo-myokine hormone produced during exercise, which shows therapeutic potential for conditions like metabolic disorders, osteoporosis, sarcopenia, obesity, type 2 diabetes, and neurodegenerative diseases, including Alzheimer's disease (AD). This review explores its potential across various pathophysiological processes that are often considered independent. Elevated in healthy states but reduced in diseases, irisin improves muscle-adipose communication, insulin sensitivity, and metabolic balance by enhancing mitochondrial function and reducing oxidative stress. It promotes osteogenesis and mitigates bone loss in osteoporosis and sarcopenia. Irisin exhibits anti-inflammatory effects by inhibiting NF-κB signaling and countering insulin resistance. In the brain, it reduces amyloid-β toxicity, inflammation, and oxidative stress, enhancing brain-derived neurotrophic factor (BDNF) signaling, which improves cognition and synaptic health in AD models. It also regulates dopamine pathways, potentially alleviating neuropsychiatric symptoms like depression and apathy. By linking physical activity to systemic health, irisin emphasizes its role in the muscle-bone-brain axis. Its multifaceted benefits highlight its potential as a therapeutic target for AD and related disorders, with applications in prevention, in treatment, and as a complement to exercise strategies.

In Japan, fatty liver cases with elevated body mass index are increasing. Because of being non-malignant, these are often neglected unless accompanied by diabetes. This study investigated the risk of glucose intolerance in individuals with non-alcoholic fatty liver. We included 165 men (mean age 56.3 years; range 29-75 years) who underwent an overnight 2-day physical examination at our Health Evaluation Center. All patients underwent abdominal ultrasonography to examine fatty liver. Fasting blood glucose and 75-g glucose tolerance test (OGTT) were conducted. alanine aminotransferase (ALT) (p < 0.01) and triglyceride (p < 0.001) levels were significantly higher in the fatty liver group (FL) than in the non-fatty liver group. HbA1c, fasting blood glucose, and blood glucose level at OGTT (0 and 30 min) did not show significant differences. In the FL, OGTT was significantly elevated at 60 min(p < 0.01)and 120 min (p < 0.001), insulin level was significantly elevated at 0 and 30 min (p < 0.001), and glucagon level was significantly elevated at 0 min (p < 0.05) and 30 min (p < 0.01), with no significant differences between the groups at 60 and 120 min. This is the first study to demonstrate elevated glucagon levels after OGTT. Metabolic dysfunction-associated steatotic liver disease (MASLD) requires treatment for insulin resistance with glucagon dysregulation likely associated with its pathogenesis.

Sarcopenia, a disorder marked by muscle loss and dysfunction, is a global health concern, particularly in aging populations. Sarcopenia is intricately related to various health conditions, including obesity, dysphagia, and frailty, which underscores the complexity. Despite recent advances in metabolomics and other omics data for early detection and treatment, the precise characterization and diagnosis of sarcopenia remains challenging. In the present review we provide an overview of the complex metabolic mechanisms that underlie sarcopenia, with particular emphasis on protein, lipid, carbohydrate, and bone metabolism. The review highlights the importance of leucine and other amino acids in promoting muscle protein synthesis and clarifies the critical role played by amino acid metabolism in preserving muscular health. In addition, the review provides insights regarding lipid metabolism on sarcopenia, with an emphasis on the effects of inflammation and insulin resistance. The development of sarcopenia is largely influenced by insulin resistance, especially with regard to glucose metabolism. Overall, the review emphasizes the complex relationship between bone and muscle health by highlighting the interaction between sarcopenia and bone metabolism. Furthermore, the review outlines various therapeutic approaches and potential biomarkers for diagnosing sarcopenia. These include pharmacological strategies such as hormone replacement therapy and anabolic steroids as well as lifestyle modifications such as exercise, nutrition, and dietary changes.

Diabetes is a prevalent metabolic condition with substantial health and economic impacts. Therefore, effective and accessible indicators are essential for early detection and prevention. This study investigates the link between the waist-to-calf circumference ratio (WCR) and diabetes risk in a large cohort from the Longevity Check-Up (Lookup) 8+ Study. The present investigation is a retrospective cross-sectional study. Diabetes was defined either as self-reported diagnosis, or fasting plasma glucose equal to or greater than 126 mg/dL, or random plasma glucose equal to or greater than 200 mg/dL. The WCR was calculated by dividing waist circumference by calf circumference. A total population of 8900 participants (mean age 57.1 ± 14.8 years, 55% women) was included in the study. The prevalence of diabetes was 9.4%. Mean WCR displayed a significant trend (p for trend < 0.001), and the analysis of covariance (ANCOVA) revealed significant differences among the normal, pre-diabetes, diabetes groups. Unadjusted logistic regression showed a positive association between higher WCR and diabetes, which remained significant in the adjusted models. Receiver operating characteristic curve analysis indicated that WCR had a higher area under the curve compared to waist circumference alone, with cut-off values of 2.35 for men and 2.12 for women providing high sensitivity (91% for men, 92% for women) and specificity (74% for men, 75% for women). Our study introduces WCR as a novel, simple, and cost-effective anthropometric measure for identifying individuals at risk of diabetes, suitable for clinical use, especially in resource-limited settings.

Existing research suggests that low muscle mass is independently associated with carotid atherosclerosis, but its relationship with lower extremity arterial atherosclerosis in type 2 diabetes mellitus (T2DM) patients remains unclear. This study aims to investigate the association between low skeletal muscle mass and lower extremity arterial atherosclerosis in T2DM patients, in hopes of providing a scientific basis for early diagnosis and treatment.

This cross-sectional study recruited a total of 276 patients with T2DM who underwent bioelectrical impedance analysis, lower limb artery ultrasonography, brachial-ankle pulse wave velocity(baPWV) arterial stiffness measurement, and blood tests. An skeletal muscle index (SMI) < 7.0kg/m2 in men and an SMI< 5.7kg/m2 in women were defined as low skeletal muscle mass. Lower limb atherosclerosis was defined as the presence of atherosclerotic plaques in the lower extremity arteries.

In our study of 276 T2DM patients, 224 (81.1%) presented with lower limb atherosclerosis: 194 (70.2%) with simple lower limb arterial plaques, 15 (5.4%) with lower limb arterial stenosis, and 15 (5.4%) with lower limb arterial occlusion. 52 (18.8%) were diagnosed with low skeletal muscle mass. Logistic regression analysis indicated the risk of having overall lower limbs atherosclerosis increased with the prevalence of low skeletal muscle (OR= 6.175,95% CI 1.328-28.711); Patients with a low skeletal muscle mass had a higher prevalence of simple arterial plaque (OR= 6.225,95% CI 1.339-28.935) and arterial occlusion (OR=12.345,95% CI 1.221-124.808); after the adjustment for clinical risk factors. Spearman's analysis showed significant negative correlations between total-P1NP and baPWV (r=-0.166, p=0.008), N-MID and baPWV (r=-0.163, p=0.009), and β-CTX and baPWV (r=-0.141, p=0.024).

Low muscle mass is independently associated with an increased risk of having lower limb atherosclerosis in T2DM patients. And there may be some relationship between BTMs and arteriosclerosis of the lower limb atherosclerosis in T2DM.

Recent studies have linked sarcopenia development to the hallmarks of diabetes, oxidative stress, and insulin resistance. The anti-oxidant and insulin sensitivityenhancing effects of incretin-based therapies may provide a promising option for the treatment of sarcopenia. This review aimed to unveil the role of oxidative stress and insulin resistance in the pathogenesis of sarcopenia and explore the potential benefits of incretin-based therapies in individuals with sarcopenia.

PubMed, the Cochrane Library, and Google Scholar databases were searched by applying keywords relevant to the main topic, to identify articles that met our selection criteria.

Incretin-based therapies manifested anti-oxidant effects by increasing the anti-oxidant defense system and decreasing free radical generation or by indirectly minimizing glucotoxicity, which was mainly achieved by improving insulin signaling and glucose homeostasis. Likewise, these drugs exhibit insulin-sensitizing activities by increasing insulin secretion, transduction, and β-cell function or by reducing inflammation and lipotoxicity.

Incretin-based therapies, as modulators of oxidation and insulin resistance, may target the main pathophysiological factors of sarcopenia, thus providing a promising strategy for the treatment of this disease.

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.

To investigate the association between metabolic syndrome (MetS) and its components with sarcopenia, and to explore the extent to which insulin resistance (IR) mediates this association, using data from the National Health and Nutrition Examination Survey (NHANES).

We analyzed cross-sectional data from 15,779 adults in the NHANES from 1999 to 2006 and 2011-2018. Multivariable logistic regression models were used to determine the odds ratios (ORs) between MetS, its components, the number of MetS components, and sarcopenia. Mediation analysis was performed to explore the role of the homeostatic model assessment of insulin resistance (HOMA-IR) in MetS and its components-induced sarcopenia.

In the fully adjusted model, MetS increased the prevalence of sarcopenia by 1.96-fold (95% CI: 1.73-2.22). Among the individual components, central obesity, hypertension, and hyperglycemia were associated with an increased prevalence of sarcopenia. Sarcopenia prevalence also increased linearly with the number of MetS components, with the highest prevalence observed in the presence of all five components (OR: 3.80, 95% CI: 2.79-5.16). Sex-stratified analysis showed that the prevalence of MetS for sarcopenia was higher in males than females. The mediating effects of HOMA-IR on the association between MetS and its components (central obesity, hypertension, and hyperglycemia) with sarcopenia were significant, with mediation effects of 51.7%, 30.7%, 33.2%, and 79.1%, respectively. There was no significant direct association between hyperglycemia and sarcopenia beyond the HOMA-IR pathway.

MetS and its individual components, excluding hypertriglyceridemia and low high density lipoprotein cholesterol, were associated with a higher prevalence of sarcopenia, especially in males. This association was partially or fully mediated by IR.

The factors determining the reversal of metabolically unhealthy obesity (MUO) to metabolically healthy obesity (MHO) after Roux-en-Y gastric bypass (RYGB) are not completely elucidated. The present study aims to evaluate body adiposity and distribution, through different indices, according to metabolic phenotypes before and 6 months after RYGB, and the relationship between these indices and transition from MUO to MHO. This study reports a prospective longitudinal study on adults with obesity who were evaluated before (T0) and 6 months (T1) after RYGB. Bodyweight, height, waist circumference (WC), BMI, waist-to-height ratio (WHR), total cholesterol (TC), HDL-c, LDL-c, triglycerides, insulin, glucose, HbA1c and HOMA-IR were evaluated. The visceral adiposity index (VAI), the conicity index (CI), the lipid accumulation product (LAP), CUN-BAE and body shape index (ABSI) were calculated. MUO was classified based on insulin resistance. MUO at T0 with transition to MHO at T1 formed the MHO-t group MHO and MUO at both T0 and T1 formed the MHO-m and MUO-m groups, respectively. At T0, 37.3% of the 62 individuals were classified as MHO and 62.7% as MUO. Individuals in the MUO-T0 group had higher blood glucose, HbA1c, HOMA-IR, insulin, TC and LDL-c compared to those in the MHO-T0 group. Both groups showed significant improvement in biochemical and body variables at T1. After RYGB, 89.2% of MUO-T0 became MHO (MHO-t). The MUO-m group presented higher HOMA-IR, insulin and VAI, compared to the MHO-m and MHO-t groups. CI and ABSI at T0 correlated with HOMA-IR at T1 in the MHO-t and MHO-m groups. CI and ABSI, indicators of visceral fat, are promising for predicting post-RYGB metabolic improvement. Additional studies are needed to confirm the sustainability of MUO reversion and its relationship with these indices.

The triad of vascular impairment, muscle atrophy, and cognitive decline represents critical age-related conditions that significantly impact health. Vascular impairment disrupts blood flow, precipitating the muscle mass reduction seen in sarcopenia and the decline in neuronal function characteristic of neurodegeneration. Our limited understanding of the intricate relationships within this triad hinders accurate diagnosis and effective treatment strategies. This review analyzes the interrelated mechanisms that contribute to these conditions, with a specific focus on oxidative stress, chronic inflammation, and impaired nutrient delivery. The aim is to understand the common pathways involved and to suggest comprehensive therapeutic approaches. Vascular dysfunctions hinder the circulation of blood and the transportation of nutrients, resulting in sarcopenia characterized by muscle atrophy and weakness. Vascular dysfunction and sarcopenia have a negative impact on physical function and quality of life. Neurodegenerative diseases exhibit comparable pathophysiological mechanisms that affect cognitive and motor functions. Preventive and therapeutic approaches encompass lifestyle adjustments, addressing oxidative stress, inflammation, and integrated therapies that focus on improving vascular and muscular well-being. Better understanding of these links can refine therapeutic strategies and yield better patient outcomes. This study emphasizes the complex interplay between vascular dysfunction, muscle degeneration, and cognitive decline, highlighting the necessity for multidisciplinary treatment approaches. Advances in this domain promise improved diagnostic accuracy, more effective therapeutic options, and enhanced preventive measures, all contributing to a higher quality of life for the elderly population.

Sarcopenic obesity, which is associated with a poorer prognosis than that of sarcopenia alone, may be positively affected by soy isoflavones, known inhibitors of muscle atrophy. Herein, we hypothesize that these compounds may prevent sarcopenic obesity by upregulating the gut metabolites with anti-inflammatory effects.

To explore the effects of soy isoflavones on sarcopenic obesity and its mechanisms, we employed both in vivo and in vitro experiments. Mice were fed a high-fat, high-sucrose diet with or without soy isoflavone supplementation. Additionally, the mouse C2C12 myotube cells were treated with palmitic acid and daidzein in vitro.

The isoflavone considerably reduced muscle atrophy and the expression of the muscle atrophy genes in the treated group compared to the control group (Fbxo32, p = 0.0012; Trim63, p < 0.0001; Foxo1, p < 0.0001; Tnfa, p = 0.1343). Elevated levels of daidzein were found in the muscles and feces of the experimental group compared to the control group (feces, p = 0.0122; muscle, p = 0.0020). The real-time PCR results demonstrated that the daidzein decreased the expression of the palmitate-induced inflammation and muscle atrophy genes in the C2C12 myotube cells (Tnfa, p = 0.0201; Il6, p = 0.0008; Fbxo32, p < 0.0001; Hdac4, p = 0.0002; Trim63, p = 0.0114; Foxo1, p < 0.0001). Additionally, it reduced the palmitate-induced protein expression related to the muscle atrophy in the C2C12 myotube cells (Foxo1, p = 0.0078; MuRF1, p = 0.0119).

The daidzein suppressed inflammatory cytokine- and muscle atrophy-related gene expression in the C2C12 myotubes, thereby inhibiting muscle atrophy.

The escalating prevalence of insulin resistance (IR) and type 2 diabetes mellitus (T2D) underscores the urgent need for improved early detection techniques and effective treatment strategies. In this context, our study presents a proteomic analysis of post-exercise skeletal muscle biopsies from individuals across a spectrum of glucose metabolism states: normal, prediabetes, and T2D. This enabled the identification of significant protein relationships indicative of each specific glycemic condition. Our investigation primarily leveraged the machine learning approach, employing the white-box algorithm relative evolutionary hierarchical analysis (REHA), to explore the impact of regulated, mixed mode exercise on skeletal muscle proteome in subjects with diverse glycemic status. This method aimed to advance the diagnosis of IR and T2D and elucidate the molecular pathways involved in its development and the response to exercise. Additionally, we used proteomics-specific statistical analysis to provide a comparative perspective, highlighting the nuanced differences identified by REHA. Validation of the REHA model with a comparable external dataset further demonstrated its efficacy in distinguishing between diverse proteomic profiles. Key metrics such as accuracy and the area under the ROC curve confirmed REHA's capability to uncover novel molecular pathways and significant protein interactions, offering fresh insights into the effects of exercise on IR and T2D pathophysiology of skeletal muscle. The visualizations not only underscored significant proteins and their interactions but also showcased decision trees that effectively differentiate between various glycemic states, thereby enhancing our understanding of the biomolecular landscape of T2D.