Clinical, laboratory and instrumental aspects of sarcopenia diagnostics

HighlightsWhat are the main findings?Adenine-induced CKD leads to a decline in muscle strength and deterioration of muscle quality, even in the absence of significant muscle mass loss.Uremic conditions upregulate CAPN2 expression and activity in skeletal muscle, suggesting a pathogenic role in muscle deterioration.Inhibition of calpain activity through CAST overexpression preserves muscle function and attenuates fibrosis, inflammation and adipogenic processes.The protective effects of CAPN inhibition occur independently of improvements in renal function.What is the implication of the main finding?CAPN2 emerges as a potential therapeutic target to prevent sarcopenia in CKD.Sarcopenia, the progressive loss of muscle mass and strength, is a common complication in patients with chronic kidney disease (CKD). This condition arises from a combination of factors including reduced physical activity, insufficient protein intake, hyperphosphatemia, chronic inflammation, and uremia itself; however, the underlying molecular mechanisms remain poorly understood. Proteolysis in skeletal muscle is primarily controlled by the ubiquitin–proteasome system, autophagy–lysosome system, and calpains (CAPNs) cysteine proteases, which degrade structural proteins and mediate cell signaling. This study aims to investigate the role of CAPNs in CKD-associated muscle deterioration. CKD was induced in mice through an adenine-rich diet for 2, 4 and 6 weeks. The involvement of CAPNs in CKD-related sarcopenia was assessed using mice that overexpressed the CAPNs endogenous inhibitor, calpastatin (CAST). Gastrocnemius muscle strength, structural integrity, and function were evaluated. Mice with CKD showed elevated CAPNs, particularly CAPN2, expression and activity in the gastrocnemius, in parallel with significant muscle deterioration, including strength loss, structural damage, and impaired muscle performance. Overexpression of CAST prevented muscle strength loss, improved muscle function and structure without affecting renal function, and reversed fibrosis, inflammation and adipogenesis expression markers. Targeting CAPN2 could be a promising therapeutic strategy to mitigate muscle damage and improve physical performance in CKD patients.

The Impact of Dairy Protein Intake on Muscle Mass, Muscle Strength, and Physical Performance in Middle-Aged to Older Adults with or without Existing Sarcopenia: A Systematic Review and Meta-Analysis.

Background: The world population is aging rapidly. This growth of the aging population is accompanied by an increased number of frail elderly people who are at risk of adverse health outcomes such as disability, co-morbidity and mortality. A dominant feature of frailty is the age related loss of muscle mass, strength and performance, also called sarcopenia. Resistance-type exercise training and dietary protein supplementation are considered promising strategies to reverse sarcopenia and subsequent frailty. However, strong evidence for the impact of protein supplementation with or without resistance exercise in frail elderly people is scarce. Well-designed intervention studies in frail elderly people are needed to define new leads for the development of nutritional and exercise interventions to effectively prevent or treat the progressive loss of muscle mass, strength and physical performance with aging. Therefore, the aims of this thesis are to study 1) the impact of protein supplementation and 2) the impact of protein supplementation during prolonged resistance-type exercise training on muscle mass, strength and physical performance in frail elderly people. Methods: First, we studied various characteristics of dietary protein intake, including the distribution of dietary protein intake throughout the day, and the use of protein-containing food sources in various elderly populations. With this knowledge, we designed two large intervention trials to study the impact of dietary protein supplementation with or without prolonged resistance-type exercise training on muscle mass, strength and physical performance in frail elderly people. In addition, we assessed the usefulness of handgrip strength as a measure of post exercise strength differences and studied the association of vitamin D status and vitamin D intake on muscle mass, strength and physical performance in a frail elderly population. Results: Dietary protein intake in frail and institutionalized elderly people were especially low at breakfast and lunch. Supplementing protein at breakfast and lunch did not increase muscle mass but improved physical performance in frail elderly people. Resistance-type exercise training improved muscle leg strength and physical performance, but not handgrip strength. Supplementing protein at breakfast and lunch was required to significantly increase muscle mass during prolonged resistance-type exercise training in frail elderly people. Furthermore, low vitamin D status and vitamin D intake were associated with impaired physical performance. Conclusions: Although dietary protein supplementation does not increase muscle mass, it represents a promising strategy to improve physical performance in frail elderly people. Prolonged resistance-type exercise training represents an effective strategy to improve strength and physical performance, but dietary protein supplementation is required to allow muscle mass gain during exercise training in frail elderly people.

the progressive loss of muscle mass, commonly termed sarcopenia, accompanies the process of healthy aging ([27][1]). The underlying basis of this condition, in a very simplistic view, would be at a more advanced age skeletal muscle proteins are being lost because of an imbalance between muscle

Effects of exercise on muscle mass, strength, and physical performance in older adults with sarcopenia: A systematic review and meta-analysis according to the EWGSOP criteria.

Relative and absolute muscle mass and muscle strength are used as diagnostic criteria for sarcopenia. We aimed to assess which diagnostic criteria are most associated with physical performance in 180 young (18-30years) and 281 healthy old participants (69-81years) of the European study MYOAGE. Diagnostic criteria included relative muscle mass (total or appendicular lean mass (ALM) as percentage of body mass), absolute muscle mass (ALM/height squared and total lean mass), knee extension torque, and handgrip strength. Physical performance comprised walking speed, Timed Up and Go test (TUG), and in a subgroup physical fitness. Diagnostic criteria for sarcopenia and physical performance were standardized, and the associations were analyzed using linear regression models stratified by age category, with adjustments for age, gender, and country. In old participants, relative muscle mass was associated with faster walking speed, faster TUG, and higher physical fitness (all p < 0.001). Absolute muscle mass was not associated with physical performance. Knee extension torque and handgrip strength were associated with faster walking speed (both p ≤ 0.003). Knee extension torque was associated with TUG (p = 0.001). Knee extension torque and handgrip strength were not associated with physical fitness. In young participants, there were no significant associations between diagnostic criteria for sarcopenia and physical performance, except for a positive association between relative muscle mass and physical fitness (p < 0.001). Relative muscle mass, defined as lean mass or ALM percentage, was most associated with physical performance. Absolute muscle mass including ALM/height squared was not associated with physical performance. This should be accounted for when defining sarcopenia.

Background: Sarcopenia is progressive loss of muscle mass and strength; this may cause increased morbidity and mortality. Rheumatic diseases as spondyloarthropathies have greater risks of developing sarcopenia. Objectives: Assessment of sarcopenia in Egyptian patients with psoriatic arthritis (PSA) and axial spondyloarthritis (axSPA) and investigate the relation between sarcopenia and different factors. Methods: This study included 56 PSA (Group I), 58 axSPA patients (Group II), and 60 healthy controls (Group III). Demographic data were collected, disease activity was assessed using Disease Activity Index for Psoriatic Arthritis (DAPSA) score for PSA patients and ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score) for axSPA patients. Functional assessment was done using Bath ankylosing spondylitis functional index (BASFI) for axSPA patients and Health Assessment Questionnaire (HAQ) for PSA patients. Sarcopenia was assessed by measuring Muscle mass, muscle strength and physical performance. Results: There was no significant difference between study groups regarding age, and BMI. None of the studied patients had definite sarcopenia, twelve PSA patients (21.43%), and fifteen axSPA patients (25.86%) had probable sarcopenia. While seven PSA, and five axSPA patients had pre-sarcopenia. We found significant differences between PSA and controls regarding muscle quantity, muscle strength, and muscle performance. While we found significant differences between axSPA and controls regarding muscle strength, and muscle performance. the risk of probable sarcopenia in axSPA patients increased with increasing age and ASDAS-CRP and in PSA patients it increased with increasing age, DAPSA and HAQ. Conclusions: probable sarcopenia was significantly increased in PsA and axSPA. Our analysis suggests that age, and disease activity were associated with the development of sarcopenia in PSA and axSPA.

Background:Sarcopenia is an age-related skeletal muscle disorder that involves a loss of muscle mass or strength and physiological function. Skeletal muscle deteriorates in both quantity and quality. The endocrine system is an important regulator of muscle metabolism. Therefore, we aimed to explore the relationship between biochemical markers and muscle mass in sarcopenia.Methods:We used the AWGS 2014 as the diagnostic criteria for sarcopenia, considering both the loss in muscle mass, muscle strength and physical performance. A total of 2837 elderly female participants over 50 years of age from the West China Health and Aging Trend (WCHAT) study were included. Insulin, glucose, 25(OH)VD, procalcitonin, alanine aminotransferase, aspartate aminotransferase, total protein, prealbumin, albumin, thyroid-stimulating hormone, free triiodothyronine, free tetraiodothyronine, triglycerides, cholesterol, high-density lipoprotein, very low-density lipoprotein, cortisol, and follicle-stimulating hormone were measured. Based on the findings of univariate analysis, multivariate regression and receiver operating characteristic (ROC) curves were established.Results:Participants with sarcopenia had significantly lower free triiodothyronine, insulin, total protein, albumin, prealbumin, albumin/prealbumin ratio (A/G), alanine aminotransferase, triglycerides, and very low-density lipoprotein concentrations (P < 0.05). Compared with those without sarcopenia, those with sarcopenia had significantly higher free tetraiodothyronine, cortisol, follicle-stimulating hormone (FSH), aspartate aminotransferase/alanine aminotransferase ratio (AST/ALT), and high-density lipoprotein concentrations (P < 0.05). Insulin (OR = 0.854), FSH (OR = 1.016), and the AST/ALT ratio (OR = 1.819) were independent risk factors for low muscle mass (P < 0.001). The AUC of insulin was the highest, followed by the AST/ALT ratio and FSH (0.691, 0.671, and 0.634, respectively), and the AUC of the mixture of the above three reached 0.736.Conclusion:In this cross-sectional study of elderly Chinese females aged over 50 years from the WCHAT, FSH, insulin, and AST/ALT ratio were associated with sarcopenia and risk factors for low muscle mass.

BACKGROUND: Corticosteroid use is associated with loss of muscle mass and strength, which is associated with an unfavorable prognosis of the underlying disease, as well as an increased risk of cardiovascular disease. Patients with multiple sclerosis (MS) have a higher baseline susceptibility to cardiovascular disease and a higher risk of adverse effects due to corticosteroid use. In clinical practice, different degrees of severity of side effects of corticosteroids are reported. This may be related to the presence of a genetic predisposition, the identification of which should allow a personalized approach to therapy. AIM: To evaluate the association of polymorphic variants of the glucocorticoid receptor gene NR3C1, the FTO gene, and the melatonin receptor genes MTNR1A, MTNR1B with the development of changes in muscle mass and strength in the context of corticosteroid use in patients with MS. MATERIALS AND METHODS: The study included 80 patients (mean age 36.3±10.0 years) with MS receiving pulse corticosteroid therapy: 4 (3; 4) g methylprednisolone. Patients were enrolled over the course of one year. To assess the primary endpoint (reduction in muscle mass and strength), muscle strength and mass were monitored before and after therapy using wrist dynamometry, the time-up-and-go test, and bioimpedancemetry. Polymorphic variants of the glucocorticoid receptor gene NR3C1, the FTO gene, and the melatonin receptor genes MTNR1A and MTNR1B were identified by real-time polymerase chain reaction. Intergenic interactions were evaluated using the multifactor dimensionality reduction (MDR) method. R (v. 3.2, R Foundation for Statistical Computing, Austria) was used for statistical analysis. RESULTS: In women with loss of muscle mass after corticosteroid therapy, there was an increased incidence of depression (p=0.01) for polymorphic variant BclI (rs41423247) of the NR3C1 gene (p=0.005). Reduced dominant arm strength in women was associated with a variant of the BclI gene (rs41423247) (p=0.02), genotypes including BclI (rs41423247) and N363S (rs56149945) (p=0.03). Men with decreased strength in the non-dominant arm were more likely to be smokers (p=0.03). Combinations of genotypes of the NR3C1, FTO, MTNR1B genes were identified with increased and decreased risk of muscle mass loss in women after corticosteroid therapy. Analysis of intergenic interactions showed a strong synergism between the polymorphic variant rs993960 of the FTO gene and rs10830963 of the MTNR1B gene. CONCLUSION: The presence of polymorphic variants BclI (rs41423247), N363S (rs56149945) of the glucocorticoid receptor gene NR3C1 is associated with loss of muscle strength and mass in women receiving corticosteroid therapy for MS. Combinations of genotypes of the NR3C1, FTO, MTNR1B genes have been identified with an increased risk of muscle mass loss in women after corticosteroid therapy. Modifiable factors associated with loss of muscle mass and strength and cardiovascular risk (depression, smoking) were identified. The data obtained can be used to personalize corticosteroid therapy and prevent cardiovascular and metabolic disorders.

FRI0631-HPR SUPPLEMENTATION WITH CREATININE, GLUTAMINE AND Β-HYDROXY-Β-METHYLBUTYRATE IMPROVES MUSCLE MASS AND STRENGTH AND QUALITY OF LIFE IN PATIENTS WITH SARCOPENIA AND KNEE OSTEOARTHRITIS: THE DIMMUS RANDOMIZED STUDY

Sarcopenia is characterized by a loss of skeletal muscle mass, a decrease in muscle strength and/or physical performance, and is one of the main causes for limiting daily activities in the elderly. This is associated with an increased incidence of many adverse events such as dysfunction, falls, frailty, hospitalization, disability, and mortality. Primary (considered as a part of the aging process) and secondary sarcopenia (due to malabsorption, immobility/bed rest, starvation, hypothyroidism, osteoporosis, immune-mediated rheumatic diseases) are united by a chronic inflammatory process of different degrees. Sarcopenia supports one of the most widely accepted theories that low-grade chronic inflammation is important in the pathogenesis of many diseases. For a long time, sarcopenia was considered an age-related disease, but recently it has been reported to be more common in young subjects with autoimmune diseases. In particular, the relationship between sarcopenia and rheumatic diseases such as rheumatoid arthritis has been studied in detail. Although the pathogenesis of sarcopenia in autoimmune diseases is not fully understood, it is believed that a chronic inflammatory process contributes to the development of loss of muscle mass and strength, and is different depending on the underlying disease. The definition of sarcopenia varies between studies, which complicates and limits direct comparisons. Therefore, in this review, we demonstrate various diagnostic criteria for sarcopenia, focusing on its prevalence in patients with rheumatic diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, axial spondylitis, psoriatic arthritis, and systemic sclerosis. We developed a structured search strategy for English language publications in PubMed using the term “sarcopenia” in combination with the following keywords: “inflammation”, “diagnosis”, “criteria”, “muscle mass”, “strength”, “outcomes”, “disability”, “mortality”, “pathophysiology”, “rheumatoid arthritis”, “juvenile arthritis”, “axial spondylitis”, “psoriatic arthritis”, “systemic sclerosis”. We focused on clinical trials, meta-analyses and review articles. Articles published only after 2000 year were included, however, we did not include major contributions published before. The search was completed on October 8, 2022.

BackgroundSarcopenia, the progressive loss of muscle mass and strength, is a significant complication in type 2 diabetes mellitus (T2DM) that worsens insulin resistance and glycemic control. Techniques such as a bioimpedance analyzer, handgrip strength (HGS) tests, and gait speed assessments serve to assess sarcopenia.AimThe aim of this study was to determine the proportion of T2DM patients with sarcopenia (T2DMS+) compared with non-diabetic patients and assess the association between sarcopenia and obesity in T2DM patients.Materials and methodsFor this observational cross-sectional study, all diabetic and non-diabetic male and female patients in the age group of 18-60 years were recruited during their routine outpatient visits. Sarcopenia was assessed using a bioimpedance analyzer for muscle mass, a handgrip dynamometer for muscle strength, and the Short Physical Performance Battery (SPPB) score for physical performance.Observation and resultsThis study compared the prevalence and impact of sarcopenia in T2DM patients and non-diabetic patients. The study population included 100 T2DM patients and 100 controls. The mean age of the T2DM group (T2DMG) was 47.79 ± 8.64 years, slightly higher than that of the control group (CG), which was 44.31 ± 9.56 years. The gender distribution was consistent, with 70% (n = 70) of female patients and 30% (n = 30) of male patients in both groups. The body mass index (BMI) was similar between the T2DMG (25.9 ± 4.91 kg/m²) and the CG (26.76 ± 5.84 kg/m², p = 0.10). Hemoglobin A1c (HbA1c) levels were markedly higher in the T2DMG (8.05 ± 1.47%) compared with the CG (5.52 ± 0.65%, p < 0.05). Sarcopenia was significantly more prevalent in the T2DM group (53%, n = 53/100) than in the control group (17%, n = 17/100) with an odds ratio of 5.54 (95% confidence interval (CI): 2.84-10.81, p < 0.001), and more frequent in obese diabetics (64.15%, n = 34/53) compared to non-obese diabetics (35.85%, n = 19/53) with an odds ratio of 3.41 (95% CI: 1.38-8.39, p = 0.0001). Compared with the non-sarcopenic T2DM patients (47%, n = 47), sarcopenic T2DM patients (53%, n = 53) were older (52 ± 7.61 years and 43.02 ± 7.17 years, respectively, p < 0.05) and had longer diabetes duration (8.45 ± 5.45 years, p < 0.05). The sarcopenic T2DM patients also had less appendicular lean mass (ALM) (18.5 ± 4.14 kg compared with 21.19 ± 3.95 kg, p < 0.0014), reduced HGS (14.97 ± 3.83 kg compared with 25.78 ± 4.34 kg, p < 0.05), lower SPPB scores (6.49 ± 1.4 compared with 10.06 ± 0.76, p < 0.05), and higher HbA1c (8.54 ± 1% compared with 7.5 ± 1.47%, p = 0.00037).ConclusionT2DM patients exhibited lower appendicular lean mass, muscle strength, and physical performance, and had significantly lower handgrip strength and SPPB scores than the non-sarcopenic T2DM patients. Further, sarcopenia was more pronounced in the older patients and those with a longer duration of diabetes.

Background/Objectives: Sarcopenia is the progressive loss of muscle mass, strength, and/or function, leading to reduced physical performance, independence, and social participation. This study aimed to analyze the effects of age-related muscle strength loss and sarcopenia on muscle function during standing in older females. Methods: This study included experimental and modeling analyses using the AnyBody Modeling System in 20 older females. Based on DEXA results, participants were divided into older females without sarcopenia (OF) and with sarcopenia (OFS). Body posture while standing was assessed using the Zebris APGMS Pointer system. A model of muscular strength changes due to natural aging and progressive sarcopenia was developed based on literature data. The experimental results informed model studies in the AnyBody Modeling System, which incorporated changes in body posture and loss of muscle strength. Results: Total muscle activity during standing increases with age; however, this increase is significantly more pronounced in individuals with sarcopenia, especially after the age of 65. At 65, total muscle activity was 15% higher in the OFS model than in the OF model, while the difference was 44% at 80. After age 65, muscle fatigue increased considerably with progressive sarcopenia. At age 80, muscle fatigue while standing with sarcopenia can be more than three times higher than in those without sarcopenia. Conclusions: Aging leads to increased muscle activity while standing, and sarcopenia further amplifies this effect, particularly in individuals over 65. Modeling results highlight the pronounced impact of sarcopenia on muscle fatigue, demonstrating its significant functional consequences in older females.

Protein supplementation alone or combined with exercise for sarcopenia and physical frailty: A systematic review and meta-analysis of randomized controlled trials.

Sarcopenia is a complex, multifactorial condition characterized by progressive loss of muscle mass, strength, and function. Despite growing awareness, the early diagnosis and pathophysiological characterization of this condition remain challenging due to the lack of integrative biomarkers. This study aimed to conduct a comprehensive multilevel profiling of clinical parameters, immune cell phenotypes, extracellular vesicle (EV) signatures, and biochemical markers to elucidate biological gradients associated with different stages of sarcopenia. A prospective cohort study enrolled adults aged 45-85 years classified as control, presarcopenic, or sarcopenic based on European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. Clinical evaluation included anthropometry, muscle strength, sarcopenia screening (SARC-F) questionnaire/Short Physical Performance Battery (SPPB) questionnaires, and quality-of-life assessment. Flow cytometry was used to characterize blood monocyte/macrophage subsets (cluster of differentiation 14 (CD14), CD68, CD163, CD206). EVs were isolated from plasma and profiled for surface tetraspanins and matrix metalloproteinases (MMP2, MMP9, tissue inhibitor of metalloproteinase-1 (TIMP-1)) using bead-based flow cytometry. Biochemical assays measured metabolic, inflammatory, and extracellular matrix (ECM)-related markers. Data were analyzed via Kruskal-Wallis testing, discriminant analysis, and principal component analysis (PCA). Sarcopenia, a muscle-wasting condition linked to aging, is characterized by chronic inflammation, proteolytic imbalance, and metabolic disturbances. Clinical deterioration is evident through reduced appendicular lean mass (ALM), appendicular skeletal muscle index (ASMI), SPPB scores, and sarcopenia quality of life (SarQoL) domains. Principal component analysis (PCA) identified four functional marker clusters: ECM degradation (MMP-positive EVs), inflammatory and homeostasis-stabilizing macrophages, and metabolic disruption (glucose, asprosin, triglycerides). Discriminant analysis emphasized vesicular and immune markers with significant classification potential, even when univariate differences were non-significant. Metabolic destabilization and inflammatory activation are detectable in presarcopenia stages. Chronic inflammation, characterized by CD14-CD163+206+ cells releasing pro-inflammatory cytokines, accelerates muscle degradation. Proteolytic dysfunction, with an imbalance between proteases and inhibitors, further contributes to muscle loss. Metabolic disorders impair energy production and nutrient utilization, exacerbating muscle wasting. A comprehensive assessment, including anthropometric, functional, physical activity, and QoL measures, is crucial for identifying high-risk individuals and understanding sarcopenia's mechanisms. Vesicular biomarkers, regulating tissue remodeling and inflammation, provide valuable insights. Standardized assessment methods are essential for enhancing diagnostic accuracy and intervention effectiveness. Future research should focus on developing and refining biomarkers to improve specificity and sensitivity, enabling targeted therapies and better QoL. Integrating clinical, immunological, and biochemical markers with EVs helps stratify sarcopenia effectively. Our data shows that EVs and macrophage profiles reflect systemic changes and metabolic stress. However, age- and gender-related variability in our cohort warrants caution in generalizing the findings. Artificial intelligence (AI) enhances patient clustering by combining these data types, enabling precise, personalized sarcopenia management, predicting disease progression, and identifying high-risk patients. AI also standardizes and optimizes analytical protocols, improving diagnostic and monitoring reliability and reproducibility.