Primary Sarcopenia Research Articles

Neurological Aspects of Sarcopenia: A Comprehensive Update on Pathophysiology, Diagnosis, and Therapeutic Advances

Sarcopenia is an age-related disorder characterized by progressive and generalized loss of skeletal muscle tissue. This condition affects approximately 9.9-40.4% of older adults, 2-34% of outpatients, and about 56% of hospitalized patients. Sarcopenia is classified into primary and secondary types, with primary sarcopenia resulting from the natural aging process and secondary sarcopenia caused by various factors such as sedentary lifestyle, disease, and nutrition. The pathophysiology of sarcopenia involves cellular mechanisms, including genetic alterations, telomere erosion, and proteostasis disruption. Mitochondrial dysfunction, epigenetic modifications, and metabolic factors also contribute to the condition. Neurological aspects, such as motor neuron loss and sodium channel dysfunction, play a crucial role in the development of sarcopenia. Prevention and treatment strategies include exercise interventions, nutritional strategies, and pharmacological interventions. Vitamin D supplementation, testosterone replacement therapy, and selective androgen receptor modulators (SARMs) are among the treatments explored. However, these treatments come with potential

Possible Extracellular Signals to Ameliorate Sarcopenia in Response to Medium-Chain Triglycerides (8:0 and 10:0) in Frail Older Adults.

In frail older adults (mean age 85 years old), a 3-month supplementation with a low dose (6 g/day) of medium-chain triglycerides (MCTs; C8:0 and C10:0) given at a meal increased muscle mass and function, relative to supplementation with long-chain triglycerides (LCTs), but it decreased fat mass. The reduction in fat mass was partly due to increased postprandial energy expenditure by stimulation of the sympathetic nervous system (SNS). However, the extracellular signals to ameliorate sarcopenia are unclear. The following three potential extracellular signals to increase muscle mass and function after MCT supplementation are discussed: (1) Activating SNS-the hypothesis for this is based on evidence that a beta2-adrenergic receptor agonist acutely (1-24 h) markedly upregulates isoforms of peroxisomal proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) mRNAs, promotes mitochondrial biogenesis, and chronically (~1 month) induces muscle hypertrophy. (2) An increased concentration of plasma acyl-ghrelin stimulates growth hormone secretion. (3) A nitrogen-sparing effect of ketone bodies, which fuel skeletal muscle, may promote muscle protein synthesis and prevent muscle protein breakdown. This review will help guide clinical trials of using MCTs to treat primary (age-related) sarcopenia.

Insights into geriatric health: primary sarcopenia and innate immunity dynamics, examining SARC-F, serum TLR 4, TLR 9, and resolvin levels

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

Sarcopenia and Dinapenia in Patients with Ulcerative Colitis (Cross-Sectional Observational Study)

Background. Sarcopenia is a generalised, progressive decline in skeletal muscle mass, strength and performance leading to reduced quality of life, increased risk of falls, hospitalisation and mortality. Primary sarcopenia results from age-related changes in muscle tissue. In certain cases, sarcopenia develops secondary as a consequence of diseases including ulcerative colitis (UC), which is associated with a systemic inflammatory process, malabsorption syndrome, restriction of patients’ physical activity and nutrient deficiencies. The term “dynapenia” or “probable sarcopenia” has been proposed to describe the decrease in muscle strength. Studies have demonstrated that muscle strength is a more relevant marker for predicting adverse outcomes because its measurement is more practical, whereas muscle mass is technically difficult to measure. Aims — to increase the effectiveness of the diagnosis of dinapenia, to assess the prevalence and risk factors of its formation in patients with UC. Methods. A single-centre, observational cross-sectional study included 80 UC patients. To identify factors associated with the development of dinapenia, patients with dinapenia were compared with patients without dinapenia. The investigated parameters in patients: sex, age, body mass index, peculiarities of the course of the disease, ongoing treatment, concomitant pathology, peculiarities of nutrition, nutritional deficiency, malabsorption syndrome, bad habits, psychological stress and sleep duration, physical activity, laboratory indicators of inflammation, myokine-adipokine profile. Statistical parameters were calculated using Statistica 10.0.1011.0 programme. Results. Dinapenia is present in 32.5% of UC patients. Risk factors for the formation of dinapenia in UC patients include female sex (p = 0.0003); nutritional insufficiency (p = 0.021); low physical activity (p = 0.010); artificial feeding in infancy (p = 0.024); inflammation, namely C-reactive protein, autoantibodies of class G against double-stranded DNA (p = 0.006; p = 0.002 respectively). Patients with UC with dinapenia significantly more often gave a positive answer to the questionnaire question “Does daily activity cause you a lot of stress?” (p = 0.048). In the group of UC patients with dinapenia, the level of cortisol in evening saliva was significantly higher than in the comparison group (p = 0.005). Conclusions. Sarcopenia and UC are multifactorial conditions with common developmental mechanisms that can burden each other. Dynamometry is not technically difficult and is justified from an economic point of view. The timely detection of dinapenia and its correction will additionally affect the mechanisms of UC pathogenesis in order to improve the quality of life and prognosis of patients.

#2439 The association between vitamin D deficiency and sarcopenia in patients with pre-dialysis CKD

Abstract Background and Aims Sarcopenia is characterized by a progressive and widespread loss of skeletal muscle, leading to muscle weakness and frailty. While primary sarcopenia is linked to aging, secondary sarcopenia can independently occur, especially in chronic conditions like chronic kidney disease (CKD). Investigating sarcopenia in CKD patients has become a focal point in research due to its significant impact on the quality of life, morbidity, and mortality of these individuals. Despite reports connecting vitamin D deficiency, prevalent in CKD, to sarcopenia in the general population, there is limited information regarding the specific relationship between vitamin D and sarcopenia in CKD. This study aims to explore the association between vitamin D deficiency and sarcopenia in patients with pre-dialysis CKD. Method This cross-sectional study enrolled 569 patients with pre-dialysis chronic kidney disease (CKD), defined as having an estimated glomerular filtration rate (eGFR) less than 60 ml/min/m2. Sarcopenia was assessed using computed tomography (CT)-derived skeletal muscle index (SMI), calculated based on the cross-sectional area of skeletal muscles at the 3rd lumbar vertebra. Using Korean-specific SMI cutoffs, patients were categorized into sarcopenic and non-sarcopenic groups. Logistic regression analyses were employed to explore associations between sarcopenia and baseline variables, including active vitamin D, specifically 1,25-dihydroxyvitamin D [1,25(OH)2D] level. Results Among the 569 patients, 278 had CKD stage 3, 198 had CKD stage 4, and 93 had CKD stage 5. The prevalence of sarcopenia increased with advancing CKD stage (CKD stage 3 vs. stage 4 vs. stage 5: 20.1% vs. 31.3% vs. 41.9%, P &amp;lt; 0.001). Univariate logistic regression analysis revealed an association between 1,25(OH)2D levels and sarcopenia. Additionally, age, male sex, diabetes, body mass index, eGFR, urinary albumin excretion levels, and serum levels of albumin, high-sensitive C-reactive protein (hsCRP), and intact parathyroid hormone were associated with sarcopenia. In multivariable logistic regression analysis, 1,25(OH)2D levels remained independently associated with sarcopenia (per 1 pg/dl increase, odds ratio [OR]: 0.84; 95% confidence interval [CI]: 0.80–0.87, P &amp;lt; 0.001). Age (per 1 year increase, OR: 1.04, 95% CI: 1.02–1.07, P &amp;lt; 0.001), diabetes (vs. non-diabetes, OR: 2.33, 95% CI: 1.39–3.89, P = 0.001), serum albumin (per 1 mg/dl increase, OR: 0.39, 95% CI: 0.22–0.71, P = 0.0023), and hsCRP (per 1 mg/dl increase, OR: 1.91, 95% CI: 1.25–2.92, P = 0.003) were also independently associated with sarcopenia. Conclusion This study revealed an independent association between 1,25(OH)2D levels and sarcopenia derived from CT scans in pre-dialysis CKD patients. This association retained significance even after adjusting for traditional risk factors for sarcopenia, such as age, diabetes, serum albumin, and hsCRP. Further prospective studies are necessary to determine whether therapy with exogenous 1,25(OH)2D drugs can improve sarcopenia in these patients.

Primary sarcopenia is associated with elevated spontaneous NET formation.

Introduction: Sarcopenia is a frequent complication of liver cirrhosis, but it can also occur independently as a result of any underlying cause. The immune system plays an important role in the pathogenesis of both liver cirrhosis and sarcopenia. Neutrophil function, including neutrophil extracellular trap (NET) formation, is linked to chronic inflammation; however, it has not been extensively studied in patients with sarcopenia. Here, we aim to study if main neutrophil functions, such as phagocytosis, reactive oxygen species (ROS) production, and NET formation, are altered in patients with sarcopenia with or without liver cirrhosis. Methods: Neutrophils from 92 patients (52 patients with liver cirrhosis and sarcopenia, 25 patients with liver cirrhosis without sarcopenia, and 15 patients with sarcopenia without liver cirrhosis) and 10 healthy controls were isolated and stimulated with heat-inactivated E. coli (250 bacteria/cell), phorbol 12-myristate 13-acetate (PMA) (100nM), or incubation medium in duplicates for 2h at 37°C. Cells were fixed with paraformaldehyde and stained with 4',6-diamidino-2-phenylindole (DAPI). Pictures of 10 random fields of vision per slide were taken with an Olympus BX51 fluorescence microscope (Olympus, Shinjuku, Tokyo, Japan) at 600x total magnification. The DNA Area and NETosis Analysis (DANA) algorithm was used to quantify the percentage of NET formation per patient. Phagocytosis and ROS production were assessed with the PhagotestTM kit and PhagoburstTM kit (Glycotope, Heidelberg, Germany) in 92 patients and 21 healthy controls, respectively. Results: Spontaneous NET formation was significantly elevated in patients with only sarcopenia compared to patients with cirrhosis and sarcopenia (p = 0.008) and healthy controls (p = 0.039). NET formation in response to PMA was significantly decreased in patients with cirrhosis (p = 0.007), cirrhosis and sarcopenia (p < 0.001), and sarcopenia (p = 0.002) compared to healthy controls. There was no significant difference in NET formation in response to E. coli between the groups. The DANA algorithm was successfully optimized and validated for assessment of clinical samples. There were no significant changes in neutrophil phagocytosis between patients' groups compared to healthy controls. A significantly lower percentage of neutrophils produced ROS in response to N-formylmethionine-leucyl-phenylalanine (fMLF) in patients compared to healthy controls. Discussion: Spontaneous NET formation might contribute to chronic inflammation and sarcopenia pathogenesis. This, however, does not result in the impairment of the NET formation function of neutrophils in response to a bacterial stimulus and, therefore, cannot be not linked with the increased risk of bacterial infections neither in sarcopenia nor in cirrhosis. The semi-automated NET formation analysis can be successfully implemented to analyze the vast amount of data generated within clinical studies. This approach opens up the possibilities to develop an NET formation-based biomarker in different diseases including sarcopenia and implement NET formation analysis into clinical settings. Phagocytosis and ROS production were not affected in patients with sarcopenia. Further research is needed to explore the mechanism of NET formation in patients with sarcopenia and its potential as a biomarker in sarcopenia.

Sarcopenia in children: Lecture

Primary sarcopenia characterizes frailty of old age. Secondary sarcopenia can occur in both adults and children with severe somatic or surgical pathology. A model for studying sarcopenia in children can be patients with cerebral palsy, whose muscle development differs from typically developing children. The lecture presents the mechanism of the development of sarcopenia, diagnostic criteria for adult patients presented in consent documents, as well as analogues of diagnostic scales used in pediatric practice. The diagnosis of sarcopenia in children has something in common with the diagnosis of the patient’s nutritional status. Diagnosis of sarcopenia in children using bioimpedansometry method was proposed by the authors, and a Eurasian patent was received. Based on the volumes of adipose and active cellular tissue in the component composition of the body: with a combination of a percentage of fat mass of 40.5% and above and a percentage of active cell mass of 37% and below, sarcopenia is diagnosed, and with a combination of a percentage of fat mass of 30.5% and above and percentage of active cell mass from 37% to 43.5% is diagnosed as presarcopenia. Options for preventing sarcopenia are presented, including patented ones. A multidisciplinary approach to working with a patient with sarcopenia includes, while treating the underlying disease, nutritious nutrition, restoration of the intestinal microflora and motor activity of the patient.

Prevalence of sarcopenia in patients with chronic kidney disease: a global systematic review and meta-analysis.

Sarcopenia is a risk factor for adverse clinical outcomes in chronic kidney disease (CKD) patients, including mortality. Diagnosis depends on adopted consensus definition and cutoff values; thus, prevalence rates are generally heterogeneous. We conducted a systematic review and meta-analysis to investigate the global prevalence of sarcopenia and its traits across the wide spectrum of CKD. A systematic search was conducted using databases, including MEDLINE and EMBASE, for observational studies reporting the prevalence of sarcopenia. We considered sarcopenia according to the consensus definition of the European Working Group on Sarcopenia in Older People (EWGSOP), the Asian Working Group for Sarcopenia, the Foundation for the National Institutes of Health Sarcopenia Project, and the International Working Group on Sarcopenia (IWGS). Subgroup analyses by CKD stages, consensus, and gender were performed. Pooled prevalence was obtained from random-effect models. A total of 140 studies (42041 patients) across 25 countries were included in this systematic review and meta-analyses. Global prevalence of sarcopenia was 24.5% [95% confidence interval (CI): 20.9-28.3) and did not differ among stages (P=0.33). Prevalence varied according to the consensus definition from 11% to 30%, with no significant difference (P=0.42). Prevalence of severe sarcopenia was 21.0% (95% CI: 11.7-32.0), with higher rates for patients on dialysis (26.2%, 95% CI: 16.6-37.1) compared to non-dialysis (3.0%, 95% CI: 0-11.1; P<0.01). Sarcopenic obesity was observed in 10.8% (95% CI: 3.5-21.2). Regarding sarcopenia traits, low muscle strength was found in 43.4% (95%CI: 35.0-51.9), low muscle mass in 29.1% (95% CI: 23.9-34.5), and low physical performance in 38.6 (95% CI: 30.9-46.6) for overall CKD. Prevalence was only higher in patients on dialysis (50.0%, 95% CI: 41.7-57.4) compared to non-dialysis (19.6%, 95% CI: 12.8-27.3; P<0.01) for low muscle strength. We found a high global prevalence of sarcopenia in the wide spectrum of CKD. Low muscle strength, the primary sarcopenia trait, was found in almost half of the overall population with CKD. Patients on dialysis were more prevalent to low muscle strength and severe sarcopenia. Nephrology professionals should be aware of regularly assessing sarcopenia and its traits in patients with CKD, especially those on dialysis.

Body Composition in Chronic Liver Disease.

Body composition has recently been attracting people's attention, not only from a cosmetic standpoint but also from the perspective of health and longevity. The body is classified into three components: fat, bone, and lean soft tissue, and it is common to see an increase in body fat and a decrease in total body muscle mass with aging. Aging-related loss of muscle mass and muscle function is referred to as primary sarcopenia, while sarcopenia caused by disease-specific conditions is referred to as secondary sarcopenia. On the other hand, the liver-muscle axis has been attracting attention in recent years, and it has become clear that the liver and the skeletal muscles interact with each other. In particular, patients with cirrhosis are prone to secondary sarcopenia due to protein-energy malnutrition, which is a characteristic pathophysiology of the disease, suggesting the importance of the organ-organ network. In this review, we would like to outline the latest findings in this field, with a focus on body composition in liver diseases such as liver cirrhosis, fatty liver disease, alcoholic liver disease, and hepatocellular carcinoma.

Systemic inflammatory response index and monocyte-to-high density lipoprotein ratio- new biomarkers remarking the inflammation in primary sarcopenia: The SIMPS study.

To investigate the relationship of sarcopenia with systemic inflammation response index (SIRI), monocyte to high-density lipoprotein ratio (MHR) and platelet parameters in geriatric patients. We designed across-sectional retrospective study in patients presented to ageriatric outpatient clinic for the first time. The diagnosis of sarcopenia was made in accordance with the EWGSOP2 criteria. SIRI, MHR, mean platelet volume /Platelet count (MPV/Plt), platelet distribution width /Platelet (PDW/Plt), platelet/lymphocyte ratio (PLR) were calculated from fasting blood test results at the time of admission. Among 262 patients, 79 patients (30.1%) with sarcopenia had significantly higher frequencies of delirium, hypothyroidism, chronic kidney disease and probable depression (p=0.010; p=0.018; p=0.034; p<0.001). Malnutrition scores and cognitive impairment scores were significantly lower in sarcopenic group (p<0.001 for both). Patients with sarcopenia had significantly higher MHR, SIRI and C-reactive protein values than patients without sarcopenia (p<0.001; p=0.001 and p=0.006, respectively). No significant difference was found between the groups in terms of MPV/Plt, PDW/Plt, PLR (p=0.605; p=0.920; p=0.510). Area under the curve for MHR was 0.675 (95% CI: 0.604-0.746, p0.99. The finding of higher MHR and SIRI in geriatric sarcopenia patients supports low-grade chronic inflammation in the pathophysiology of sarcopenia. These non-invasive, cost-effective and simple parameters based on traditional peripheral blood cell counts may be warning signs for sarcopenia in the geriatric population (Tab. 3, Fig. 1, Ref. 25). Text in PDF www.elis.sk Keywords: primary sarcopenia, inflammation, systemic inflammation response index, monocyte/high-density lipoprotein ratio, platelet parameters.

Causes and Implications of Type I Myofiber Grouping in Parkinson's Disease: A Brief Scoping Review

Purpose: The purpose of this study was to review the alterations in muscle fibers in Parkinson's disease(PD). The following were our review questions. (1)How has research on type I myofiber grouping in PD developed over time? (2)What kinds of muscles are affected in which patients? (3)What are some possible pathophysiology and mechanisms? Does type I myofiber grouping in PD differ from primary sarcopenia that occurs with aging? (4)What are the clinical implications and possible therapeutic approaches for type I myofiber grouping in PD?.&#x0D; Method: To investigate the questions, we used combinations of keywords such as “Parkinson”, “skeletal muscle”, “myofiber type”, “fast twitch”, “slow twitch”, “myofiber grouping”, and “motor unit” in PubMed and Google Scholar. Articles on PD patients and normal elderlies that dealt with type I myofiber grouping and motor unit alterations were included. References in the included articles were also considered.&#x0D; Results: Research over the past five decades has identified various motor abnormalities and myofiber alterations in PD patients, including the hypertrophy of slow-twitch type I myofibers and atrophy of fast-twitch type II myofibers across different muscles. One important finding is that Type I myofiber grouping, which is common in aging, is more severe in PD, which could be due to the selective activation of low-threshold motor units and could be also linked to abnormal alpha-synuclein aggregation, a factor associated with PD.&#x0D; Conclusion: Research suggests that type I myofiber grouping in muscles, not just dopaminergic cell damage in the substantia nigra, could influence motor symptoms of PD, indicating that alternative treatments beyond dopaminergic drugs, such as high-intensity exercise, might be beneficial. However, given the limitations in these studies, such as small participant numbers and the complexity of PD pathophysiology, future research is needed to fully understand the phenomena in different PD subtypes and to develop more effective treatments.

366. SARCOPENIA DECIDED FROM LOWER PSOAS MUSCLE INDEX IS STRONGLY POOR PROGNOSTIC FACTOR FOR ELDERLY ESOPHAGEAL CANCER PATIENTS

Abstract Background Elderly esophageal cancer patients undergoing esophagectomy are increasing. Although esophageal cancer patients suffering sarcopenia are already well known to have poor prognosis, the impact of sarcopenia for each age group may differ, since older patients have a higher frequency of primary sarcopenia than younger patients. Methods To clarify the relationship between sarcopenia and surgical outcomes in elderly esophageal cancer patients, we measured the psoas muscle index (PMI) in 103 elderly esophageal cancer patients aged 75 years or older who underwent radical esophagectomy from 2007 to 2021. The patients were then classified into two groups, sarcopenia group and non-sarcopenia group, using the 25th percentile of PMI as a cut-off value, and the relationship with outcomes of surgery and neoadjuvant chemotherapy (NAC) was examined. Results The 103 patients included 83 males and 20 females. The sarcopenia group had significantly lower BMI, but there was no correlation with oncological factors such as tumor depth or lymph node metastasis. NAC (FP) was performed in 39 patients and there was no clear correlation between completion, efficacy, or adverse events and sarcopenia. Thoracoscopic esophagectomy was performed in 93 patients, and there was no clear correlation between short-term surgical outcomes and sarcopenia. However, the 5-year overall survival and 5-year disease free survival were significantly lower in the sarcopenia group, resulted sarcopenia was an independent poor prognostic factor. Conclusion In elderly esophageal cancer patients over 75-year-old who underwent radical esophagectomy, sarcopenia does not significantly affect short-term surgical outcomes, and NAC is possibly able to administer as in the non-sarcopenia group. However, the indication of surgery to sarcopenic patients should be carefully decided because they have worse long-term prognosis than non-sarcopenic patients.

Is dexamethasone-induced muscle atrophy an alternative model for naturally aged sarcopenia model?

Primary sarcopenia is usually known as age-related skeletal muscle loss; however, other factors like endocrine, lifestyle and inflammation can also cause muscle loss, known as secondary sarcopenia. Although many studies have used different sarcopenia animal models for exploring the underlying mechanism and therapeutic approaches for sarcopenia, limited study has provided evidence of the relevance of these animal models. This study aims to investigate the similarity and difference in muscle qualities between primary and secondary sarcopenia mice models, using naturally aged mice and dexamethasone-induced mice. 21-month-old mice were used as naturally aged primary sarcopenia mice and 3-month-old mice received daily intraperitoneal injection of dexamethasone (20 mg/ kg body weight) for 10 days were used as secondary sarcopenia model. This study provided measurements for muscle mass and functions, including Dual-energy X-ray absorptiometry (DXA) scanning, handgrip strength test and treadmill running to exhaustion test. Besides, muscle contraction, muscle fibre type measurements and gene expression were also performed to provide additional information on muscle qualities. The results suggest two sarcopenia animal models shared a comparable decrease in forelimb lean mass, muscle fibre size, grip strength and muscle contraction ability. Besides, the upregulation of protein degradation genes was also observed in two sarcopenia animal models. However, only primary sarcopenia mice were identified with an early stage of mtDNA deletion. Collectively, this study evaluated that the dexamethasone-induced mouse model could be served as an alternative model for primary sarcopenia, according to the comparable muscle mass and functional changes. However, whether dexamethasone-induced mice can be used as an animal model when studying the molecular mechanisms of sarcopenia needs to be carefully evaluated. The purpose of sarcopenia research is to investigate appropriate treatments for reversing the loss of skeletal muscle mass and functions. Using animal models for the preclinical study could predict the safety and efficacy of the treatments. This study compared the typical age-related sarcopenia mice model and dexamethasone-induced secondary sarcopenia mice to provide evidence of the pathological and functional changes in the mice models.

Gene polymorphisms associated with heterogeneity and senescence characteristics of sarcopenia in chronic obstructive pulmonary disease.

Sarcopenia, or loss of skeletal muscle mass and decreased contractile strength, contributes to morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). The severity of sarcopenia in COPD is variable, and there are limited data to explain phenotype heterogeneity. Others have shown that COPD patients with sarcopenia have several hallmarks of cellular senescence, a potential mechanism of primary (age-related) sarcopenia. We tested if genetic contributors explain the variability in sarcopenic phenotype and accelerated senescence in COPD. To identify gene variants [single nucleotide polymorphisms (SNPs)] associated with sarcopenia in COPD, we performed a genome-wide association study (GWAS) of fat free mass index (FFMI) in 32 426 non-Hispanic White (NHW) UK Biobank participants with COPD. Several SNPs within the fat mass and obesity-associated (FTO) gene were associated with sarcopenia that were validated in an independent COPDGene cohort (n=3656). Leucocyte telomere length quantified in the UK Biobank cohort was used as a marker of senescence. Experimental validation was done by genetic depletion of FTO in murine skeletal myotubes exposed to prolonged intermittent hypoxia or chronic hypoxia because hypoxia contributes to sarcopenia in COPD. Molecular biomarkers for senescence were also quantified with FTO depletion in murine myotubes. Multiple SNPs located in the FTO gene were associated with sarcopenia in addition to novel SNPs both within and in proximity to the gene AC090771.2, which transcribes long non-coding RNA (lncRNA). To replicate our findings, we performed a GWAS of FFMI in NHW subjects from COPDGene. The SNP most significantly associated with FFMI was on chromosome (chr) 16, rs1558902A>T in the FTO gene (β=0.151, SE=0.021, P=1.40×10-12 for UK Biobank |β=0.220, SE=0.041, P=9.99×10-8 for COPDGene) and chr 18 SNP rs11664369C>T nearest to the AC090771.2 gene (β=0.129, SE=0.024, P=4.64×10-8 for UK Biobank |β=0.203, SE=0.045, P=6.38×10-6 for COPDGene). Lower handgrip strength, a measure of muscle strength, but not FFMI was associated with reduced telomere length in the UK Biobank. Experimentally, in vitro knockdown of FTO lowered myotube diameter and induced a senescence-associated molecular phenotype, which was worsened by prolonged intermittent hypoxia and chronic hypoxia. Genetic polymorphisms of FTO and AC090771.2 were associated with sarcopenia in COPD in independent cohorts. Knockdown of FTO in murine myotubes caused a molecular phenotype consistent with senescence that was exacerbated by hypoxia, a common condition in COPD. Genetic variation may interact with hypoxia and contribute to variable severity of sarcopenia and skeletal muscle molecular senescence phenotype in COPD.

Comparative Analysis on the Effect of Sarcopenia in Patients with Knee Osteoarthritis before and after Total Knee Arthroplasty.

Primary sarcopenia is an age-related disease that occurs mainly in older adults, while its possibility of appearance increases with age. Secondary sarcopenia is related to the presence of a disease. At times, studies have implied a connection between various diseases and the appearance of sarcopenia. Due to pain, patients with knee osteoarthritis limit their everyday activities, leading to a decrease in muscle mass and physical function. This study aimed to investigate the impact of the coexistence of sarcopenia and osteoarthritis on patients' rehabilitation and symptoms, such as pain, after total knee arthroplasty, compared with patients with osteoarthritis without sarcopenia. This cross-sectional study material consisted of 20 patients with osteoarthritis, who were hospitalized at Papageorgiou Hospital of Thessaloniki for total knee arthroplasty from November 2021 to April 2022. The patients were evaluated for sarcopenia according to the FNIH criteria. The two groups were asked to complete the KOOS score questionnaire in order to evaluate the condition of their knee in two phases, before surgery and 3 months after surgery. The two groups, 5 sarcopenic patients and 15 non-sarcopenic, did not show a statistically significant difference in muscle strength measurements. However, the lean mass indices, ALM (15.18 ± 3.98 versus 19.96 ± 3.65, respectively; p = 0.023) and ALM/height2 (5.53 ± 1.40 versus 6.98 ± 0.75, respectively; p = 0.007) had significant differences, since the sarcopenic group showed a reduced lean mass, especially in patients with a comorbidity of cancer. Sarcopenic patients showed a smaller increase in KOOS score compared to non-sarcopenic patients before (0.38 ± 0.09 vs. 0.35 ± 0.09, respectively; p = 0.312) and after surgery (0.54 ± 0.08 vs. 0.59 ± 0.10, respectively; p = 0.909), but without a statistically significant difference. The score increased for both groups, with the time factor playing a greater role than the group. Both the sarcopenic group and the control group did not show significant differences in their scores for the assessment of the affected limb in any of the two phases while completing the questionnaire. However, there was an improvement in their osteoarthritis symptoms before and after arthroplasty in both groups. Further research with a larger sample and longer recovery time is needed to draw more accurate conclusions and confirm the present results.

Irisin ameliorates D-galactose-induced skeletal muscle fibrosis via the PI3K/Akt pathway

Primary sarcopenia is a multicausal skeletal muscle disease associated with muscle strength and mass loss. Skeletal muscle fibrosis is one of the significant pathological manifestations associated with the development of age-related sarcopenia. Irisin, which is cleaved by the extracellular domain of fibronectin type Ⅲ domain-containing protein 5 (FNDC5), has previously been reported to exert antifibrotic effects on the heart, liver, and pancreas, but whether it can rescue skeletal muscle fibrosis remains unknown. In this study, we examined the effects of irisin on D-galactose (D-gal)-induced skeletal muscle fibroblasts. We found that D-gal-induced senescence, fibrosis, and redox imbalance were inhibited by irisin treatment. Mechanistically, irisin or FNDC5 overexpression attenuated D-gal-induced senescence, redox imbalance, and fibrosis by regulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Overall, irisin might be a promising therapeutic candidate for age-related skeletal muscle fibrosis.

Clinical Importance of Sarcopenia And How It Impacts Orthopaedic-Trauma Patients and The Surgical Outcomes

Highlights: Sarcopenia can cause deleterious effects on patients. The Asian Working Group for Sarcopenia (AWGS) and the European Working Group on Sarcopenia in Older People (EWGSOP) provide the most widely used criteria to diagnose sarcopenia. Knowledge of sarcopenia should be a trigger for clinicians and surgeons to evaluate the treatment plan and anticipate the implications experienced by the patients. Abstract: Sarcopenia is a condition of low muscle strength, mass, and low physical performance that is affected by age (primary sarcopenia) and one or combination of systemic diseases, physical inactivity, and insufficient intake of energy (secondary sarcopenia). This condition affects one in ten healthy adults aged ≥60 years. There are two widely used criteria to diagnose sarcopenia, the Asian Working Group for Sarcopenia (AWGS) and the European Working Group on Sarcopenia in Older People (EWGSOP). These working groups created algorithms to facilitate the diagnosis. Establishing the diagnosis is crucial because it has deleterious impacts on patients, such as increasing risks of mortality, morbidity, falls, complications during and after surgery, disability, prolonged hospitalization, and fractures. Sarcopenia is considered an independent mortality risk. It is paramount for physicians to assess this condition before treating the patients because it can predict the risk and plan better treatment options to achieve better outcomes. Early assessment is crucial, even for surgeons. Sarcopenia also negatively impacts patients who had surgery. Up to 44% patients who underwent orthopedic trauma surgery had sarcopenia. The high percentage was affected by the increased risk of falls and fractures. On that account, this condition needs to be treated. The main treatments for this condition are exercise dan adequate nutrition intake. The recommended exercise as a first-line treatment is resistance or strength training. Overall, knowledge on sarcopenia can prepare clinicians and surgeons in anticipating the implications of sarcopenia.

Preoperative diagnosis of sarcopenia and postoperative outcome in patients with non-small-cell lung cancer.

Sarcopenia is a progressive and generalized skeletal muscle disorder associated with an increased likelihood of adverse outcomes including falls, fractures, physical disability and mortality [1]. In 1989, Irwin Rosenberg proposed the term ‘sarcopenia’ (Greek ‘sarx’ or flesh + ‘penia’ or loss) to describe this age-related decrease in muscle mass. Sarcopenia is now formally recognized as a muscle disease with an ICD-10-MC Diagnosis Code. In recent years, the number of sarcopenia-related studies has increased rapidly: 241 in 2010, 1112 in 2016 and 3152 in 2021, according to a PubMed search on ‘sarcopenia’. This rapid increase in research on sarcopenia may reflect increases in aged populations worldwide. Sarcopenia is classified into primary or secondary based on its cause. Primary sarcopenia is mainly related to ageing, while secondary sarcopenia has multiple contributing factors, such as low activity, nutrition and diseases including heart disease, pulmonary disease and malignant disease. The European Working Group on Sarcopenia in Older People (EWGSOP) defined sarcopenia in 2010 as the presence of both low muscle mass and low muscle function (strength or performance) [2]. In 2018, the EWGSOP met again, updating the definition to reflect current scientific and clinical evidence [1]. It emphasized muscle weakness in case identification, with muscle mass measurements as diagnosis confirmation, and physical performance as a severity indicator. The updated EWGSOP2 recommendation aims to increase sarcopenia awareness and risks, promoting early detection and treatment by healthcare professionals treating patients at risk of sarcopenia.

Fatigue and primary sarcopenia in geriatric patients.

This study aimed to investigate the frequency of fatigue in geriatric patients with primary sarcopenia and to evaluate the relationship between fatigue and symptoms such as depression and sleepiness. This case-control study was conducted between December 2020 and August 2021 in the geriatrics outpatient clinic of Istanbul University-Cerrahpasa. The European Working Group on Sarcopenia in Older People 2 criteria were considered for the diagnosis of sarcopenia. Demographic data, accompanying chronic diseases, comprehensive geriatric assessments, and laboratory values of the patients were noted. Scales used to assess fatigue in all participants include Fatigue Assessment Scale, Fatigue Severity Scale, and Fatigue Impact Scale and associated symptoms include Geriatric Depression Scale and Epworth Sleepiness Scale. The mean (standard deviation) age was 75.3 (7.1) for 51 primary sarcopenia (38 female) patients and 73.5 (5.8) for 51 control (37 female) patients. There was no significant difference between the two groups in terms of gender and age (p=0.822, p=0.171). The prevalence of hypertension was higher, and the level of education was lower in the sarcopenic group than in the nonsarcopenic group (p=0.017, p=0.013). Fatigue Assessment Scale, Fatigue Severity Scale, Fatigue Impact Scale total, Fatigue Impact Scale cognitive, Fatigue Impact Scale physical, and Fatigue Impact Scale social questionnaire scores were significantly higher in the sarcopenic group (all p<0.001). The Geriatric Depression Scale score was statistically higher in the sarcopenic group; however, there was no significant difference in the Epworth Sleepiness Scale score between the two groups (p=0.014, p=0.072). Multivariate analysis was performed on education level, hypertension, fatigue questionnaires, and Geriatric Depression Scale, which were found to be significant in the univariate logistic regression analysis. In the multivariate logistic regression analysis, only the Fatigue Impact Scale total was determined to be associated with sarcopenia [odds ratio 1.161, 95% confidence interval (1.084-1.242)]. In primary sarcopenia, there is mental and social fatigue as well as physical fatigue. Therefore, the prevention and treatment of sarcopenia in geriatric patients is important.

Association of Primary Sarcopenia with Serum MMP2, TIMP2 Levels, and MMP2/TIMP2 Ratio

Association of Primary Sarcopenia with Serum MMP2, TIMP2 Levels, and MMP2/TIMP2 Ratio