Journal of Cachexia, Sarcopenia and Muscle最新文献

{"title":"Respiratory sarcopenia is a predictor of all-cause mortality in community-dwelling older adults—The Otassha Study","authors":"Takeshi Kera,&nbsp;Hisashi Kawai,&nbsp;Manami Ejiri,&nbsp;Kumiko Ito,&nbsp;Hirohiko Hirano,&nbsp;Yoshinori Fujiwara,&nbsp;Kazushige Ihara,&nbsp;Shuichi Obuchi","doi":"10.1002/jcsm.13266","DOIUrl":"https://doi.org/10.1002/jcsm.13266","url":null,"abstract":"<p>As individuals age, skeletal muscle mass and function, including lean body mass and grip strength, and respiratory muscle mass and strength, tend to decline.<span>^{1, 2}</span> The term ‘respiratory sarcopenia’ emerged during a discussion on sarcopenia. Respiratory sarcopenia should encompass respiratory muscle mass and strength or function to adhere to the original sarcopenia definition, which considers whole-body muscle mass, grip strength, and gait speed. However, the decreasing respiratory muscle mass associated with aging has not been adequately discussed. The concept may appear simple; however, defining respiratory sarcopenia has not been extensively explored.</p><p>Inspiratory and expiratory maximal mouth pressure measurement as direct evidence of respiratory muscle strength is simple; however, access to relevant measuring equipment is limited. Moreover, evaluating respiratory muscle mass is challenging, and the respiratory sarcopenia using low respiratory muscle mass cannot be virtually established. Therefore, we proposed defining respiratory sarcopenia using the peak expiratory flow rate (PEFR) as an alternative to directly measuring respiratory muscle strength.<span>³</span> Subsequently, the Japanese Working Group of Respiratory Sarcopenia of the Japanese Association of Rehabilitation Nutrition (JARN) published criteria for respiratory sarcopenia, which was defined based on a decline in the maximal mouth pressure and respiratory muscle mass and the presence of whole-body-sarcopenia, as measured using skeletal muscle mass, strength, and physical performance.<span>⁴</span> However, this definition has not been established due to a lack of consensus. Moreover, to the best of our knowledge, the future health-related outcomes of respiratory sarcopenia have never been evaluated. Therefore, this survey confirmed whether respiratory sarcopenia, defined using PEFR and the JARN criteria, is associated with future mortality among community-dwelling older adults.</p><p>We assessed respiratory sarcopenia-related mortality after a 5-year follow-up of 470 participants (185 men aged 75.2 ± 5.5 years and 285 women aged 74.2 ± 5.4 years) who participated in a comprehensive health checkup program called ‘The Otassha Study’ conducted in the Tokyo Metropolitan Institute for Geriatrics and Gerontology in 2015. Participants who underwent spirometry and sarcopenia assessment were included; however, patients with chronic obstructive pulmonary disease (COPD) were excluded.</p><p>An electronic spirometer (Autospiro AS-507, Minato, Osaka, Japan) was used to measure pulmonary function. The PEFR as a percentage of the predicted value (%PEFR), vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 s (FEV₁), VC as a percentage of the predicted value (%VC), FVC as a percentage of the predicted value (%FVC), lower limit of normal FVC (FVC_LLN), and FEV₁/FVC were assessed.</p><p>A","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 4","pages":"1894-1899"},"PeriodicalIF":8.9,"publicationDate":"2023-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13266","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6232689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RhoA/ROCK signalling activated by ARHGEF3 promotes muscle weakness via autophagy in dystrophic mdx mice","authors":"Jae-Sung You,&nbsp;Yongdeok Kim,&nbsp;Soohyun Lee,&nbsp;Rashid Bashir,&nbsp;Jie Chen","doi":"10.1002/jcsm.13278","DOIUrl":"https://doi.org/10.1002/jcsm.13278","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Duchenne muscular dystrophy (DMD), caused by dystrophin deficiency, leads to progressive and fatal muscle weakness through yet-to-be-fully deciphered molecular perturbations. Emerging evidence implicates RhoA/Rho-associated protein kinase (ROCK) signalling in DMD pathology, yet its direct role in DMD muscle function, and related mechanisms, are unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Three-dimensionally engineered dystrophin-deficient <i>mdx</i> skeletal muscles and <i>mdx</i> mice were used to test the role of ROCK in DMD muscle function <i>in vitro</i> and <i>in situ</i>, respectively. The role of ARHGEF3, one of the RhoA guanine nucleotide exchange factors (GEFs), in RhoA/ROCK signalling and DMD pathology was examined by generating <i>Arhgef3</i> knockout <i>mdx</i> mice. The role of RhoA/ROCK signalling in mediating the function of ARHGEF3 was determined by evaluating the effects of wild-type or GEF-inactive ARHGEF3 overexpression with ROCK inhibitor treatment. To gain more mechanistic insights, autophagy flux and the role of autophagy were assessed in various conditions with chloroquine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Inhibition of ROCK with Y-27632 improved muscle force production in 3D-engineered <i>mdx</i> muscles (+25% from three independent experiments, <i>P</i> &lt; 0.05) and in mice (+25%, <i>P</i> &lt; 0.001). Unlike suggested by previous studies, this improvement was independent of muscle differentiation or quantity and instead related to increased muscle quality. We found that ARHGEF3 was elevated and responsible for RhoA/ROCK activation in <i>mdx</i> muscles, and that depleting ARHGEF3 in <i>mdx</i> mice restored muscle quality (up to +36%, <i>P</i> &lt; 0.01) and morphology without affecting regeneration. Conversely, overexpressing ARHGEF3 further compromised <i>mdx</i> muscle quality (−13% vs. empty vector control, <i>P</i> &lt; 0.01) in GEF activity- and ROCK-dependent manner. Notably, ARHGEF3/ROCK inhibition exerted the effects by rescuing autophagy which is commonly impaired in dystrophic muscles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings uncover a new pathological mechanism of muscle weakness in DMD involving the ARHGEF3-ROCK-autophagy pathway and the therapeutic potential of targeting ARHGEF3 in DMD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 4","pages":"1880-1893"},"PeriodicalIF":8.9,"publicationDate":"2023-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13278","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5673867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between sarcopenia and frailty in elderly patients with chronic kidney disease","authors":"Che Wang,&nbsp;Xinru Guo,&nbsp;Xieguanxuan Xu,&nbsp;Shuang Liang,&nbsp;Wenling Wang,&nbsp;Fanglei Zhu,&nbsp;Siyang Wang,&nbsp;Jie Wu,&nbsp;Li Zhang,&nbsp;Xuefeng Sun,&nbsp;Xiangmei Chen,&nbsp;Guangyan Cai,&nbsp;The Chinese observational prospective study of ageing population with chronic kidney disease (C-OPTION)","doi":"10.1002/jcsm.13275","DOIUrl":"https://doi.org/10.1002/jcsm.13275","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Frailty and sarcopenia are prevalent in chronic kidney disease (CKD) populations and could increase the risk for adverse health outcomes. Few studies assess the correlation between frailty, sarcopenia and CKD in non-dialysis patients. Therefore, this study aimed to determine frailty-associated factors in elderly CKD stage I–IV patients, expected to early identify and intervene in the frailty of elderly CKD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 774 elderly CKD I–IV patients (&gt;60 years of age) recruited from 29 clinical centers in China between March 2017 and September 2019 were included in this study. We established a Frailty Index (FI) model to evaluate frailty risk and verified the distributional property of FI in the study population. Sarcopenia was defined according to the criteria of the Asian Working Group for Sarcopenia 2019. Multinomial logistic regression analysis was used to assess the associated factors for frailty.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seven hundred seventy-four patients (median age 67 years, 66.0% males) were included in this analysis, with a median estimated glomerular filtration rate of 52.8 mL/min/1.73 m². The prevalence of sarcopenia was 30.6%. The FI exhibited a right-skewed distribution. The age-related slope of FI was 1.4% per year on a logarithmic scale (<i>r</i>² = 0.706, 95% CI 0.9, 1.8, <i>P</i> &lt; 0.001). The upper limit of FI was around 0.43. The FI was related to mortality (HR = 1.06, 95% CI 1.00, 1.12, <i>P</i> = 0.041). Multivariate multinomial logistic regression analysis showed that sarcopenia, advanced age, CKD stage II–IV, low level of serum albumin and increased waist–hip ratio were significantly associated with high FI status, while advanced age and CKD stage III–IV were significantly associated with for median FI status. Moreover, the results from the subgroup were consistent with the leading results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Sarcopenia was independently associated with an increased risk for frailty in elderly CKD I-IV patients. Patients with sarcopenia, advanced age, high CKD stage, high waist–hip ratio and low serum albumin level should be assessed for frailty.</p>\u0000 </section>\u0000 </div>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 4","pages":"1855-1864"},"PeriodicalIF":8.9,"publicationDate":"2023-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13275","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6148134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning models to predict outcomes at 30-days using Global Leadership Initiative on Malnutrition combinations with and without muscle mass in people with cancer","authors":"Nicole Kiss,&nbsp;Belinda Steer,&nbsp;Marian de van der Schueren,&nbsp;Jenelle Loeliger,&nbsp;Roohallah Alizadehsani,&nbsp;Lara Edbrooke,&nbsp;Irene Deftereos,&nbsp;Erin Laing,&nbsp;Abbas Khosravi","doi":"10.1002/jcsm.13259","DOIUrl":"https://doi.org/10.1002/jcsm.13259","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Equipment to assess muscle mass is not available in all health services. Yet we have limited understanding of whether applying the Global Leadership Initiative on Malnutrition (GLIM) criteria without an assessment of muscle mass affects the ability to predict adverse outcomes. This study used machine learning to determine which combinations of GLIM phenotypic and etiologic criteria are most important for the prediction of 30-day mortality and unplanned admission using combinations including and excluding low muscle mass.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a cohort of 2801 participants from two cancer malnutrition point prevalence studies, we applied the GLIM criteria with and without muscle mass. Phenotypic criteria were assessed using ≥5% unintentional weight loss, body mass index, subjective assessment of muscle stores from the PG-SGA. Aetiologic criteria included self-reported reduced food intake and inflammation (metastatic disease). Machine learning approaches were applied to predict 30-day mortality and unplanned admission using models with and without muscle mass.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Participants with missing data were excluded, leaving 2494 for analysis [49.6% male, mean (SD) age: 62.3 (14.2) years]. Malnutrition prevalence was 19.5% and 17.5% when muscle mass was included and excluded, respectively. However, 48 (10%) of malnourished participants were missed if muscle mass was excluded. For the nine GLIM combinations that excluded low muscle mass the most important combinations to predict mortality were (1) weight loss and inflammation and (2) weight loss and reduced food intake. Machine learning metrics were similar in models excluding or including muscle mass to predict mortality (average accuracy: 84% vs. 88%; average sensitivity: 41% vs. 38%; average specificity: 85% vs. 89%). Weight loss and reduced food intake was the most important combination to predict unplanned hospital admission. Machine learning metrics were almost identical in models excluding or including muscle mass to predict unplanned hospital admission, with small differences observed only if reported to one decimal place (average accuracy: 77% vs. 77%; average sensitivity: 29% vs. 29%; average specificity: 84% vs. 84%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results indicate predictive ability is maintained, although the ability to identify all malnourished patients is compromised, when muscle mass is excluded from the GLIM diagnosis. This has important implications for assessme","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 4","pages":"1815-1823"},"PeriodicalIF":8.9,"publicationDate":"2023-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13259","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5909718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Weight variability, physical functioning and incident disability in older adults","authors":"Katie J. McMenamin,&nbsp;Tamara B. Harris,&nbsp;Joshua F. Baker","doi":"10.1002/jcsm.13239","DOIUrl":"https://doi.org/10.1002/jcsm.13239","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This study aimed to determine if greater variability in body mass index (BMI) is associated with declines in physical functioning and incident disability in older adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Included were participants from the Health, Aging and Body Composition Study who had semi-annual BMI data during the first 3 years of follow-up. Participants were categorized into quintiles of BMI variability, using two methods. The first method used average successive variability, whereas the second method adjusted these values to remove the variability due to net change in BMI over the 3-year period. Linear regression was used to assess the relationship between the two measures of BMI variability and net changes in BMI, fat mass index, appendicular lean mass index, and Health, Aging and Body Composition Physical Performance Score during the first 3 years of the study. Cox proportional hazard models were used to assess the relationship of BMI variability with the subsequent incidence of new disability, adjusting for confounding factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 2121 participants, those in the highest BMI variability quintile were more likely to lose both body mass (<i>β</i>: −0.086 [95% confidence interval, CI: −0.133, −0.040], <i>P</i> &lt; 0.01) and fat mass (<i>β</i>: −0.059 [95% CI: −0.117, −0.002], <i>P</i> = 0.04) and had greater declines in physical performance score (<i>β</i>: −0.094 [95% CI: −0.162, −0.026], <i>P</i> &lt; 0.01) compared to participants with the least variability in BMI. Participants with high BMI variability also had higher rates of incident disability (hazard ratio: 1.36 [95% CI: 1.07, 1.72], <i>P</i> = 0.01), independent of net BMI change.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>BMI variability in older adults is associated with decline in physical performance and incident disability. This relationship cannot be explained by net weight loss alone, supporting it as an independent feature of frailty.</p>\u0000 </section>\u0000 </div>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 4","pages":"1648-1656"},"PeriodicalIF":8.9,"publicationDate":"2023-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13239","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5930474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urinary metabolomic biomarker candidates for skeletal muscle wasting in patients with rheumatoid arthritis","authors":"Marianne S. Oliveira,&nbsp;Rafaela C.E. Santo,&nbsp;Jordana M.S. Silva,&nbsp;Paulo V.G. Alabarse,&nbsp;Claiton V. Brenol,&nbsp;Steve P. Young,&nbsp;Ricardo M. Xavier","doi":"10.1002/jcsm.13240","DOIUrl":"https://doi.org/10.1002/jcsm.13240","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Rheumatoid arthritis (RA) is an autoimmune disease that affects the joints, leading to chronic synovial inflammation and local tissue destruction. Extra-articular manifestations may also occur, such as changes in body composition. Skeletal muscle wasting is often observed in patients with RA, but methods for assessing loss of muscle mass are expensive and not widely available. Metabolomic analysis has shown great potential for identifying changes in the metabolite profile of patients with autoimmune diseases. In this setting, urine metabolomic profiling in patients with RA may be a useful tool to identify skeletal muscle wasting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients aged 40–70 years with RA have been recruited according to the 2010 ACR/EULAR classification criteria. Further, the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) determined the disease activity. The muscle mass was measured by Dual X-ray absorptiometry (DXA) to generate the appendicular lean mass index (ALMI) by summing the lean mass measurements for both arms and legs and dividing them by height squared (kg/height²). Finally, urine metabolomic analysis by ¹H nuclear magnetic resonance (¹H-NMR) spectroscopy was performed and the metabolomics data set analysed using the BAYESIL and MetaboAnalyst software packages. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were applied to the ¹H-NMR data, followed by Spearman's correlation analysis. The combined receiver operating characteristic curve (ROC) was calculated, as well as the logistic regression analyses to establish a diagnostic model. The significance level at <i>P</i> &lt; 0.05 was set for all analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The total set of subjects investigated included 90 patients with RA. Most patients were women (86.7%), with a mean age of 56.5 ± 7.3 years old and a median DAS28-CRP of 3.0 (IQR 1.0–3.0). Fifteen metabolites were identified in the urine samples with high variable importance in projection (VIP scores) by MetaboAnalyst. Of these, dimethylglycine (<i>r</i> = 0.205; <i>P</i> = 0.053), oxoisovalerate (<i>r</i> = −0.203; <i>P</i> = 0.055), and isobutyric acid (<i>r</i> = −0.249; <i>P</i> = 0.018) were significantly correlated with ALMI. Based on the low muscle mass (ALMI ≤6.0 kg/m² for women and ≤8.1 kg/m² for men) a diagnostic model have been established with dimethylglycine (area under the curve [AUC] = 0.65), oxoisovalerate (AUC = 0.49), and isobutyric acid (AUC = 0.83) with significant sensit","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 4","pages":"1657-1669"},"PeriodicalIF":8.9,"publicationDate":"2023-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13240","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5730451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical exercise attenuates age-related muscle atrophy and exhibits anti-ageing effects via the adiponectin receptor 1 signalling","authors":"Yuan-Li Chen,&nbsp;Yi-Cheng Ma,&nbsp;Jie Tang,&nbsp;Dan Zhang,&nbsp;Qiu Zhao,&nbsp;Jian-Jun Liu,&nbsp;Hong-Shu Tang,&nbsp;Jin-Yu Zhang,&nbsp;Guang-Hui He,&nbsp;Chi-Hui Zhong,&nbsp;Yu-Tong Wu,&nbsp;Heng-Ruo Wen,&nbsp;Lan-Qing Ma,&nbsp;Cheng-Gang Zou","doi":"10.1002/jcsm.13257","DOIUrl":"https://doi.org/10.1002/jcsm.13257","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although the adiponectin signalling exerts exercise-mimicking effects, whether this pathway contributes to the anti-ageing benefits of physical exercise has not been established yet.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Swim exercise training and wheel running were used to measure lifespan in the nematode <i>Caenorhabditis elegans</i> and skeletal muscle quality in mice, respectively. Muscle weight, muscle fibre cross-sectional area (CSA) and myonuclei number were used to evaluate muscle mass. RNA sequencing (RNA-Seq) analysis of skeletal muscle in exercised mice was used to study the underlying mechanisms. Western blot and immunofluorescence were performed to explore autophagy- and senescence-related markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The <i>C. elegans</i> adiponectin receptor PAQR-1/AdipoR1, but not PAQR-2/AdipoR2, was activated (3.55-fold and 3.48-fold increases in p-AMPK on Days 1 and 6, respectively, <i>P</i> &lt; 0.001), which was involved in lifespan extension in exercised worms. Exercise training increased skeletal muscle mass index (1.29-fold, <i>P</i> &lt; 0.01), muscle weight (1.75-fold, <i>P</i> &lt; 0.001), myonuclei number (1.33-fold, <i>P</i> &lt; 0.05), muscle fibre CSA (1.39-fold, <i>P</i> &lt; 0.05) and capillary abundance (2.19-fold, <i>P</i> &lt; 0.001 for capillary density; 1.58-fold, <i>P</i> &lt; 0.01 for capillary number) in aged mice. Physical exercise reduced protein (2.94-fold, <i>P</i> &lt; 0.001) and mRNA levels (1.70-fold, <i>P</i> &lt; 0.001) of p16^INK4a, a marker for cellular senescence, in skeletal muscle of aged mice. These beneficial effects of exercise on skeletal muscle of mice were dependent on AdipoR1. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis for differentially expressed genes in skeletal muscle between exercised mice with and without AdipoR1 knockdown by RNA-Seq analysis revealed that several KEGG pathways, such as ‘AMPK signalling pathway’ (<i>P</i> &lt; 0.001), ‘FOXO signalling pathway’ (<i>P</i> &lt; 0.001) and ‘autophagy’ (<i>P</i> &lt; 0.001) were overrepresented. Knockdown of <i>FoxO3a</i> inhibited exercise-mediated beneficial effects on skeletal muscle quality of mice by inhibiting autophagy/mitophagy (3.81-fold reduction in LC3-II protein, <i>P</i> &lt; 0.001; 1.53-fold reduction in BNIP3 protein, <i>P</i> &lt; 0.05). Knockdown of <i>daf-16</i>, the FoxO homologue in <i>C. elegans</i>, reduced autophagy (2.77-fold and 2.06-fold reduction in GFP::LGG-1 puncta in seam cells and the intestine, respectively, <i>P</i> &lt; 0.05) and blocked lifespan extension by exercise in worms.</p>\u0000 </section>\u0000 ","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 4","pages":"1789-1801"},"PeriodicalIF":8.9,"publicationDate":"2023-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13257","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5840442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kidney function in cachexia and sarcopenia: Facts and numbers","authors":"Masatsugu Okamura,&nbsp;Masaaki Konishi,&nbsp;Javed Butler,&nbsp;Kamyar Kalantar-Zadeh,&nbsp;Stephan von Haehling,&nbsp;Stefan D. Anker","doi":"10.1002/jcsm.13260","DOIUrl":"https://doi.org/10.1002/jcsm.13260","url":null,"abstract":"<p>Cachexia, in the form of unintentional weight loss &gt;5% in 12 months or less, and secondary sarcopenia in the form of muscle wasting are serious conditions that affect clinical outcomes. A chronic disease state such as chronic kidney disease (CKD) often contributes to these wasting disorders. The purpose of this review is to summarize the prevalence of cachexia and sarcopenia, their relationship with kidney function, and indicators for evaluating kidney function in patients with CKD. It is estimated that approximately half of all persons with CKD will develop cachexia with an estimated annual mortality rate of 20%, but few studies have been conducted on cachexia in CKD. Hence, the true prevalence of cachexia in CKD and its effects on kidney function and patient outcomes remain unclear. Some studies have highlighted the concept of protein-energy wasting (PEW) which usually include sarcopenia and cachexia. Several studies have examined kidney function and CKD progression in patients with sarcopenia. Most studies use serum creatinine levels to estimate kidney function. However, creatinine may be influenced by muscle mass, and creatinine-based glomerular filtration rate may overestimate kidney function in patients with reduced muscle mass or muscle wasting. Cystatin C, which is least affected by muscle mass, has been used in some studies, and creatinine-to-cystatin-C ratio has emerged as an important prognostic marker. A previous study incorporating 428 320 participants reported that participants with CKD and sarcopenia had a 33% higher hazard of mortality compared with those without (7% to 66%, <i>P</i> = 0.011), and that those with sarcopenia were twice as likely to develop end-stage kidney disease (hazard ratio: 1.98; 1.45 to 2.70, <i>P</i> &lt; 0.001). Future studies on cachexia and sarcopenia in patients with CKD are needed to report rigorously defined cachexia concerning kidney function. Moreover, in studies on sarcopenia with CKD, it is desirable to accumulate studies using cystatin C to accurately estimate kidney function.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 4","pages":"1589-1595"},"PeriodicalIF":8.9,"publicationDate":"2023-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13260","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6026390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-reported ability to walk 4 m and to wash: New clinical endpoints and predictors of survival in patients with pre-terminal cancer","authors":"Markus S. Anker,&nbsp;Alessia Lena,&nbsp;Eric J. Roeland,&nbsp;Jan Porthun,&nbsp;Sebastian Schmitz,&nbsp;Sara Hadzibegovic,&nbsp;Philipp Sikorski,&nbsp;Ursula Wilkenshoff,&nbsp;Ann-Kathrin Fr?hlich,&nbsp;Luisa Valentina Ramer,&nbsp;Matthias Rose,&nbsp;Jan Eucker,&nbsp;Tienush Rassaf,&nbsp;Matthias Totzeck,&nbsp;Lorenz H. Lehmann,&nbsp;Stephan von Haehling,&nbsp;Andrew J.S. Coats,&nbsp;Tim Friede,&nbsp;Javed Butler,&nbsp;Stefan D. Anker,&nbsp;Hanno Riess,&nbsp;Ulf Landmesser,&nbsp;Lars Bullinger,&nbsp;Ulrich Keller,&nbsp;Johann Ahn","doi":"10.1002/jcsm.13247","DOIUrl":"https://doi.org/10.1002/jcsm.13247","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Maintaining the ability to perform self-care is a critical goal in patients with cancer. We assessed whether the patient-reported ability to walk 4 m and wash oneself predict survival in patients with pre-terminal cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a prospective observational study on 169 consecutive hospitalized patients with cancer (52% female, 64 ± 12 years) and an estimated 1–12 months prognosis at an academic, inpatient palliative care unit. Patients answered functional questions for ‘today’, ‘last week’, and ‘last month’, performed patient-reported outcomes (PROs), and physical function assessments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ninety-two (54%) patients reported the ability to independently walk 4 m and 100 (59%) to wash ‘today’. The median number of days patients reported the ability to walk 4 m and wash were 6 (IQR 0–7) and 7 (0–7) days (‘last week’); and 27 (5–30) and 26 (10–30) days (‘last month’). In the last week, 32% of patients were unable to walk 4 m on every day and 10% could walk on 1–3 days; 30% were unable to wash on every day and 10% could wash on 1–3 days. In the last months, 14% of patients were unable to walk 4 m on every day and 10% could only walk on 1–10 days; 12% were unable to wash on every day and 11% could wash on 1–10 days. In patients who could walk ‘today’ average 4 m gait speed was 0.78 ± 0.28 m/s. Patients who reported impaired walking and washing experienced more symptoms (dyspnoea, exertion, and oedema) and decreased physical function (higher Eastern Cooperative Oncology Group Performance Status, and lower Karnofsky Performance Status and hand-grip strength [unable vs. able to walk ‘today’: 205 ± 87 vs. 252 ± 78 Newton, <i>P</i> = 0.001; unable vs. able to wash ‘today’: 204 ± 86 vs. 250 ± 80 Newton, <i>P</i> = 0.001]). During the 27 months of observation, 152 (90%) patients died (median survival 46 days). In multivariable Cox proportional hazards regression analyses, all tested parameters were independent predictors of survival: walking 4 m ‘today’ (HR 0.63, <i>P</i> = 0.015), ‘last week’ (per 1 day: HR 0.93, <i>P</i> = 0.011), ‘last month’ (per 1 day: HR 0.98, <i>P</i> = 0.012), 4 m gait speed (per 1 m/s: HR 0.45, <i>P</i> = 0.002), and washing ‘today’ (HR 0.67, <i>P</i> = 0.024), ‘last week (per 1 day HR 0.94, p=0.019), and ‘last month’ (per 1 day HR 0.99, <i>P</i> = 0.040). Patients unable to walk and wash experienced the shortest survival and most reduced functional status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 ","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 4","pages":"1670-1681"},"PeriodicalIF":8.9,"publicationDate":"2023-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13247","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5807879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the prognostic value of computed tomography-derived body composition in patients undergoing endovascular aneurysm repair","authors":"Nicholas A. Bradley,&nbsp;Amy Walter,&nbsp;Ross Dolan,&nbsp;Alasdair Wilson,&nbsp;Tamim Siddiqui,&nbsp;Campbell S.D. Roxburgh,&nbsp;Donald C. McMillan,&nbsp;Graeme J.K. Guthrie","doi":"10.1002/jcsm.13262","DOIUrl":"https://doi.org/10.1002/jcsm.13262","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Endovascular aneurysm repair (EVAR) is the most common mode of repair of abdominal aortic aneurysms (AAA) in the UK. EVAR ranges from standard infrarenal repair to complex fenestrated and branched EVAR (F/B-EVAR). Sarcopenia is defined by lower muscle mass and function, which is associated with inferior perioperative outcomes. Computed tomography-derived body composition analysis offers prognostic value in patients with cancer. Several authors have evaluated the role of body composition analysis in predicting outcomes in patients undergoing EVAR; however, the evidence base is limited by heterogeneous methodology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Six hundred seventy-four consecutive patients (58 (8.6%) female, mean (SD) age 74.4 (6.8) years) undergoing EVAR and F/B-EVAR at three large tertiary centres were retrospectively recruited. Subcutaneous and visceral fat indices (SFI and VFI), psoas and skeletal muscle indices, and skeletal muscle density were measured at the L3 vertebral level from pre-operative computed tomographies. The maximally selected rank statistic technique was used to define optimal thresholds to predict mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There were 191 deaths during the median follow-up period of 60.0 months. Mean (95% CI) survival in the low SMI versus high SMI subgroups was 62.6 (58.5–66.7) versus 82.0 (78.7–85.3) months (<i>P</i> &lt; 0.001). Mean (95% CI) survival in the low SFI versus high SFI subgroups was 56.4 (48.2–64.7) versus 77.1 (74.2–80.1) months (<i>P</i> &lt; 0.001). One-year mortality in the low SMI versus high SMI subgroups was 10% versus 3% (<i>P</i> &lt; 0.001). Low SMI was associated with increased odds of one-year mortality (OR 3.19, 95% CI 1.60–6.34, <i>P</i> &lt; 0.001). Five-year mortality in the low SMI versus high SMI subgroups was 55% versus 28% (<i>P</i> &lt; 0.001). Low SMI was associated with increased odds of five-year mortality (OR 1.54, 95% CI 1.11–2.14, <i>P</i> &lt; 0.01). On multivariate analysis of all patients, low SFI (HR 1.90, 95% CI 1.30–2.76, <i>P</i> &lt; 0.001) and low SMI (HR 1.88, 95% CI 1.34–2.63, <i>P</i> &lt; 0.001) were associated with poorer survival. On multivariate analysis of asymptomatic AAA patients, low SFI (HR 1.54, 95% CI 1.01–2.35, <i>P</i> &lt; 0.05) and low SMI (HR 1.71, 95% CI 1.20–2.42, <i>P</i> &lt; 0.01) were associated with poorer survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Low SMI and SFI are associated with poorer long-term survival following EVAR and F/B-EVAR. The relation","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 4","pages":"1836-1847"},"PeriodicalIF":8.9,"publicationDate":"2023-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13262","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5688973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}