Laure M. G. Verstraeten, Esmee M. Reijnierse, Thom Spoelstra, Carel G. M. Meskers, Andrea B. Maier
{"title":"The impact of mobility limitations on geriatric rehabilitation outcomes: Positive effects of resistance exercise training (RESORT)","authors":"Laure M. G. Verstraeten, Esmee M. Reijnierse, Thom Spoelstra, Carel G. M. Meskers, Andrea B. Maier","doi":"10.1002/jcsm.13557","DOIUrl":"10.1002/jcsm.13557","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Regaining walking ability is a key target in geriatric rehabilitation. This study evaluated the prevalence of walking ability at (pre-)admission and related clinical characteristics in a cohort of geriatric rehabilitation inpatients; in inpatients without walking ability, feasibility and effectiveness of progressive resistance exercise training (PRT) were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Inpatients within RESORT, an observational, longitudinal cohort of geriatric rehabilitation inpatients, were stratified in those with and without ability to walk independently (defined by Functional Ambulation Classification (FAC) score ≤ 2) at admission; further subdivision was performed by pre-admission walking ability. Clinical characteristics at admission, length of stay, and changes in physical and functional performance throughout admission were compared depending on (pre-)admission walking ability. Feasibility (relative number of PRT sessions given and dropout rate) and effectiveness [change in Short Physical Performance Battery, FAC, independence in (instrumental) activities of daily living (ADL/IADL)] of PRT (<i>n</i> = 11) in a subset of inpatients without ability to walk independently at admission (able to walk pre-admission) were investigated compared with usual care (<i>n</i> = 11) (LIFT-UP study).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Out of 710 inpatients (median age 83.5 years; 58.0% female), 52.2% were not able to walk independently at admission, and 7.6% were not able to walk pre-admission. Inpatients who were not able to walk independently at admission, had a longer length of stay, higher prevalence of cognitive impairment and frailty and malnutrition risk scores, and a lower improvement in independence in (I)ADL compared with inpatients who were able to walk at both admission and pre-admission. In LIFT-UP, the relative median number of PRT sessions given compared with the protocol (twice per weekday) was 11 out of 44. There were no dropouts. PRT improved FAC (<i>P</i> = 0.028) and ADL (<i>P</i> = 0.034) compared with usual care.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>High prevalence of inpatients who are not able to walk independently and its negative impact on independence in (I)ADL during geriatric rehabilitation highlights the importance of tailored interventions such as PRT, which resulted in improvement in FAC and ADL.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138797","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}
Fabio Sarto, Martino V. Franchi, Jamie S. McPhee, Daniel W. Stashuk, Matteo Paganini, Elena Monti, Maira Rossi, Giuseppe Sirago, Sandra Zampieri, Evgeniia S. Motanova, Giacomo Valli, Tatiana Moro, Antonio Paoli, Roberto Bottinelli, Maria A. Pellegrino, Giuseppe De Vito, Helen M. Blau, Marco V. Narici
{"title":"Neuromuscular impairment at different stages of human sarcopenia","authors":"Fabio Sarto, Martino V. Franchi, Jamie S. McPhee, Daniel W. Stashuk, Matteo Paganini, Elena Monti, Maira Rossi, Giuseppe Sirago, Sandra Zampieri, Evgeniia S. Motanova, Giacomo Valli, Tatiana Moro, Antonio Paoli, Roberto Bottinelli, Maria A. Pellegrino, Giuseppe De Vito, Helen M. Blau, Marco V. Narici","doi":"10.1002/jcsm.13531","DOIUrl":"10.1002/jcsm.13531","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Degeneration of the motoneuron and neuromuscular junction (NMJ) and loss of motor units (MUs) contribute to age-related muscle wasting and weakness associated with sarcopenia. However, these features have not been comprehensively investigated in humans. This study aimed to compare neuromuscular system integrity and function at different stages of sarcopenia, with a particular focus on NMJ stability and MU properties.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We recruited 42 young individuals (Y) (aged 25.98 ± 4.6 years; 57% females) and 88 older individuals (aged 75.9 ± 4.7 years; 55% females). The older group underwent a sarcopenia screening according to the revised guidelines of the European Working Group on Sarcopenia in Older People 2. In all groups, knee extensor muscle force was evaluated by isometric dynamometry, muscle morphology by ultrasound and MU potential properties by intramuscular electromyography (iEMG). MU number estimate (iMUNE) and blood samples were obtained. Muscle biopsies were collected in a subgroup of 16 Y and 52 older participants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirty-nine older individuals were non-sarcopenic (NS), 31 pre-sarcopenic (PS) and 18 sarcopenic (S). A gradual decrease in quadriceps force, cross-sectional area and appendicular lean mass was observed across the different stages of sarcopenia (for all <i>P</i> < 0.0001). Handgrip force and the Short Physical Performance Battery score also showed a diminishing trend. iEMG analyses revealed elevated near fibre segment jitter in NS, PS and S compared with Y (Y vs. NS and S: <i>P</i> < 0.0001; Y vs. PS: <i>P</i> = 0.0169), suggestive of age-related impaired NMJ transmission. Increased C-terminal agrin fragment (<i>P</i> < 0.0001) and altered caveolin 3 protein expression were consistent with age-related NMJ instability in all the older groups. The iMUNE was lower in all older groups (<i>P</i> < 0.0001), confirming age-related loss of MUs. An age-related increase in MU potential complexity was also observed. These observations were accompanied by increased muscle denervation and axonal damage, evinced by the increase in neural cell adhesion molecule-positive fibres (Y vs. NS: <i>P</i> < 0.0001; Y vs. S: <i>P</i> = 0.02) and the increase in serum concentration of neurofilament light chain (<i>P</i> < 0.0001), respectively. Notably, most of these MU and NMJ parameters did not differ when comparing older individuals with or without sarcopenia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Al","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138796","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}
Janelle Tarum, Graham Ball, Thomas Gustafsson, Mikael Altun, Lívia Santos
{"title":"Artificial neural network inference analysis identified novel genes and gene interactions associated with skeletal muscle aging","authors":"Janelle Tarum, Graham Ball, Thomas Gustafsson, Mikael Altun, Lívia Santos","doi":"10.1002/jcsm.13562","DOIUrl":"10.1002/jcsm.13562","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sarcopenia is an age-related muscle disease that increases the risk of falls, disabilities, and death. It is associated with increased muscle protein degradation driven by molecular signalling pathways including Akt and FOXO1. This study aims to identify genes, gene interactions, and molecular pathways and processes associated with muscle aging and exercise in older adults that remained undiscovered until now leveraging on an artificial intelligence approach called artificial neural network inference (ANNi).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Four datasets reporting the profile of muscle transcriptome obtained by RNA-seq of young (21–43 years) and older adults (63–79 years) were selected and retrieved from the Gene Expression Omnibus (GEO) data repository. Two datasets contained the transcriptome profiles associated to muscle aging and two the transcriptome linked to resistant exercise in older adults, the latter before and after 6 months of exercise training. Each dataset was individually analysed by ANNi based on a swarm neural network approach integrated into a deep learning model (Intelligent Omics). This allowed us to identify top 200 genes influencing (drivers) or being influenced (targets) by aging or exercise and the strongest interactions between such genes. Downstream gene ontology (GO) analysis of these 200 genes was performed using Metacore (Clarivate™) and the open-source software, Metascape. To confirm the differential expression of the genes showing the strongest interactions, real-time quantitative PCR (RT-qPCR) was employed on human muscle biopsies obtained from eight young (25 ± 4 years) and eight older men (78 ± 7.6 years), partaking in a 6-month resistance exercise training programme.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>CHAD</i>, <i>ZDBF2</i>, <i>USP54</i>, and <i>JAK2</i> were identified as the genes with the strongest interactions predicting aging, while <i>SCFD1</i>, <i>KDM5D</i>, <i>EIF4A2</i>, and <i>NIPAL3</i> were the main interacting genes associated with long-term exercise in older adults. RT-qPCR confirmed significant upregulation of <i>USP54</i> (<i>P</i> = 0.005), <i>CHAD</i> (<i>P</i> = 0.03), and <i>ZDBF2</i> (<i>P</i> = 0.008) in the aging muscle, while exercise-related genes were not differentially expressed (<i>EIF4A2 P</i> = 0.99, <i>NIPAL3 P</i> = 0.94, <i>SCFD1 P</i> = 0.94, and <i>KDM5D P</i> = 0.64). GO analysis related to skeletal muscle aging suggests enrichment of pathways linked to bone development (adj <i>P</i>-value 0.006), immune response (adj <i>P</i>-value <0.001), and apoptosis (adj <i>P</i>-value 0.01). In older exercising adults,","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13562","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100690","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}
Di Lu, Zhihang Hu, Hao Chen, Abid Ali Khan, Qingguo Xu, Zuyuan Lin, Huigang Li, Jianyong Zhuo, Chiyu He, Li Zhuang, Zhe Yang, Siyi Dong, Jinzhen Cai, Shusen Zheng, Xiao Xu
{"title":"Myosteatosis and muscle loss impact liver transplant outcomes in male patients with hepatocellular carcinoma","authors":"Di Lu, Zhihang Hu, Hao Chen, Abid Ali Khan, Qingguo Xu, Zuyuan Lin, Huigang Li, Jianyong Zhuo, Chiyu He, Li Zhuang, Zhe Yang, Siyi Dong, Jinzhen Cai, Shusen Zheng, Xiao Xu","doi":"10.1002/jcsm.13554","DOIUrl":"10.1002/jcsm.13554","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sarcopenia is associated with unfavourable long-term survival in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC). However, the impact of myosteatosis and muscle loss on patient prognosis has not been investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Seven hundred fifty-six HCC patients who received LT at 3 transplant centres were included. Computed tomography (CT) images of recipients were collected to measure skeletal muscle index (SMI) and skeletal muscle radiodensity (SMRA). The impact of myosteatosis on the prognosis of sarcopenic and non-sarcopenic patients was studied separately. Muscle status was evaluated based on the presence of sarcopenia and myosteatosis. The muscle loss of 342 males was calculated as the relative change of SMI between pre- and post-LT evaluations. Cox regression models were used to identify predictors of overall survival (OS) and recurrence-free survival (RFS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study comprised 673 males and 83 females. The median follow-up time was 31 months (interquartile range, 19–43 months). Prior to LT, 267 (39.7%) and 187 (27.8%) males were defined as sarcopenic (low-SMI) and myosteatotic (low-SMRA), respectively. For sarcopenic recipients, the presence of myosteatosis was followed by a 23.6% decrease in 5 year OS (<i>P</i> < 0.001) and a 15.0% decrease in 5 year RFS (<i>P</i> = 0.014). Univariate and multivariate analyses revealed that muscle status was an independent predictor of OS [hazard ratio (HR), 1.569; 95% confidence interval (CI), 1.317–1.869; <i>P</i> < 0.001] and RFS (HR, 1.369; 95% CI, 1.182–1.586; <i>P</i> < 0.001). Postoperatively, a muscle loss >14.2% was an independent risk factor for poor OS (HR, 2.286; 95% CI, 1.358–3.849; <i>P</i> = 0.002) and RFS (HR, 2.219; 95% CI, 1.418–3.471; <i>P</i> < 0.001) in non-sarcopenic recipients (<i>N</i> = 209).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Pre-transplant myosteatosis aggravated the adverse impact of sarcopenia on liver transplant outcomes in male HCC patients. Post-transplant muscle loss might assist in prognostic stratification of recipients without pre-existing sarcopenia, intriguing new insights into individualized management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078630","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}
Jia-He Yang, Jun Gao, Ya-Qi E, Li-Jie Jiao, Ren Wu, Qiu-Yi Yan, Zi-Yi Wei, Guo-Liang Yan, Jin-Long Liang, Hong-Zhu Li
{"title":"Hydrogen sulfide inhibits skeletal muscle ageing by up-regulating autophagy through promoting deubiquitination of adenosine 5’-monophosphate (AMP)-activated protein kinase α1 via ubiquitin specific peptidase 5","authors":"Jia-He Yang, Jun Gao, Ya-Qi E, Li-Jie Jiao, Ren Wu, Qiu-Yi Yan, Zi-Yi Wei, Guo-Liang Yan, Jin-Long Liang, Hong-Zhu Li","doi":"10.1002/jcsm.13560","DOIUrl":"10.1002/jcsm.13560","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hydrogen sulfide (H<sub>2</sub>S), the third gasotransmitter discovered, regulates a variety of physiological functions. Whether H<sub>2</sub>S alleviates skeletal muscle ageing by regulating autophagy has not been reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Mice were administered 150 mg/kg/day of <span>D</span>-galactose (<span>D</span>-gal), and C2C12 myotubes were cultured in 20 g/L <span>D</span>-gal to induce ageing. Sodium hydrosulfide (NaHS) was employed as an exogenous donor in the treatment group. The intracellular concentration of H<sub>2</sub>S was quantified by the 7-azido-4-methylcoumarin fluorescence probe. The proteins involved in the ubiquitin-mediated degradation of AMPKα1 were detected by liquid chromatography tandem mass spectrometry (LC–MS/MS) and co-immunoprecipitation (Co-IP). S-sulfhydration of USP5 was tested by a biotin-switch assay. Associated proteins were analysed by western blot.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>NaHS was found to effectively restore the H<sub>2</sub>S content in both ageing gastrocnemius (+91.89%, <i>P</i> < 0.001) and C2C12 myotubes (+27.55%, <i>P</i> < 0.001). In comparison to the D-gal group, NaHS was observed to increase the mean cross-sectional area of muscle fibres (+44.91%, <i>P</i> < 0.001), to decrease the collagen volume fraction of gastrocnemius (−81.32%, <i>P</i> = 0.001) and to reduce the β-galactosidase-positive area of C2C12 myotubes (−28.74%, <i>P</i> < 0.001). NaHS was also found to reverse the expression of muscle atrophy F box protein (MAFbx), muscle-specific RING finger protein 1 (MuRF1), Cyclin D1 and p21 in the ageing gastrocnemius tissue (MAFbx: −31.73%, <i>P</i> = 0.008; MuRF1: −32.37%, <i>P</i> = 0.003; Cyclin D1: +45.34%, <i>P</i> = 0.010; p21: −25.53%, <i>P</i> = 0.022) and C2C12 myotubes (MAFbx: −16.38%, <i>P</i> < 0.001; MuRF1: −16.45%, <i>P</i> = 0.003; Cyclin D1: +40.23%, <i>P</i> < 0.001; p21: −35.85%, <i>P</i> = 0.026). The AMPKα1–ULK1 pathway was activated and autophagy was up-regulated in NaHS-treated gastrocnemius tissue (p-AMPKα1: +61.61%, <i>P</i> = 0.018; AMPKα1: +30.64%, <i>P</i> = 0.010; p-ULK1/ULK1: +85.87%, <i>P</i> = 0.005; p62: −29.07%, <i>P</i> < 0.001; Beclin1: +24.75%, <i>P</i> = 0.007; light chain 3 II/I [LC3 II/I]: +55.78%, <i>P</i> = 0.004) and C2C12 myotubes (p-AMPKα1: +77.49%, <i>P</i> = 0.018; AMPKα1: +26.18%, <i>P</i> = 0.022; p-ULK1/ULK1: +38.34%, <i>P</i> = 0.012; p62: −9.02%, <i>P</i> = 0.014; Beclin1: +13.36%, <i>P</i> < 0.001; LC3 II/I: +79.38%, <i>P</i> = 0.017; autophagy flux: +24.88%, <i>P</i> = 0.034) compared with the <span>D</span>-gal group. The effe","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071597","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":"AWGC2023 cachexia consensus as a valuable tool for predicting prognosis and burden in Chinese patients with cancer","authors":"Hailun Xie, Lishuang Wei, Guotian Ruan, Heyang Zhang, Jinyu Shi, Shiqi Lin, Chenan Liu, Xiaoyue Liu, Xin Zheng, Yue Chen, Junqiang Chen, Hanping Shi","doi":"10.1002/jcsm.13555","DOIUrl":"10.1002/jcsm.13555","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The Asian Working Group for Cachexia (AWGC) proposed the first consensus report on diagnostic criteria for cachexia in Asians in 2023. However, the current consensus lacks cohort evidence to validate its effectiveness and practicality. We aimed to explore the value of the AWGC2023 criteria for predicting the prognosis and medical burden of patients with cancer through a retrospective post hoc cross-sectional analysis of the Investigation on Nutrition Status and its Clinical Outcome of Common Cancers (INSCOC) project in China.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Cox regression analyses were performed to assess the independent association between cachexia and long-term survival. We utilized C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), inflammatory burden index (IBI), albumin (ALB) and Glasgow prognostic score (GPS) as diagnostic markers for cachexia, designating them as CRP-based cachexia, NLR-based cachexia, IBI-based cachexia, ALB-based cachexia and GPS-based cachexia, respectively. Additionally, we diagnosed cachexia using body mass index (BMI) cutoff values of 18.5, 20, 21 and 22 kg/m<sup>2</sup>, respectively, and subsequently compared their prognostic predictive value through Harrell's concordance index (C-index). Logistic regression models were used to assess the association between cachexia and medical burden.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 5426 patients with cancer were enrolled in this study. Cox regression analysis confirmed that cachexia based on the AWGC2023 criteria was an independent predictor of long-term survival in patients with cancer. Patients with cachexia had significantly poorer long-term survival than patients without cachexia (66.4% vs. 49.7%, P < 0.001). Inflammatory biomarker-based cachexia was as an independent predictor of prognosis in patients with cancer, with inflammatory burden index (IBI)-based cachexia demonstrating the optimal prognostic discriminatory ability. The C-index indicated that cachexia based on BMI cutoff values of 18.5, 20, and 22 kg/m<sup>2</sup> did not perform as well as a BMI cutoff value of 21 kg/m<sup>2</sup>. Logistic regression models revealed that using the AWGC2023 criteria, patients with cachexia had a 16.6% higher risk of prolonged hospitalization and a 16.0% higher risk of high medical expenses than patients without cachexia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The AWGC2023 criteria represent a valuable tool for predicting survival and medical burden among Chinese patients with can","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078629","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}
Ai Guo, Ke Huang, Quanyi Lu, Bailong Tao, Kai Li, Dianming Jiang
{"title":"TRIM16 facilitates SIRT-1-dependent regulation of antioxidant response to alleviate age-related sarcopenia","authors":"Ai Guo, Ke Huang, Quanyi Lu, Bailong Tao, Kai Li, Dianming Jiang","doi":"10.1002/jcsm.13553","DOIUrl":"10.1002/jcsm.13553","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Age-related sarcopenia, characterized by reduced skeletal muscle mass and function, significantly affects the health of the elderly individuals. Oxidative stress plays a crucial role in the development of sarcopenia. Tripartite motif containing 16 (TRIM16) is implicated in orchestrating antioxidant responses to mitigate oxidative stress, yet its regulatory role in skeletal muscle remains unclear. This study aims to elucidate the impact of TRIM16 on enhancing antioxidant response through SIRT-1, consequently mitigating age-related oxidative stress, and ameliorating muscle atrophy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Aged mouse models were established utilizing male mice at 18 months with D-galactose (D-gal, 200 mg/kg) intervention and at 24 months with natural aging, while 3-month-old young mice served as controls. Muscle cell senescence was induced in C2C12 myoblasts using 30 g/L D-gal. TRIM16 was overexpressed in the skeletal muscle of aged mice and silenced/overexpressed in C2C12 myoblasts. The effects of TRIM16 on skeletal muscle mass, grip strength, morphological changes, myotube formation, myogenic differentiation, and muscle atrophy indicators were evaluated. Reactive oxygen species (ROS) levels and oxidative stress-related parameters were measured. The SIRT-1 inhibitor EX-527 was employed to elucidate the protective role of TRIM16 mediated through SIRT-1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Aged mice displayed significant reductions in lean mass (−11.58%; −14.47% vs. young, <i>P</i> < 0.05), hindlimb lean mass (−17.38%; −15.95% vs. young, <i>P</i> < 0.05), and grip strength (−22.29%; −31.45% vs. young, <i>P</i> < 0.01). Skeletal muscle fibre cross-sectional area (CSA) decreased (−29.30%; −24.12% vs. young, <i>P</i> < 0.05). TRIM16 expression significantly decreased in aging skeletal muscle (−56.82%; −66.27% vs. young, <i>P</i> < 0.001) and senescent muscle cells (−46.53% vs. control, <i>P</i> < 0.001). ROS levels increased (+69.83% vs. control, <i>P</i> < 0.001), and myotube formation decreased in senescent muscle cells (−56.68% vs. control, <i>P</i> < 0.001). Expression of myogenic differentiation and antioxidant indicators decreased, while muscle atrophy markers increased in vivo and in vitro (all <i>P</i> < 0.05). Silencing TRIM16 in myoblasts induced oxidative stress and myotube atrophy, while TRIM16 overexpression partially mitigated aging effects on skeletal muscle. TRIM16 activation enhanced SIRT-1 expression (+75.38% vs. control, <i>P</i> < 0.001). SIRT-1 inhibitor EX-527 (100 μM) suppressed TRIM16's antioxidant response and mitigating muscle at","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078631","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":"Betaine delays age-related muscle loss by mitigating Mss51-induced impairment in mitochondrial respiration via Yin Yang1","authors":"Si Chen, Tongtong He, Jiedong Chen, Dongsheng Wen, Chen Wang, Wenge Huang, Zhijun Yang, Mengtao Yang, Mengchu Li, Siyu Huang, Zihui Huang, Huilian Zhu","doi":"10.1002/jcsm.13558","DOIUrl":"10.1002/jcsm.13558","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mitochondrial dysfunction is one of the hallmarks of aging and a leading contributor to sarcopenia. Nutrients are essential for improving mitochondrial function and skeletal muscle health during the aging process. Betaine is a nutrient with potential muscle-preserving properties. However, whether and how betaine could regulate the mitochondria function in aging muscle are poorly understood. We aimed to explore the molecular target and underlying mechanism of betaine in attenuating the age-related mitochondrial dysfunction in skeletal muscle.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Young mice (YOU, 2 months), old mice (OLD, 15 months), and old mice with betaine treatment (BET, 15 months) were fed for 12 weeks. The effects of betaine on muscle mass, strength, function, and subcellular structure of muscle fibres were assessed. RNA sequencing (RNA-seq) was conducted to identify the molecular target of betaine. The impacts of betaine on mitochondrial-related molecules, superoxide accumulation, and oxidative respiration were examined using western blotting (WB), immunofluorescence (IF) and seahorse assay. The underlying mechanism of betaine regulation on the molecular target to maintain mitochondrial function was investigated by luciferase reporter assay, chromatin immunoprecipitation and electrophoretic mobility shift assay. Adenoassociated virus transfection, succinate dehydrogenase staining (SDH), and energy expenditure assessment were performed on 20-month-old mice for validating the mechanism <i>in vivo</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Betaine intervention demonstrated anti-aging effects on the muscle mass (<i>P</i> = 0.017), strength (<i>P</i> = 0.010), and running distance (<i>P</i> = 0.013). Mitochondrial-related markers (ATP5a, Sdha, and Uqcrc2) were 1.1- to 1.5-fold higher in BET than OLD (all <i>P</i> ≤ 0.036) with less wasted mitochondrial vacuoles accumulating in sarcomere. Bioinformatic analysis from RNA-seq displayed pathways related to mitochondrial respiration activity was higher enriched in BET group (NES = −0.87, FDR = 0.10). The quantitative real time PCR (qRT-PCR) revealed betaine significantly reduced the expression of a novel mitochondrial regulator, Mss51 (−24.9%, <i>P</i> = 0.002). In C2C12 cells, betaine restored the Mss51-mediated suppression in mitochondrial respiration proteins (all <i>P</i> ≤ 0.041), attenuated oxygen consumption impairment, and superoxide accumulation (by 20.7%, <i>P</i> = 0.001). Mechanically, betaine attenuated aging-induced repression in <i>Yy1</i> mRNA expression (BET vs. OLD: 2.06 vs. 1.02, <i>P</i> = 0.009). Yy1 transcriptionally suppress","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071595","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}
Sahoko Takagi, Shosuke Satake, Ken Sugimoto, Masafumi Kuzuya, Masahiro Akishita, Hidenori Arai, Ivan Aprahamian, Andrew J. Coats, Tatiana Klompenhouwer, Stefan D. Anker, Hidetaka Wakabayashi
{"title":"Survey on the knowledge and practices in anorexia of aging diagnosis and management in Japan","authors":"Sahoko Takagi, Shosuke Satake, Ken Sugimoto, Masafumi Kuzuya, Masahiro Akishita, Hidenori Arai, Ivan Aprahamian, Andrew J. Coats, Tatiana Klompenhouwer, Stefan D. Anker, Hidetaka Wakabayashi","doi":"10.1002/jcsm.13566","DOIUrl":"10.1002/jcsm.13566","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Anorexia of aging (AA) is a condition in older adults that includes loss of appetite and reduced food intake. There is a lack of detailed analysis of the potential influence of educational initiatives in addressing AA. This study aimed to clarify the current state of knowledge and practice regarding AA and its relationship with the availability of continuing education opportunities among Japanese healthcare professionals involved in treating older patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The Japan Geriatrics Society and the Japanese Association on Sarcopenia and Frailty, in collaboration with the Society on Sarcopenia, Cachexia, and Wasting Disorders, conducted an online questionnaire survey on the knowledge and practices in AA detection and management. Questions were asked in the areas of demographics, screening, definition/diagnosis, treatment, referral, and awareness, with those who ‘participate’ in continuing education and professional development programmes in nutrition for their patients were classified as the ‘education group’ and those who ‘do not participate’ were classified as the ‘non-education group’. The results for each question were compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The analysis included 870 participants (physicians, 48%; registered dietitians, 16%; rehabilitation therapists, 14%; pharmacists, 12%; nurses, 6%; and other professionals, 5%). The education group (45%) was more likely than the non-education group (55%) to use the Mini-Nutritional Assessment Short Form (MNA-SF) to screen for AA (49% vs. 27%) and less likely not to use a validated tool (33% vs. 47%). More participants used evidence-based tools and materials for AA care (38% vs. 12%), and fewer used their clinical judgement (23% vs. 35%) or were unaware of the tools and materials (9% vs. 23%). The proportion using a team of professionals experienced in AA care were 47% and 24% of the education and non-education groups, respectively. By profession, few physicians used specific validated tools and resources for AA screening and treatment. More than half of the dietitians used the MNA-SF regardless of training opportunity availability. Regarding professional availability and team use, differences in educational opportunities were particularly large among physicians.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Participation in continuing education programmes on nutrition is associated with responsiveness to AA screening and treatment and the availability of a team of professionals, which may infl","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142015778","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":"Novel metabolic and lipidomic biomarkers of sarcopenia","authors":"Wei-Hsiang Hsu, San-Yuan Wang, Yen-Ming Chao, Ke-Vin Chang, Der-Sheng Han, Yun-Lian Lin","doi":"10.1002/jcsm.13567","DOIUrl":"10.1002/jcsm.13567","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The pathophysiology of sarcopenia is complex and multifactorial and has not been fully elucidated. The impact of resistance training and nutritional support (RTNS) on metabolomics and lipodomics in older adults with sarcopenia remains uncertain. This study aimed to explore potential biomarkers of sarcopenia and clinical indicators of RTNS in older sarcopenic adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Older individuals diagnosed with sarcopenia through routine health checkups at a community hospital were recruited for a 12-week randomized controlled trial focusing on RTNS. Plasma metabolomic and lipidomic profiles of 45 patients with sarcopenia and 47 matched controls were analysed using <sup>1</sup>H-nuclear magnetic resonance (<sup>1</sup>H-NMR) and liquid chromatography-mass spectrometer (LC–MS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At baseline, the patient and control groups had similar age, sex, and height distribution. The patient group had significantly lower weight, BMI, grip strength, gait speed, skeletal muscle index, lean mass of both the upper and lower limbs, and lower limb bone mass. There was a significant difference in 12 metabolites between the control and patient groups. They are isoleucine (patient/control fold change [FC] = 0.86 ± 0.04, <i>P</i> = 0.0005), carnitine (FC = 1.05 ± 0.01, <i>P</i> = 0.0110), 1-methylhistamine/3-methylhistamine (FC = 1.24 ± 0.14, <i>P</i> = 0.0039), creatinine (FC = 0.71 ± 0.04, <i>P</i> < 0.0001), carnosine (FC = 0.71 ± 0.04, <i>P</i> = 0.0007), ureidopropionic acid (FC = 0.61 ± 0.10, <i>P</i> = 0.0107), uric acid (FC = 0.88 ± 0.03, <i>P</i> = 0.0083), PC (18:2/20:0) (FC = 0.69 ± 0.03, <i>P</i> = 0.0010), PC (20:2/18:0) (FC = 0.70 ± 0.06, <i>P</i> = 0.0014), PC (18:1/20:1) (FC = 0.74 ± 0.05, <i>P</i> = 0.0015), PI 32:1 (FC = 4.72 ± 0.17, <i>P</i> = 0.0006), and PI 34:3 (FC = 1.88 ± 0.13, <i>P</i> = 0.0003). Among them, carnitine, 1-methylhistamine/3-methylhistamine, creatinine, ureidopropionic acid, uric acid, PI 32:1, and PI 34:3 were first identified. Notably, PI 32:1 had highest diagnostic accuracy (0.938) for sarcopenia. 1-Methylhistamine/3-methylhistamine, carnosine, PC (18:2/20:0), PI 32:1, and PI 34:3 levels were not different from the control group after RTNS. These metabolites are involved in amino acid metabolism, lipid metabolism, and the PI3K-AKT/mTOR signalling pathway through the ingenuity pathway analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings provide information on metabolic changes, lipid pertur","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142015740","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}