Journal of Cachexia Sarcopenia and Muscle最新文献

{"title":"PrPC Glycoprotein Is Indispensable for Maintenance of Skeletal Muscle Homeostasis During Aging","authors":"Wenduo Liu, Thi Thu Trang Kieu, Zilin Wang, Hyun-Jaung Sim, Seohyeong Lee, Jeong-Chae Lee, Yoonjung Park, Sang Hyun Kim, Sung-Ho Kook","doi":"10.1002/jcsm.13706","DOIUrl":"10.1002/jcsm.13706","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The cellular prion protein (PrP<sup>C</sup>), a glycoprotein encoded by the <i>PRNP</i> gene, is known to modulate muscle mass and exercise capacity. However, the role of PrP<sup>C</sup> in the maintenance and regeneration of skeletal muscle during ageing remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study investigated the change in PrP<sup>C</sup> expression during muscle formation using C2C12 cells and evaluated muscle function in <i>Prnp</i> wild-type (WT) and knock-out (KO) mice at different ages (1, 9 and 15 months). To determine the role of PrP<sup>C</sup> in skeletal muscle homeostasis during ageing, we conducted regeneration experiments via cardiotoxin injection in <i>Prnp</i> mice to assess the effects of PrP<sup>C</sup> deficiency on the senescence of satellite stem cells (SCs) and regenerative capacity in skeletal muscle.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our data demonstrate that PrP<sup>C</sup> expression increased significantly during muscle differentiation (<i>p</i> < 0.01), correlating with myogenin (immunofluorescence at the differentiation stage). PrP<sup>C</sup> deficiency disrupted muscle homeostasis, leading to age-associated mitochondrial autophagy (Pink-1, +180%, <i>p</i> < 0.001; Parkin, +161%, <i>p</i> < 0.01) and endoplasmic reticulum stress (SERCA, −26%, <i>p</i> < 0.05; IRE1<i>α</i>, +195%, <i>p</i> < 0.001) while decreasing the level of mitochondrial biogenesis (SIRT-1, −50%, <i>p</i> < 0.01; PGC-1<i>α</i>, −36%, <i>p</i> < 0.05; VDAC, −27%, <i>p</i> < 0.001), and activated oxidative stress (serum myoglobin, +23%, <i>p</i> < 0.001; MDA, +23%, <i>p</i> < 0.05; NF<i>κ</i>B, +117%, p < 0.05) during ageing, which accelerated reduced muscle growth or mass accumulation (tibialis anterior muscle mass, −23%, <i>p</i> < 0.001; gastrocnemius muscle mass, −30%, <i>p</i> < 0.001; muscle fibre size, −48%, <i>p</i> < 0.05; MSTN, +160%, <i>p</i> < 0.01; MAFbx, +83%, <i>p</i> < 0.05). Furthermore, PrP<sup>C</sup> deficiency induced the senescence (<i>β</i>-galactosidase, +60%, <i>p</i> < 0.05; p16, +103%, <i>p</i> < 0.001) of SCs, which was directly related to the defect in muscle recovery, with the senescence-mediated enhancement of adipogenesis (PPAR<i>γ</i>, +74%, <i>p</i> < 0.05) during the regeneration process after cardiotoxin-induced muscle injury.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings demonstrate that PrP<sup>C</sup> is indispensable for maintaining skeletal muscle homeostas","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13706","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050824","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":"Aptamer-Conjugated Exosomes Ameliorate Diabetes-Induced Muscle Atrophy by Enhancing SIRT1/FoxO1/3a-Mediated Mitochondrial Function","authors":"Jia Song, Mengmeng Yang, Longqing Xia, Liming Wang, Kewei Wang, Yingyue Xiang, Jun Cheng, Jun Chen, Jidong Liu, Ruxing Zhao, Fuqiang Liu, Zheng Sun, Xinguo Hou, Nan Zang, Li Chen","doi":"10.1002/jcsm.13717","DOIUrl":"10.1002/jcsm.13717","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Muscle atrophy is associated with Type 2 diabetes mellitus, which reduces the quality of life and lacks effective treatment strategies. Previously, it was determined that human umbilical cord mesenchymal stromal cell (hucMSC)–derived exosomes (EXOs) ameliorate diabetes-induced muscle atrophy. However, the systemic application of EXOs is less selective for diseased tissues, which reduces their efficacy and safety associated with their nonspecific biological distribution in vivo. Therefore, improving exosomal targeting is imperative. In this study, a skeletal muscle–specific aptamer (Apt) was used to explore the effects of Apt-functionalized EXOs derived from hucMSCs in diabetes-associated muscle atrophy and its specific mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Diabetic db/db mice and C2C12 myotubes were used to explore the effects of MSC-EXOs or Apt-EXOs in alleviating muscle atrophy. Grip strength, muscle weight and muscle fibre cross-sectional area (CSA) were used to evaluate skeletal muscle strength and muscle mass. Western blot analysis of muscle atrophy signalling, including MuRF1 and Atrogin 1 and the mitochondrial complex and Seahorse analysis were performed to investigate the underlying mechanisms of MSC-EXOs or Apt-EXOs on muscle atrophy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MSC-EXOs increased grip strength (<i>p</i> = 0.0002) and muscle mass (<i>p</i> = 0.0044 for tibialis anterior (TA) muscle, <i>p</i> = 0.002 for soleus (SO) muscle) in db/db mice. It also increased the CSA of muscle fibres (<i>p</i> = 0.0011 for all fibres, <i>p</i> = 0.0036 for slow muscle fibres and <i>p</i> = 0.0089 for fast muscle fibres) and the percentage of slow-to-fast muscle fibres (<i>p</i> = 0.0109). However, Atrogin 1 (<i>p</i> = 0.0455) and MuRF1 expression (<i>p</i> = 0.0168) was reduced. MSC-EXOs activated SIRT1/FoxO1/3a signalling and enhanced mitochondrial function in db/db mice and C2C12 myotubes. SIRT1 knockdown decreased the beneficial antiatrophic effects of MSC-EXOs. Additionally, Apt conjugation increased the effect of MSC-EXOs on muscle atrophy and myofiber-type transition (<i>p</i> = 0.0133 for grip strength, <i>p</i> = 0.0124 for TA muscle weight, <i>p</i> = 0.0008 for SO muscle weight, <i>p</i> < 0.0001 for CSA of all muscle fibres, <i>p</i> = 0.0198 for CSA of slow muscle fibres, <i>p</i> = 0.0213 for CSA of fast muscle fibres, <i>p</i> = 0.011 for percentage of slow–fast muscle fibres, <i>p</i> = 0.0141 for Atrogin 1 expression and <i>p</i> = 0.005 for MuRF1 expression).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conc","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13717","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050823","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":"A Natural Autophagy Activator Castanea crenata Flower Alleviates Skeletal Muscle Ageing","authors":"So-Hyun Park, Pyeong Geun Choi, Hee-Soo Kim, Eunyoung Lee, Da-Hye Lee, Min Jung Kim, Daedong Kim, Hyo-Deok Seo, Jeong-Hoon Hahm, Tae-Il Jeon, Yang-Hoon Huh, Jiyun Ahn, Tae-Youl Ha, Chang Hwa Jung","doi":"10.1002/jcsm.13710","DOIUrl":"10.1002/jcsm.13710","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sarcopenia, characterized by a gradual decline in skeletal muscle mass and function with age, significantly impacts both quality of life and mortality. Autophagy plays a crucial role in maintaining muscle health. There is growing interest in leveraging autophagy to mitigate muscle ageing effects. The impact of natural autophagy activators on skeletal muscle ageing remains elusive. This study aims to identify natural autophagy activators and assess their effects on skeletal muscle ageing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To discover novel autophagy activators, we screened 493 natural products and identified <i>Castanea crenata</i> flower extract (CCFE) as a promising candidate. We investigated the effect of CCFE on cellular senescence in C2C12 cells induced by etoposide. In animal experiments, aged mice (18 months old) were fed a diet supplemented with 0.1% and 0.2% CCFE for 3 months. We assessed exercise capacity, mitochondrial function and autophagic flux to determine the impact of CCFE on skeletal muscle ageing. The components present in CCFE were analysed using LC-MS/MS, and their functional properties were examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CCFE enhanced autophagic flux (LC3II 80% increase, <i>p</i> < 0.05) and reduced senescence-associated β-galactosidase activity (32.78% decrease, <i>p</i> < 0.001). In aged mice, a 3-month supplementation with CCFE improved muscle weight (18% increase, <i>p</i> < 0.05) and function (treadmill performance increased by 60%, <i>p</i> < 0.5; grip strength increased by 25%, <i>p</i> < 0.05). It alleviated mitochondrial dysfunction (basal oxygen consumption rate increased by 59%, <i>p</i> < 0.05) and restored autophagy. CCFE enhanced autophagy by activating AMPK (80% increase, <i>p</i> < 0.01) and inhibiting Atg5 protein acetylation (65% decrease, <i>p</i> < 0.001), with contributions from ellagic acid and polyamines. CCFE supplementation restored polyamine levels (serum spermidine increased from 0.98 ± 0.08 to 2.22 ± 0.05 μg/mL, <i>p</i> < 0.001) and increased urolithin levels (serum urolithin A increased from 0 to 18.79 ± 0.062 ng/mL, <i>p</i> < 0.001), metabolites produced by the gut microbiome from ellagic acid in aged mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CCFE effectively suppressed skeletal muscle ageing by preventing mitochondrial dysfunction and restoring autophagic flux in aged mice. It achieved this by modulating AMPK and EP300 acetyltransferase activity, with contributions from its co","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13710","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050926","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":"Erector Spinae Muscle to Epicardial Visceral Fat Ratio on Chest CT Predicts the Severity of Coronavirus Disease 2019","authors":"Takashi Shimada,&nbsp;Tomoki Maetani,&nbsp;Shotaro Chubachi,&nbsp;Naoya Tanabe,&nbsp;Takanori Asakura,&nbsp;Ho Namkoong,&nbsp;Hiromu Tanaka,&nbsp;Shuhei Azekawa,&nbsp;Shiro Otake,&nbsp;Kensuke Nakagawara,&nbsp;Takahiro Fukushima,&nbsp;Mayuko Watase,&nbsp;Yusuke Shiraishi,&nbsp;Hideki Terai,&nbsp;Mamoru Sasaki,&nbsp;Soichiro Ueda,&nbsp;Yukari Kato,&nbsp;Norihiro Harada,&nbsp;Shoji Suzuki,&nbsp;Shuichi Yoshida,&nbsp;Hiroki Tateno,&nbsp;Kaoruko Shimizu,&nbsp;Susumu Sato,&nbsp;Yoshitake Yamada,&nbsp;Masahiro Jinzaki,&nbsp;Toyohiro Hirai,&nbsp;Yukinori Okada,&nbsp;Ryuji Koike,&nbsp;Makoto Ishii,&nbsp;Akinori Kimura,&nbsp;Seiya Imoto,&nbsp;Satoru Miyano,&nbsp;Seishi Ogawa,&nbsp;Takanori Kanai,&nbsp;Koichi Fukunaga","doi":"10.1002/jcsm.13721","DOIUrl":"10.1002/jcsm.13721","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chest computed tomography (CT) is a valuable tool for diagnosing and predicting the severity of coronavirus disease 2019 (COVID-19) and assessing extrapulmonary organs. Reduced muscle mass and visceral fat accumulation are important features of a body composition phenotype in which obesity and muscle loss coexist, but their relationship with COVID-19 outcomes remains unclear. In this study, we aimed to investigate the association between the erector spinae muscle (ESM) to epicardial adipose tissue (EAT) ratio (ESM/EAT) on chest CT and disease severity in patients with COVID-19.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed data from 1074 COVID-19 patients enrolled in the Japan COVID-19 Task Force database. The primary outcome was the rate of critical outcomes (requiring high-flow oxygen therapy, invasive ventilator support or death). The incidence of critical outcomes was compared between patients with high and low ESM/EAT ratios.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The low ESM/EAT group (<i>n</i> = 353) had a higher incidence of critical outcomes (13.3% vs. 5.13%, <i>p</i> &lt; 0.001) and mortality (2.55% vs. 0.69%, <i>p</i> = 0.019) than the high ESM/EAT group (<i>n</i> = 721). In multivariable analysis, the low ESM/EAT ratio was associated with critical outcomes (adjusted odds ratio [aOR] 2.11, 95% confidence interval [CI] 1.22–3.66) independently of the known COVID-19 severity factors including age, sex, body mass index (BMI), smoking history, lifestyle-related comorbidities and pneumonia volume.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The low ESM/EAT ratio in COVID-19 patients can be obtained on chest CT and used to predict critical outcomes after disease onset, demonstrating the importance of detailed body composition assessments in COVID-19 practice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13721","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044706","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":"Characterization of SARS-CoV-2 Entry Genes in Skeletal Muscle and Impacts of In Vitro Versus In Vivo Infection","authors":"Salyan Bhattarai,&nbsp;Eva Kaufmann,&nbsp;Feng Liang,&nbsp;Yumin Zheng,&nbsp;Ekaterina Gusev,&nbsp;Qutayba Hamid,&nbsp;Jun Ding,&nbsp;Maziar Divangahi,&nbsp;Basil J. Petrof","doi":"10.1002/jcsm.13705","DOIUrl":"10.1002/jcsm.13705","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;COVID-19 has been associated with both respiratory (diaphragm) and non-respiratory (limb) muscle atrophy. It is unclear if SARS-CoV-2 infection of skeletal muscle plays a role in these changes. This study sought to: 1) determine if cells comprising skeletal muscle tissue, particularly myofibres, express the molecular components required for SARS-CoV-2 infection; 2) assess the capacity for direct SARS-CoV-2 infection and its impact on atrophy pathway genes in myogenic cells; and 3) in an animal model of COVID-19, examine the relationship between viral infection of skeletal muscle and myofibre atrophy within the diaphragm and limb muscles.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We used in silico bioinformatics analysis of published human single cell RNA-seq datasets, as well as direct qPCR examination of human myotubes and diaphragm biopsies, to assess expression of key genes involved in SARS-CoV-2 cellular entry. In Vitro, we determined the ability of SARS-CoV-2 to directly infect myogenic cells and employed qPCR to assess the impact on muscle atrophy pathway genes (ubiquitin-proteasome, autophagy). In vivo, the diaphragm and quadriceps of Roborovski hamsters with SARS-CoV-2 respiratory infection were examined at day 3 post-inoculation to evaluate the relationship between atrophy pathway and SARS-CoV-2 transcripts by qPCR, as well as histological measurements of myofibre morphology.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Angiotensin converting enzyme 2 (ACE2), the primary receptor for SARS-CoV-2, as well as cooperating proteases (furin, cathepsins B and L), are expressed by myofibres. ACE2 expression was increased 5-fold (&lt;i&gt;p&lt;/i&gt; = 0.01) in the diaphragms of mechanically ventilated human subjects compared to controls. In Vitro, a time-dependent increase of SARS-CoV-2 transcript levels was observed in myotubes directly exposed to the virus (&lt;i&gt;p&lt;/i&gt; = 0.002). This was associated with downregulation of the ubiquitin ligase MuRF1 (by 64%, &lt;i&gt;p&lt;/i&gt; = 0.002) and the autophagy gene LC3B (by 31%, &lt;i&gt;p&lt;/i&gt; = 0.009). In contrast, in vivo infection led to upregulation of MuRF1 in quadriceps (23-fold, &lt;i&gt;p&lt;/i&gt; = 0.0007) and autophagy genes in both quadriceps (5.2-fold for Gabarapl1, &lt;i&gt;p&lt;/i&gt; = 0.03; 7-fold for p62, &lt;i&gt;p&lt;/i&gt; = 0.0002) and diaphragm (2.2-fold for Gabarapl1, &lt;i&gt;p&lt;/i&gt; = 0.03; 2.3-fold for p62, &lt;i&gt;p&lt;/i&gt; = 0.057). In infected hamsters the diaphragm lacked viral transcripts but exhibited atrophy (48% decrease in myofibre area; &lt;i&gt;p&lt;/i&gt; = 0.02), whereas the quadriceps lacked myofibre atrophy despite elevated viral transcripts in the muscle.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;s","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13705","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050807","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":"Testosterone Modulation of Muscle Transcriptomic Profile During Lifestyle Therapy in Older Men with Obesity and Hypogonadism","authors":"Viola Viola,&nbsp;Tagari Samanta,&nbsp;Maria Liza Duremdes Nava,&nbsp;Alessandra Celli,&nbsp;Reina Armamento-Villareal,&nbsp;Ngoc Ho Lam Nguyen,&nbsp;Georgia Colleluori,&nbsp;Yoann Barnouin,&nbsp;Nicola Napoli,&nbsp;Clifford Qualls,&nbsp;Benny Abraham Kaipparettu,&nbsp;Dennis T. Villareal","doi":"10.1002/jcsm.13697","DOIUrl":"10.1002/jcsm.13697","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Testosterone replacement therapy (TRT) added to lifestyle therapy can mitigate weight-loss–induced reduction of muscle mass and bone mineral density (BMD) in older men with obesity and hypogonadism.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;To investigate the molecular mechanisms underlying the attenuation of muscle and BMD loss in response to TRT during intensive lifestyle intervention in this high-risk older population.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Among 83 older (≥ 65 years) men with obesity (BMI ≥ 30 kg/m&lt;sup&gt;2&lt;/sup&gt;) and hypogonadism (early AM testosterone persistently &lt; 300 ng/dL) associated with frailty (Modified Physical Performance Test score ≤ 31) randomized into 26-week lifestyle therapy plus testosterone (LT+TRT) or placebo (LT+Pbo) in the LITROS trial, 38 underwent serial muscle biopsies for the muscle transcriptomics substudy.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Despite similar ~10% weight loss, lean body mass and thigh muscle volume decreased less in LT+TRT than LT+Pbo (−2% vs. −4%, respectively; &lt;i&gt;p&lt;/i&gt; = 0.04). Hip BMD was preserved in LT+TRT compared with LT+Pbo (0.4% vs. −1.3%; &lt;i&gt;p&lt;/i&gt; = 0.03). Muscle strength increased similarly in LT+TRT and LT+Pbo (23% vs. 24%; &lt;i&gt;p&lt;/i&gt; = 0.95). Total testosterone increased more in LT+TRT than LT+Pbo (133% vs. 32%; &lt;i&gt;p&lt;/i&gt; = 0.005). Based on Next Generation Sequencing, of the 39 160 and 39 115 genes detected in LT+TRT and LT+Pbo, respectively, 195 were differentially expressed in LT+TRT and 158 in LT+Pbo. Gene Ontology enrichment analyses revealed that in LT+TRT, just four muscle-related pathways (muscle organ development, muscle organ morphogenesis, regulation of skeletal muscle contraction, muscle atrophy) were downregulated and one pathway (muscle system process) was upregulated. In contrast, in LT+Pbo, nine muscle-related pathways (muscle system process, muscle tissue development, muscle organ development, skeletal muscle tissue development, skeletal muscle organ development, skeletal muscle cell differentiation, muscle organ morphogenesis, response to stimuli involved in regulation of muscle adaptation, muscle atrophy) and one pathway related to bone (bone mineralization involved in bone maturation) were downregulated. Muscle system process was upregulated in LT+TRT but downregulated in LT+Pbo. RT-PCR analyses showed that LT+TRT resulted in a higher expression of MYOD1 (&lt;i&gt;p&lt;/i&gt; = 0.02) and WNT4 (&lt;i&gt;p&lt;/i&gt; = 0.02), key genes involved in muscle and bone metabolism, respectively, compared with LT+Pbo. We also obse","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13697","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044274","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":"Transcriptomic Profiling Reveals 17β-Estradiol Treatment Represses Ubiquitin-Proteasomal Mediators in Skeletal Muscle of Ovariectomized Mice","authors":"Georgios Kararigas,&nbsp;Mara C. Ebeling,&nbsp;Gengyun Le,&nbsp;Shaojuan Lai,&nbsp;Chunmei Cui,&nbsp;Qinghua Cui,&nbsp;Dawn A. Lowe","doi":"10.1002/jcsm.13698","DOIUrl":"10.1002/jcsm.13698","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>With a decline of 17β-estradiol (E2) at menopause, E2 has been implicated in the accompanied loss of skeletal muscle mass and strength. We aimed at characterizing transcriptomic responses of skeletal muscle to E2 in female mice, testing the hypothesis that genes and pathways related to contraction and maintenance of mass are differentially expressed in ovariectomized mice with and without E2 treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Soleus and tibialis anterior (TA) muscles from C57BL/6 ovariectomized mice treated with placebo (OVX) or E2 (OVX + E2) for 60 days, or from skeletal muscle-specific ERα knockout (skmERαKO) mice and wild-type littermates (skmERαWT), were used for genome-wide expression profiling, quantitative real-time PCR and immunoblotting. Computational detection of estrogen response elements (EREs) was performed with EREFINDER.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found 155 significantly regulated probe sets in response to E2 (<i>p</i> ≤ 0.001). Pathway analyses identified proteasome and ubiquitin-mediated proteolysis as two downregulated pathways in the E2 group. We confirmed downregulation (<i>p</i> ≤ 0.05) in levels of <i>Fbxw7</i>, <i>Psmb6</i>, <i>Ube2h</i> and <i>Ubxn1</i>, as well as pro-apoptotic <i>Bnip3</i> and inflammatory factor <i>Nfkbia</i>. Computational analysis identified ERE in the promoter regions of <i>Psmb6</i>, <i>Ube2h</i>, <i>Bnip3</i> and <i>Nfkbia</i>. The overall content of ubiquitinated proteins was modestly but significantly lower in TA muscles from OVX + E2 vs. OVX mice (<i>p</i> = 0.039). There were no differences between skmERαKO and skmERαWT mice or between skmERαKO/OVX and skmERαKO/OVX + E2 mice for any genes assessed, indicating that ERα is required for E2 regulation of those genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results suggest that a mechanism whereby E2 protects against losses of skeletal muscle mass and strength is regulation of ubiquitin-proteasomal mediators.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13698","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030925","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":"Descriptive Epidemiology and Prognostic Significance of Diaphragm Thickness in the General Population: The Nagahama Study","authors":"Yasuharu Tabara,&nbsp;Takeshi Matsumoto,&nbsp;Kimihiko Murase,&nbsp;Takahisa Kawaguchi,&nbsp;Kazuya Setoh,&nbsp;Tomoko Wakamura,&nbsp;Toyohiro Hirai,&nbsp;Kazuo Chin,&nbsp;Fumihiko Matsuda","doi":"10.1002/jcsm.13690","DOIUrl":"10.1002/jcsm.13690","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Diaphragm thickness is a potential marker of sarcopenia in addition to muscle mass and strength at extremities. We aimed to clarify the descriptive epidemiology and prognostic significance of diaphragm thickness in the general population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study participants were 3324 community residents (mean age: 61.4 ± 12.8 years) who participated in a longitudinal cohort study. Clinical parameters were obtained during the follow-up survey of the study population. Diaphragm thickness was measured from B-mode ultrasound images obtained in a supine position. Clinical and physical factors independently associated with diaphragm thickness were assessed by a linear regression model and a causal mediation analysis. All-cause mortality was determined by reviewing residential registry records. Prognostic significance of diaphragm thickness for all-cause mortality was examined using a Cox proportional hazard model analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Diaphragm thickness was greater in men than women (end-expiration, β = 0.161, <i>p</i> &lt; 0.001; end-inspiration, β = 0.156, <i>p</i> &lt; 0.001) and associated with waist circumference (end-expiration, β = 0.259, <i>p</i> &lt; 0.001; end-inspiration, β = 0.128, <i>p</i> &lt; 0.001). Handgrip strength, smoking habit, insulin resistance and exercise habit were not associated with diaphragm thickness. Skeletal muscle mass index showed apparent association with diaphragm thickness, though this association was not observed after adjusting for waist circumference. Over a mean follow-up of 1686 days (15 358 person-years), there were 56 cases of all-cause mortality. Weak handgrip strength (hazard ratio = 0.95, <i>p</i> = 0.044) and low forced vital capacity (hazard ratio = 0.57, <i>p</i> = 0.045) were associated with all-cause mortality, though none of the diaphragm thickness parameters showed a significant association (thickness at end-expiration, <i>p</i> = 0.722; thickness at end-inspiration, <i>p</i> = 0.277; thickening fraction, <i>p</i> = 0.219).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Waist circumference but not parameters of sarcopenia was independently associated with diaphragm thickness. Diaphragm thickness was not associated with all-cause mortality. Diaphragm thickness may not be a marker of systemic sarcopenia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13690","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030924","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":"Prevalence of Cachexia and Outcomes in Patients With Chronic Diseases: A National Database Analysis of 5 484 103 Hospitalisations","authors":"Mitja Lainscak,&nbsp;Tina Zupanic,&nbsp;Daniel Omersa,&nbsp;Ivan Erzen,&nbsp;Jerneja Farkas","doi":"10.1002/jcsm.13688","DOIUrl":"10.1002/jcsm.13688","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cachexia is a frequent companion of chronic diseases and a well-established predictor of poor patient performance and outcome. Since cachexia as a discharge diagnosis is not much investigated, we aimed to investigate prevalence of cachexia in hospitalised patients and their outcome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective analysis of the National Hospital Health Care Statistics Database using the 10th revision of the International Classification of Diseases codes. During period 2004–2019, patients with cachexia were identified, as well as patients with cancer, heart failure, chronic obstructive pulmonary disease and chronic kidney disease. The primary endpoint was the discharge code of cachexia; secondary endpoints were length of hospital stay, in-hospital and post discharge all-cause mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In period 2004–2019, 5 484 103 hospitalisations were screened; cachexia was coded 19 348 times (0.35%) in 14 089 patients (67 ± 13 years, 42% women). From 2004 to 2019, prevalence of cachexia increased steadily from 1.2% to 1.9%, which was most prominent for cancer and chronic obstructive pulmonary disease. At one year post discharge, 49% patients with cachexia were dead as compared to 26% in patients without cachexia. In Cox multivariate analysis, cachexia predicted post-discharge death in any of chronic diseases (hazard ratio of 1.28 in heart failure to 1.47 in chronic kidney disease).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In our report from a National Hospital Health Care Statistics Database, we found that cachexia was underreported as ICD-10 coded discharge diagnosis in patients with chronic diseases. When diagnosed, it was associated with higher hazard of post discharge mortality.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13688","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990556","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":"Muscle Loss During First-Line Chemotherapy Impairs Survival in Advanced Pancreatic Cancer Despite Adapted Physical Activity","authors":"Pauline Parent,&nbsp;Frédéric Pigneur,&nbsp;Marc Hilmi,&nbsp;Aurélien Carnot,&nbsp;Marie-Line Garcia Larnicol,&nbsp;Dewi Vernerey,&nbsp;Alain Luciani,&nbsp;Pascal Hammel,&nbsp;Julie Henriques,&nbsp;Cindy Neuzillet,&nbsp;Anthony Turpin","doi":"10.1002/jcsm.13595","DOIUrl":"10.1002/jcsm.13595","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Advanced pancreatic ductal adenocarcinoma (aPDAC) is often accompanied by significant muscle mass loss, contributing to poor prognosis. SarcAPACaP, an ancillary study of the GERCOR-APACaP phase III trial, evaluated the role of adapted physical activity (APA) in aPDAC Western patients receiving first-line chemotherapy. The study aimed to assess (1) the potential impact of computed tomography (CT)–quantified muscle mass before and during treatments on health-related quality of life (HRQoL) and overall survival (OS) and (2) the role of APA in mitigating muscle mass loss.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In the APACaP trial, aPDAC patients with ECOG performance status (PS) 0–2 were randomized 1:1 to usual care including first-line chemotherapy or usual care plus a 16-week home-based APA program. In the SarcAPACaP study, the surface muscular index (SMI) was determined from L3 CT scan slices. Two patient populations were analysed: those with CT scan available at baseline (modified[m] intent-to-treat [ITT]1-W0) and those with CT scans available at both W0 and W16 (mITT2 W0–W16). Low muscle mass was defined by low SMI with SMI &lt; 41 cm&lt;sup&gt;2&lt;/sup&gt;/m&lt;sup&gt;2&lt;/sup&gt; for women and &lt; 43 and &lt; 53 cm&lt;sup&gt;2&lt;/sup&gt;/m&lt;sup&gt;2&lt;/sup&gt; for men with body max index &lt; 25.0 and ≥ 25.0 kg/m&lt;sup&gt;2&lt;/sup&gt;, respectively. Muscle loss was defined by the relative difference of SMI between W0 and W16 (100*[SMI W16–SMI W0]/SMI W0). In mITT2 W0–W16, patients were stratified into three groups based on the severity of muscle loss: none, moderate (0%–10%) and high (≥ 10%). Associations between muscle mass loss and OS, time until definitive deterioration (TUDD) of HRQoL and the effect of APA on loss of muscle mass were assessed.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Between October 2014 and May 2020, 313 patients were prospectively enrolled, with 225 in mITT1 W0 and 128 in mITT2 W0–W16, with 65 assigned to the APA arm. Both groups had similar baseline characteristics with comparable OS and TUDD. A low SMI at W0 was not associated with OS and TUDD of HRQoL in either group. Among mITT2 W0–W16 patients, high muscle mass loss (&lt;i&gt;n&lt;/i&gt; = 27) independently predicted OS (&lt;i&gt;p&lt;/i&gt; = 0.012) and showed a trend toward negatively affecting TUDD of HRQoL. Notably, APA did not mitigate muscle loss in our study population.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Longitudinal muscle mass loss emerged as a predictive factor for both OS and HRQoL in aPDAC patients undergoing chemotherapy, while a low SMI at diagnosis did not prov","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13595","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988834","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}