Journal of Cachexia Sarcopenia and Muscle最新文献

{"title":"Heavy Strength Training in Older Adults: Implications for Health, Disease and Physical Performance","authors":"Tiril Tøien,&nbsp;Ole Kristian Berg,&nbsp;Roberto Modena,&nbsp;Mathias Forsberg Brobakken,&nbsp;Eivind Wang","doi":"10.1002/jcsm.13804","DOIUrl":"https://doi.org/10.1002/jcsm.13804","url":null,"abstract":"<p>Older adults typically exhibit reductions in skeletal muscle maximal strength and the ability to produce force rapidly. These reductions are often augmented by concomitant acute and chronic diseases, resulting in attenuated physical performance and higher propensity of falls and injuries. With the proportion of older adults in the population increasing, there is an alarming need for cost-effective strategies to improve physical performance and combat a multitude of age-related diseases. Surprisingly, despite convincing evidence emerging over three decades that strength training can substantially improve maximal strength (1RM), rate of force development (RFD) and power, contributing to improved health, physical performance and fall prevention, it appears that it has not fully arrived at the older adults' doorsteps. The aim of the current narrative review is to accentuate the convincing benefits of strength training in healthy and diseased older adults. As intensity appears to play a key role for improvements in 1RM, RFD and power, this review will emphasize training performed with heavy (80%–84% of 1RM) and very heavy loads (≥ 85% of 1RM), where the latter is often referred to as maximal strength training (MST). MST uses loads of ~90% of 1RM, which can only be performed a maximum of 3–5 times, 3–5 sets and maximal intentional concentric velocity. Strength training performed with loads in the heavy to very heavy domain of the spectrum may, because of the large increases in muscle strength, focuses on neural adaptations and relatively low risk, provides additional benefits for older adults and contrasts current guidelines which recommend low-to-moderate intensity (60%–70% of 1RM) and slow-moderate concentric velocity. This review also provides information on practical application of MST aimed at practitioners who are involved with preventive and/or rehabilitative health care for older adults.</p>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13804","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840799","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":"Housing Temperature Impacts the Systemic and Tissue-Specific Molecular Responses to Cancer in Mice","authors":"Andrea Irazoki,&nbsp;Emma Frank,&nbsp;Tang Cam Phung Pham,&nbsp;Jessica L. Braun,&nbsp;Amy M. Ehrlich,&nbsp;Mark Haid,&nbsp;Fabien Riols,&nbsp;Camilla Hartmann Friis Hansen,&nbsp;Anne-Sofie Rydal Jørgensen,&nbsp;Nicoline Resen Andersen,&nbsp;Laura Hidalgo-Corbacho,&nbsp;Roberto Meneses-Valdes,&nbsp;Mona Sadek Ali,&nbsp;Steffen Henning Raun,&nbsp;Johanne Louise Modvig,&nbsp;Samantha Gallero,&nbsp;Steen Larsen,&nbsp;Zach Gerhart-Hines,&nbsp;Thomas Elbenhardt Jensen,&nbsp;Maria Rohm,&nbsp;Jonas T. Treebak,&nbsp;Val Andrew Fajardo,&nbsp;Lykke Sylow","doi":"10.1002/jcsm.13781","DOIUrl":"https://doi.org/10.1002/jcsm.13781","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;Cancer cachexia, affecting up to 80% of patients with cancer, is characterized by muscle and fat loss with functional decline. Preclinical research seeks to uncover the molecular mechanisms underlying cachexia to identify potential targets. Housing laboratory mice at ambient temperature induces cold stress, triggering thermogenic activity and metabolic adaptations. Yet, the impact of housing temperature on preclinical cachexia remains unknown.&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;Colon 26 carcinoma (C26)-bearing and PBS-inoculated (Ctrl) mice were housed at standard (ST; 20°C–22°C) or thermoneutral temperature (TN; 28°C–32°C). They were monitored for body weight, composition, food intake and systemic factors. Upon necropsy, tissues were weighed and used for evaluation of ex vivo force and respiration, or snap frozen for biochemical assays.&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;C26 mice lost 7.5% body weight (&lt;i&gt;p&lt;/i&gt; = 0.0001 vs. Ctrls), accounted by decreased fat mass (−35%, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001 vs. Ctrls), showing mild cachexia irrespective of housing temperature. All C26 mice exhibited reduced force (−40%, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001 vs. Ctrls) and increased atrogene expression (3-fold, &lt;i&gt;p&lt;/i&gt; &lt; 0.003 vs. Ctrls). Cancer altered white adipose tissue (WAT)'s functional gene signature (49%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05 vs. Ctrls), whereas housing temperature reduced brown adipose tissue (BAT)'s (−78%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05 vs. ST Ctrl). Thermogenic capacity measured by &lt;i&gt;Ucp1&lt;/i&gt; expression decreased upon cancer in both WAT and BAT (−93% and −63%, &lt;i&gt;p&lt;/i&gt; &lt; 0.0044 vs. Ctrls). Cancer-driven glucose intolerance was noted at ST (26%, &lt;i&gt;p&lt;/i&gt; = 0.0192 vs. ST Ctrl), but restored at TN (−23%, &lt;i&gt;p&lt;/i&gt; = 0.005 vs. ST C26). Circulating FGF21, GDF-15 and IL-6 increased in all C26 mice (4-fold, &lt;i&gt;p&lt;/i&gt; &lt; 0.009 vs. Ctrls), with a greater effect on IL-6 at TN (76%, &lt;i&gt;p&lt;/i&gt; = 0.0018 vs. ST C26). Tumour and WAT &lt;i&gt;Il6&lt;/i&gt; mRNA levels remained unchanged, while cancer induced skeletal muscle (SkM) &lt;i&gt;Il6&lt;/i&gt; (2-fold, &lt;i&gt;p&lt;/i&gt; = 0.0016 vs. Ctrls) at both temperatures. BAT &lt;i&gt;Il6&lt;/i&gt; was only induced in C26 mice at TN (116%, &lt;i&gt;p&lt;/i&gt; = 0.0087 vs. ST C26). At the bioenergetics level, cancer increased SkM SERCA ATPase activity at ST (4-fold, &lt;i&gt;p&lt;/i&gt; = 0.0108 vs. ST Ctrl) but not at TN. In BAT, O&lt;sub&gt;2&lt;/sub&gt; consumption enhanced in C26 mice at ST (119%, &lt;i&gt;p&lt;/i&gt; &lt; 0.03 vs. ST Ctrl) but was blunted at TN (−44%, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001 vs. ST C26). Cancer increased BAT ATP levels regardless of temperature (2-fold, &lt;i&gt;p&lt;/i&gt; = 0.0046 vs. Ctrls), while SERCA ATPase activity remained unchanged at ST and decreased at TN (−","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13781","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835942","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":"Loss of popdc3 Impairs Mitochondrial Function and Causes Skeletal Muscle Atrophy and Reduced Swimming Ability in Zebrafish","authors":"Chen-Chen Sun,&nbsp;Zhang-Lin Chen,&nbsp;Dong Yang,&nbsp;Jiang-Ling Xiao,&nbsp;Xiang-Tao Chen,&nbsp;Xi-Yang Peng,&nbsp;Xiu-Shan Wu,&nbsp;Chang-Fa Tang","doi":"10.1002/jcsm.13794","DOIUrl":"https://doi.org/10.1002/jcsm.13794","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;The Popeye domain containing 3 (POPDC3) protein is essential for the maintenance of skeletal muscle homeostasis. POPDC3 is a pathogenic variant gene of limb-girdle muscular dystrophy (LGMD), and its variants lead to LGMDR26. At the animal level, zebrafish larvae with &lt;i&gt;popdc3&lt;/i&gt; mutations develop tail curls and muscle atrophy. However, the mechanism of skeletal muscle atrophy induced by &lt;i&gt;POPDC3&lt;/i&gt; variants/loss remains unclear.&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;Eight-month-old male WT and &lt;i&gt;popdc3&lt;/i&gt; mKO zebrafish were used for this research. Loli Track (Denwmark) and Loligo Swimming Respirometer were used to observe the zebrafish's swimming ability. The zebrafish skeletal muscle structure and cross-sectional area (CSA) were observed and counted by transmission electron microscopy (TEM), H&amp;E and wheat germ agglutinin (WGA). Enriched genes and signalling pathways were analysed using RNA sequencing, and the effects of &lt;i&gt;popdc3&lt;/i&gt; mKO on zebrafish skeletal muscle mitochondrial respiration, biogenesis and dynamics were examined to investigate possible mechanisms.&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;The swimming ability of &lt;i&gt;popdc3&lt;/i&gt; mKO zebrafish was reduced, and as evidenced by the reluctance to move, fewer movement trajectories, the total distance travelled (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), the average velocity of movement (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), oxygen consumption (MO&lt;sub&gt;2&lt;/sub&gt;) (&lt;i&gt;p&lt;/i&gt; &lt; 0.01), maximum oxygen consumption (MO&lt;sub&gt;2max&lt;/sub&gt;) (&lt;i&gt;p&lt;/i&gt; &lt; 0.05), critical swimming speed (U&lt;sub&gt;crit&lt;/sub&gt;) (&lt;i&gt;p&lt;/i&gt; &lt; 0.01) and relative swimming speed (U&lt;sub&gt;crit-r&lt;/sub&gt;) (&lt;i&gt;p&lt;/i&gt; &lt; 0.01) were significantly decreased and increased of the exhaustive swimming time (&lt;i&gt;p&lt;/i&gt; &lt; 0.01). In addition, loss of &lt;i&gt;popdc3&lt;/i&gt; reduced zebrafish skeletal muscle weight (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), muscle/body weight (&lt;i&gt;p&lt;/i&gt; &lt; 0.01), myofibre size and CSA (&lt;i&gt;p&lt;/i&gt; &lt; 0.01), increased protein degradation (ubiquitination and autophagy) (&lt;i&gt;p&lt;/i&gt; &lt; 0.05) and decreased protein synthesis (&lt;i&gt;p&lt;/i&gt; &lt; 0.05), suggesting that &lt;i&gt;popdc3&lt;/i&gt; deficiency induces zebrafish skeletal muscle atrophy. Further, &lt;i&gt;popdc3&lt;/i&gt; mKO zebrafish mitochondrial function is reduced, as evidenced by impaired mitochondrial respiration, decreased biogenesis and kinetic imbalance (&lt;i&gt;p&lt;/i&gt; &lt; 0.05).&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;POPDC3, a Popeye protein, plays an important role in controlling mitochondrial function and skeletal muscle mass and strength. Loss of &lt;i&gt;popdc3&lt;/i&gt; decreases m","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13794","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835941","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":"Transcriptional Intermediary Factor 1γ–Induced Irisin in Skeletal Muscle Attenuates Renal Fibrosis in Diabetic Nephropathy","authors":"Jin Hyun Kim,&nbsp;Seunghye Lee,&nbsp;Hani Jang,&nbsp;Sehyun Jung,&nbsp;Myeong Hee Jung,&nbsp;Jeong Won Yun,&nbsp;Haejin Jeon,&nbsp;Hyun-Jung Kim,&nbsp;Se-Ho Chang,&nbsp;Eun Ju Lee,&nbsp;Hyo-Soo Kim","doi":"10.1002/jcsm.13810","DOIUrl":"https://doi.org/10.1002/jcsm.13810","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;Transcriptional intermediary factor 1γ (TIF1γ) is a negative regulator of TGF-β1 signalling and has been associated with patient survival in renal cell carcinoma. However, its role in diabetes mellitus (DM), particularly in diabetic nephropathy (DN), remains unclear. DN is the leading cause of chronic kidney disease (CKD). We investigated the potential role of TIF1γ in mitigating multiple DM-related complications.&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;Mice were divided into four groups: &lt;i&gt;db&lt;/i&gt;/m+, &lt;i&gt;db/db&lt;/i&gt; and &lt;i&gt;db/db&lt;/i&gt; mice treated with cytomegalovirus- or TGF-TIF1γ plasmids (40 μg/mouse; intraperitoneally weekly for 16 weeks). Renal injury, fibrosis, function and gene expression related to fibrosis and epithelial–mesenchymal transition (EMT) in the kidneys were assessed. Muscle atrophy, regeneration markers, myokine levels and exercise capacity were evaluated. C2C12 cells were exposed to palmitate with or without TIF1γ transfection, and irisin expression and secretion were measured. Muscle-kidney crosstalk was analysed using conditioned media (CM) from TIF1γ-transfected C2C12 cells in palmitate-treated human kidney (HK)-2 cells. Additionally, HK-2 cells were incubated in CM from fibronectin type III domain-containing protein (FNDC)5-knockdown C2C12 cells to confirm irisin-mediated kidney crosstalk by TIF1γ.&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;TIF1γ treatment in &lt;i&gt;db/db&lt;/i&gt; mice resulted in a significant attenuation of renal tubulointerstitial fibrosis (1.5-fold decrease), glomerular injury (1.8-fold improvement), tubular injury (1.6-fold improvement), renal dysfunction (1.7-fold improvement) and a reduction in EMT-related factors (1.8-fold decrease) (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). The levels of administered TIF1γ plasmids were higher in skeletal muscle than in renal tissues. TIF1γ expression was significantly elevated in the skeletal muscle of &lt;i&gt;db/db&lt;/i&gt; mice treated with TIF1γ plasmids (6.5-fold) (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Mice receiving both plasmids exhibited a 1.8-fold reduction in pathological muscle morphology and atrophy-related gene expression, a 3.0-fold increase in regeneration-related gene expression and a 1.6-fold improvement in muscle function (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Irisin expression increased by 2.1-fold in skeletal muscle and serum (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). In TIF1γ-transfected C2C12 cells, irisin secretion was elevated by 1.5-fold (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). CM from TIF1γ-transfected C2C12 cells attenuated EMT in palmitate-treated HK-2 cells, compared with medium from nontransfected C2C12 cells (1.9-fold improvement [&lt;i&gt;p&lt;/i&gt; &lt; 0.05]). Conversely, FNDC5 knockdown in C2C12 cells accel","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13810","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835874","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":"Nutritional Status Predicts Functional Recovery and Adverse Outcomes in Older Adults: A Prospective Cohort Study","authors":"Ludiane Alves do Nascimento,&nbsp;Marlon Juliano Romero Aliberti,&nbsp;Natalia Golin,&nbsp;Erika Suíter,&nbsp;Christian Valle Morinaga,&nbsp;Thiago Junqueira Avelino Silva,&nbsp;Pedro Kallas Curiati","doi":"10.1002/jcsm.13819","DOIUrl":"https://doi.org/10.1002/jcsm.13819","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;Despite the high prevalence of malnutrition in acutely ill older patients, nutritional status is rarely assessed in emergency departments (EDs), and the impact of nutritional risk screening on functional recovery is poorly understood. This study aimed to investigate the association between nutritional parameters and a range of outcomes in older patients admitted through the ED.&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;A prospective cohort study was conducted at tertiary hospital, enrolling patients aged 65 years or older between November 2021 and April 2022. We collected data on various patient parameters, including demographics, clinical factors (Charlson Comorbidity Index [CCI], National Early Warning Score 2), nutritional status (Nutritional Risk Screening 2002; Global Leadership Initiative on Malnutrition criteria) and geriatric measures (Clinical Frailty Scale, Katz Index of Independence in Activities of Daily Living [ADL], Lawton and Brody Instrumental ADL, and PRO-AGE vulnerability tool). The primary outcome was functional recovery, and secondary outcomes included nosocomial infection, prolonged length of stay (LoS), in-hospital and postdischarge mortality, and hospital readmissions up to 6 months. Fine–Gray competing risks regression and multivariable logistic regressions were employed and adjusted for age, sex, education, CCI, functional status, LoS and initial allocation to intensive care.&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;A total of 780 patients (mean age 80 ± 9 years, predominantly male) were included, with 32.2% identified as at nutritional risk and 22.1% diagnosed with malnutrition. Patients with no nutritional risk had a higher significantly functional recovery up to 6 months (79% vs. 66%, sub-HR = 1.28, 95%CI 1.04–1.57, &lt;i&gt;p&lt;/i&gt; = 0.029), whereas nutritional risk was independently associated with in-hospital (13% vs. 2%, OR = 4.24, 95%CI 1.53–11.74, &lt;i&gt;p&lt;/i&gt; = 0.005) and postdischarge (14% vs. 4%, OR = 2.76, 95%CI 1.17–6.49, &lt;i&gt;p&lt;/i&gt; = 0.02) mortality. Finally, malnutrition was independently associated with nosocomial infection (12% vs. 2%, OR = 5.43, 95%CI 2.56–11.5, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), prolonged LoS (56% vs. 22%, OR = 2.79, 95%CI 1.84–4.22, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) and postdischarge mortality (13% vs. 4%, OR = 2.76, 95%CI 1.36–5.61, &lt;i&gt;p&lt;/i&gt; = 0.005).&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;Nutritional parameters were significant predictors of functional recovery, nosocomial infection, prolonged LoS and mortality in older patients admitted through the ED. Early ident","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13819","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835772","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":"Comprehensive Evaluation of Frailty and Sarcopenia Markers to Predict Survival in Glioblastoma Patients","authors":"Chao Yang,&nbsp;Chao Ma,&nbsp;Cheng-Shi Xu,&nbsp;Si-Rui Li,&nbsp;Chen Li,&nbsp;Ze-Fen Wang,&nbsp;Zhi-Qiang Li","doi":"10.1002/jcsm.13809","DOIUrl":"https://doi.org/10.1002/jcsm.13809","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;Glioblastoma (GBM) is the most common primary malignant brain tumour in adults. Patients with GBM are particularly susceptible to moderate-to-high frail. Frailty status has been associated with the outcome of many types of cancer, including GBM, although there is still little consensus regarding the specific criteria for assessing frailty status. This study aimed to determine the predictive significance of the modified frailty score (mFS) in GBM patients using haematological and sarcopenia indicators.&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;Between January 2016 and September 2022, we enrolled 309 adult GBM patients. Data on demographics, haematological examination, and temporal muscle thickness (TMT) were collected and assessed. The prognostic relevance of the frailty parameters was established using Kaplan–Meier and Cox proportional model. The scoring systems were created by integrating these indicators. Variables with independent prognostic values were used to construct the nomograms. Nomogram accuracy was evaluated using the calibration curve, Harrell's concordance index (C-index), and time-dependent receiver operating characteristic curves. Clinical practicality was assessed using decision curve analysis.&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;The baseline characteristics of the 309 participants revealed a median age of 59 years (interquartile range 52–66) with a predominance of male patients (58.58%). TMT (hazard ratio [HR] = 3.787, 95% confidence interval [CI] 2.576–5.566, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), prognostic nutritional index (HR = 1.722, 95% CI 1.098–2.703, &lt;i&gt;p&lt;/i&gt; = 0.018), and mean corpuscular volume (HR = 1.958, 95% CI 1.111–3.451, &lt;i&gt;p&lt;/i&gt; = 0.020) were identified as independent prognostic markers. The constructed mFS, obtained by integrating these three indices, exhibited independent prognostic significance (HR = 2.461, 95% CI 1.751–3.457, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). The patients in the low-risk group had a median overall survival (OS) of 13.9 months, while the patients in the high risk had a median OS of 5.8 months. Importantly, the mFS demonstrated significant independent prognostic value in the subgroup aged &gt; 65 (HR = 1.822, 95% CI 1.011–3.284, &lt;i&gt;p&lt;/i&gt; = 0.046). The nomogram, which included the mFS, demonstrated high accuracy, with a c-index of 0.781. The nomogram bootstrapped calibration plot also performed well compared to the ideal model. Nomograms showed promising discriminative potential, with time-dependent areas under the curves of 0.945, 0.835, and 0.820 for 0.5-, 1-, and 2-year overall survival prediction, respectively.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13809","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835868","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":"HD6277 Suppresses Muscle Atrophy by Promoting Myogenic Factors and Inhibiting Proteolysis in Aged Mice","authors":"Joo Won Kim,&nbsp;SukHwan Yun,&nbsp;Min Jeong Park,&nbsp;Eyun Song,&nbsp;Sooyeon Jang,&nbsp;Ahreum Jang,&nbsp;Kyung Mook Choi,&nbsp;Sei Hyun Baik,&nbsp;Hwan-Jin Hwang,&nbsp;Hye Jin Yoo","doi":"10.1002/jcsm.13805","DOIUrl":"https://doi.org/10.1002/jcsm.13805","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>G protein–coupled receptor 40 (GPR40) acts as a modulator of various physiological functions, including glycaemic lowering, anti-inflammation and antioxidative stress, in several tissues. However, the role of GPR40 in skeletal muscles remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To investigate the roles of muscle GPR40, C2C12 myoblasts and myotubes were stimulated with palmitate and HD6277, a GPR40 agonist. Muscle strength and myofiber thickness were measured in obese and aged mice fed HD6277.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In C2C12 myoblasts, the addition of HD6277 induced phosphorylated Akt levels and expression of the myogenic factors, myogenin (MyoG), myocyte enhancer factor 2C (Mef2c) and myosin heavy chain (MyHC, <i>p</i> &lt; 0.05). These changes resulted in accelerated muscle differentiation from myoblasts to myotubes (MyHC-positive area +56.52%; myotube width +34.08% vs. Veh, <i>p</i> &lt; 0.05). In C2C12 myotubes, a palmitate-mediated decrease in the phosphorylation of forkhead box protein O1A (FOXO1A) and increase in the expression of E3 ubiquitin ligases, atrogin-1 and muscle RING-finger protein 1 (MuRF1) were reversed by HD6277 (<i>p</i> &lt; 0.05). Additionally, HD6277 inhibited palmitate-induced apoptotic events such as the Bcl-2 (Bcl2)-associated X protein (Bax)/Bcl-2 ratio, caspase 3 cleavage and nuclear fragmentation in C2C12 myoblasts and myotubes (<i>p</i> &lt; 0.05). These beneficial HD6277-mediated actions disappeared after the addition of an Akt inhibitor (<i>p</i> &lt; 0.05). Similar to in vitro studies, HD6277 administration in obese and aged mice increased myogenic factors and decreased E3 ubiquitin ligase expression and apoptotic events (<i>p</i> &lt; 0.05). HD6277 increased muscle strength (+9.88% vs. Aged, <i>p</i> &lt; 0.05) and myofiber thickness (+29.01% vs. Aged, <i>p</i> &lt; 0.05) in aging mice but only improved myofiber thickness (+11.84% vs. HFD, <i>p</i> &lt; 0.05) in obese mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>HD6277 can increase myogenic factors and reduce E3 ligase-mediated proteolysis to inhibit muscle atrophy in aged mice. Our results suggest that GPR40 agonists may have potential as therapeutic agents for sarcopenia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13805","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143830984","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 of Appendicular Skeletal Muscle Mass Index and Insulin Resistance With Mortality in Multi-Nationwide Cohorts","authors":"Shinje Moon,&nbsp;Jong Wook Choi,&nbsp;Jung Hwan Park,&nbsp;Dong Sun Kim,&nbsp;Youhern Ahn,&nbsp;Yeongmin Kim,&nbsp;Sung Hye Kong,&nbsp;Chang-Myung Oh","doi":"10.1002/jcsm.13811","DOIUrl":"https://doi.org/10.1002/jcsm.13811","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;Although sarcopenia and insulin resistance are closely related, there is limited evidence regarding how they interact to influence mortality across different population groups. The purpose of this study was to examine the relationship between skeletal muscle mass and insulin resistance and its impact on mortality and cardiovascular disease risk using large-scale national data from Korea and the United States.&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 analysed data from the National Health and Nutrition Examination Survey (NHANES) 1999–2006 and 2011–2018 and the Korea National Health and Nutrition Examination Survey (KNHANES) 2008–2011, with mortality follow-up through to 2019. Cox regression models were used to assess the effects of muscle mass (appendicular skeletal mass index, ASMI) and insulin resistance on all-cause and major adverse cardiovascular and cerebrovascular events (MACCE)–related mortality. Mediation analysis was performed to examine direct and indirect effects.&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;The study included 8036 participants from NHANES and 14 449 from KNHANES. The sarcopenia group demonstrated a lower homeostasis model assessment for insulin resistance and better metabolic indices than the normal group despite having a higher mortality rate. Insulin resistance positively correlated with muscle mass (&lt;i&gt;r&lt;/i&gt; = 0.203, &lt;i&gt;p&lt;/i&gt; &lt; 0.001 in the NHANES; &lt;i&gt;r&lt;/i&gt; = 0.143, &lt;i&gt;p&lt;/i&gt; &lt; 0.001 in the KNHANES), and both insulin resistance and sarcopenia were identified as independent risk factors for all-cause and MACCE-related mortality. When the participants were categorized into four groups based on the presence or absence of insulin resistance and sarcopenia, those with both conditions exhibited the highest risk of all-cause mortality (hazard ratio [HR]: 2.30, 95% confidence interval [CI]: 1.72–3.08 in the NHANES; HR: 2.60, 95% CI: 2.14–3.16 in the KNHANES) and MACCE-related mortality among the groups (HR: 3.18, 95% CI: 1.99–5.08 in the NHANES; HR: 2.47, 95% CI: 1.66–3.69 in the KNHANES). Mediation analysis revealed that low muscle mass was associated with decreased insulin resistance but directly increased both all-cause mortality and MACCE-related mortality (NHANES: total natural direct effects [TNDE], HR: 2.08, 95% CI: 1.57–2.76; KNHANES: TNDE, HR: 1.69, 95% CI: 1.28–2.23).&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;This study found that low ASMI was inversely associated with insulin resistance and positively associated with mortality risk in both cohorts. The","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13811","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831448","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":"Comment on ‘Impact of Resistance Training and Chicken Intake on Vascular and Muscle Health in Elderly Women’ by Fujie et al.","authors":"Pincheng Luo,&nbsp;Yihan Shi,&nbsp;Yanxue Lian","doi":"10.1002/jcsm.13803","DOIUrl":"https://doi.org/10.1002/jcsm.13803","url":null,"abstract":"&lt;p&gt;We read with great interest the recent article by Fujie et al. [&lt;span&gt;1&lt;/span&gt;] published in your esteemed journal. The study provides valuable insights into the effects of moderate-to-high-intensity resistance training (RT) combined with high-protein intake (steamed chicken breast) on arterial stiffness, muscle mass, strength and quality in elderly women. However, we would like to highlight several limitations and areas for future research that could enhance its impact.&lt;/p&gt;&lt;p&gt;First, the study lacks a personalized training approach tailored to individual participants. The study employed a standardized resistance training protocol, adjusting weights every 2 weeks based on one-repetition maximum (1-RM) measurements. While this approach ensures consistency, it does not account for individual variations in baseline fitness, recovery capacity or adaptive response to training. Although the authors note no significant differences in one-repetition maximum (1-RM) of leg extension or leg curl at baseline RT and resistance training plus higher dietary animal protein intake (RT + HP) groups, this does not negate the need for personalized programming. Research has shown that tailoring exercise regimens by modifying intensity, frequency and exercise selection can lead to greater improvements in muscle function and cardiovascular health [&lt;span&gt;2&lt;/span&gt;]. Future studies could benefit from incorporating personalized training plans to optimize individual outcomes.&lt;/p&gt;&lt;p&gt;Second, the study focused primarily on lower limb exercises, overlooking other muscle groups essential for functional independence and overall health. Resistance training programmes for elderly individuals should ideally include exercises targeting the upper body, core and postural muscles to address the multifactorial nature of age-related decline. A more comprehensive approach to exercise programming, incorporating a wider range of exercises tailored to individual needs and functional goals, could enhance the study's applicability and outcomes.&lt;/p&gt;&lt;p&gt;Finally, the authors propose that the attenuation of arterial stiffness in the resistance training plus higher dietary animal protein intake (RT + HP) group may be due to angiotensin-converting enzyme (ACE) inhibition by high-protein intake. While this is a plausible hypothesis, it remains speculative without direct evidence. Although baseline data showed no significant differences in circulating angiotensin II (Ang II) levels among the groups, this alone is insufficient to confirm the proposed mechanism. Measuring ACE activity or expression in vascular tissues, along with circulating Ang II levels, could provide more conclusive insights into this potential pathway.&lt;/p&gt;&lt;p&gt;In conclusion, while the study offers valuable contributions to the field, addressing these limitations in future research could further elucidate the mechanisms underlying the observed benefits and optimize interventions for improving vascular and muscle health in elderly women","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13803","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831454","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 Novel Research Paradigm for Sarcopenia of Limb Muscles: Lessons From the Perpetually Working Diaphragm's Anti-Aging Mechanisms","authors":"Enhui Li,&nbsp;Rui Wang,&nbsp;Yanli Li,&nbsp;Xiang Zan,&nbsp;Shufen Wu,&nbsp;Yiru Yin,&nbsp;Xiaorong Yang,&nbsp;Litian Yin,&nbsp;Yu Zhang,&nbsp;Jianguo Li,&nbsp;Xin Zhao,&nbsp;Ce Zhang","doi":"10.1002/jcsm.13797","DOIUrl":"https://doi.org/10.1002/jcsm.13797","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;Skeletal muscle function and mass continuously decrease during aging. Most studies target limb muscles owing to their direct impact on mobility and falls risk. The diaphragm (DIA), also a type of skeletal muscle with different phenotype, has received less attention. Comparative research of the DIA and limb muscles can reveal their distinct aging characteristics. Critically, the potential endogenous anti-aging mechanisms of DIA that may provide new insights into the mechanisms of sarcopenia in limb muscles remain scarce.&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;Treadmill and grip tests assessed limb muscle function, while a lung function system evaluated respiratory function in both adult (6-month-old) and old (22-month-old) mice. Histological assessments evaluated muscle mass in both the DIA and tibialis anterior (TA). Transcriptome sequencing identified differentially expressed genes (DEGs) between the DIA and TA with aging. Adeno-associated virus (AAV)-encoding short hairpin (sh) RNA targeting gene was injected into adult mice's TA muscles to knockdown target gene level in TA, and AAV-gene was injected into old mice's TA to overexpress target gene level.&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;Old mice displayed significantly reduced running distance (&lt;i&gt;p&lt;/i&gt; = 0.0026), maximal speed (&lt;i&gt;p&lt;/i&gt; = 0.0019), time to exhaustion (&lt;i&gt;p&lt;/i&gt; = 0.0033) and grip strength (&lt;i&gt;p&lt;/i&gt; = 0.0055) compared with adult mice, alongside TA's weight loss, decreased myofibre cross-sectional area (CSA) and autophagy deficiency. However, lung function indicators (respiratory rate, tidal volume, minute ventilation volume, forced vital capacity and ratio of forced expiratory volume in 100 or 200 ms to forced vital capacity), as well as DIA weight and morphology remained stable in old mice. Transcriptional analysis revealed 61 DEGs, with significant upregulation or downregulation observed in TA, but without changes in DIA during aging. &lt;i&gt;Smox&lt;/i&gt; (spermine oxidase) is one of the DEGs, responsible for catalysing the conversion of spermine to spermidine. It was reported that in muscle atrophy models such as limb immobilisation, fasting and denervation, &lt;i&gt;Smox'&lt;/i&gt;s levels are positively correlated with muscle mass and function. Additionally, an increase in &lt;i&gt;Smox&lt;/i&gt; also promotes mitochondrial biogenesis. In our study, AAV-shSmox adult mice decreased running distance, speed and time, myofibre CSA alongside mitochondrial function, compared with controls. In contrast, old mice with &lt;i&gt;Smox&lt;/i&gt; overexpression showed enhanced mitochondrial function.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13797","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826680","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}