Ludiane Alves do Nascimento, Marlon Juliano Romero Aliberti, Natalia Golin, Erika Suíter, Christian Valle Morinaga, Thiago Junqueira Avelino Silva, Pedro Kallas Curiati
{"title":"Nutritional Status Predicts Functional Recovery and Adverse Outcomes in Older Adults: A Prospective Cohort Study","authors":"Ludiane Alves do Nascimento, Marlon Juliano Romero Aliberti, Natalia Golin, Erika Suíter, Christian Valle Morinaga, Thiago Junqueira Avelino Silva, Pedro Kallas Curiati","doi":"10.1002/jcsm.13819","DOIUrl":"https://doi.org/10.1002/jcsm.13819","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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, <i>p</i> = 0.029), whereas nutritional risk was independently associated with in-hospital (13% vs. 2%, OR = 4.24, 95%CI 1.53–11.74, <i>p</i> = 0.005) and postdischarge (14% vs. 4%, OR = 2.76, 95%CI 1.17–6.49, <i>p</i> = 0.02) mortality. Finally, malnutrition was independently associated with nosocomial infection (12% vs. 2%, OR = 5.43, 95%CI 2.56–11.5, <i>p</i> < 0.001), prolonged LoS (56% vs. 22%, OR = 2.79, 95%CI 1.84–4.22, <i>p</i> < 0.001) and postdischarge mortality (13% vs. 4%, OR = 2.76, 95%CI 1.36–5.61, <i>p</i> = 0.005).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>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, Chao Ma, Cheng-Shi Xu, Si-Rui Li, Chen Li, Ze-Fen Wang, Zhi-Qiang Li","doi":"10.1002/jcsm.13809","DOIUrl":"https://doi.org/10.1002/jcsm.13809","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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, <i>p</i> < 0.001), prognostic nutritional index (HR = 1.722, 95% CI 1.098–2.703, <i>p</i> = 0.018), and mean corpuscular volume (HR = 1.958, 95% CI 1.111–3.451, <i>p</i> = 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, <i>p</i> < 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 > 65 (HR = 1.822, 95% CI 1.011–3.284, <i>p</i> = 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.</p>\u0000 </section>\u0000 \u0000 <","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}
Joo Won Kim, SukHwan Yun, Min Jeong Park, Eyun Song, Sooyeon Jang, Ahreum Jang, Kyung Mook Choi, Sei Hyun Baik, Hwan-Jin Hwang, Hye Jin Yoo
{"title":"HD6277 Suppresses Muscle Atrophy by Promoting Myogenic Factors and Inhibiting Proteolysis in Aged Mice","authors":"Joo Won Kim, SukHwan Yun, Min Jeong Park, Eyun Song, Sooyeon Jang, Ahreum Jang, Kyung Mook Choi, Sei Hyun Baik, Hwan-Jin Hwang, 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> < 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> < 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> < 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> < 0.05). These beneficial HD6277-mediated actions disappeared after the addition of an Akt inhibitor (<i>p</i> < 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> < 0.05). HD6277 increased muscle strength (+9.88% vs. Aged, <i>p</i> < 0.05) and myofiber thickness (+29.01% vs. Aged, <i>p</i> < 0.05) in aging mice but only improved myofiber thickness (+11.84% vs. HFD, <i>p</i> < 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}
Shinje Moon, Jong Wook Choi, Jung Hwan Park, Dong Sun Kim, Youhern Ahn, Yeongmin Kim, Sung Hye Kong, Chang-Myung Oh
{"title":"Association of Appendicular Skeletal Muscle Mass Index and Insulin Resistance With Mortality in Multi-Nationwide Cohorts","authors":"Shinje Moon, Jong Wook Choi, Jung Hwan Park, Dong Sun Kim, Youhern Ahn, Yeongmin Kim, Sung Hye Kong, Chang-Myung Oh","doi":"10.1002/jcsm.13811","DOIUrl":"https://doi.org/10.1002/jcsm.13811","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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 (<i>r</i> = 0.203, <i>p</i> < 0.001 in the NHANES; <i>r</i> = 0.143, <i>p</i> < 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).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>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, Yihan Shi, Yanxue Lian","doi":"10.1002/jcsm.13803","DOIUrl":"https://doi.org/10.1002/jcsm.13803","url":null,"abstract":"<p>We read with great interest the recent article by Fujie et al. [<span>1</span>] 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.</p><p>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 [<span>2</span>]. Future studies could benefit from incorporating personalized training plans to optimize individual outcomes.</p><p>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.</p><p>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.</p><p>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, Rui Wang, Yanli Li, Xiang Zan, Shufen Wu, Yiru Yin, Xiaorong Yang, Litian Yin, Yu Zhang, Jianguo Li, Xin Zhao, Ce Zhang","doi":"10.1002/jcsm.13797","DOIUrl":"https://doi.org/10.1002/jcsm.13797","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Old mice displayed significantly reduced running distance (<i>p</i> = 0.0026), maximal speed (<i>p</i> = 0.0019), time to exhaustion (<i>p</i> = 0.0033) and grip strength (<i>p</i> = 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. <i>Smox</i> (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, <i>Smox'</i>s levels are positively correlated with muscle mass and function. Additionally, an increase in <i>Smox</i> 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 <i>Smox</i> overexpression showed enhanced mitochondrial function.</p>\u0000 </section>\u0000 \u0000 <section>\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}
Antoine Naëgel, Magalie Viallon, Hélène Ratiney, Thu Nguyen, Benjamin Leporq, Djahid Kennouche, Thomas Grenier, Franziska Grundler, Robin Mesnage, Jean-Michel Guy, Robin Schultze, Françoise Wilhelmi de Toledo, Pierre Croisille
{"title":"Impact of Long-Term Fasting on Skeletal Muscle: Structure, Energy Metabolism and Function Using 31P/1H MRS and MRI","authors":"Antoine Naëgel, Magalie Viallon, Hélène Ratiney, Thu Nguyen, Benjamin Leporq, Djahid Kennouche, Thomas Grenier, Franziska Grundler, Robin Mesnage, Jean-Michel Guy, Robin Schultze, Françoise Wilhelmi de Toledo, Pierre Croisille","doi":"10.1002/jcsm.13773","DOIUrl":"https://doi.org/10.1002/jcsm.13773","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Fasting shows promise for public health, but concerns about muscle loss hinder its acceptance, particularly among the elderly. We explored the impact of long-term fasting (12 days, 250 kcal/day) on muscle structure, metabolism and performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We prospectively assessed muscle volume, composition, relaxometry data and lipid metabolism in 32 subjects (16 men; 50% over 50 years old) before fasting, at the end of fasting and 1 month post-fasting. Techniques included high-resolution 3D Dixon MR imaging, multiecho CSE and single-voxel MR spectroscopy. Dynamic <sup>31</sup>P-MRS, quantitative MRI, maximal voluntary contraction (MVC) measurements and exercise testing (VO<sub>2</sub>peak) were repeated throughout the protocol.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Although the average body weight loss was 5.9 kg (7.4%, <i>p</i> < 0.001), the skeletal muscle volume change measured on the right calf muscle was 271 mL (5.4%, <i>p</i> < 0.001). This closely aligns with expected losses of glycogen (1%–2%) and bound water (3%–4%), estimated to total 404–505 mL. MVC (anaerobic lactic metabolism) remained preserved in both thighs and calf muscles, regardless of sex or age. Unchanged T2 showed that fasting did not induce structural or inflammatory changes. MRI/MRS revealed fat redistribution among tissues, with subcutaneous fat decrease (by 417.2 cm<sup>3</sup>, <i>p</i> < 0.01) and total fat fraction increase (by 0.2%, <i>p</i> < 0.05) in muscle. The intramyocellular lipid pool increased by 2.2 times (<i>p</i> < 0.05), whereas the extracellular lipid pool decreased to 1.4 times (<i>p</i> < 0.05), revealing rapid lipid trafficking and adaptation. During fasting, the T2* value increased by 1.2 ms (<i>p</i> < 0.001), likely because of changes in the configuration of intracellular lipid droplets, with an increased proportion of lipid droplets of smaller size, optimizing accessibility of lipid fuels and mitochondrial FA. Exercise testing (VO<sub>2</sub>peak) showed no change in maximal oxygen uptake, but fat oxidation improved with a 10% decrease in the exercise respiratory exchange ratio (<i>p</i> < 0.001). Mitochondrial oxidative capacity and PCr resynthesis rates in muscle were maintained. Females improved their mitochondrial function by D + 12, with τPCr decreasing to 29.61 s (<i>p</i> < 0.01), surpassing males and demonstrating better fat oxidation capabilities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Long-term fasting did not alter mus","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13773","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818709","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}
Daiki Setoyama, Dohyun Han, Jingwen Tian, Ho Yeop Lee, Hyun Suk Shin, Ha Thi Nga, Thi Linh Nguyen, Ji Sun Moon, Hyo Ju Jang, Evonne Kim, Seong-Kyu Choe, Sang Hyeon Ju, Dae Eun Choi, Obin Kwon, Hyon-Seung Yi
{"title":"Comparative Analysis of Primary Sarcopenia and End-Stage Renal Disease–Related Muscle Wasting Using Multi-Omics Approaches","authors":"Daiki Setoyama, Dohyun Han, Jingwen Tian, Ho Yeop Lee, Hyun Suk Shin, Ha Thi Nga, Thi Linh Nguyen, Ji Sun Moon, Hyo Ju Jang, Evonne Kim, Seong-Kyu Choe, Sang Hyeon Ju, Dae Eun Choi, Obin Kwon, Hyon-Seung Yi","doi":"10.1002/jcsm.13749","DOIUrl":"https://doi.org/10.1002/jcsm.13749","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Age-related primary sarcopenia and end-stage renal disease (ESRD)–related muscle wasting are discrete entities; however, both manifest as a decline in skeletal muscle mass and strength. The etiological pathways differ, with aging factors implicated in sarcopenia and a combination of uremic factors, including haemodialysis, contributing to ESRD-related muscle wasting. Understanding these molecular nuances is imperative for targeted interventions, and the integration of proteomic and metabolomic data elucidate these intricate processes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We generated detailed clinical data and multi-omics data (plasma proteomics and metabolomics) for 78 participants to characterise sarcopenia (<i>n</i> = 28; mean age, 72.6 ± 7.0 years) or ESRD (<i>n</i> = 22; 61.6 ± 5.5 years) compared with controls (<i>n</i> = 28; 69.3 ± 5.7 years). Muscle mass was measured using bioelectrical impedance analysis and handgrip strength. Five-times sit-to-stand test performance was measured for all participants. Sarcopenia was diagnosed in accordance with the 2019 Consensus Guidelines from the Asian Working Group for Sarcopenia. An abundance of 234 metabolites and 722 protein groups was quantified in all plasma samples using liquid chromatography with tandem mass spectrometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Muscle mass, handgrip strength and lower limb muscle function significantly lower in the sarcopenia group and the ESRD group compared with those in the control group. Metabolomics revealed altered metabolites, highlighting exclusive differences in ESRD-related muscle wasting. Metabolite set enrichment analysis revealed the involvement of numerous metabolic intermediates associated with urea cycle, amino acid metabolism and nucleic acid metabolism. Catecholamines, including epinephrine, dopamine and serotonin, are significantly elevated in the plasma of patients within the ESRD group. Proteomics data exhibited a clearer distinction among the three groups compared with the metabolomics data, particularly in distinguishing the control group from the sarcopenia group. The ciliary neurotrophic factor receptor was top-ranked in terms of the variable importance of projection scores. Plasma AHNAK protein levels was higher in the sarcopenia group but was lower in the ESRD group. Proteomic set enrichment analysis revealed enrichment of several pathways related to sarcopenia, such as hemopexin, defence response and cell differentiation, in sarcopenia group. Multi-omic integration analysis revealed associations between relevant metabolites, including catecholamines, and a group of annotated prote","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13749","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809525","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}
Brandon M. Roberts, Alyssa V. Geddis, Alexandra Ciuciu, Marinaliz Reynoso, Nikhil Mehta, Alyssa N. Varanoske, Alyssa M. Kelley, Maximus C. Leiss, Alexander L. Kolb, Julie M. Hughes, Marshall A. Naimo, Ryan E. Tomlinson, Jeffery S. Staab
{"title":"Ibuprofen, Flurbiprofen or Naproxen Sodium Minimally Influences Musculoskeletal Adaptations to Treadmill Exercise in Rats","authors":"Brandon M. Roberts, Alyssa V. Geddis, Alexandra Ciuciu, Marinaliz Reynoso, Nikhil Mehta, Alyssa N. Varanoske, Alyssa M. Kelley, Maximus C. Leiss, Alexander L. Kolb, Julie M. Hughes, Marshall A. Naimo, Ryan E. Tomlinson, Jeffery S. Staab","doi":"10.1002/jcsm.13798","DOIUrl":"https://doi.org/10.1002/jcsm.13798","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Non-steroidal anti-inflammatory drugs (NSAIDs) may influence musculoskeletal health. The purpose of this study was to compare the effects of three different NSAIDS: naproxen sodium, ibuprofen, flurbiprofen or a placebo on musculoskeletal adaptations in rodents with or without 6 weeks of aerobic exercise.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Nine-week-old male Wistar rats (<i>n</i> = 80) were randomized to either exercise (EX) or no-exercise control (CON) conditions and treated with naproxen, ibuprofen (IBU), flurbiprofen (FLU) or placebo (PLA). For exercise, rats ran 5 days per week for 6 weeks at a 5% incline on a motorized treadmill for 30 min. Three-point bending (3 PB) and microcomputed tomography (microCT) were measured in the femur. Anabolic muscle signalling pathways were measured in the quadriceps. Muscle fibre cross-sectional area (CSA) and fibre type were measured in the soleus. Data were analysed using a two-way ANOVA for treatment by condition and is visualized as mean ± standard deviation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>For 3 PB, there was an exercise effect for ultimate bending energy, postyield energy, toughness, postyield toughness, postyield displacement, ultimate strain and postyield strain (all, <i>p</i> < 0.05). There was a treatment by condition effect for Young's Modulus, where placebo exercise was less than placebo control (PLA EX: 3256.44 ± 463.41 MPa, PLA CON: 4849.94 ± 836.70 MPa, <i>p</i> < 0.05). For microCT, there was a treatment by condition effect for trabecular thickness (<i>p</i> = 0.047) and the IBU EX group increased thickness compared with the IBU CON group (IBU EX: 0.133 ± 0.011 mm, IBU CON: 0.121 ± 0.007 mm, <i>p</i> = 0.027). In the quadriceps, for myosin heavy chain abundance, there was a treatment by condition effect (<i>p</i> = 0.046) and ibuprofen exercise was lower than ibuprofen control (IBU EX: 0.636 ± 0.513 AU, IBU CON: 1.81 ± 1.012 AU, <i>p</i> = 0.016). There was no treatment by condition effect for phosphorylation of the AKT, AMPK or ERK pathways (all, <i>p</i> > 0.05). In the soleus, there was no treatment by condition effect for fibre type percentage or muscle CSA (<i>p</i> > 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>NSAIDs did not have a strong negative or positive effect on musculoskeletal adaptations to 6 weeks of treadmill running in young healthy male rodents.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13798","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818451","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}
Jakub Mesinovic, Anoohya Gandham, Mavil May Cervo, Paul Jansons, Costas Glavas, Michael Braude, Juan Pena Rodriguez, Barbora De Courten, Ayse Zengin, Belinda R. Beck, Peter R. Ebeling, David Scott
{"title":"Resistance and Impact Training During Weight Loss Improves Physical Function and Body Composition in Older Adults With Obesity","authors":"Jakub Mesinovic, Anoohya Gandham, Mavil May Cervo, Paul Jansons, Costas Glavas, Michael Braude, Juan Pena Rodriguez, Barbora De Courten, Ayse Zengin, Belinda R. Beck, Peter R. Ebeling, David Scott","doi":"10.1002/jcsm.13789","DOIUrl":"https://doi.org/10.1002/jcsm.13789","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Weight loss achieved via energy restriction leads to significant losses in muscle and bone mass, potentially increasing risk for sarcopenia and osteoporosis. High-intensity resistance and impact training (HiRIT) might attenuate weight loss–induced musculoskeletal declines. Our objective was to compare changes in physical function and body composition in older adults with obesity undertaking dietary weight loss combined with HiRIT or aerobic training (AT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sixty older adults (aged ≥ 60 years) with obesity (dual-energy x-ray absorptiometry determined body fat percentage ≥ 30% in men and ≥ 40% in women) and a mobility limitation (Short Physical Performance Battery [SPPB] score ≤ 11) were randomly assigned to either 12 weeks of supervised, centre-based HiRIT or self-directed, home-based AT while consuming a hypocaloric diet (750–1000 kcal/day reduction in energy intake). Changes in physical function (primary outcome: gait speed) and body composition were compared between groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 49/60 randomised participants (mean age: 69.6 ± 6 years; 58% women; mean BMI: 32.9 ± 4.1 kg/m<sup>2</sup>) completed the trial. Gait speed increased following HiRIT compared with AT (mean difference: 0.07 m/s [95% CI: 0.01, 0.13]). Chair stand times decreased in both groups (HiRIT: −1.3 s [95% CI: −2.1, −0.4] vs. AT: −0.8 s [95% CI: −1.6, −0.04]) and HiRIT, but not AT, increased handgrip strength (HiRIT: 2.2 kg [95% CI: 0.6, 3.9] vs. AT: 0.7 kg [95% CI: −0.9, 2.3]) and SPPB scores (HiRIT: 0.9 [95% CI: 0.4, 1.3] vs. AT: 0.4 [95% CI: −0.04, 0.8]). Similar decreases in total body mass (HiRIT: −5.1 kg [95% CI: −6.7, −3.4] vs. AT: −4.9 kg [95% CI: −6.5, −3.3]), fat mass (HiRIT: −3.6 kg [95% CI: −5.0, −2.2] vs. AT: −3.3 kg [95% CI: −4.7, −2.0]), visceral fat (HiRIT: −32.1 cm<sup>2</sup> [95% CI: −47.4, −16.8] vs. AT: −31.4 cm<sup>2</sup> [95% CI: −46.1, −16.8]) and appendicular lean mass (HiRIT: −0.8 kg [95% CI: −1.4, −0.2] vs. AT: −1.2 kg [95% CI: −1.8, −0.6]) were observed. HiRIT was well tolerated with only seven minor adverse events compared with five reported in those who completed AT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>HiRIT appears to be safe and more effective than AT for improving gait speed in older adults with obesity undertaking dietary weight loss. Additional trials with larger sample sizes and longer durations are warranted to explore whether HiRIT can attenuate weight loss–related muscle and bone mass declines. <b>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13789","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809505","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}