Journal of Cachexia Sarcopenia and Muscle最新文献

{"title":"HMGB1 in Septic Muscle Atrophy: Roles and Therapeutic Potential for Muscle Atrophy and Regeneration","authors":"Si-Yuan Qi,&nbsp;Qiqi Wu,&nbsp;Peng-Hui Xiang,&nbsp;Chao-Yao Hou,&nbsp;Zhaofeng Kang,&nbsp;Meng-Qi Chen,&nbsp;Chengla Yi,&nbsp;Xiangjun Bai,&nbsp;Tianyu Li,&nbsp;Zhanfei Li,&nbsp;Wei-Ming Xie","doi":"10.1002/jcsm.13711","DOIUrl":"https://doi.org/10.1002/jcsm.13711","url":null,"abstract":"<p>Currently, the treatment of septic myopathy presents significant challenges with implications for increased mortality rates and prolonged hospitalizations. Effective therapeutic strategies for septic myopathy remain elusive, highlighting an urgent need for novel therapeutic approaches. High-mobility group box 1 (HMGB1) is a conserved nonhistone nuclear protein that is released passively from deceased cells or actively secreted by activated immune cells, influencing both infectious and noninfectious inflammatory responses. Studies have indicated that HMGB1 likely plays a pivotal role in the pathogenesis of septic myopathy by crucial pathways associated with muscle atrophy and contributing to muscle regeneration under certain conditions. This review aims to summarize the possible mechanisms of HMGB1 in muscle atrophy and its potential in muscle regeneration, providing a theoretical basis for HMGB1 treatment of septic myopathy. Research shows that the dual role of HMGB1 is related to its specific forms, which are influenced to varying degrees by environmental factors. HMGB1 is a key participant in septic muscle atrophy, whereas HMGB1 shows therapeutic potential in muscle regeneration. One key mechanism by which HMGB1 contributes to septic muscle atrophy is through the exacerbation of inflammation. HMGB1 can amplify the inflammatory response by promoting the release of pro-inflammatory cytokines, which further damages muscle tissue. HMGB1 is also involved in promoting cell death in sepsis, which contributes to muscle degradation. Another important mechanism is the regulation of protein degradation systems. HMGB1 can activate the ubiquitin–proteasome system and autophagy–lysosome pathway, both of which are crucial for the breakdown of muscle proteins during atrophy. Conversely, targeting HMGB1 has shown the potential to ameliorate muscle atrophy in various diseases. For instance, HMGB1 has been shown to promote muscle vascular regeneration, modify stem cell status and enhance stem cell migration and differentiation, all of which are beneficial for muscle repair and recovery. Pharmacological inhibition of HMGB1 has been explored, with several drugs demonstrating efficacy in reducing inflammation and muscle degradation in sepsis models. These findings suggest that HMGB1 inhibition could be a viable therapeutic approach for septic myopathy. However, the function of promoting muscle regeneration in septic myopathy needs further research. HMGB1 emerges as a promising therapeutic target for the treatment of muscle atrophy in sepsis. This review focuses on identifying the correlation between HMGB1 and septic myopathy, analysing the possible role of HMGB1 in disease development and examining the feasibility of HMGB1 as a therapeutic target.</p>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13711","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431698","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":"Cortisol Circadian Rhythm and Sarcopenia in Patients With Type 2 Diabetes: A Cross-Sectional Study","authors":"Fupeng Liu,&nbsp;Qing Yang,&nbsp;Kai Yang,&nbsp;Jing Sun,&nbsp;Yanying Li,&nbsp;Bo Ban,&nbsp;Yangang Wang,&nbsp;Mei Zhang","doi":"10.1002/jcsm.13727","DOIUrl":"https://doi.org/10.1002/jcsm.13727","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;Patients with Type 2 diabetes mellitus (T2DM) have elevated late-night cortisol levels and a flattened circadian rhythm. Cortisol oversecretion mediates muscle breakdown and reduces muscle strength and mass, thus possibly leading to sarcopenia. This study first investigated the association between cortisol circadian rhythm and sarcopenia in patients with T2DM.&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;Patients with T2DM and adrenal nodules were screened for eligibility. Skeletal muscle index (SMI) and skeletal muscle density (SMD) were obtained by analysing computed tomography images at Lumbar 3 level. Sarcopenia was defined as the presence of both myopenia and myosteatosis. Cortisol and adrenocorticotropic hormone levels at 8 AM, 4 PM and 0 AM were measured. The cumulative logit models and receiver operating characteristic (ROC) curve analyses were performed to evaluate the association between cortisol circadian rhythm and sarcopenia.&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;In total, 128 patients with T2DM and nonfunctional adrenal adenomas were enrolled in this study, of whom 25 were diagnosed with sarcopenia. The mean age was 54.4 years, and 83 (64.8%) patients were male. Patients with sarcopenia showed higher nighttime cortisol levels at 0 AM (Cor 0 AM) (4.91 [4.05, 9.95] vs. 2.44 [1.55, 4.77] μg/dL, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) than those without. The Cor 0 AM was negatively correlated with both SMI and SMD (&lt;i&gt;r&lt;/i&gt; = −0.318, &lt;i&gt;p&lt;/i&gt; &lt; 0.001 and −0.284, &lt;i&gt;p&lt;/i&gt; &lt; 0.001, respectively). As the Cor 0 AM tertiles increased, the odds ratios (ORs) for sarcopenia consistently increased (OR = 4.69 [0.93, 23.53], &lt;i&gt;p&lt;/i&gt; = 0.061, for the intermediate group and OR = 11.39 [2.41, 53.84], &lt;i&gt;p&lt;/i&gt; = 0.002, for the high group). After adjustment for multiple risk factors, the high Cor 0 AM group still showed a significantly higher risk of sarcopenia than the low group (OR = 7.92 [1.45, 43.29], &lt;i&gt;p&lt;/i&gt; = 0.017). ROC curve analyses showed that Cor 0 AM had the highest predictive power for sarcopenia, with an area under the ROC curve (AUC) of 0.760, compared to haemoglobin, age, alanine transaminase and sex (AUC = 0.703, 0.695, 0.679, and 0.633, respectively).&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;The cortisol circadian rhythm is associated with sarcopenia in patients with T2DM. Patients with higher levels of nighttime cortisol, rather than morning or afternoon cortisol, have a higher risk of sarcopenia. This result offers a new strategy for the further research of sarcopenia.&lt;/p&gt;\u0000 ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13727","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424200","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":"Cachexia Alters Central Nervous System Morphology and Functionality in Cancer Patients","authors":"Estefania Simoes,&nbsp;Ricardo Uchida,&nbsp;Mariana P. Nucci,&nbsp;Fabio L. S. Duran,&nbsp;Joanna D. C. C. Lima,&nbsp;Leonardo R. Gama,&nbsp;Naomi A. Costa,&nbsp;Maria C. G. Otaduy,&nbsp;Fang C. Bin,&nbsp;Jose P. Otoch,&nbsp;Paulo Alcantara,&nbsp;Alexandre Ramos,&nbsp;Alessandro Laviano,&nbsp;Mauricio Berriel Diaz,&nbsp;Margaret M. Esiri,&nbsp;Gabriele C. DeLuca,&nbsp;Stephan Herzig,&nbsp;Geraldo Busatto Filho,&nbsp;Marilia Seelaender","doi":"10.1002/jcsm.13742","DOIUrl":"https://doi.org/10.1002/jcsm.13742","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;Cachexia is a clinically challenging multifactorial and multi-organ syndrome, associated with poor outcome in cancer patients, and characterised by inflammation, wasting and loss of appetite. The syndrome leads to central nervous system (CNS) function dysregulation and to neuroinflammation; nevertheless, the mechanisms involved in human cachexia remain 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;We used in vivo structural and functional magnetic resonance imaging &lt;i&gt;(Cohort 1),&lt;/i&gt; as well as postmortem neuropathological analyses &lt;i&gt;(Cohort 2)&lt;/i&gt; in cachectic cancer (CC) patients compared to weight stable cancer (WSC) patients. &lt;i&gt;Cohort 1&lt;/i&gt; included treatment-naïve adults diagnosed with colorectal cancer, further divided into WSC (&lt;i&gt;n&lt;/i&gt; = 12; 6/6 [male/female], 61.3 ± 3.89 years) and CC (&lt;i&gt;n&lt;/i&gt; = 10; 6/4, 63.0 ± 2.74 years). &lt;i&gt;Cohort 2&lt;/i&gt; was composed by human postmortem cases where gastrointestinal carcinoma was the underlying cause of death (WSC &lt;i&gt;n&lt;/i&gt; = 6; 3/3, 82.7 ± 3.33 years and CC &lt;i&gt;n&lt;/i&gt; = 10; 5/5, 84.2 ± 2.28 years).&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;Here we demonstrate that the CNS of CC patients presents regional structural differences within the grey matter (GM). Cachectic patients presented an augmented area within the region of the orbitofrontal cortex, olfactory tract and the gyrus rectus (coordinates &lt;i&gt;X&lt;/i&gt;, &lt;i&gt;Y&lt;/i&gt;, &lt;i&gt;Z&lt;/i&gt; = 6, 20,−24; 311 voxels; pFWE = 0.023); increased caudate and putamen volume (−10, 20, −8; 110 voxel; pFWE = 0.005); and reduced GM in superior temporal gyrus and rolandic operculum (56,0,2; 156 voxels; pFWE = 0.010). Disrupted functional connectivity was found in several regions such as the salience network, subcortical and temporal cortical areas of cachectic patients (20 decreased and 5 increased regions connectivity pattern, pFDR &lt; 0.05). Postmortem neuropathological analyses identified abnormal neuronal morphology and density, increased microglia/macrophage burden, astrocyte profile disruption and mTOR pathway related neuroinflammation (&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;Our results indicate that cachexia compromises CNS morphology mostly causing changes in the GM of cachectic patients, leading to alterations in regional volume patterns, functional connectivity, neuronal morphology, neuroglia profile and inducing neuroinflammation, all of which may contribute to the loss of homeostasis control and to deficient information processing, as well as to the metabolic and behavioural derangement","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13742","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431403","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":"ArfGAP3 Protects Mitochondrial Function and Promotes Autophagy Through Rab5a-Mediated Signals in Ageing Skeletal Muscle","authors":"Mao Chen,&nbsp;Xiaoyu Huang,&nbsp;Bingshu Li,&nbsp;Ya Xiao,&nbsp;Liying Chen,&nbsp;Fangyi Zhu,&nbsp;Shasha Hong,&nbsp;Jianming Tang,&nbsp;Suting Li,&nbsp;Jie Min,&nbsp;Wenyi Jin,&nbsp;Yubiao Zhang,&nbsp;Lian Yang,&nbsp;Yang Li,&nbsp;Shufei Zhang,&nbsp;Li Hong","doi":"10.1002/jcsm.13725","DOIUrl":"https://doi.org/10.1002/jcsm.13725","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;Few researches have investigated the molecular mechanism responsible for the age-related loss of the pelvic floor muscle (PFM) mass and functionality—a pivotal contributor to pelvic organ prolapse and diminished physical well-being. ADP ribosylation factor GTPase activating protein 3 (ArfGAP3) is a member of ArfGAPs, which regulates the vesicular trafficking pathway and intracellular proteins transporting. However, its effects on skeletal muscle ageing remain largely 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;Mouse models of natural ageing and D-gal (D-galactose)–induced ageing were subject to analyse the structure, function and pathological alterations of the PFM and the expression of ArfGAP3. Stable ArfGAP3 knockdown and overexpression C2C12 cell lines were established to investigate the anti-senescence effects of ArfGAP3 and the underlying mechanisms in ageing process, complemented by Rab5a genetic intervention and mRFP-GFP-LC3 adenoviral particles transfection. In vivo experiments entailed ArfGAP3 overexpression in mice alongside autophagy inhibitor treatment, with assessments encompassing tissue mass, bladder leak point pressure (BLPP), submicroscopic structure, antioxidative stress system and muscle regeneration.&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;Aged (24-month-old) mice exhibited significant physiological alterations in PFMs, including decreased muscle mass, diminished cross-sectional area (CSA), deteriorated supporting function (as evidenced by reduced BLPP), impaired autophagy and increased levels of oxidative stress (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). Utilizing ageing C2C12 model, we observed a dose-dependent relationship between D-gal induction and cellular senescence, impaired differentiation and mitochondrial damage. Remarkably, the expression levels of ArfGAP3 were markedly downregulated in both in vitro and in vivo ageing models. Knockdown of ArfGAP3 exacerbated impaired differentiation potential and induced aberrant mitochondrial morphology and functional dysfunction in ageing C2C12 myoblasts, whereas ArfGAP3 overexpression largely mitigated these effects. Mechanistically, our findings revealed an interplay between ArfGAP3 and Rab5a, indicating their coordinated regulation. ArfGAP3-mediated activation of Rab5a-associated autophagy and IRS1-AKT-mTOR signalling pathways during cellular senescence and myogenesis was identified, leading to enhanced autophagic flux and improved resistance to oxidative stress. In vivo, ArfGAP3 overexpression ameliorated D-gal–induced loss of muscle mass and function, while promoting antioxidant responses and muscle regeneration in mice. However, these pro","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13725","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431441","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":"Keratocan Improves Muscle Wasting in Sarcopenia by Promoting Skeletal Muscle Development and Fast-Twitch Fibre Synthesis","authors":"Xu Chen,&nbsp;Yanyan Zhang,&nbsp;Zhibo Deng,&nbsp;Chao Song,&nbsp;Linhai Yang,&nbsp;Rongsheng Zhang,&nbsp;Peng Zhang,&nbsp;Yu Xiu,&nbsp;Yibin Su,&nbsp;Jun Luo,&nbsp;Jie Xu,&nbsp;Hanhao Dai","doi":"10.1002/jcsm.13724","DOIUrl":"https://doi.org/10.1002/jcsm.13724","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;Osteosarcopenia refers to the co-occurrence of osteoporosis and sarcopenia, which are characterized by progressive bone density and muscle mass loss, respectively. Muscle and bone are regulated by many common genes and pathways, enabling potential co-treatment. Because keratocan protects against osteoporosis, we hypothesized it may also protect against sarcopenia, implying a new co-intervention target. This study aimed to elucidate the role and molecular mechanisms of keratocan in skeletal muscle.&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 keratocan expression in the muscles of aged mice and patients with osteosarcopenia and during the differentiation of C2C12 myoblasts. The regulatory role of keratocan was assessed by knocking down or overexpressing keratocan in C2C12 cells and examining any effects on myogenic proliferation and differentiation. RNA sequencing analysis was also performed on these cells. The relationship between keratocan and enriched signalling pathways was verified using pathway inhibitors or agonists. Finally, adeno-associated virus-9 containing a muscle-specific promoter was injected into SAMP8 senile mice to observe the effects of keratocan overexpression.&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;Keratocan expression was significantly lower in the skeletal muscles of aging mice (−2.02-fold, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) and patients with osteosarcopenia (−1.78-fold, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) compared with that in controls. Keratocan overexpression resulted in a significant increase in the proliferation indices CCND1 (+1.43-fold, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), Ki67 (+2.30-fold, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) and PCNA (+1.975-fold, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) and the differentiation indices MyoD1 (+2.156-fold, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), MyoG (+1.52-fold, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) and myosin heavy chain (MyHC; +2.849-fold, &lt;i&gt;p&lt;/i&gt; &lt; 0.01); conversely, the muscle atrophy indices MuRF-1 (−30%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01), atrogin-1 (−87%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) and myostatin (−24%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) were significantly decreased. PI3K/AKT/mTOR was identified as a potential pathway for keratocan regulation in C2C12 cells. PI3K inhibitor LY294002 reversed the promotion of myogenesis by keratocan overexpression, while PI3K activator 740Y-P reversed the inhibitory effect of keratocan knockdown on myogenesis, promoting myofibre development and ameliorating muscle atrophy in SAMP8 aging mice. This was evidenced by increased mean muscle cross-sectional area (+38%, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) and muscle mass (+7%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) and decreased fibrosis (−40%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01). Furthermore, keratocan facilitated the conversion of slow-to-","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13724","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431442","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":"Sarcopenia and Insulin Resistance Collective Effect on Atrial Fibrillation Risk: A Non-Diabetic Elderly Cohort Study","authors":"Weike Liu,&nbsp;Xin Wang,&nbsp;Yuqi Guo,&nbsp;Yumei Gao,&nbsp;Huajing Song,&nbsp;Yanli Yao,&nbsp;Hua Zhang,&nbsp;Zhendong Liu,&nbsp;Juan Wang","doi":"10.1002/jcsm.13736","DOIUrl":"https://doi.org/10.1002/jcsm.13736","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;Appendicular skeletal muscle mass index (ASMI), a crucial indicator of sarcopenia and estimated glucose disposal rate (eGDR), a surrogate marker of insulin resistance (IR), are associated with the risk of cardiovascular diseases. However, it remains unclear whether the collective effects, including the impact of the temporal progression of ASMI and eGDR, affect atrial fibrillation (AF) risk. This study aims to elucidate the association between the collective effects of ASMI and eGDR and AF risk in the non-diabetic 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;A total of 8060 non-diabetic older individuals from a community-based cohort study were used to prospectively analyse the association between the collective effects of baseline ASMI and eGDR and AF risk. Among them, 7651 were eligible and used for dual-trajectory analysis of the association between dual trajectory of ASMI and eGDR and AF risk. The temporal development of ASMI and eGDR over time was determined using a dual-trajectory model. Statistical analyses involved restricted cubic splines and Fine–Gray competing risk models, adjusting for potential confounders.&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;In the prospective analysis, the hazard ratio (HR) of AF was 1.762 (95% confidence interval [CI]: 1.528–2.032) in the low ASMI group compared to the normal ASMI group in total participants. Restricted cubic splines analysis demonstrated L-shaped associations between AF risk and ASMI and eGDR, with inflection points at 7.23 kg/m&lt;sup&gt;2&lt;/sup&gt; and 7.85 mg/kg/min, respectively. Low ASMI and moderate and low eGDR exhibited a significant interplay for increasing AF risk (HR: 1.290 and 1.666, 95% CI: 1.136–1.464 and 1.492–1.861, respectively, &lt;i&gt;p&lt;/i&gt;&lt;sub&gt;adj.&lt;/sub&gt; &lt; 0.001). One-SD increment ASMI and eGDR synergistically reduced AF risk (HR: 0.896, 95% CI: 0.839–0.957, &lt;i&gt;p&lt;/i&gt;&lt;sub&gt;adj.&lt;/sub&gt; &lt; 0.001). In the dual-trajectory analysis for total participants, five distinct dual trajectories of ASMI and eGDR were identified. Group 4, characterized by moderate-stable ASMI and moderate-stable eGDR, exhibited the lowest incidence of AF (7.03 per 1000 person-years) and was used as a reference for further analyses. Group 1, characterized by high-decrease ASMI and high-decrease eGDR, had the highest AF risk (HR: 2.255, 95% CI: 1.769–2.876, &lt;i&gt;p&lt;/i&gt;&lt;sub&gt;adj.&lt;/sub&gt; &lt; 0.001), followed by Group 5, with high-decrease ASMI and low-stable eGDR (HR: 1.893, 95% CI: 1.491–2.403, &lt;i&gt;p&lt;/i&gt;&lt;sub&gt;adj.&lt;/sub&gt; &lt; 0.001) when compared to Group 4 after adjustment for potential confounders including baseline ASMI and eGDR.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13736","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424236","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":"Aged-Related Fibroblast Activation Protein Expression in Skeletal Muscles Evaluated by PET Imaging","authors":"Minseok Suh,&nbsp;Joonhyung Gil,&nbsp;Yeon-Koo Kang,&nbsp;Hongyoon Choi,&nbsp;Gi Jeong Cheon","doi":"10.1002/jcsm.13730","DOIUrl":"https://doi.org/10.1002/jcsm.13730","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Fibroblast activation protein (FAP) is prominently involved in the tumour microenvironment and tissue remodelling processes in most cancers, and its expression is also noted in normal skeletal muscle. This study aims to explore the relationship between FAP expression and age-related muscle characteristics through FAP inhibitor (FAPI) PET/CT imaging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective analysis studied 54 patients with lung cancer (<i>n</i> = 27) and pancreatic cancer (<i>n</i> = 27) using FAPI PET/CT. Imaging-based muscle features including the mean standardised uptake value (SUVmean), skeletal muscle index (SMI) and Hounsfield units (HU) were evaluated. Age-related FAP expression in skeletal muscles was also evaluated using the Genotype-Tissue Expression (GTEx) dataset. Statistical analyses included Spearman's rank correlation and Kruskal–Wallis test, with a <i>p</i>-value of less than 0.05 considered significant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Analysis revealed a moderate to strong positive correlation between FAPI SUVmean and age (<i>ρ</i> = 0.368, <i>p</i> = 0.006), with older age groups showing higher muscle uptake. Within specific cohorts, the FAPI-74 group demonstrated a stronger correlation (<i>ρ</i> = 0.500, <i>p</i> = 0.008) compared to the FAPI-46 group (<i>ρ</i> = 0.319, <i>p</i> = 0.105). SUVmean also correlated negatively with muscle density (HU) (<i>ρ</i> = −0.298, <i>p</i> = 0.029), suggesting an association with higher fat infiltration. GTEx data supported these findings, showing a significant increase in FAP expression across age groups (<i>p</i> &lt; 0.001), with the highest median FAP in the 70–79 age group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study demonstrates an age-related increase in FAPI uptake in skeletal muscle, correlated with changes in muscle density and fat infiltration. The role of FAP extends beyond pathology to normal muscle, indicating broader biological functions. Accordingly, FAPI PET shows promise for assessing age-related muscle health and quality.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13730","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423994","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":"Device-Measured Physical Activity, Sedentary Behaviour and Risk of Chronic Kidney Diseases Across Levels of Grip Strength","authors":"Yu He,&nbsp;Jing Wang,&nbsp;Weijie Zhang,&nbsp;Xinru Chen,&nbsp;Qiqi Wu,&nbsp;Yuxuan Li,&nbsp;Yiliang Ou,&nbsp;Yaping Liu,&nbsp;Hongliang Feng,&nbsp;Jihui Zhang,&nbsp;Sizhi Ai,&nbsp;Yannis Yan Liang,&nbsp;Yuping Ning,&nbsp;Jun Zhang","doi":"10.1002/jcsm.13726","DOIUrl":"https://doi.org/10.1002/jcsm.13726","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The study aimed to investigate whether the associations of accelerometer-measured physical activity (PA) and sedentary behaviour (SB) with incident chronic kidney disease (CKD) vary based on different levels of hand grip strength, identifying the modifying role of grip strength in these associations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study included 87 487 adults from the UK Biobank. PA and SB were quantified using accelerometers over 7-day period, while grip strength was assessed using a hand dynamometer. CKD events were ascertained through hospital records or death registries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Participants had a mean age of 62.3 years, with 57.2% (50 062) identifying as female and 97% as White. Over a median follow-up of 7.0 years, the total incidence rate of CKD was 4.7 per 1000 person-years. Participants who performed higher volumes of PA were more likely to be younger; have better control of body weight, blood glucose and blood pressure; and have fewer major comorbidities (<i>p</i> &lt; 0.001). Total PA, moderate-to-vigorous intensity PA (MVPA), and light intensity PA (LPA), were inversely associated with CKD risk in a dose–response manner (all <i>p</i>_overall &lt; 0.050). In contrast, SB was associated with a higher risk of CKD (<i>p</i>_overall &lt; 0.001). Hand grip strength significantly modified the relationship between PA, SB, and CKD risk (<i>p</i>_interaction &lt; 0.10). The associations of total PA (HR, 0.70; 95% CI, 0.59–0.84), MVPA (HR, 0.75; 95% CI, 0.65–0.88), LPA (HR, 0.81; 95% CI, 0.69–0.94), and SB (HR, 1.43; 95% CI, 1.21–1.69) with CKD risk were more remarkable among individuals with lower hand grip strength. Of note, physical inactivity ranked higher in relative strength for predicting CKD than hypertension, diabetes, and obesity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Hand grip strength could significantly modify the associations of accelerometer-measured PA and SB with the risk of CKD. Regardless of intensity, PA consistently correlates with reduced risk of CKD, while SB is associated with increased risk, especially among individuals with lower grip strength. Notably, physical inactivity was found to be as predictive of CKD as traditional risk factors, highlighting the importance of promoting PA, especially among those with lower grip strength.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13726","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423995","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":"The Effects of Vitamin D on Muscle Strength Are Influenced by Testosterone Levels","authors":"Aolin Yang,&nbsp;Qingqing Lv,&nbsp;Ziyu Han,&nbsp;Shimiao Dai,&nbsp;Yao Li,&nbsp;Mengru Hao,&nbsp;Ruirui Yu,&nbsp;Junying Zhu,&nbsp;Chenggang Yang,&nbsp;Zhan Shi,&nbsp;Ji-Chang Zhou","doi":"10.1002/jcsm.13733","DOIUrl":"https://doi.org/10.1002/jcsm.13733","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 the role of vitamin D receptor (VDR) in muscle mass and strength is well established, the effects of vitamin D (VD) on muscle remain controversial due to various factors. Herein, the influence of sex on the effects of VD on muscle function and the underlying reasons was explored.&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;Male and female &lt;i&gt;Sod1&lt;/i&gt; gene knockout (SKO) mice, serving as a model for skeletal muscle atrophy, were treated with the VD active analogue calcipotriol, and RNA sequencing was employed to investigate this potential signalling pathway. The National Health and Nutrition Examination Survey (NHANES) database was utilized to explore whether testosterone affects the correlation between VD and grip strength in human participants. Experiments involving C2C12 cells and castrated male mice subjected to immobilization were conducted to demonstrate the enhancing effects of testosterone on VD function.&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;In male SKO mice, &lt;i&gt;Vdr&lt;/i&gt; expression in the gastrocnemius muscle was positively correlated with grip strength (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.4689, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), whereas no such correlation was identified in female mice. At 28 weeks of age, both male and female SKO mice exhibited significantly reduced grip strength compared to &lt;i&gt;Sod1&lt;/i&gt; wild-type (SWT) mice, and calcipotriol restored grip strength in male SKO mice (SWT-veh: 0.0716 ± 0.0006, SWT-cal: 0.0686 ± 0.0010, SKO-veh: 0.0601 ± 0.0010, SKO-cal: 0.0703 ± 0.0007; &lt;i&gt;p&lt;/i&gt; &lt; 0.05). Calcipotriol increased muscle protein synthesis and mitochondrial biogenesis while decreasing inflammation and atrogenes in gastrocnemius muscle of male SKO mice. However, the effect of calcipotriol on muscle was not significant in female SKO mice. Compared to wild-type mice, both male and female SKO mice exhibited reduced levels of 1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D&lt;sub&gt;3&lt;/sub&gt; due to ROS-induced hepatic CYP3A4 overexpression, thereby excluding the influence of baseline VD levels. The serum 25(OH)D&lt;sub&gt;3&lt;/sub&gt; and testosterone interactively affect grip strength in adults (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Using C2C12 cells differentiated into myotubes, testosterone significantly enhanced the inducing effects of VD on VDR, androgen receptor (AR), P-AKT, PGC1α, Beclin1 and LC3B. Calcipotriol improved grip strength in sham-operated mice but had a negligible effect on grip strength in castrated mice. However, a significant improvement in grip strength was observed in castrated mice following testosterone restoration (&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;","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13733","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423993","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":"Diagnostic Criteria for Cancer-Associated Cachexia: Insights from a Multicentre Cohort Study","authors":"Zhenyu Huo,&nbsp;Feifei Chong,&nbsp;Na Li,&nbsp;Siyu Luo,&nbsp;Liangyu Yin,&nbsp;Jie Liu,&nbsp;Mengyuan Zhang,&nbsp;Jing Guo,&nbsp;Yang Fan,&nbsp;Ling Zhang,&nbsp;Xin Lin,&nbsp;Hongmei Zhang,&nbsp;Muli Shi,&nbsp;Xiumei He,&nbsp;Zongliang Lu,&nbsp;Ning Tong,&nbsp;Wei Li,&nbsp;Jiuwei Cui,&nbsp;Zengqing Guo,&nbsp;Qinghua Yao,&nbsp;Fuxiang Zhou,&nbsp;Ming Liu,&nbsp;Zhikang Chen,&nbsp;Huiqing Yu,&nbsp;Minghua Cong,&nbsp;Tao Li,&nbsp;Zengning Li,&nbsp;Pingping Jia,&nbsp;Min Weng,&nbsp;Chunhua Song,&nbsp;Hanping Shi,&nbsp;Hongxia Xu,&nbsp;The Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) Group","doi":"10.1002/jcsm.13703","DOIUrl":"https://doi.org/10.1002/jcsm.13703","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;To explore the association between cachexia, as defined by different diagnostic criteria, and the risk of mortality in individuals with cancer. We also examined which diagnostic criteria are more feasible and appropriate for cancer-associated cachexia in clinical practice.&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 multicentre cohort study was conducted, which involved 5769 participants with cancer. The diagnosis of cachexia was made by applying the initial Fearon criteria (with the appendicular skeletal muscle mass index [ASMI]) and six modified criteria: (1) evaluating the muscle mass through the mid-upper-arm muscle area (MAMA), (2) fat-free mass index (FFMI), (3) calf circumference (CC), (4) hand grip strength (HGS), (5) neutrophil-to-lymphocyte ratio (NLR) and (6) omission of reduced muscle mass. The correlations between cancer cachexia diagnosed by different definitions and survival were assessed using Kaplan–Meier analyses and multivariable-adjusted Cox models. The sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, AUC value, Youden index and weighted kappa coefficient were calculated for each set of criteria.&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 final analysis included 5110 patients diagnosed with 15 different types of cancer, with a median age of 56. Out of these, 2490 (48.7%) were male. The prevalence of cancer cachexia based on the Fearon criteria was 26.5%, ranging from 21.8% to 32.2% with the six modified criteria. Following adjustment for age, sex, clinical stage and cancer site, cachexia defined by Fearon criteria was associated with a noteworthy increase in mortality (HR, 1.275; 95% CI, 1.136–1.430; &lt;i&gt;p&lt;/i&gt; &lt; 0.001), ranging from 1.237 (95% CI, 1.106–1.383; &lt;i&gt;p&lt;/i&gt; &lt; 0.001) to 1.382 (95% CI, 1.226–1.557; &lt;i&gt;p&lt;/i&gt; &lt; 0.001) by the six modified criteria. All six modified criteria presented adequate performance indicators (all &lt;i&gt;p&lt;/i&gt; &lt; 0.001), with sensitivity ranging from 82.4% (95% CI, 80.2%–84.3%) to 90.7% (95% CI, 89.0%–92.2%), specificity ranging from 86.9% (95% CI, 85.7%–87.9%) to 100.0% (95% CI, 99.9%–100.0%) and AUC ranging from 0.860 (95% CI, 0.850–0.869) to 0.932 (95% CI, 0.925–0.939). The modified criteria also showed strong (Fearon criteria with NLR: &lt;i&gt;κ&lt;/i&gt; = 0.673, 95% CI, 0.651–0.695) to almost perfect (Fearon criteria without reduced muscle mass [RMM]: &lt;i&gt;κ&lt;/i&gt; = 0.873, 95% CI, 0.857–0.888) consistency with the original Fearon criteria.&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;Cachexia defined by the Fearon ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13703","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404654","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}